Bidentate organic tellurium salt catalyst as well as preparation method and application thereof

Abstract

The invention provides a bidentate organic tellurium salt catalyst as well as a preparation method and application thereof. The bidentate organic tellurium salt catalyst has a structure as shown in a formula (I). According to the bidentate organic tellurium salt prepared by the invention, the activity of a chalcogenide bond catalyst is improved by introducing an electron-deficient aryl substituent and optimizing a linking group. A series of bidentate organic tellurium catalysts are efficiently developed and have excellent performance in activation of an azetidine structure and an aziridine structure, and it is proved that the chalcogenide bond action capacity of the bidentate organic tellurium catalysts is enhanced. This activation in turn initiates a [4 + 2] cycloaddition reaction with an unactivated olefin or alkyne.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of chemical catalysis technology, and provides a bidentate organotelluride salt catalyst as well as a preparation method and application thereof. BACKGROUND

[0002] Tellurium is the largest and most stable chalcogen element in terms of atomic radius, and mainly exists in monetary metal ores on earth, especially in sulfide deposits related to volcanic activity, with a content of up to several hundred ppm. Although tellurium is relatively rare on earth, it is widely distributed and has become a very important element, which can be used for the preparation of special alloys, and applied in photovoltaic solar cells and photoreceptors. In the past few decades, most applications of tellurium have relied on the inorganic chemical properties of tellurium, while the application of tellurium in the field of organic chemistry is very limited.

[0003] In 2018, Matile and his team pioneered the report of a neutral divalent organotelluride compound with two pentafluorophenyl substituents, and evaluated its catalytic potential through chloride extraction reaction [1] . Subsequently, the Mamane team [2] and the team [3] designed cationic form of tellurium (IV) organocatalysts, respectively. This ingenious modification not only enhances the catalytic activity, but also lays the foundation for its catalytic application in a variety of conventional reactions. Drawing on this strategy, Wang and his colleagues developed a class of highly active tellurium (VI) salts with limited active sites, with the help of which they successfully realized more challenging catalytic conversion reactions [4] .

[0004] Another solution is to propose to improve the activity of chalcogen bond (ChB) catalysts through bidentate activation mode. This idea was first confirmed by the Huber team in 2019. They found that a dicationic tellurium (II) organocatalyst derived from 1,3-bis (triazole) benzene could effectively promote the Michael addition reaction [5-6] . Inspired by the observation of this synergistic effect, and his colleagues designed a novel bidentate dicationic compound, which can be easily prepared from 9,9-dimethylxanthene-4,5-diboronic acid derivatives and phenoxatellurine. Based on its excellent affinity for chloride ions, this study focuses on exploring the potential of the compound as an activator in metal-catalyzed reactions [7] . Despite these achievements, due to the limited types of catalysts and insufficient catalytic ability, tellurium-based chalcogen bond catalysis is still largely limited to benchmark reactions. In this context, developing more active and stable tellurium catalysts will be an effective means to broaden the types of reactions. The designed bidentate dicationic structure has not yet been applied to catalytic systems, but its inherent advantages include modular synthetic routes and precise electronic tunability, laying a solid foundation for the design of the next generation of catalysts.

[0005] Most small organic molecule catalysts are physically stable, not sensitive to air and water, and do not require anhydrous and anaerobic conditions for catalytic reactions. Therefore, as a new type of small organic molecule catalyst, the catalytic activity and stability of organic telluride catalysts are a major problem in this field. At this stage, there is a significant limitation in the type of organic telluride catalytic reaction, and the root cause of this situation is the relatively limited catalytic mode. Specifically, the oxygen group bond can mainly activate halogen (such as fluorine, chlorine, bromine), compounds containing π bonds (such as alkenes, alkynes), and compounds containing nitrogen and oxygen heteroatoms. This relatively fixed catalytic mode makes the range of reaction types it can initiate relatively narrow, and at the same time, it also limits the application range of the substrate. In addition, most organic telluride catalytic reactions are reactions that can also be achieved by other small organic molecule catalysts. In this case, even if low-activity reaction substrates are used, it is difficult to highlight the high activity characteristics of the oxygen group bond catalyst itself, and it is even more difficult to demonstrate the advantages of the unique activation mode of the organic telluride catalyst. More importantly, using new organic telluride catalysts to catalyze reactions that existing organic catalysts cannot achieve is indeed rare. This current situation to a large extent restricts the role of oxygen group bond catalysis in a wider field, and further highlights the urgency and necessity of developing new catalytic modes for oxygen group bond catalysis and expanding its catalytic reaction types.

[0006] REFERENCES:

[0007] [1] S. Benz, A. I. Poblador-Bahamonde, N. Low-Ders, S. Matile, Angew. Chem. Int. Ed. 2018, 57, 5408-5412.

[0008] [2] R. Weiss, E. Aubert, P. Pale, V. Mamane, Angew. Chem. Int. Ed. 2021, 60, 19281-19286.

[0009] [3] B. Zhou, Organometallics 2021, 40, 2371-2374.

[0010] [4] X. Li, Y. Liu, W. Wang, Y. Wang, J. Am. Chem. Soc. 2025, 147, 3233-3242.

[0011] [5] P. Wonner, A. Dreger, L. Vogel, E. Engelage, S. M. Huber, Angew. Chem. Int. Ed. 2019, 58, 16923-16927.

[0012] [6] P. Wonner, T. Steinke, L. Vogel, S. M. Huber, Chem. Eur. J. 2020, 26, 1258-1262.

[0013] [7] B. Zhou, J. Am. Chem. Soc. 2021, 143, 8625-8630. SUMMARY

[0014] Based on the above technical purposes, the present application provides a bidentate organotelluride salt catalyst and its preparation method and application. The bidentate organotelluride salt prepared by the present application enhances the activity of chalcogen bond catalysts by introducing electron-deficient aryl substituents and optimizing the linking groups. The present application efficiently develops a series of bidentate organotelluride catalysts, and they all have excellent performance in the activation of azetidine structure and aziridine structure, which confirms the enhancement of their chalcogen bond action ability. This activation in turn triggers the [4+2] cycloaddition reaction with unactivated olefins or alkynes.

[0015] In a first aspect, the present application provides a bidentate organotelluride salt catalyst and its enantiomers or diastereomers or pharmaceutically acceptable salts thereof, having a structure as shown in formula (I):

[0016]

[0017] wherein m is selected from an integer from 0 to 4, for example, selected from 0, 1, 2, 3, 4;

[0018] n is selected from an integer from 0 to 5, for example, selected from 0, 1, 2, 3, 4 or 5;

[0019] each R is independently H, -F, -Cl, -Br, -I, -NH2, -CN, -CHO, -COOH, -SO3H, alkyl-C(=O)-, aryl-C(=O)-, aryl-SO2-, -CONH2, -NHCOOH, -B(OH)2, -pinacol boronic acid, nitro, alkoxy, alkylthio, haloalkyl, haloalkenyl, haloalkynyl, haloalkoxy, haloalkenyloxy, haloalkynyloxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl or alkyl;

[0020] X is BF 4 - or BArF 4-; BArF 4 - is B[3,5-(CF3)2C6H3] 4- ;

[0021] A is absent, a bond, -Z-, -N(R 1 ) y -, -C(=Z)-, -((C(R 2 ) p ) q -, -S(=O) y -, -NR 1 -C(=O)-, -NR 1 -C(=O)-NR 1 -, -C(=O)-NR 1 -, -((C(R 2 ) p ) q -Z) x -(C(R 2 ) p ) q - ;

[0022] each Y is independently absent, a bond, -N(R 1 ) y -, -C(=Z)-, -((C(R 2 ) p ) q -, -S(=O) y -, -NR 1 -C(=O)-, -NR 1 -C(=O)-NR 1 -, -C(=O)-NR 1 -, -((C(R 2 ) p ) q -Z) x -(C(R 2 ) p ) q - ;

[0023] each Z is independently selected from O or S;

[0024] each p is independently selected from 0, 1 or 2;

[0025] each y is independently selected from 0 or 1 ;

[0026] q and x are each independently selected from an integer from 0 to 30, for example from 0 to 20 or 0 to 10 or 0, 1, 2, 3, 4, 5, 6, 7 or 8;

[0027] each R 1 is independently H, cycloalkyl or alkyl;

[0028] each R 2 is independently H, -F, -CI, -Br, -I, -NH2, -CN, -CHO, -COOH, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkenyl, alkynyl, or alkyl;

[0029] each R 1 , R 2 , and A are further optionally each independently substituted with the same or different substituents R 0 , which are monosubstituted or polysubstituted; the substituents R 0 are hydrogen, -F, -CI, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -alkyl-COOH, -SO3H, -alkyl-SO3H, alkyl-C(=O)-, aryl-C(=O)-, aryl-SO2-, amino, nitro, alkoxy, alkylthio, haloalkyl, -Si(alkyl)2H, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkenyl, alkynyl, or alkyl.

[0030] In some embodiments, the substituents R 0 are hydrogen, -F, -CI, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -C 1-12 alkyl-COOH, -SO3H, -C 1-12 alkyl-SO3H, C 1-12 alkyl-C(=O)-, C 6-12 aryl-C(=O)-, C 6-12 aryl-SO2-, amino, nitro, C 1-12 alkoxy, C 1-12 alkylthio, C 1-12 haloalkyl, -Si(C 1-12 alkyl)2H, C 3-12 cycloalkyl, C 2-12 heterocyclyl, C 6-12 aryl, C 1-12 heteroaryl, C 2-12 alkenyl, C 2-12 alkynyl, or C 1-12 alkyl.

[0031] In some embodiments, the substituents R 0 are hydrogen, -F, -CI, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -C 1-6 alkyl-COOH, -SO3H, -C 1-6 alkyl-SO3H, C 1-6 alkyl-C(=O)-, C 6-12aryl-C(=0)-, C 6-12 aryl-S02-, amino, nitro, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkyl, -Si(C 1-6 alkyl)2H, C 3-12 cycloalkyl, C 2-12 heterocyclyl, C 6-12 aryl, C 1-12 heteroaryl, C 2-6 alkenyl, C 2-6 alkynyl or C 1-6 alkyl.

[0032] In some embodiments, the substituents R 0 are hydrogen, -F, -CI, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -methyl-COOH, -SO3H, -methyl-SO3H, methyl-C(=0)-, C 6-12 aryl-C(=0)-, C 6-12 aryl-S02-, amino, nitro, methoxy, methylthio, trifluoromethyl, -Si(methyl)2H, phenyl, naphthyl, methyl, ethyl, iso-propyl, n-propyl, n-butyl or t-butyl.

[0033] In some embodiments, each R is independently H, -F, -CI, -Br, -I, -NH2, -CN, -CHO, -COOH, -SO3H, C 1-6 alkyl-C(=0)-, C 6-12 aryl-C(=0)-, C 6-12 aryl-S02-, -CONH2, -NHCOOH, -B(OH)2, -pinacol boronic ester, nitro, C 1-12 alkoxy, C 1-12 alkylthio, C 1-12 haloalkyl, C 2-12 haloalkenyl, C 2-12 haloalkynyl, C 1-12 haloalkoxy, C 2-12 haloalkenyloxy, C 2-12 haloalkynyloxy, C 3-12 cycloalkyl, C 2-12 heterocycloalkyl, C 6-12 aryl, C 1-12 heteroaryl, C 2-12 alkenyl, C 2-12 alkynyl or C 1-12 alkyl; which can be further substituted by the same or different substituents R 0 monosubstituted or polysubstituted.

[0034] H, -F, -CI, -Br, -I, -NH2, -CN, -CHO, -COOH, -SO3H, -CONH2, -NHCOOH, -B(OH)2, nitro, methoxy, methylthio, trifluoromethyl, monofluoromethyl, difluoromethyl, chloroethyl, methyl, ethyl, i-propyl, n-propyl, n-butyl, t-butyl or n-hexyl; can be further substituted by the same or different substituents R as described in the present application 1-6 alkyl-C(=0)-, C 6-12 aryl-C(=0)-, C 6-12 aryl-SO2-, -CONH2, -NHCOOH, -B(OH)2, -boronic pinacol ester, nitro, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkyl, C 2-6 haloalkenyl, C 2-6 haloalkynyl, C 1-6 haloalkoxy, C 2-6 haloalkenyloxy, C 2-6 haloalkynyloxy, C 3-6 cycloalkyl, C 2-6 heterocycloalkyl, C 6-12 aryl, C 1-12 heteroaryl, C 2-6 alkenyl, C 2-6 alkynyl or C 1-6 alkyl; can be further substituted by the same or different substituents R as described in the present application 0 monosubstituted or polysubstituted.

[0035] H, -F, -CI, -Br, -I, -NH2, -CN, -CHO, -COOH, -SO3H, -CONH2, -NHCOOH, -B(OH)2, nitro, methoxy, methylthio, trifluoromethyl, monofluoromethyl, difluoromethyl, chloroethyl, methyl, ethyl, i-propyl, n-propyl, n-butyl, t-butyl or n-hexyl; can be further substituted by the same or different substituents R as described in the present application 0 monosubstituted or polysubstituted.

[0036] H, C 1 alkyl; can be further substituted by the same or different substituents R as described in the present application 3-12 cycloalkyl or C 1-12 alkyl; can be further substituted by the same or different substituents R as described in the present application 0 monosubstituted or polysubstituted.

[0037] H, C 1 alkyl; can be further substituted by the same or different substituents R as described in the present application 3-6 cycloalkyl or C 1-6 alkyl; can be further substituted by the same or different substituents R as described in the present application 0 monosubstituted or polysubstituted.

[0038] H, C 2independently H, -F, -CI, -Br, -I, -NH2, -CN, -CHO, -COOH, C 1-12 haloalkyl, C 2-12 haloalkenyl, C 2-12 haloalkynyl, C 3-12 cycloalkyl, C 2-12 heterocycloalkyl, C 6-12 aryl, C 1-12 heteroaryl, C 2-12 alkenyl, C 2-12 alkynyl or C 1-12 alkyl; which can be further substituted by the same or different substituents R 0 monosubstituted or polysubstituted.

[0039] in some embodiments, each R 2 independently H, -F, -CI, -Br, -I, -NH2, -CN, -CHO, -COOH, C 1-6 haloalkyl, C 2-6 haloalkenyl, C 2-6 haloalkynyl, C 3-6 cycloalkyl, C 2-6 heterocycloalkyl, C 6-12 aryl, C 1-12 heteroaryl, C 2-6 alkenyl, C 2-6 alkynyl or C 1-6 alkyl; which can be further substituted by the same or different substituents R 0 monosubstituted or polysubstituted.

[0040] in some embodiments, each R 2 independently H, -F, -CI, -Br, -I, -NH2, -CN, -CHO, -COOH, methyl, ethyl, isopropyl, n-propyl, n-butyl, tert-butyl, phenyl, naphthyl, 4-methoxyphenyl or 4-fluorophenyl.

[0041] in some embodiments, the bidentate organotelluride salt catalyst and enantiomers or diastereomers thereof or pharmaceutically acceptable salts thereof, have one of the following structures:

[0042]

[0043] wherein each R, n, X, each R 2 , m have the definitions as described herein.

[0044] in some embodiments, the bidentate organotelluride salt catalyst and enantiomers or diastereomers thereof or pharmaceutically acceptable salts thereof, are selected from one of the following structural formulae:

[0045]

[0046] In a second aspect, the present application provides a method for preparing a bidentate organotelluride salt catalyst of formula (I) and enantiomers or diastereomers thereof or pharmaceutically acceptable salts thereof, comprising the following steps:

[0047]

[0048] Step 1): the diaryl telluride compound (3.S1) is reacted with NFSI and cesium fluoride to form a difluorodiaryl telluride compound (3.S2);

[0049] Step 2): the difluorodiaryl telluride compound (3.S2) and the diaryl boronic acid (3.S3) are reacted in the presence of boron trifluoride etherate solution and sodium tetrafluoroborate to obtain the bidentate organotelluride salt catalyst of formula (I);

[0050] R, n, Y, A have the definitions as described above.

[0051] In some embodiments, in step 1), the molar ratio of the diaryl telluride compound (3.S1) to cesium fluoride is 1:1-5, preferably 1:1, 1:2, 1:3, 1:4 or 1:5, and any one of the ranges formed by any two of the above values.

[0052] In some embodiments, in step 1), the molar ratio of the diaryl telluride compound (3.S1) to NFSI (N-fluorobenzenesulfonamide) is 1:1-5, preferably 1:1, 1:2, 1:3, 1:4 or 1:5, and any one of the ranges formed by any two of the above values.

[0053] In some embodiments, in step 1), the solvent used is selected from one of toluene, chlorobenzene, dichloromethane, ethyl acetate, anisole, diethyl ether, methanol, ethanol, propanol, acetone and butanol.

[0054] In some embodiments, in step 1), the diaryl telluride compound (3.S1) and cesium fluoride are added to dichloromethane under ice bath, NFSI dissolved in dichloromethane is added, and the reaction is completed at room temperature overnight. The difluorodiaryl telluride compound (3.S2) is obtained by filtration.

[0055] In the present application, room temperature refers to 15-35℃, preferably 20-25℃.

[0056] In some embodiments, in step 2), the molar ratio of the difluoro diaryl telluride compound (3.S2) to the bis-aryl boronic acid is 1-5:1-5, preferably 1:1, 2:1, 3:1, 4:1, 5:1, 1:2, 1:2.05, 1:2.1, 1:2.2, 1:2.5, 1:3, 1:4 or 1:5, and any one of ranges formed by any two of the above values.

[0057] In some embodiments, the bis-aryl boronic acid is selected from

[0058] In some embodiments, in step 2), the molar ratio of the bis-aryl boronic acid to the boron trifluoride diethyl ether solution is 1-5:1-5, preferably 1:1, 2:1, 3:1, 4:1, 5:1, 3:2, 1:2, 1:2.05, 1:2.1, 1:2.2, 1:2.5, 1:3, 1:4 or 1:5, and any one of ranges formed by any two of the above values.

[0059] In some embodiments, in step 2), the molar ratio of the bis-aryl boronic acid to the sodium tetrafluoroborate is 1-5:10-55, preferably 1:10, 1:11, 1:12, 1:13, 1:14 or 1:15, and any one of ranges formed by any two of the above values.

[0060] In some embodiments, in step 2), the solvent used is selected from one of toluene, chlorobenzene, dichloromethane, ethyl acetate, anisole, diethyl ether, methanol, ethanol, propanol, acetone and butanol.

[0061] In some embodiments, in step 2), under argon atmosphere, the difluoro diaryl telluride compound (3.S2) and the bis-aryl boronic acid are dissolved in dichloromethane, and the boron trifluoride diethyl ether solution is added under ice bath, and the reaction is carried out at room temperature overnight; the aqueous sodium tetrafluoroborate solution is added, and the reaction is carried out at room temperature for 2 hours, and the post-processing obtains the bidentate organotellurium salt catalyst of formula (I).

[0062] In a third aspect, the present application provides a bidentate organotellurium salt catalyst of formula (I) and an enantiomer or diastereomer thereof or a pharmaceutically acceptable salt thereof, and the application includes the use of the bidentate organotellurium salt catalyst of formula (I) for the synthesis of a piperidine derivative.

[0063] In some embodiments, the synthesis of the piperidine derivative includes: reacting compound 1, compound 2 and the bidentate organotellurium salt catalyst of formula (I) in a solvent to obtain compound 3,

[0064]

[0065] wherein z is 0 or 1;

[0066] M is Ts-, Ns-, -SO2-Et, Boc, Ph- or Ph-SO2-;

[0067] each R 4 is independently cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0068] R 5 , R 6 , R 7a , R 7b is each independently H, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkenyl, alkynyl or alkyl; R 5 and R 7a together with the carbon atom to which they are attached form an E ring; R 6 and R 7b together with the carbon atom to which they are attached form an F ring; the E ring and F ring are each independently cycloalkyl, heterocycloalkyl, aryl or heteroaryl; R 7b and R 7a together with the carbon atom to which they are attached form a chemical bond, i.e. the single bond connecting is changed to an olefinic bond or the olefinic bond connecting is changed to an acetylenic bond;

[0069] the R 4 , R 5 , R 6 , R 7a , R 7b , E ring and F ring are further optionally each independently mono- or poly-substituted with identical or different substituents R a ; the substituents R a are hydrogen, =0, -F, -Cl, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -alkyl-COOH, -SO3H, -alkyl-SO3H, alkyl-C(=0)-, aryl-C(=0)-, aryl-SO2-, amino, nitro, alkoxy, alkylthio, haloalkyl, -Si(alkyl)2H, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkenyl, alkynyl or alkyl.

[0070] In some embodiments, the substituents R a are hydrogen, =0, -F, -Cl, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -C 1-12 alkyl-COOH, -SO3H, -C 1-12 alkyl-SO3H, C 1-12 alkyl-C(=0)-, C 6-12 aryl-C(=0)-, C 6-12 aryl-SO2-, amino, nitro, C 1-12 alkoxy, C 1-12 alkylthio, C1-12 Haloalkyl, -Si(C) 1-12 Alkyl)2H,C 3-12 cycloalkyl, C 2-12 Heterocyclic group, C 6-12 Aryl, C 1-12 heteroaryl, C 2-12 alkenyl, C 2-12 alkynyl or C 1-12 alkyl.

[0071] In some embodiments, the substituent R a - Hydrogen, =O, -F, -Cl, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl group, -COOH, -C 1-6 Alkyl groups -COOH, -SO3H, -C 1-6 Alkyl-SO3H, C 1-6 Alkyl-C(=O)-, C 6-12 Aryl-C(=O)-, C 6-12 Aryl-SO2-, amino, nitro, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Haloalkyl, -Si(C) 1-6 Alkyl)2H,C 3-12 cycloalkyl, C 2-12 Heterocyclic group, C 6-12 Aryl, C 1-12 heteroaryl, C 2-6 alkenyl, C 2-6 alkynyl or C 1-6 alkyl.

[0072] In some embodiments, the substituent R a Hydrogen, =O, -F, -Cl, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -methyl-COOH, -SO3H, -methyl-SO3H, methyl-C(=O)-, C 6-12 Aryl-C(=O)-, C 6-12 Aryl-SO2-, amino, nitro, methoxy, methylthio, trifluoromethyl, -Si(methyl)2H, phenyl, naphthyl, methyl, ethyl, isopropyl, n-propyl, n-butyl or tert-butyl.

[0073] In some embodiments, each R 4 Independently for C 3-12 cycloalkyl, C 2-12 Heterocyclic alkyl, C 6-20 Aryl or C 1-20 Heteroaryl groups; which may be further substituented by the same or different substituents R described in this invention. a Single or multiple substitutions.

[0074] In some embodiments, each R 4 is independently phenyl,

[0075] In some embodiments, R 5 , R 6 , R 7a , R 7b is each independently H, C 1-12 haloalkyl, C 2-12 haloalkenyl, C 2-12 haloalkynyl, C 3-20 cycloalkyl, C 2-20 heterocycloalkyl, C 6-20 aryl, C 1-20 heteroaryl, C 2-12 alkenyl, C 2-12 alkynyl, or C 1-12 alkyl; each of the E and F rings is independently C 3-20 cycloalkyl, C 2-20 heterocycloalkyl, C 6-20 aryl, or C 1-20 heteroaryl; R 5 , R 6 , R 7a , R 7b , E ring, and F ring can be further mono- or poly-substituted with the same or different substituents R a as described herein.

[0076] In some embodiments, R 5 , R 6 , R 7a , R 7b is each independently H, C 3-6 cycloalkyl, C 2-6 heterocycloalkyl, C 6-20 aryl, C 1-12 heteroaryl, or C 1-6 alkyl; each of the E and F rings is independently C 3-8 cycloalkyl, C 2-6 heterocycloalkyl, C 6-12 aryl, or C 1-6 heteroaryl; R 5 , R 6 , R 7a , R 7b , E ring, and F ring can be further mono- or poly-substituted with the same or different substituents R a as described herein.

[0077] In some embodiments, R 5 , R 6 , R7a R 7b Each of the following is independently H, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, The E ring and F ring are each independently cyclobutyl, cyclopentyl, or cyclohexyl; R 5 R 6 R 7a R 7b The E and F rings can be further substituented with the same or different substituents R as described in this invention. a Single or multiple substitutions.

[0078] In some embodiments, the structural formula of compound 1 includes

[0079] In some embodiments, compound 1 is selected from one of the following structural formulas:

[0080]

[0081] In some embodiments, the structural formula of compound 2 includes and

[0082] In some embodiments, the structural formula of compound 3 includes and

[0083] In some embodiments, R 7aa R 7ba Each of the following is independently H, haloalkyl, haloalkenyl, haloynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkenyl, ynyl, or alkyl; R 5 and R 7aa Together with the attached carbon atom, it forms an E ring; R 6 and R 7ba Together with the attached carbon atom, it forms an F ring; the E ring and F ring are each independently a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group;

[0084] The R 7aa R 7ba The E and F rings are further optionally and independently substituented by the same or different substituents R. a Mono- or poly-substituted; the substituent R a It can be hydrogen, =O, -F, -Cl, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -alkyl-COOH, -SO3H, -alkyl-SO3H, alkyl-C(=O)-, aryl-C(=O)-, aryl-SO2-, amino, nitro, alkoxy, alkylthio, haloalkyl, -Si(alkyl)2H, cycloalkyl, heterocyclic, aryl, heteroaryl, alkenyl, alkynyl, or alkyl.

[0085] In some embodiments, R 7aa R 7ba H and C are independent of each other. 1-12 Haloalkyl, C 2-12 Haloalkenyl, C 2-12 Halogenated alkynyl group, C 3-20 cycloalkyl, C 2-20 Heterocyclic alkyl, C 6-20 Aryl, C 1-20 heteroaryl, C 2-12 alkenyl, C 2-12 alkynyl or C 1-12 Alkyl; R 7aa R 7ba It can be further modified by the same or different substituents R described in this invention. a Single or multiple substitutions.

[0086] In some embodiments, R 7aa R 7ba H and C are independent of each other. 3-6 cycloalkyl, C 2-6 Heterocyclic alkyl, C 6-20 Aryl, C 1-12 heteroaryl or C 1-6 Alkyl; R 7aa R 7ba It can be further modified by the same or different substituents R described in this invention. a Single or multiple substitutions.

[0087] In some embodiments, the E ring and the F ring are each independently C. 3-8 cycloalkyl, C 2-6 Heterocyclic alkyl, C 6-12 Aryl or C 1-6 Mixed aromatic compounds.

[0088] In some embodiments, R 7aa R 7ba Each of the following is independently H, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, The E ring and F ring are each independently cyclobutyl, cyclopentyl, or cyclohexyl; R 7aa R 7ba The E and F rings can be further substituented with the same or different substituents R as described in this invention. a Single or multiple substitutions.

[0089] In some embodiments, the structural formula of compound 3 is selected from one of the following structures:

[0090]

[0091]

[0092] Advantages

[0093] The application enhances the catalytic activity of the oxygen bond catalyst by introducing different strong electron-withdrawing groups into the aromatic ring, and designs and synthesizes a series of bidentate organotelluride oxygen bond catalysts with diversified structures.

[0094] The bidentate organotelluride catalyst of the application is applied to the (4+2) cycloaddition reaction of azetidine and non-activated olefin and alkyne.

[0095] The bidentate organotelluride catalyst prepared by the application can efficiently realize the (4+2) cycloaddition reaction of azetidine and non-activated olefin, and a total of 28 piperidine compounds (45%-90%) are synthesized.

[0096] Under the catalysis of the bidentate organotelluride catalyst prepared by the application, the (4+2) cycloaddition reaction of azetidine and alkyne can be efficiently realized, and a total of 36 structurally diversified tetrahydropyridine compounds are synthesized with a highest yield of 90%, which enriches the diversity of the compound library, develops a new mode of organic catalysis, expands the type of organic catalytic reaction, and opens a new situation for efficient organic catalysis.

[0097] The bidentate organotelluride catalyst prepared by the application uses 9,9-dimethylxanthene as a bridging group to connect two cationic tellurium centers. Compared with the bidentate skeleton of CB1-7 [7] , removing the tert-butyl group can not only simplify the skeleton structure, but also reduce the electronic density of the whole molecule. Subsequently, a series of telluronium dicationic compounds are formed by coupling with various diaryl tellurium compounds. In addition, CB8 and CB9 are also quickly prepared by using dibenzodithiophene and dibenzofuran as connecting groups, respectively. Through anion exchange with NaBArF4, telluronium tetra[3,5-bis(trifluoromethyl)phenyl]borate CB10-18 is obtained.

[0098] The prepared bidentate organotelluride salt catalyst has excellent stability in solid state, air and humidity environment.

[0099] The application designs a class of bidentate organotellurium catalysts to enhance the weak chalcogen bond (ChB) interaction. The improvement of the reactivity enables the chalcogen bond to activate azetidine by catalysis for the first time, and further initiates the [4+2] cycloaddition reaction with unactivated olefins and alkynes. The study of the mixed system of telluronium salt and Ph3PO 31 P NMR monitoring found that: the coordination ability of the counter anion and the electron-withdrawing ability of the aryl substituent of the telluronium center have a significant impact on the strength of the chalcogen bond interaction. X-ray diffraction analysis and mechanism research show that the transformation is realized by chalcogen bond catalysis, and the core is the novel bidentate activation mode formed between the ditelluronium dication and azetidine. This study not only provides an efficient method for the synthesis of piperidine and tetrahydropyridine structures, but also develops a series of high-activity tellurium catalysts, which lays a foundation for exploring unknown catalytic reactivity and applications in other fields.

[0100] Terminology

[0101] The present application is intended to embrace all alternatives, modifications and equivalents that fall within the scope of the present application as defined by the claims appended hereto. It will be clear to those of ordinary skill in the art that many methods and materials similar or equivalent to those described herein can be used in the practice of the present application. The present application is in no way limited to the methods and materials described herein. In the event that any one or more of the incorporated literature, patents, and similar materials differs from or contradicts the subject application, including but not limited to defined terms, term application, described techniques, etc., the subject application controls.

[0102] It should be further recognized that certain of the features of the present application, while described in the context of a number of separate embodiments, can also be provided in combination in a single embodiment. Conversely, various features of the present application, while described in the context of a single embodiment, can also be provided separately or in any appropriate subcombination.

[0103] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. All patents and publications referred to in this application are incorporated herein by reference in their entirety.

[0104] In the description of the specification, reference to "one embodiment", "some embodiments", "an example", "a specific example", or "some examples" means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the application. The appearances of the phrases "in one embodiment" or "in some embodiments" in various places in the specification are not necessarily all referring to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics can be combined in any suitable manner in one or more embodiments or examples. Additionally, the disclosure of a particular feature, structure, material, or characteristic is not to be construed as being in the prior art unless expressly stated to be in the prior art.

[0105] In the following disclosure, all numbers disclosed herein are approximate. Each numerical value should be construed in light of the accompanying discourse of the specification. Whenever a numerical range is disclosed, any number or value falling within the range is expressly stated. The use of "about" or "approximately" in connection with a range applies to both the start and end range values. In the disclosure, the use of "or" as a conjunction, means "and / or" unless specifically stated otherwise.

[0106] As described herein, the compounds of the application can optionally be substituted with one or more substituents, such as described herein for the compounds of the general formulae above, or as described in particular examples, subclasses, and genus of compounds contained in the application. It is understood that the term "optionally substituted" is used interchangeably with the term "substituted or unsubstituted". In general, the term "optionally" whether applied to a term, such as "substituted", means that one or more hydrogen portion of the given structure can be replaced with a particular substituent. Unless otherwise indicated, an optionally substituted group can have a substituent at each substitutable position. When a given structure is substituted with more than one substituent, the substituents can be the same or different at each occurrence. The substituents described can be, but are not limited to, hydroxyl, amino, halogen, cyano, aryl, heteroaryl, alkoxy, alkyl, alkenyl, alkynyl, heterocyclyl, thiol, nitro, aryloxy, and the like.

[0107] The term "alkyl" or "alkyl group" as used herein denotes a saturated straight chain or branched chain monovalent hydrocarbon radical of from 1 to 20 carbon atoms. The alkyl group can be independently and optionally substituted with one or more substituents as described herein. Unless otherwise specified, the alkyl group contains 1 to 20 carbon atoms, with some embodiments the alkyl group contains 1 to 10 carbon atoms, with other embodiments the alkyl group contains 1 to 8 carbon atoms, with other embodiments the alkyl group contains 1 to 6 carbon atoms, with other embodiments the alkyl group contains 1 to 4 carbon atoms, with other embodiments the alkyl group contains 1 to 3 carbon atoms. Examples of alkyl groups include, but are not limited to, such as methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, i-butyl, sec-butyl, t-butyl, n-pentyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-l-butyl, 2-methyl-l-butyl, n-hexyl, 2-hexyl, 3-hexyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl, 3,3-dimethyl-2-butyl, n-heptyl, n-octyl, and the like. The terms "alkyl" and the prefix "alk" as used herein encompass both straight chain and branched chain saturated carbon chains. "Alkylene" denotes a saturated divalent hydrocarbon radical obtained by the removal of two hydrogen atoms from a straight chain or branched chain saturated hydrocarbon, examples of which include, but are not limited to, methylene, ethylene, isopropylene, ethane- 1,1-diyl, 2-methoxypropane- 1,1-diyl, 2-hydroxypropane- 1,1-diyl, 2-methyl-2-hydroxypropane- 1,1-diyl, and the like. Heteroalkyl moieties can include four optionally different heteroatoms (e.g., O, N, S, Si, or P).

[0108] The term "alkenyl" denotes a straight chain or branched chain monovalent hydrocarbon radical of from 2 to 12 carbon atoms, or from 2 to 8 carbon atoms, or from 2 to 6 carbon atoms, or from 2 to 4 carbon atoms, wherein at least one position is in an unsaturated state, i.e., one C-C is an sp2 double bond, wherein the alkenyl group can be independently and optionally substituted with one or more substituents as described herein, including the positioning of the group as "trans", "cis", or "E", "Z", wherein specific examples of alkenyl include, but are not limited to, ethenyl (-CH=CH2), allyl (-CH2CH=CH2), and the like.

[0109] The term "alkynyl" denotes a straight-chain or branched one valent hydrocarbon group of 2 to 12 carbon atoms, or 2 to 8 carbon atoms, or 2 to 6 carbon atoms, or 2 to 4 carbon atoms, in which at least one position is in an unsaturated state, i.e. one C-C is a sp-triple bond, wherein the alkynyl group can be independently and optionally substituted with one or more substituents as described herein, wherein specific examples of alkynyl include, but are not limited to, ethynyl (-C≡CH), propargyl (-CH2C≡CH) and the like.

[0110] The term "alkoxy" denotes an alkyl group, wherein the alkyl group has the meaning as described herein, attached to the remainder of the molecule through an oxygen atom. Unless otherwise specifically indicated, the alkyl group contains 1 to 20 carbon atoms, wherein some embodiments are that the alkyl group contains 1 to 10 carbon atoms, further embodiments are that the alkyl group contains 1 to 8 carbon atoms, further embodiments are that the alkyl group contains 1 to 6 carbon atoms, further embodiments are that the alkyl group contains 1 to 4 carbon atoms, further embodiments are that the alkyl group contains 1 to 3 carbon atoms. Examples of alkyl groups include, but are not limited to, methoxy, ethoxy, 1-propoxy, 2-propoxy, 1-butoxy, 2-methyl-l-propoxy, 2-butoxy, 2-methyl-2-propoxy, 1-pent- oxy, 2-pentoxy, 3-pentoxy, 2-methyl-2-butoxy, 3-methyl-2-butoxy, 3-methyl-l-butoxy, 2-methyl-l-butoxy, and the like.

[0111] The term "alkenyloxy" denotes an alkenyl group, wherein the alkenyl group has the meaning as described herein, attached to the remainder of the molecule through an oxygen atom.

[0112] The term "alkynyloxy" denotes an alkynyl group, wherein the alkynyl group has the meaning as described herein, attached to the remainder of the molecule through an oxygen atom.

[0113] The terms "haloalkyl" and "haloalkoxy" denote an alkyl or alkoxy group, respectively, which is substituted by one or more halogen atoms. Examples include, but are not limited to, trifluoromethyl, difluoromethyl, difluoroethyl, trifluoromethoxy and the like.

[0114] The terms "haloalkenyl" and "haloalkenyloxy" denote an alkenyl or alkenyloxy group, respectively, which is substituted by one or more halogen atoms.

[0115] The terms "haloalkynyl" and "haloalkynyloxy" denote an alkynyl or alkynyloxy group, respectively, which is substituted by one or more halogen atoms.

[0116] The terms "cycloaliphatic," "carbocyclic," "carbocyclyl," or "cycloalkyl" mean a monovalent or multivalent, non-aromatic, saturated or partially unsaturated ring, including a monocyclic ring of 3-12 carbon atoms or a bicyclic ring of 7-12 carbon atoms. Bicyclic carbocyclic rings having 7-12 atoms can be bicyclo[4,5], [5,5], [5,6] or [6,6] systems, while bicyclic carbocyclic rings having 9 or 10 atoms can be bicyclo[5,6] or [6,6] systems. Suitable cycloaliphatic groups include, but are not limited to, cycloalkyl, cycloalkenyl and cycloalkynyl groups. Examples of carbocyclic or cycloalkyl groups further include, but are in no way limited to, cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopentyl-1- enyl, 1-cyclopentyl-2-enyl, 1-cyclopentyl-3-enyl, cyclohexyl, 1-cyclohexyl-1-enyl, 1-cyclohexyl-2-enyl, 1-cyclohexyl-3-enyl, cyclohexadienyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, spiro[2.4]heptyl, spiro[4.4]nonyl, hexahydro-furo[3,2-b]furan, 2,3,3a,4,7,7a-hexahydro-1 H-indene, fused bicyclo[3.3.0]octane, fused bicyclo[3.1.0]hexane, bicyclo[2.2.1]heptane, 2-azabicyclo[2.2.1]heptane, 1,2,3,4,4a,5,8,8a-octahydronaphthalene, and the like. Also, the "cycloaliphatic" (or "carbocyclic," "carbocyclyl," "cycloalkyl") can be substituted or unsubstituted, where the substituents can be, but are not limited to, hydroxyl, amino, halogen, cyano, aryl, heteroaryl, alkoxy, alkyl, alkenyl, alkynyl, heterocyclyl, thiol, nitro, aryloxy, and the like. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, and the like.

[0117] In some embodiments, cycloalkyl represents a monovalent or multivalent monocyclic, bicyclic or tricyclic ring system (e.g., a monocyclic ring such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, or a bicyclic ring including spiro, fused or bridged systems (such as bicyclo[l. l. l]pentyl, bicyclo[2.2. l]heptyl, bicyclo[3.2. l]octyl or bicyclo[5.2.0]nonyl, decalinyl, and the like) containing carbon atoms, which can be fully saturated or contain one or more degrees of unsaturation, but no aromatic ring. In one embodiment, the cycloalkyl group contains 3-6 carbon atoms, such as C 3-6 saturated or partially unsaturated cycloalkyl. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, and the like. In one embodiment, the saturated or partially unsaturated cycloalkyl is selected from the group consisting of: saturated monocyclic cycloalkyl, saturated bicyclic cycloalkyl, saturated tricyclic cycloalkyl, partially unsaturated monocyclic cycloalkyl, partially unsaturated bicyclic cycloalkyl, partially unsaturated tricyclic cycloalkyl.4-7 Cycloalkyl represents a cycloalkyl group having 4 to 7 ring atoms. 3-6 Cycloalkyl represents a cycloalkyl group having 3 to 6 ring atoms.

[0118] The terms "heterocycle," "heterocyclyl," "heteroalicyclic," or "heterocyclic" are used interchangeably herein and refer to a monocyclic, bicyclic, or tricyclic ring system in which one or more of the rings in the ring system is or are heteroatom-containing, the ring(s) can be completely saturated or contain one or more unsaturated bonds, but is not aromatic, and has only one point of attachment to the rest of the molecule. One or more rings in the ring system are independently optionally substituted with one or more substituents described herein. In some embodiments, the "heterocycle," "heterocyclyl," "heteroalicyclic," or "heterocyclic" group is a 3-7 membered monocyclic ring (1-6 carbon atoms and 1-3 heteroatoms selected from N, O, P, S, wherein S or P is optionally substituted with one or more oxygen atoms to provide groups such as SO, SO2, PO, PO2, when the ring is a 3-membered ring, and wherein only one of the heteroatoms is present when the ring is a 3-membered ring) or a 7-10 membered bicyclic ring (4-9 carbon atoms and 1-3 heteroatoms selected from N, O, P, S, wherein S or P is optionally substituted with one or more oxygen atoms to provide groups such as SO, SO2, PO, PO2). The heterocyclyl group can be carbocyclic or heteroatom-containing. "Heterocyclyl" also includes groups in which the heterocyclic group is fused to a saturated or partially unsaturated ring or heterocyclic ring.Examples of heterocycles include, but are not limited to, pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, thioxazolidinyl, piperazinyl, homopiperazinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, epoxide propyl, azepanyl, oxazepanyl, thiazepanyl, 2-pyrrolinyl, 3-pyrrolinyl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dithianyl, dithiolanyl, dihydrothienyl, pyrazolidinyl imidazolinyl, imidazolidinyl, 1,2,3,4-tetrahydroisoquinolinyl, 3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[4.1.0]heptyl, azabicyclo[2.2.2]hexyl, 3H-indolyl, quinolizinyl, 2,7- diazaspiro[4.4]non-2-yl, 7-oxo-2-azaspiro[4.5]dec-2-yl, 4-azaspiro[2.4]heptan-5-yl, 4-oxaspiro[2.4]heptan-5-yl, 5-azaspiro[2.4]heptan-5-yl, spiro[2.4]heptanyl, spiro[4.4]nonanyl, 7-hydroxy-5-azaspiro[2.4]heptan-5-yl, 4-azaspiro[2.4]heptan-5-yl, 4-oxaspiro[2.4]heptan-5-yl, 5-azaspiro[2.4]heptan-5-yl, 7-hydroxy-5-azaspiro[2.4]heptan-5-yl, 5-azaspiro[2.4]heptan-6-yl, 1,4-dioxa-7-azaspiro[4.4]nonan-8-yl, 2,7-diazaspiro[4.4]nonan-2-yl, 7-oxo-2-azaspiro[4.5]dec-2-yl, 4-azaspiro[2.4]heptan-5-yl, 4-oxaspiro[2.4]heptan-5-yl, 5-azaspiro[2.4]heptan-5-yl, N-pyridyl urea, dihydrofuranyl, dioxolanyl, dioxanyl, dithianyl, piperazinyl, pyrrolidine, dihydropyranyl, oxathiolanyl, dithiolane, oxothienyl, thiomorpholino, oxiranyl, aziridinyl, oxetanyl, oxepanyl, azetidinyl, tetrahydrofuranyl, tetrahydrothiopyranyl, pyrrolidinyl, tetrahydropyranyl, piperidinyl, morpholinyl, piperazinyl, azepanyl, oxepanyl, oxazepanyl, oxepanyl, thiepanyl, azepanyl, dioxepanyl, and diazepanyl. Examples of heterocyclic groups also include 1,1-dioxothiomorpholinyl, and where two carbon atoms in the ring are replaced by an oxygen atom such as pyrimidinedionyl. In some embodiments, examples of heterocycloalkyl include, but are not limited to, 1-(1,2,5,6-tetrahydropyridinyl), 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothiophene-2-yl, tetrahydrothiophene-3-yl, 1-piperazinyl, 2-piperazinyl, and the like.

[0119] The term "heteroatom" means one or more O, S, N, P and Si atoms, including forms of N, S and P in any oxidation state; forms of primary, secondary, tertiary amines and quaternary ammonium salts; or forms in which the hydrogen on a nitrogen atom in a heterocycle is replaced by a substituent, for example, N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or NR (as in N-substituted pyrrolidinyl).

[0120] The terms "haloalkyl", "haloalkenyl" and "haloalkoxy" mean instances in which an alkyl, alkenyl or alkoxy group, respectively, can be substituted with one or more halogen atoms. Examples of such include, but are not limited to, trifluoromethyl, 2-chloro-ethenyl, trifluoromethoxy and the like.

[0121] The term "halogen" means F, Cl, Br or I.

[0122] "Alkylene", "cycloalkylene", "heterocycloalkylene", "arylene" and "heteroarylene" alone or as part of another substituent group, mean divalent groups derived from alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl groups, respectively.

[0123] The term "aryl" can be used alone or as part of "aralkyl", "aralkoxy" or "aryloxyalkyl" and means monocyclic, bicyclic, tricyclic and tetracyclic carbocyclic ring systems containing a total of 6 to 25 ring members, where at least one ring system is aromatic, where each ring system contains 3 to 7 ring members, and only one attachment point is connected to the rest of the molecule. The term "aryl" can be used interchangeably with the term "aromatic ring" such that an aromatic ring can include phenyl, naphthyl and anthracene. The aryl group can be a monocyclic, fused to form a bicyclic or tricyclic group, or tetracyclic group, or linked through a bond to form a biaryl group. Representative aryl groups include phenyl, naphthyl and biphenyl. Other aryl groups include benzyl groups having a methylene linking group. The aryl group can be substituted or unsubstituted. The term "arylene" means that the aryl group has two attachment points to the rest of the molecule. Examples of such include, but are not limited to, phenylene, p-fluorophenylene and the like, where the aryl group has the meaning as described herein.

[0124] The term "heteroaryl" can be used alone or as part of the terms "heteroarylalkyl" or "heteroarylalkoxy" and refers to monocyclic, bicyclic, and tricyclic ring systems having a total of 5 to 14 ring members, wherein at least one ring system is aromatic, and at least one ring system contains one or more heteroatoms, wherein each ring system contains 3 to 7 ring members, and only one point of attachment to the rest of the molecule. The term "heteroaryl" can be used interchangeably with the terms "heteroaromatic" or "heteroaromatic compound". Also, the heteroaryl group can be substituted or unsubstituted. Heteroaryl groups include, but are not limited to, the following monocyclic rings: 2-furanyl, 3-furanyl, N-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, N-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, pyridazinyl (e.g., 3-pyridazinyl), 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, tetrazolyl (e.g., 5-tetrazolyl), triazolyl (e.g., 2-triazolyl and 5-triazolyl), 2-thiophenyl, 3-thiophenyl, pyrazolyl (e.g., 2-pyrazolyl), isothiazolyl, 1,2,3-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3-triazolyl, 1,2,3-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, pyrazinyl, 1,3,5-triazinyl; and the following bicyclic rings, but are not limited to these bicyclic rings: benzimidazolyl, benzofuranyl, benzothiophenyl, indolyl (e.g., 2-indolyl), purinyl, quinolinyl (e.g., 2-quinolinyl, 3-quinolinyl, 4-quinolinyl), and isoquinolinyl (e.g., 1-isoquinolinyl, 3-isoquinolinyl, or 4-isoquinolinyl), and also include groups such as pyrrole, pyridine, imidazole, pyrazole, triazole, tetrazole, pyrazine, pyrimidine, pyridazine, triazine (1,2,3-, 1,2,4- and 1,3,5-isomers), benzopyrrole, e.g., indole and isoindole, benzopyridine, e.g., quinoline and isoquinoline, benzopyrazine (quinoxaline), benzopyrimidine (quinazoline), and the like. The term "heteroarylene" means that the heteroaryl group has two points of attachment to the rest of the molecule. Examples of such include, but are not limited to, pyridylene, pyrrolylene, thiazolylene, imidazolylene, and the like, wherein the heteroaryl groups have the meaning as described herein.

[0125] The terms "comprising", "comprise" and "comprised of" are open-ended transition terms that are synonymous with "including", "includes" or "having", and are used synonymously therewith.

[0126] Unless otherwise stated, the structural formulas described herein encompass all tautomeric forms (e.g., enantiomeric, diastereomeric, and geometric (or conformational) isomers): for example, the R, S configurations for centers of asymmetry, the (Z), (E) isomers for double bonds, and the (Z), (E) conformations for imines. Thus, individual stereochemically isomeric or geometrically isomeric (or conformational) forms of compounds of the present application, as well as mixtures of such isomers, are within the scope of the present application.

[0127] The term "tautomer" or "tautomeric forms" as used herein means structural isomers that can interconvert by a low energy barrier. For example, prototropic tautomers (i.e., proton shift) include tautomers that interconvert by proton migration, such as keto-enol tautomerism and imine-enamine isomerization. Valence tautomers include tautomers that interconvert by reorganization of some of the bonding electrons.

[0128] The definitions and conventions used in connection with stereochemistry and conformational analysis generally follow S. P. Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York; and Eliel, E. and Wilen, S., "Stereochemistry of Organic Compounds", John Wiley & Sons, Inc., New York, 1994. The compounds of the present application can encompass asymmetric centers or chiral centers and therefore exist in different stereoisomeric forms. All stereoisomeric forms of the compounds of the present application, including but not limited to, diastereomeric, enantiomeric, atropisomeric, and mixtures thereof, such as racemic mixtures, form part of the present application. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D, L or R, S are used to denote the absolute configuration of the molecule. The prefixes d and 1 or (+) and (-) are employed to designate the sign of the rotation of plane-polarized light by the compound, (-) or 1 meaning that the compound is levorotatory. The chemical structures of these stereoisomers are identical except that they are mirror images of one another. A specific stereoisomer can be referred to as an enantiomer or a mixture of such isomers is often designated as an enantiomeric mixture. A 50:50 mixture of enantiomers is known as a racemic mixture or racemate, which can result from racemization of an optically active compound, or from the undirected synthesis of the compound. The terms "racemic mixture" and "racemate" mean a mixture of equal amounts of R and S enantiomers in no specific relationship to each other.

[0129] The terms "tautomer" or "tautomerism form" refer to isomers of different energies that can interconvert through a low energy barrier. For example, proton tautomers (i.e., proton-transfer tautomers) include interconversions via proton transfer, such as isomerization between keto-enol and imine-enamine forms. Valence tautomers include interconversions involving the recombination of bonding electrons.

[0130] As used in this invention, "pharmaceutically acceptable salt" refers to the organic and inorganic salts of the compounds of this invention. Pharmaceutically acceptable salts are well known in the art, as described in SMBerge et al., J. Pharmaceutical Sciences, 66, 1-19, 1977. Salts formed from pharmaceutically acceptable non-toxic acids include, but are not limited to, inorganic acid salts formed by reactions with amino groups, such as hydrochlorides, hydrobroms, phosphates, sulfates, and perchlorates, and organic acid salts such as acetates, oxalates, maleates, tartrates, citrates, succinates, and malonates, or these salts obtained by other methods described in the literature, such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, cyclopentylpropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, transbutenedioic acid, glucono-p-gluconate, glyceryl phosphate, gluconate, hemisulfate, heptaate, hexanoate, hydroiodate, 2-hydroxy-ethanesulfonate, lacturonate, lactate, laurate, lauryl sulfate, malate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, palmitate, pyruvate, pectinate, persulfate, 3-phenylpropionate, picrate, p-pentanoate, propionate, stearate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc. Salts obtained by means of appropriate bases include alkali metals, alkaline earth metals, ammonium, and N+(C1-4 alkyl)4 salts. This invention also envisions the formation of quaternary ammonium salts from any compound containing an N-group. Water-soluble, oil-soluble, or dispersed products can be obtained via quaternization. Alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, etc. Pharmaceutically acceptable salts further include suitable, non-toxic ammonium, quaternary ammonium salts, and amine cations that resist the formation of equilibrium ions, such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, C1-8 sulfonates, and aromatic sulfonates.

[0131] In this article The key can be placed in any reasonable combination on the ring, and can be represented as follows: And so on; and so on.

[0132] In this invention, Y being "non-existent" means that the two groups connected to Y are not linked together, for example... When Y does not exist, the structural formula is represented as The same applies to the rest.

[0133] In this invention, the structural formula In the middle, when "R" 7b and R 7a When "forming chemical bonds together with the attached carbon atoms", it indicates that the structural formula is The same applies to the rest.

[0134] Ns- is an abbreviation for 4-nitrobenzenesulfonyl, also known as p-nitrobenzenesulfonyl.

[0135] Ts- is an abbreviation for tosyl (abbreviated as Ts or OTs).

[0136] tBu: tert-butyl.

[0137] Boc: tert-butyloxycarbonyl. Attached Figure Description

[0138] Figure 1 This is a single-crystal structure diagram of the bidentate organic tellurium catalyst CB1.

[0139] Figure 2 This is a single-crystal structure diagram of the bidentate organic tellurium catalyst CB2.

[0140] Figure 3 This is a single-crystal structure diagram of the bidentate organic tellurium catalyst CB6.

[0141] Figure 4 This is a single-crystal structure diagram of the bidentate organic tellurium catalyst CB7.

[0142] Figure 5 This is a single-crystal structure diagram of the bidentate organic tellurium catalyst CB8.

[0143] Figure 6 CB7 is a bidentate organic tellurium salt catalyst. 2+ The lowest unoccupied molecular orbital (LUMO) energy and electrostatic potential (ESP) plot.

[0144] Figure 7 A bidentate organic tellurium salt catalyst using triphenylphosphine oxide (Ph3PO) as a probe. 31 P NMR analysis plot. In the plot, CB1 / 10 represents CB1 and CB10, and so on.

[0145] Figure 8Reaction pathway diagram for the preparation of piperidine derivatives catalyzed by the bidentate organotelluride salt catalyst prepared in the present invention. DETAILED DESCRIPTION

[0146] In order to make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below with reference to examples. The specific examples described herein are only used to explain the present invention and do not constitute any limitation on the present invention. In addition, in the following description, the description of well-known structures and technologies is omitted to avoid unnecessary confusion of the concepts of the present disclosure. Such structures and technologies are also described in many publications.

[0147] The reagents used in the present invention can be purchased from the market or can be prepared by the methods described in the present invention, and are used directly without further purification unless otherwise specified. Analytical thin layer chromatography (TLC) is performed on pre-coated silica gel 60GF 254 plates. Flash column chromatography is performed using Qingdao silica gel (60 mesh, particle size 0.040-0.063 mm). Visualization of TLC is achieved by ultraviolet light (254 nm). 1 H NMR and 13 C NMR spectra are recorded on a Bruker 400 MHz or 600 MHz spectrometer with CDCl3, CD2Cl2or DMSO-d6as solvent and tetramethylsilane (TMS) as internal standard. Chemical shifts are expressed in ppm and coupling constants in Hz. 1 H NMR data are recorded as follows: chemical shift (δ, ppm), peak shape (s = singlet; d = doublet; t = triplet; q = quartet; m = multiplet; br s = broad singlet), coupling constant (Hz), integral area. 13 C NMR data are recorded as follows: chemical shift (δ, ppm), peak shape (s = singlet; d = doublet; q = quartet), coupling constant (Hz). 19 F NMR data are recorded as follows: chemical shift (δ, ppm), peak shape (s = singlet; d = doublet; t = triplet; q = quartet), coupling constant (Hz). 125 Te NMR data are expressed as chemical shift (δ, ppm). High resolution mass spectrometry (HRMS) analysis is performed on a Q-Exactive (Thermo Scientific) mass spectrometer (HESI source). X-ray crystallographic analysis of single crystals is performed on an Agilent SuperNova-CCD X-ray diffractometer.

[0148] Azetidines la-ln, lr were prepared according to literature procedures [8]. Azetidine lo was prepared according to literature procedures [9]. Azetidine lp was prepared according to literature procedures

[10] . Azetidine lq, (S)-la were prepared according to literature procedures

[11] . The reaction of lq and lr with olefin 2a or alkyne 4a failed to proceed.

[0149] [8] Ghorai, M. K.; Das, S.; Das, K.; Kumar, A. Stereoselective Synthesis of Activated 2-Arylazetidines via Imino-Aldol Reaction. Org. Biomol. Chem. 2015, 13, 9042-9049.

[0150] [9] Parisi, G.; Capitanelli, E.; Pierro, A.; Romanazzi, G.; Clarkson, G. J.; Degennaro, L.; Luisi, R. Easy Access to Constrained Peptidomimetics and 2,2- Disubstituted Azetidines by the Unexpected Reactivity Profile of a-Lithiated N-Boc- azetidines. Chem. Commun. 2015, 51, 15588-15591.

[0151]

[10] Wu, X.; Yuan, X.; Yang, H.; Fu, H. Chiral Phosphoric Acid Catalyzed Asymmetric Addition of 2-(Vinyloxy)ethanol to Imines and Applications of the Products. Org. Lett. 2019, 21, 5335-5340.

[0152]

[11] Takeda, Y.; Toyoda, K.; Sameera, W. M. C; Tohnai, N.; Minakata, S. Palladium-Catalyzed Regioselective and Stereospecific Ring-Opening Suzuki-Miyaura Arylative Cross-Coupling of 2-Arylazetidines with Arylboronic Acids. Adv. Synth. Catal. 2021, 363, 2796-2805.

[0153] Example 1-9 Synthesis of bidentate organotelluride salt catalysts

[0154]

[0155] Step 1) Ascorbic acid (10 mmol, 0.5 equiv.) and diarylditelluride (3.S1a) (20 mmol, 1.0 equiv.) were weighed into a 250 mL Schlenk flask, and the flask was purged with argon three times. Aniline (3.S1b) (60 mmol, 3.0 equiv.) was dissolved in 50 mL of ultradry acetonitrile and added to the reaction system. tert-Butyl nitrite (60 mmol, 3.0 equiv.) was slowly added, and the reaction was stirred at room temperature for 12 hours. The reaction was monitored by thin layer chromatography (TLC). The reaction solvent was dried by rotary evaporation, and the product was separated by silica gel column chromatography (petroleum ether as developing agent). Diaryltelluride compounds (3.S1-3.S7) were obtained. (Diaryltelluride compounds (3.S1-1), (3.S1-2), (3.S1-3), (3.S1-8) can be purchased directly; the preparation method of diaryltelluride compound (3.S1-7) can also refer to the literature Groslambert, Loic; et al, Chemistry-A European Journal 2024, 30(7), e202302933.)

[0156] Step 2) Under an argon atmosphere, add diaryl tellurium compound (3.S1) (10 mmol, 1.0 equiv.) and cesium fluoride (20 mmol, 2.0 equiv.). Transfer to an ice-water bath, add 30 mL of ultra-dry dichloromethane, then weigh out NFSI (10 mmol, 1.0 equiv.), dissolve and dilute in 50 mL of ultra-dry dichloromethane, and slowly add to the reaction system. Remove the ice-water bath and react at room temperature overnight. As the reaction proceeds, a large amount of white solid will be generated. After the reaction is complete, filter directly, wash the white solid with dichloromethane, and evaporate the dichloromethane to obtain difluorodiaryl tellurium compound (3.S2). Since difluorodiaryl tellurium compound (3.S2) is unstable, no separation and purification is required in this step; it can be directly used in the next reaction.

[0157] Step 3) Weigh the unpurified difluorodiaryltelluric acid compound (3.S2) (6 mmol, 2.0 eq, by solid mass) and arylboronic acid (3.S3) (3 mmol, 1.0 eq) obtained in Step 2) into a 100 mL Shrek flask. Vacuum the flask three times. Under an argon atmosphere, add 60 mL of ultra-dry DCM. Transfer the reaction mixture to an ice-water bath, and then slowly add boron trifluoride diethyl ether solution (6 mmol, 2.0 eq). Remove the ice-water bath and react at room temperature overnight. Add a 50 mL solution of borate (18 mmol, 12.0 eq) in water to the reaction system. If some solid remains undissolved, add dichloromethane. React at room temperature for 2 hours, and detect complete reaction by thin-layer chromatography (TLC). Add dichloromethane and extract using dichloromethane extraction. The organic phase was dried with anhydrous sodium sulfate, and then the organic phase was evaporated and subjected to silica gel column chromatography (V(DCM):V(MeCN)=3:1) to obtain a white solid with slight impurities. The pure bidentate organic tellurium salt catalyst of formula (I) was obtained by recrystallization from dichloromethane and n-hexane.

[0158] The structural formula of the compound is shown below:

[0159] The structures of diaryl tellurium compounds (3.S1) are as follows:

[0160]

[0161] Diaryl tellurium compound (3.S1-4): HRMS (ESI) calcd for C14H8F6Te, m / z: 419.96

[0162] Diaryl tellurium compound (3.S1-5): HRMS (ESI) calcd for C12H6F4Te, m / z: 355.95

[0163] Diaryl tellurium compounds (3.S1-6): HRMS (ESI) calcd for C12H4F6Te, m / z: 391.93

[0164] The structures of difluoro diaryl tellurium compounds (3.S2) are:

[0165]

[0166] Difluoro diaryl tellurium compound (3.S2-1): HRMS (ESI) calcd for C12H10F2Te, m / z: 321.98 Difluoro diaryl tellurium compound (3.S2-2): HRMS (ESI) calcd for C12H8F4Te, m / z: 357.96 Difluoro diaryl tellurium compound (3.S2-3): HRMS (ESI) calcd for C14H8F8Te, m / z: 457.96 Difluoro diaryl tellurium compound (3.S2-4): HRMS (ESI) calcd for C14H8F8Te, m / z: 457.96 Difluoro diaryl tellurium compound (3.S2-5): HRMS (ESI) calcd for C12H6F6Te, m / z: 393.94 Difluoro diaryl tellurium compound (3.S2-6): HRMS (ESI) calcd for C12H4F8Te, m / z: 429.92 Difluoro diaryl tellurium compound (3.S2-7): HRMS (ESI) calcd for C16H6F14Te, m / z: 593.93 Difluoro diaryl tellurium compound (3.S2-8): HRMS (ESI) calcd for C12H8F2Te, m / z: 319.97 The structures of bisaryl boronic acids (3.S3) are:

[0167]

[0168] The structures of bidentate organotellurium salt catalysts of formula (I) are:

[0169]

[0170] The specific structural conditions of each substance in Table 1

[0171]

[0172] The obtained bidentate organotellurium salt catalysts were detected by hydrogen spectrum, carbon spectrum, phosphorus spectrum and mass spectrum, and the results are as follows:

[0173] Characterization of bidentate organotellurium salt catalyst CB1 ((9,9-dimethyl-9H-xanthene-4,5-diyl) bis(diphenyl telluronium) tetrafluoroborate): 1H NMR (400 MHz, CD3CN) δ 8.00 - 7.92 (m, 2H), 7.74 - 7.53 (m, 20H), 7.44 - 7.34 (m, 2H), 7.22 - 7.04 (m, 2H), 1.75 (s, 6H).

[0174] 13 C NMR (100 MHz, CD3CN) δ 150.3, 135.2, 133.8, 133.6, 133.4, 132.5, 132.1, 128.0, 121.3, 118.0, 110.7, 35.7, 32.4.

[0175] 19 F NMR (376 MHz, CD3CN) δ -149.2, -149.3.

[0176] 125 Te NMR (126 MHz, CD3CN) δ 723.5.

[0177] HRMS (ESI) calcd for [M-BF4 2+ ] C 39 H 32 OTe2 2+ m / z: 776.0567; found: 776.0552.

[0178] Characterization of the bidentate organotellurium salt catalyst CB2 ((9,9-dimethyl-9H-xanthene-4,5-diyl)bis(bis(4-fluorophenyl)telluronium)) tetrafluoroborate): 1 H NMR (400 MHz, CD3CN) δ 8.02 - 7.91 (m, 2H), 7.72 - 7.55 (m, 8H), 7.50 - 7.38 (m, 2H), 7.37 - 7.27 (m, 8H), 7.17 - 7.03 (m, 2H), 1.76 (s, 6H).

[0179] 13 C NMR (100 MHz, CD3CN) δ 166.2 (d, J = 260.0 Hz), 150.2, 138.1 (d, J = 9.0 Hz), 133.6 (d, J = 2.0 Hz), 132.7, 128.2, 119.5 (d, J = 23.0 Hz), 116.2 (d, J = 3.0 Hz), 110.9, 35.8, 32.5.

[0180] 19 F NMR (376 MHz, CD3CN) δ -106.0, -149.1, -149.2.

[0181] 125 Te NMR (126MHz, CD3CN) δ 726.2.

[0182] HRMS(ESI)calcd for [M-BF4] 2+ C 39 H 28 F4OTe2 2+ ,m / z:848.0190; found:848.0188.

[0183] Characterization of the bidentate organic tellurium catalyst CB3 ((9,9-dimethyl-9H-xanthon-4,5-diyl)bis(bis(4-(trifluoromethyl)phenyl)tellurium)tetrafluoroborate):

[0184] 1 H NMR (400MHz, CD3CN) δ8.03-7.96(m,2H),7.94-7.79(m,16H),7.58-7.34(m,2H),7.32-7.06(m,2H),1.76(s,6H).

[0185] 13 C NMR (100MHz, CDCl3) δ150.3, 135.8, 133.9 (q, J = 33.0Hz), 133.4, 132.9, 132.4 ,127.8(q,J=4.0Hz),127.7,127.3,123.5(q,J=270.0Hz),111.1,35.4,31.5.

[0186] 19 FNMR(376MHz,CD3CN)δ-63.9,-148.5,-148.5.

[0187] 125 Te NMR (126MHz, CD3CN) δ 732.6.

[0188] HRMS(ESI)calcd for [M-BF4] 2+ C 43 H 28 F 12 OTe2 2+ ,m / z:1048.0062;found:1048.0054.

[0189] Characterization of the bidentate organic tellurium catalyst CB4 ((9,9-dimethyl-9H-xanthon-4,5-diyl)bis(bis(3-(trifluoromethyl)phenyl)tellurium)tetrafluoroborate):

[0190] 1H NMR (400 MHz, CD3CN) δ 8.24 - 7.91 (m, 14H), 7.83 (t, J = 8.0 Hz, 4H), 7.50 (t, J = 7.9 Hz, 2H), 7.38 (d, J = 7.9 Hz, 2H), 1.79 (s, 6H).

[0191] 13 C NMR (100 MHz, CDC13) δ 151.1, 139.2, 133.8 (d, J = 44.0 Hz), 133.1, 133.0, 132.7, 132.2 (q, J = 4.0 Hz), 130.5 (d, J = 4.0 Hz), 128.2, 124.4, 124.0 (q, J = 271.0 Hz), 111.8, 36.1, 31.9.

[0192] 19 F NMR (100 MHz, CDC13) δ -63.4, -147.5, -147.6.

[0193] 125 Te NMR (100 MHz, CDC13) δ 738.4.

[0194] HRMS (ESI) calcd for [M-BF4 2+ ] C 39 H 28 F4OTe2 2+ , m / z: 1048.0062; found: 1048.0060.

[0195] Characterization of the bidentate organotellurium salt catalyst CB5 ((9,9-dimethyl-9H-xanthene-4,5-diyl)bis(bis(3,5-difluorophenyl)telluronium) tetrafluoroborate):

[0196] 1 H NMR (400 MHz, DMSO) δ 8.14 (d, J = 7.8 Hz, 2H), 7.76 (t, J = 9.2 Hz, 4H), 7.61 - 7.43 (m, 10H), 7.21 (d, J = 7.7 Hz, 2H), 1.77 (s, 6H).

[0197] 13C NMR (100 MHz, DMSO) δ 164.8 (d, J = 11.0 Hz), 162.2 (d, J = 12.0 Hz), 148.8, 133.6, 133.3, 131.7, 128.4, 126.4 (t, J = 8.0 Hz), 118.9 (d, J = 27.0 Hz), 115.2, 109.7 (t, J = 26.0 Hz), 35.2, 33.2.

[0198] 19 FNMR (376 MHz, DMSO) δ -104.6, -148.0, -148.1.

[0199] 125 Te NMR (126 MHz, DMSO) δ 777.3.

[0200] HRMS (ESI) calcd for [M-BF4 2+ ] C 39 H 24 F8OTe2 2+ , m / z: 919.9813; found: 919.9815.

[0201] Characterization of the bidentate organotellurium salt catalyst CB6 ((9,9-dimethyl-9H-xanthene-4,5-diyl)bis(bis(3,4,5-trifluorophenyl)telluronium) tetrafluoroborate):

[0202] 1 H NMR (400 MHz, CD3CN) δ 8.04 (d, J = 7.8 Hz, 2H), 7.66 - 7.44 (m, 10H), 7.36 (d, J = 7.8 Hz, 2H), 1.79 (s, 6H).

[0203] 13 C NMR (100 MHz, CD3CN) δ 153.5 (dd, J = 10.0, 3.0 Hz), 150.9 (dd, J = 10.0, 3.0 Hz), 150.1, 144.50 (t, J = 15.0 Hz), 141.9 (t, J = 14.0 Hz), 133.7 (d, J = 25.0 Hz), 132.1, 127.7, 120.3 (d, J = 24.0 Hz), 120.2 (d, J = 10.0 Hz), 116.2 (q, J = 6.0 Hz), 110.5, 35.2, 32.0.

[0204] 19F NMR (376 MHz, CD3CN) δ -130.6 (d, J = 18.8 Hz), -146.3, -146.4, -153.3 (d, J = 18.8 Hz).

[0205] 125 Te NMR (126 MHz, CD3CN) δ 771.4.

[0206] HRMS (ESI) calcd for [M-BF4 2+ ] C 39 H 20 F 12 OTe2 2+ m / z: 991.9436; found: 991.9430.

[0207] Characterization of the bidentate organotellurium salt catalyst CB7 ((9,9-dimethyl-9H-xanthene-4,5-diyl)bis(bis(3,5-bis(trifluoromethyl)phenyl)telluriumyl)tetrafluoroborate):

[0208] 1 H NMR (400 MHz, CD3CN) δ 8.38 (d, J = 9.5 Hz, 12 H), 8.07 (d, J = 7.6 Hz, 2 H), 7.61 (d, J = 7.6 Hz, 2 H), 7.56 - 7.45 (m, 2 H), 1.81 (s, 6 H).

[0209] 13 C NMR (100 MHz, CD3CN) δ 151.6, 136.4 (d, J = 4.0 Hz), 134.4, 133.8 (d, J = 34.0 Hz), 133.3, 133.0, 128.1, 127.9, 126.9, 123.4 (q, J = 271.0 Hz), 112.1, 36.1, 32.4.

[0210] 19 F NMR (376 MHz, CD3CN) δ -63.6, -145.5, -145.6.

[0211] 125 Te NMR (126 MHz, CD3CN) δ 770.5.

[0212] HRMS (ESI) calcd for [M-BF4 2+ ] C 47 H 24 F 24 OTe2 2+ m / z: 1319.9557; found: 1319.9540.

[0213] Characterization of bidentate organotelluride catalyst CB8 (5,5'-(9,9-dimethyl- 9H-xanthene-4,5-diyl)bis(5H-dibenzo[b,d]telluraphene-5-ium) tetrafluoroborate):

[0214] 1 H NMR (400 MHz, CD3CN) δ 8.35 (dd, J = 8.0, 1.3 Hz, 4H), 8.26 (dd, J = 7.9, 1.2 Hz, 4H), 7.92 (td, J = 7.6, 1.2 Hz, 4H), 7.80 - 7.66 (m, 6H), 7.13 - 7.03 (m, 2H), 6.76 (dd, J = 7.9, 1.4 Hz, 2H), 1.67 (s, 6H).

[0215] 13 C NMR (100 MHz, CD3CN) δ 151.3, 148.1, 134.7, 133.9, 133.0, 132.7, 132.4, 131.7, 131.6, 127.3, 126.9, 113.4, 34.0, 32.0.

[0216] 19 F NMR (376 MHz, CD3CN) δ -149.1, -149.2.

[0217] 125 Te NMR (126 MHz, CD3CN) δ 699.8.

[0218] HRMS (ESI) calcd for [M-BF4 2+ ] C 39 H 28 OTe2 2+ m / z: 772.0254; found: 772.0241.

[0219] Characterization of bidentate organotelluride catalyst CB9 (dibenzo[b,d]furan-4,6-diylbis(diphenyltelluronium) tetrafluoroborate): 1 H NMR (400 MHz, CD3CN) δ 8.48 (dd, J = 7.8, 1.1 Hz, 2H), 7.69 - 7.55 (m, 22H), 7.48 (dd, J = 7.8, 1.2 Hz, 2H).

[0220] 13C NMR (100 MHz, CD3CN) δ 157.2, 135.5, 135.3, 135.2, 134.2, 133.9, 132.1, 132.0, 131.9, 127.7, 127.2, 125.6, 121.5, 105.0.

[0221] 19 FNMR (376 MHz, CD3CN) δ -150.7, -150.8.

[0222] 125 Te NMR (126 MHz, CD3CN) δ 729.7.

[0223] HRMS (ESI) calcd for [M-BF4 2+ ] C 36 H 26 OTe2 2+ m / z: 734.0097; found: 734.0082.

[0224] Single crystals of CB1, CB2, CB6, CB7 and CB8 were prepared based on the ditopic organotellurium salt catalysts prepared in Examples 1-9, and X-ray diffraction analysis was performed on them, which confirmed the structures of these novel organotellurium salts. In addition, it was found that the tellurium atoms in these structures exhibit trigonal pyramidal geometry (as shown in Figures 1-5 and Table 2).

[0225] Table 2 Crystal data of ditopic organotellurium salt catalysts

[0226]

[0227]

[0228] Taking the crystal structure analysis of CB7 (Cambridge Crystallographic Data Centre No. 2443060) as an example, it illustrates the ditopic chalcogen bonding (ChB) interaction related to the tellurium center. At the same time, it is also detected that the distance between the tellurium atom and the fluorine atom in the tetrafluoroborate counter anion is relatively short: the distance of Te(l)-F(l) and Te(2)-F(2) is the distance of Te(l)-F(3) is the distance of Te(2)-F(4) is These data show that all Te···F distances are less than the sum of the van der Waals radii of the two It is noted that there is a non-covalent interaction between the tellurium atom and the fluorine atom. It is also noted that the tetrafluoroborate anion is bound to two tellurium cations through a unique bridging mode: each tellurium atom interacts with two anions, and the interaction directions are approximately perpendicular. The nearly linear bond angles C-Te(l)···F(l) (172.2°) and C-Te(2)···F(4) (173.5°) indicate that the tellurium atom in this structure can act as a bidentate chalcogen bond donor.

[0229] The present application is directed to CB7 2+ Computational studies were carried out. As shown in Figure 6 the calculated results confirm that CB7 2+ the lowest unoccupied molecular orbitals (LUMO) and LUMO+1 have σ*(Te-C) character, which is consistent with its role as a tellurium-based chalcogen bond (ChB) donor. The energies of these orbitals are very close, indicating that all the binding sites should have similar chalcogen bond properties. CB7 2+ The electrostatic potential (ESP) map around the tellurium center further validates these findings. The VS,max value (maximum electrostatic potential value) accurately reflects the expected σ-hole corresponding to the σ*(Te-C) orbital. CB7 2+ forms a strong positive potential region between the two tellurium centers, which helps it to interact with Lewis bases and form chalcogen bonds.

[0230] Example 10-18 Preparation of bidentate organotellurium salt catalysts of formula (I)

[0231] The bidentate organotellurium salt catalysts CB1-9 (1.0 eq) were dissolved in dichloromethane, NaBAr F 4 (2.0 eq) was added, and after stirring vigorously for 5 hours, the resulting suspension was filtered, and the filtrate was evaporated under reduced pressure to give CB10-18 as a colorless powder. The specific materials are shown in Table 3 below:

[0232] Table 3 Material matching of Examples 10-18

[0233] Examples Starting materials Bidentate organotelluride salt catalyst of formula (I) Yield of bidentate organotelluride salt catalyst of formula (I) 10 CB1 CB10 99％ 11 CB2 CB11 98％ 12 CB3 CB12 99％ 13 CB4 CB13 97％ 14 CB5 CB14 90％ 15 CB6 CB15 96％ 16 CB7 CB16 99％ 17 CB8 CB17 99％ 18 CB9 CB18 97％

[0234] The specific structures of CB10-CB18 are as follows:

[0235]

[0236] Characterization of bidentate organotellurium salt catalyst CB10 ((9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenyl tellurium) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate):

[0237] 1H NMR (400 MHz, CD3CN) δ 7.96 (dd, J = 7.9, 1.5 Hz, 2H), 7.81 (dt, J = 5.3, 2.4 Hz, 16H), 7.75 - 7.58 (m, 28H), 7.41 (t, J = 7.9 Hz, 2H), 7.13 (dd, J = 7.9, 1.4 Hz, 2H), 1.78 (s, 6H).

[0238] 13 C NMR (100 MHz, CD3CN) δ 162.4 (q, J = 50.0 Hz), 150.1, 135.4, 134.1, 133.9, 133.6, 132.6, 132.3, 129.7 (q, J = 30.0 Hz), 128.3, 125.2 (q, J = 270.0 Hz), 121.0, 118.3 (t, J = 4.0 Hz), 110.5, 35.7, 32.6.

[0239] 19 F NMR (376 MHz, CD3CN) δ -63.2.

[0240] 125 Te NMR (126 MHz, CD3CN) δ 722.6.

[0241] HRMS (ESI) calcd for [M-BAr F 4 2+ ] C 39 H 32 OTe2 2+ , m / z: 776.0567; found: 776.0545.

[0242] Characterization of the bidentate organotellurium salt catalyst CB11 ((9,9-dimethyl-9H-xanthene-4,5-diyl)bis(bis(4-fluorophenyl)telluronium)) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate:

[0243] 1 H NMR (400 MHz, CD3CN) δ 7.99 (dd, J = 7.9, 1.4 Hz, 2H), 7.82 - 7.73 (m, 16H), 7.72 - 7.63 (m, 16H), 7.48 - 7.34 (m, 10H), 7.10 (dd, J = 7.9, 1.4 Hz, 2H), 1.79 (s, 6H).

[0244] 13C NMR (100 MHz, CD3CN) δ 165.8 (d, J = 260.0 Hz), 161.7 (q, J = 50.0 Hz), 149.3, 137.5 (d, J = 9.0 Hz), 134.7, 133.2 (d, J = 4.0 Hz), 132.1, 128.9 (q, J = 31.0 Hz), 127.8, 124.5 (q, J = 270.0 Hz), 119.2 (d, J = 23.0 Hz), 117.7 (t, J = 4.0 Hz), 115.0 (d, J = 3.0 Hz), 109.8, 35.1, 32.1.

[0245] 19 F NMR (376 MHz, CD3CN) δ -63.2, -105.4.

[0246] 125 Te NMR (126 MHz, CD3CN) δ 724.2.

[0247] HRMS (ESI) calcd for [M-BAr F 4 2+ ]C 39 H 28 F4OTe2 2+ m / z: 848.0190; found: 848.0175.

[0248] Bidentate organotelluride catalyst CB12 ((9,9-dimethyl-9H-xanthene-4,5-diyl)bis(bis(4- (trifluoromethyl)phenyl)telluronium)) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate) characterization:

[0249] 1 H NMR (400 MHz, CD3CN) δ 8.03 - 7.98 (m, 2H), 7.97 - 7.84 (m, 16H), 7.77 (s, 16H), 7.69 (s, 8H), 7.50 - 7.41 (m, 2H), 7.27 - 7.17 (m, 2H), 1.79 (s, 6H).

[0250] 13C NMR (100 MHz, CD3CN) δ 162.3 (q, J = 50.0 Hz), 150.5, 136.4, 135.3, 134.9 (q, J = 32.0 Hz), 134.3, 133.9, 133.0, 129.6 (q, J = 30.0 Hz), 128.7 (q, J = 4.0 Hz), 126.8, 125.4, 125.1 (q, J = 270.0 Hz), 122.6, 118.3 (t, J = 4.0 Hz), 111.0, 35.9, 32.3.

[0251] 19 F NMR (376 MHz, CD3CN) δ -63.3, -64.1.

[0252] 125 Te NMR (126 MHz, CD3CN) δ 731.6.

[0253] HRMS (ESI) calcd for [M-BAr F 4 2+ ]C 43 H 28 F 12 OTe2 2+ m / z: 1048.0062; found: 1048.0062.

[0254] Characterization of the bidentate organotellurium salt catalyst CB13 ((9,9-dimethyl-9H-xanthene-4,5-diyl)bis(bis(3-(trifluoromethyl)phenyl)telluronium) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate):

[0255] 1 H NMR (400 MHz, CD3CN) δ 8.09 (s, 4H), 8.06 - 7.99 (m, 6H), 7.92 (d, J = 8.1 Hz, 4H), 7.88 - 7.73 (m, 20H), 7.70 (s, 8H), 7.52 - 7.40 (m, 2H), 7.34 - 7.25 (m, 2H), 1.78 (s, 6H).

[0256] 13C NMR (100 MHz, CD3CN) δ 162.4 (q, J = 50.0 Hz), 150.6, 139.2, 135.4, 134.2, 133.9, 133.5, 133.1, 132.3 (q, J = 5.0 Hz), 130.9 (q, J = 4.0 Hz), 129.6 (q, J = 30.0 Hz), 128.7, 125.2 (q, J = 270.0 Hz), 123.2, 122.5, 121.11, 118.3 (t, J = 4.0 Hz), 111.1, 36.0, 32.0.

[0257] 19 F NMR (376 MHz, CD3CN) δ -63.3, -63.6.

[0258] 125 Te NMR (126 MHz, CD3CN) δ 735.9.

[0259] HRMS (ESI) calcd for [M-BAr F 4 2+ ] C 43 H 28 F 12 OTe2 2+ m / z: 1048.0062; found: 1048.0059.

[0260] Characterization of the bidentate organotellurium salt catalyst CB14 ((9,9-dimethyl-9H-xanthene-4,5-diyl)bis(bis(3,5-difluorophenyl)telluronium) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate):

[0261] 1 H NMR (400 MHz, CD3CN) δ 8.02 (dd, J = 7.9, 1.4 Hz, 2H), 7.79 (s, 16H), 7.71 (s, 8H), 7.53 - 7.47 (m, 2H), 7.43 - 7.24 (m, 14H), 1.80 (s, 6H).

[0262] 13C NMR (100 MHz, CD3CN) δ 164.5 (dd, J = 12.0 Hz, J = 255.0 Hz), 162.4 (q, J = 50.0 Hz), 150.2, 135.4, 134.4 (q, J = 4.0 Hz), 132.9, 129.6 (q, J = 30.0 Hz), 128.8, 125.1 (q, J = 270.0 Hz), 123.1 (q, J = 8.0 Hz), 119.2 (d, J = 28.0 Hz), 119.2 (d, J = 11.0 Hz), 118.3 (p, J = 4.0 Hz), 110.7, 110.3 (d, J = 23.0 Hz), 110.2, 35.8, 32.7.

[0263] 19 F NMR (376 MHz, CD3CN) δ -63.3, -104.7.

[0264] 125 Te NMR (126 MHz, CD3CN) δ 759.4.

[0265] HRMS (ESI) calcd for [M-BAr F 4 2+ ] C 39 H 24 F8OTe2 2+ , m / z: 919.9813; found: 919.9811.

[0266] Characterization of the bidentate organotellurium salt catalyst CB15 ((9,9-dimethyl-9H-xanthene-4,5-diyl)bis(bis(3,4,5-trifluorophenyl)telluronium) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate):

[0267] 1 H NMR (400 MHz, CD3CN) δ 8.03 (dd, J = 7.9, 1.4 Hz, 2H), 7.87 - 7.74 (m, 16H), 7.70 (s, 8H), 7.59 - 7.45 (m, 10H), 7.28 (dd, J = 7.9, 1.4 Hz, 2H), 1.80 (s, 6H).

[0268] 13C NMR (100 MHz, CD3CN) δ 162.4 (q, J = 50 Hz), 154.5 (dd, J = 7 Hz, J = 10.0 Hz), 151.9 (dd, J = 7 Hz, J = 10.0 Hz), 150.2, 145.5 (t, J = 15.0 Hz), 142.9 (t, J = 15.0 Hz), 135.4, 134.5 (d, J = 22.0 Hz), 133.0, 129.6 (q, J = 30.0 Hz), 128.9, 125.2 (q, J = 270.0 Hz), 120.9 (d, J = 24.0 Hz), 118.3 (p, J = 4.0 Hz), 115.7 (q, J = 6.0 Hz), 110.5, 35.8, 32.7.

[0269] 19 F NMR (376 MHz, CD3CN) δ -63.3, -129.7 (d, J = 18.8 Hz), -152.3 (d, J = 18.8 Hz). 125 Te NMR (126 MHz, CD3CN) δ 767.1.

[0270] HRMS (ESI) calcd for [M-BAr F 4 2+ ]C 39 H 20 F 12 OTe2 2+ ,m / z: 991.9436; found: 991.9435.

[0271] Characterization of the bidentate organotellurium salt catalyst CB16 (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(bis(3,5-bis(trifluoromethyl)phenyl)telluronium) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate):

[0272] 1 H NMR (400 MHz, CD3CN) δ 8.47 - 8.31 (m, 12H), 8.05 (d, J = 7.8 Hz, 2H), 7.87 - 7.75 (m, 12H), 7.70 (s, 6H), 7.62 (d, J = 7.3 Hz, 2H), 7.57 - 7.50 (m, 2H), 1.79 (s, 6H).

[0273] 13C NMR (100 MHz, CD3CN) δ 162.4 (q, J = 50 Hz), 136.4 (d, J = 4.0 Hz), 135.5, 134.7, 134.4, 134.1, 129.8 (q, J = 30 Hz), 128.7, 128.2, 127.4, 126.6, 123.9, 123.4 (q, J = 272.0 Hz), 121.2, 118.4 (p, J = 4.0 Hz), 36.3, 32.0. 19 F NMR (376 MHz, CD3CN) δ -63.3, -63.7.

[0274] 125 Te NMR (126 MHz, CD3CN) δ 763.1.

[0275] HRMS (ESI) calcd for [M-BAr F 4 2+ ] C 47 H 24 F 24 OTe2 2+ m / z: 1319.9557; found: 1319.9550.

[0276] Characterization of the bidentate organotellurium salt catalyst CB17 (5,5'-(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(5H-dibenzo[b,d]telluraphene-5-ium) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate):

[0277] 1 H NMR (400 MHz, CD2CI2) δ 8.04 (d, J = 8.0 Hz, 4H), 7.86 (d, J = 7.8 Hz, 4H), 7.79 - 7.50 (m, 22H), 7.49 - 7.25 (m, 12H), 7.06 - 6.93 (m, 2H), 6.66 (d, J = 8.0 Hz, 2H), 1.51 (s, 6H).

[0278] 13 C NMR (100 MHz, CD2CI2) δ 161.8 (q, J = 50 Hz), 150.4, 147., 134.8, 134.6, 134.0, 133.3, 133.1, 132.0, 131.2, 128.9 (q, J = 30 Hz), 128.3, 127.1, 124.6 (q, J = 271.0 Hz), 117.5 (p, J = 4.0 Hz), 109.7, 35.7, 31.9.

[0279] 19F NMR (376 MHz, CD2Cl2) δ -62.7.

[0280] 125 Te NMR (126 MHz, CD2Cl2) δ 641.1.

[0281] HRMS (ESI) calcd for [M-BAr F 4 2+ ] C 39 H 28 OTe2 2+ , m / z: 772.0254; found: 772.0255.

[0282] Characterization of the bidentate organotelluride catalyst CB18 (dibenzo[b,d]furan-4,6-diylbis(diphenyl telluride) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate):

[0283] 1 H NMR (400 MHz, CD2Cl2) δ 8.50 (dd, J = 7.8, 1.0 Hz, 2H), 8.02 - 7.94 (m, 16H), 7.83 - 7.76 (m, 6H), 7.74 - 7.65 (m, 16H), 7.65 - 7.55 (m, 8H), 7.51 (dd, J = 7.9, 1.0 Hz, 2H).

[0284] 13 C NMR (100 MHz, CD2Cl2) δ 162.0 (q, J = 50 Hz), 156.5, 135.0, 133.3 (d, J = 131 Hz), 133.1, 129.1 (q, J = 30 Hz), 128.3 (d, J = 36.0 Hz), 125.6, 124.7 (q, J = 271.0 Hz), 117.7 (p, J = 4.0 Hz), 116.6, 99.82.

[0285] 19 F NMR (376 MHz, CD2Cl2) δ -62.6.

[0286] 125 Te NMR (126 MHz, CD2Cl2) δ 683.1.

[0287] HRMS (ESI) calcd for [M-BAr F 4 2+ ] C 36 H 26 OTe2 2+ , m / z: 734.0097; found: 734.0095.

[0288] Inspired by these encouraging structural discoveries, the inventors subsequently extended their research on bidentate organic tellurium salts to solution systems. For this purpose, they chose triphenylphosphine oxide (Ph3PO) as the chalcogenide (ChB) acceptor. By directly monitoring the interacting atoms using NMR, the interaction strength between the oxygen atom in Ph3PO and the σ-vacancy in tellurium could theoretically be measured. Upon adding Ph3PO to a deuterated dichloromethane (CD2Cl2) solution of bidentate organic tellurium salts, the expected changes in 31P... 125 The NMR signal of Te will undergo a significant shift. However, due to the low solubility of some catalysts, this leads to... 125 The Te signal is weak or undetectable; therefore, this study is limited to monitoring the mixture of catalyst and Ph3PO using 31PNMR. Figure 7 As shown, compared to BF4 - and BARF4 - 31PNMR analysis of the anion revealed a correlation between the electron-withdrawing effect and the depth of tellurium σ-holes in organic tellurium salts. BF4 - When used as an anti-anion, the maximum chemical shift deviation is 4.58 ppm (CB7); while BArF4 - The chemical shift deviation of the salt ranged from 5.38 ppm (CB18) to 9.49 ppm (CB16). These results not only indicate that BArF4 has weak coordination ability - Tellurium salts with anions typically exhibit stronger catalytic activity, further confirming the conclusion that introducing stronger electron-withdrawing substituents onto the aromatic ring enhances chalcogenide interactions. The observed differences in chemical shift bias may be attributed to variations in the antianion binding affinity. In contrast, BF4… - Its binding ability is greater than that of BArF4 - It is much stronger, and therefore more effectively prevents competitive binding to Ph3PO, resulting in a relatively small chemical shift deviation. It is worth mentioning that... The team reported a chemical shift deviation of 7.9 ppm for the bistellurium dication compound. [7] .

[0289] Application Examples: Cycloaddition Reactions

[0290] Example 20: Optimization of conditions for the cycloaddition reaction of azahexacyclic butane with an olefin

[0291]

[0292] Compound 1a (0.1 mmol), compound 2a (0.3 mmol), and catalyst (10 mol%) were reacted in a solvent (1 mL) at a certain temperature for a certain period of time to prepare compound 3a. Specific reaction conditions are shown in Table 4.

[0293] Table 4 Reaction condition screening

[0294] [a] ]]> ​ Catalyst Solvent Temperature Yield (%) [b] ]] 1 CB10 CH2Cl2 r.t. n.r. 2 CB11 CH2Cl2 r.t. n.r. 3 CB12 CH2Cl2 r.t. n.r. 4 CB13 CH2Cl2 r.t. n.r. 5 CB14 CH2Cl2 r.t. n.r. 6 CB15 CH2Cl2 r.t. 7 7 CB16 CH2Cl2 r.t. 31 8 CB17 CH2Cl2 r.t. n.r. 9 CB18 CH2Cl2 r.t. n.r. 10 CB16 CH2Cl2 50℃ 41 11 CB16 CH2Cl2 70℃ 50 12 CB16 DCE 70℃ 21 13 CB16 CHCl3 70℃ 28 14 CB16 Toluene 70℃ 13 15 CB16 THF 70℃ n.r. 16 CB16 MeCN 70℃ n.r. 17 [c] ]] CB16 CH2Cl2 70℃ 55 18 [d] ]] CB16 CH2Cl2 70℃ 60 19 [d],[e] ]] CB16 CH2Cl2 70℃ 65 20 [d],[f] ]] CB16 CH2Cl2 70℃ 72 21 [g] ]] CB16 CH2Cl2 70℃ 70

[0295] In the present application, r.t. means room temperature, preferably 20-25°C. n.r. means no reaction.

[0296] [a] The reaction time is 12 h. [b] Determined by H NMR analysis of the crude mixture. 1 H NMR analysis. [c] 2 mL of dichloromethane. [d] 4 mL of dichloromethane. [e] The reaction time is 24 h. [f] The reaction time is 36 h. [g] The reaction condition is: 1a (0.2 mmol), 2b (0.6 mmol) and CB16 (10 mol%) in dichloromethane (8 mL) at 70°C for 36 h.

[0297] From the optimization of reaction conditions in Example 20, it can be seen that the reaction condition No. 20 in Table 4 is the best reaction condition.

[0298] Example 21 Cycloaddition reaction of azetidine with olefin

[0299] After determining the best reaction condition, Example 21 investigates the substrate applicability of the cycloaddition reaction.

[0300]

[0301] A solution of azetidine 1-1 (0.2 mmol, 1.0 eq) and CB16 (10 mol%) in dichloromethane (8 mL) was added to olefin 2-2 (0.6 mmol, 3.0 eq) and the mixture was stirred at 70°C for 36 h. After the reaction solution was concentrated by evaporation, the target product 3-2 was obtained by silica gel column chromatography (V(ethyl acetate) / V(petroleum ether)=20 / 1).

[0302] The specific selection of each substituent in azetidine 1-1, olefin 2-2 and target product 3-2 is shown in Table 5 below:

[0303] Table 5 Matching of each substituent

[0304]

[0305]

[0306] In Table 5, the structural formula W is:

[0307] Using the best reaction condition of Example 20, the following products with the following structural formula were prepared:

[0308]

[0309] When the reaction scale was expanded to 0.2 mmol, the isolated yield of 3a could reach 70%. The replacement of diethyl with dimethyl (3b), cyclobutyl (3c), cyclopentyl (3d), or cyclohexyl (3e) resulted in a decrease in yield. 2,3-Dimethyl-2-butene could be used in this reaction to generate the cyclization product 3f with a yield of 45%. The present application also attempted the mono-aryl substituted olefins to generate the expected products (as a pair of diastereomers 3g-3s) with a diastereomeric ratio (dr value) of 6:1 to 1:1. Overall, these substrates reacted with higher efficiency than the alkyl substituted olefins, except for piperidines 3p and 3r (both bearing a bromo substituent at the meta and ortho positions, respectively). (E)-1-phenylpropene could be converted to the target product 3s with a yield of 85% and a dr value of 3:1. It is worth noting that the reaction proceeded smoothly when the olefin derived from estrone was involved to generate the corresponding product 3t with a good yield (74%). It is noted that 3s-3t were obtained as a mixture of diastereomers (which could not be separated), while 3g-3r could be separated by flash column chromatography. 1 H NMR spectral analysis indicated that the cis diastereomer was dominant in the diastereoselective reaction. Subsequently, the present application investigated the effect of the aromatic ring substituent on the azetidine. Unfortunately, the yield decreased to different extents after introducing different electronic nature substituents at the para, meta, or ortho positions (3u-3ac). It is noted that the bromo substituent (3m, 3p, 3r, 3y, 3aa, and 3ac) was fully compatible in the organotellurium catalytic system, which provided an effective site for subsequent derivatization.

[0310] Verification data of compound 3a: 1 H NMR (400 MHz, CDC13) δ 8.38 (d, J = 8.5 Hz, 2H), 8.11 (d, J = 8.5 Hz, 2H), 7.43-7.30 (m, 2H), 7.30-7.16 (m, 3H), 4.03-3.84 (m, 1H), 3.44-3.22 (m, 1H), 3.00-2.78 (m, 1H), 2.34-2.12 (m, 1H), 2.12-2.00 (m, 1H), 1.99-1.63 (m, 6H), 1.08-0.85 (m, 6H).

[0311] Verification data of compound 3b: 1H NMR (400 MHz, CDC13) δ 8.36 (d, J = 8.7 Hz, 2H), 8.04 (d, J = 8.7 Hz, 2H), 7.43 - 7.27 (m, 2H), 7.26 - 7.13 (m, 3H), 4.36 - 4.10 (m, 1H), 3.30 (td, J = 13.0, 2.6 Hz, 1H), 3.01 - 2.81 (m, 1H), 2.16 - 1.96 (m, 1H), 1.85 - 1.66 (m, 2H), 1.66 - 1.60 (m, 1H), 1.47 (s, 3H), 1.34 (s, 3H).

[0312] Verification data for compound 3c: 1 H NMR (400 MHz, CDC13) δ 8.37 (d, J = 8.7 Hz, 2H), 8.04 (d, J = 8.7 Hz, 2H), 7.40 - 7.27 (m, 2H), 7.27 - 7.10 (m, 3H), 4.11 (dd, J = 13.7, 3.2 Hz, 1H), 3.15 - 3.01 (m, 1H), 2.99 - 2.85 (m, 1H), 2.64 - 2.50 (m, 1H), 2.33 - 2.20 (m, 1H), 2.19 - 2.07 (m, 1H), 2.05 - 1.80 (m, 5H), 1.77 - 1.62 (m, 2H).

[0313] Verification data for compound 3d: 1 H NMR (400 MHz, CDC13) δ 8.34 (d, J = 8.9 Hz, 2H), 8.02 (d, J = 8.8 Hz, 2H), 7.41 - 7.28 (m, 2H), 7.25 - 7.16 (m, 3H), 4.48 - 4.32 (m, 1H), 3.39 - 3.23 (m, 1H), 3.02 - 2.88 (m, 1H), 2.35 - 2.20 (m, 1H), 2.16 - 2.04 (m, 1H), 2.03 - 1.93 (m, 1H), 1.90 - 1.46 (m, 9H).

[0314] Verification data for compound 3e: 1H NMR (400 MHz, CDC13) δ 8.38 (d, J = 8.9 Hz, 2H), 8.06 (d, J = 8.8 Hz, 2H), 7.41 - 7.32 (m, 2H), 7.30 - 7.19 (m, 3H), 4.59 - 4.24 (m, 1H), 3.57 - 3.43 (m, 1H), 2.94 - 2.80 (m, 1H), 2.53 - 2.35 (m, 2H), 2.30 - 2.16 (m, 1H), 2.12 - 1.99 (m, 1H), 1.91 - 1.76 (m, 1H), 1.73 - 1.46 (m, 6H), 1.44 - 1.31 (m, 2H), 1.15 - 1.06 (m, 1H).

[0315] Validation data for compound 3f: 1 H NMR (400 MHz, CDC13) δ 8.38 (d, J = 8.9 Hz, 2H), 8.06 (d, J = 8.8 Hz, 2H), 7.41 - 7.32 (m, 2H), 7.30 - 7.19 (m, 3H), 4.59 - 4.24 (m, 1H), 3.57 - 3.43 (m, 1H), 2.94 - 2.80 (m, 1H), 2.53 - 2.35 (m, 2H), 2.30 - 2.16 (m, 1H), 2.12 - 1.99 (m, 1H), 1.91 - 1.76 (m, 1H), 1.73 - 1.46 (m, 6H), 1.44 - 1.31 (m, 2H), 1.15 - 1.06 (m, 1H).

[0316] Validation data for compound 3g:

[0317] trans diastereomers:

[0318] 1 H NMR (400 MHz, CDC13) δ 8.38 (d, J = 8.9 Hz, 2H), 8.06 (d, J = 8.8 Hz, 2H), 7.41 - 7.32 (m, 2H), 7.30 - 7.19 (m, 3H), 4.59 - 4.24 (m, 1H), 3.57 - 3.43 (m, 1H), 2.94 - 2.80 (m, 1H), 2.53 - 2.35 (m, 2H), 2.30 - 2.16 (m, 1H), 2.12 - 1.99 (m, 1H), 1.91 - 1.76 (m, 1H), 1.73 - 1.46 (m, 6H), 1.44 - 1.31 (m, 2H), 1.15 - 1.06 (m, 1H).

[0319] cis diastereomers:

[0320] 1H NMR (400 MHz, CDC13) δ 8.10 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.8 Hz, 2H), 7.32 - 7.27 (m, 2H), 7.24 - 7.04 (m, 8H), 4.45 - 4.35 (m, 1H), 4.20 (dt, J = 12.9, 5.0 Hz, 1H), 3.45 - 3.32 (m, 1H), 2.86 - 2.69 (m, 1H), 2.29 - 2.17 (m, 1H), 2.13 - 2.05 (m, 2H), 2.00 - 1.87 (m, 1H).

[0321] Validation data for compound 3h:

[0322] trans diastereomers:

[0323] 1 H NMR (400 MHz, CDC13) δ 8.36 (d, J = 8.8 Hz, 2H), 8.07 (d, J = 8.8 Hz, 2H), 7.33 - 7.24 (m, 2H), 7.24 - 7.09 (m, 5H), 7.06 - 6.90 (m, 2H), 5.46 (d, J = 5.1 Hz, 1H), 4.07 (dd, J = 14.3, 4.3 Hz, 1H), 3.38 - 3.13 (m, 1H), 2.83 - 2.63 (m, 1H), 2.52 - 2.41 (m, 1H), 2.34 (s, 3H), 1.95 - 1.79 (m, 1H), 1.77 - 1.66 (m, 1H), 1.61 - 1.43 (m, 1H). cis diastereomers:

[0324] 1 H NMR (400 MHz, CDC13) δ 8.09 (d, J = 8.8 Hz, 2H), 7.52 (d, J = 8.8 Hz, 2H), 7.38 - 7.27 (m, 2H), 7.24 - 7.14 (m, 3H), 6.98 (d, J = 7.8 Hz, 2H), 6.85 (d, J = 7.8 Hz, 2H), 4.40 - 4.29 (m, 1H), 4.28 - 4.16 (m, 1H), 3.40 - 3.22 (m, 1H), 2.86 - 2.69 (m, 1H), 2.36 - 2.16 (m, 4H), 2.15 - 2.02 (m, 2H), 2.00 - 1.86 (m, 1H).

[0325] Validation data for compound 3i:

[0326] trans diastereomers:

[0327] 1H NMR (400 MHz, CDC13) δ 8.27 (d, J = 8.7 Hz, 2H), 7.97 (d, J = 8.7 Hz, 2H), 7.31 - 7.24 (m, 2H), 7.22 - 7.18 (m, 2H), 7.15 - 7.04 (m, 3H), 7.00 - 6.92 (m, 2H), 5.38 (d, J = 5.1 Hz, 1H), 4.10 - 3.94 (m, 1H), 3.26 - 3.05 (m, 1H), 2.83 - 2.62 (m, 1H), 2.46 - 2.34 (m, 1H), 1.90 - 1.75 (m, 1H), 1.67 (d, J = 13.1 Hz, 1H), 1.52 - 1.46 (m, 1H), 1.24 (s, 9H).

[0328] cis diastereomers:

[0329] 1 H NMR (400 MHz, CDC13) δ 8.27 (d, J = 8.7 Hz, 2H), 7.97 (d, J = 8.7 Hz, 2H), 7.31 - 7.24 (m, 2H), 7.22 - 7.18 (m, 2H), 7.15 - 7.04 (m, 3H), 7.00 - 6.92 (m, 2H), 5.38 (d, J = 5.1 Hz, 1H), 4.10 - 3.94 (m, 1H), 3.26 - 3.05 (m, 1H), 2.83 - 2.62 (m, 1H), 2.46 - 2.34 (m, 1H), 1.90 - 1.75 (m, 1H), 1.67 (d, J = 13.1 Hz, 1H), 1.52 - 1.46 (m, 1H), 1.24 (s, 9H).

[0330] Validation data for compound 3j:

[0331] cis diastereomers:

[0332] 1 H NMR (400 MHz, CDC13) δ 8.27 (d, J = 8.7 Hz, 2H), 7.97 (d, J = 8.7 Hz, 2H), 7.31 - 7.24 (m, 2H), 7.22 - 7.18 (m, 2H), 7.15 - 7.04 (m, 3H), 7.00 - 6.92 (m, 2H), 5.38 (d, J = 5.1 Hz, 1H), 4.10 - 3.94 (m, 1H), 3.26 - 3.05 (m, 1H), 2.83 - 2.62 (m, 1H), 2.46 - 2.34 (m, 1H), 1.90 - 1.75 (m, 1H), 1.67 (d, J = 13.1 Hz, 1H), 1.52 - 1.46 (m, 1H), 1.24 (s, 9H).

[0333] Validation data for compound 3k:

[0334] trans diastereomers:

[0335] 1 H NMR (400 MHz, CDC13) δ 8.51 - 8.25 (m, 2H), 8.18 - 7.95 (m, 2H), 7.35 - 7.24 (m, 4H), 7.24 - 7.17 (m 1H), 7.06 (t, J = 8.6 Hz, 2H), 7.01 - 6.90 (m, 2H), 5.47 (d, J = 5.1 Hz, 1H), 4.07 (dd, J = 14.9, 3.6 Hz, 1H), 3.31 - 3.09 (m, 1H), 2.81 - 2.61 (m, 1H), 2.44 (dd, J = 13.7, 2.9 Hz, 1H), 1.92 - 1.80 (m, 1H), 1.78 - 1.69 (m, 1H), 1.52 - 1.42 (m, 1H).

[0336] cis diastereomers:

[0337] 1 H NMR (400 MHz, CDC13) δ 8.18 (d, J = 8.8 Hz, 2H), 7.59 (d, J = 8.8 Hz, 2H), 7.38 - 7.26 (m, 2H), 7.24 - 7.15 (m, 3H), 7.15 - 7.07 (m, 2H), 6.89 - 6.72 (m, 2H), 4.38 - 4.28 (m, 1H), 4.28 - 4.13 (m, 1H), 3.38 - 3.25 (m, 1H), 2.81 - 2.60 (m, 1H), 2.26 - 2.14 (m, 1H), 2.10 - 2.01 (m, 2H), 2.00 - 1.85 (m, 1H).

[0338] Verification data for compound 3l:

[0339] trans diastereomers:

[0340] 1 H NMR (400 MHz, CDC13) δ 8.41 (d, J = 8.5 Hz, 2H), 8.10 (d, J = 8.5 Hz, 2H), 7.35 (d, J = 8.5 Hz, 2H), 7.28 - 7.24 (m, 4H), 7.23 - 7.18 (m, 1H), 7.02 - 6.89 (m, 2H), 5.47 (d, J = 5.2 Hz, 1H), 4.07 (dd, J = 14.5, 4.3 Hz, 1H), 3.30 - 3.08 (m, 1H), 2.77 - 2.59 (m, 1H), 2.44 (d, J = 13.9 Hz, 1H), 1.92 - 1.79 (m, 1H), 1.71 (d, J = 13.2 Hz, 1H), 1.51 - 1.42 (m, 1H).

[0341] cis diastereomers:

[0342] 1 H NMR (400 MHz, CDC13) δ 8.19 (d, J = 8.8 Hz, 2H), 7.60 (d, J = 8.9 Hz, 2H), 7.35 - 7.27 (m, 2H), 7.25 - 7.19 (m, 1H), 7.19 - 7.12 (m, 2H), 7.12 - 6.92 (m, 4H), 4.36 - 4.25 (m, 1H), 4.25 - 4.10 (m, 1H), 3.41 - 3.24 (m, 1H), 2.80 - 2.61 (m, 1H), 2.26 - 2.14 (m, 1H), 2.10 - 2.01 (m, 2H), 2.00 - 1.87 (m, 1H).

[0343] Validation data for compound 3m:

[0344] trans diastereomers:

[0345] 1 H NMR (400 MHz, CDC13) δ 8.40 (d, J = 8.8 Hz, 2H), 8.10 (d, J = 8.8 Hz, 2H), 7.50 (d, J = 8.5 Hz, 2H), 7.28 - 7.24 (m, 2H), 7.24 - 7.17 (m, 3H), 7.03 - 6.82 (m, 2H), 5.45 (d, J = 5.1 Hz, 1H), 4.16 - 3.97 (m, 1H), 3.28 - 3.08 (m, 1H), 2.79 - 2.61 (m, 1H), 2.49 - 2.36 (m, 1H), 1.91 - 1.78 (m, 1H), 1.71 (d, J = 13.3 Hz, 1H), 1.54 - 1.40 (m, 1H).

[0346] cis diastereomers:

[0347] 1H NMR (400 MHz, CDC13) δ 8.20 (d, J = 8.8 Hz, 2H), 7.60 (d, J = 8.9 Hz, 2H), 7.34 - 7.27 (m, 2H), 7.25 - 7.19 (m, 3H), 7.19 - 7.13 (m, 2H), 7.02 (d, J = 8.4 Hz, 2H), 4.35 - 4.25 (m, 1H), 4.25 - 4.14 (m, 1H), 3.38 - 3.24 (m, 1H), 2.86 - 2.64 (m, 1H), 2.21 (q, J = 4.5 Hz, 1H), 2.10 - 2.00 (m, 2H), 2.00 - 1.89 (m, 1H).

[0348] Validation data for compound 3n:

[0349] trans diastereomers:

[0350] 1 H NMR (400 MHz, CDC13) δ 8.37 (d, J = 8.8 Hz, 2H), 8.06 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 6.1 Hz, 2H), 7.24 - 7.15 (m, 2H), 7.13 - 6.93 (m, 5H), 5.47 (d, J = 5.2 Hz, 1H), 4.17 - 3.99 (m, 1H), 3.36 - 3.17 (m, 1H), 2.83 - 2.66 (m, 1H), 2.49 - 2.39 (m, 1H), 2.30 (s, 3H), 1.98 - 1.82 (m, 1H), 1.74 (d, J = 13.2 Hz, 1H), 1.56 - 1.43 (m, 1H). cis diastereomers:

[0351] 1 H NMR (400 MHz, CDC13) δ 8.08 (d, J = 8.8 Hz, 2H), 7.53 (d, J = 8.8 Hz, 2H), 7.35 - 7.26 (m, 2H), 7.24 - 7.16 (m, 3H), 7.04 - 6.89 (m, 3H), 6.82 (s, 1H), 4.50 - 4.32 (m, 1H), 4.26 - 4.15 (m, 1H), 3.47 - 3.30 (m, 1H), 2.90 - 2.64 (m, 1H), 2.28 - 2.18 (m, 1H), 2.16 - 2.00 (m, 5H), 1.99 - 1.81 (m, 1H).

[0352] Validation data for compound 3o:

[0353] trans diastereomers:

[0354] 1 H NMR (400 MHz, CDC13) δ 8.31 (d, J = 8.5 Hz, 2H), 8.05 (d, J = 8.5 Hz, 2H), 7.48 (d, J = 7.6 Hz, 1H), 7.46 - 7.37 (m, 5H), 7.37 - 7.32 (m, 1H), 7.29 - 7.19 (m, 5H), 7.05 (d, J = 7.5 Hz, 2H), 5.58 (d, J = 5.1 Hz, 1H), 4.31 - 4.01 (m, 1H), 3.41 - 3.19 (m, 1H), 2.85 - 2.63 (m, 1H), 2.59 - 2.46 (m, 1H), 2.09 - 1.91 (m, 1H), 1.79 (d, J = 13.2 Hz, 1H), 1.70 - 1.60 (m, 1H).

[0355] cis diastereomers:

[0356] 1 H NMR (400 MHz, CDC13) δ 7.96 (d, J = 8.9 Hz, 2H), 7.50 (d, J = 8.8 Hz, 2H), 7.43 - 7.26 (m, 8H), 7.25 - 7.13 (m, 6H), 4.59 - 4.39 (m, 1H), 4.36 - 4.14 (m, 1H), 3.50 - 3.27 (m, 1H), 2.92 - 2.76 (m, 1H), 2.28 - 2.10 (m, 3H), 2.09 - 1.85 (m, 1H).

[0357] Validation data for compound 3p:

[0358] trans diastereomers:

[0359] 1 H NMR (400 MHz, CDC13) δ 8.39 (d, J = 8.4 Hz, 2H), 8.06 (d, J = 8.5 Hz, 2H), 7.44 - 7.36 (m, 1H), 7.30 - 7.21 (m, 6H), 7.01 (d, J = 7.4 Hz, 2H), 5.48 (d, J = 5.2 Hz, 1H), 4.20 - 3.96 (m, 1H), 3.31 - 3.16 (m, 1H), 2.67 (t, J = 12.5 Hz, 1H), 2.42 (d, J = 13.8 Hz, 1H), 2.00 - 1.84 (m, 1H), 1.76 (d, J = 13.2 Hz, 1H), 1.64 - 1.45 (m, 1H). cis diastereomers:

[0360] 1H NMR (400 MHz, CDC13) δ 8.16 (d, J = 8.5 Hz, 2H), 7.56 (d, J = 8.6 Hz, 2H), 7.32 - 7.23 (m, 4H), 7.21 - 7.16 (m, 3H), 7.10 - 6.92 (m, 2H), 4.44 - 4.34 (m, 1H), 4.30 - 4.19 (m, 1H), 3.45 - 3.35 (m, 1H), 2.87 - 2.69 (m, 1H), 2.31 - 2.17 (m, 1H), 2.13 - 1.89 (m, 3H).

[0361] Verification data for compound 3q:

[0362] cis diastereomers:

[0363] 1 H NMR (400 MHz, CDC13) δ 8.04 - 7.95 (m, 2H), 7.47 - 7.28 (m, 4H), 7.28 - 7.23 (m, 3H), 7.19 - 7.13 (m, 1H), 7.06 - 6.99 (m, 1H), 6.96 - 6.86 (m, 1H), 6.79 (d, J = 7.4 Hz, 1H), 4.69 - 4.53 (m, 1H), 4.44 - 4.32 (m, 1H), 3.50 - 3.33 (m, 1H), 3.00 - 2.84 (m, 1H), 2.41 - 2.34 (m, 1H), 2.25 - 2.16 (m, 1H), 2.13 (s, 3H), 2.08 - 1.96 (m, 2H).

[0364] Verification data for compound 3r: cis diastereomers:

[0365] 1 H NMR (400 MHz, CDC13) δ 8.04 - 7.95 (m, 2H), 7.47 - 7.28 (m, 4H), 7.28 - 7.23 (m, 3H), 7.19 - 7.13 (m, 1H), 7.06 - 6.99 (m, 1H), 6.96 - 6.86 (m, 1H), 6.79 (d, J = 7.4 Hz, 1H), 4.69 - 4.53 (m, 1H), 4.44 - 4.32 (m, 1H), 3.50 - 3.33 (m, 1H), 3.00 - 2.84 (m, 1H), 2.41 - 2.34 (m, 1H), 2.25 - 2.16 (m, 1H), 2.13 (s, 3H), 2.08 - 1.96 (m, 2H).

[0366] Verification data for compound 3s: cis,trans diastereomers:

[0367] 1 H NMR (400 MHz, CDC13) δ 8.34 (d, J = 8.8 Hz, 2H), 8.01 (d, J = 8.8 Hz, 2H), 7.44 - 7.16 (m, 9H), 7.11 - 6.97 (m, 2H), 5.26 (s, 1H), 4.21 - 4.07 (m, 1H), 3.43 - 3.28 (m, 1H), 3.02 - 2.86 (m, 1H), 2.74 - 2.58 (m, 1H), 2.23 - 2.03 (m, 1H), 1.64 - 1.60 (m, 1H), 0.85 (d, J = 7.0 Hz, 3H).

[0368] trans,trans diastereomers:

[0369] 1 H NMR (400 MHz, CDC13) δ 8.34 (d, J = 8.8 Hz, 2H), 8.01 (d, J = 8.8 Hz, 2H), 7.44 - 7.16 (m, 9H), 7.11 - 6.97 (m, 2H), 5.26 (s, 1H), 4.21 - 4.07 (m, 1H), 3.43 - 3.28 (m, 1H), 3.02 - 2.86 (m, 1H), 2.74 - 2.58 (m, 1H), 2.23 - 2.03 (m, 1H), 1.64 - 1.60 (m, 1H), 0.85 (d, J = 7.0 Hz, 3H).

[0370] Validation data for compound 3t: 1 H NMR (400 MHz, CDC13) δ 8.34 (d, J = 8.8 Hz, 2H), 8.01 (d, J = 8.8 Hz, 2H), 7.44 - 7.16 (m, 9H), 7.11 - 6.97 (m, 2H), 5.26 (s, 1H), 4.21 - 4.07 (m, 1H), 3.43 - 3.28 (m, 1H), 3.02 - 2.86 (m, 1H), 2.74 - 2.58 (m, 1H), 2.23 - 2.03 (m, 1H), 1.64 - 1.60 (m, 1H), 0.85 (d, J = 7.0 Hz, 3H). 1H NMR (400 MHz, CDC13) δ 8.36 (d, J = 8.9 Hz, 2H), 8.08 (d, J = 8.8 Hz, 2H), 7.13 (d, J = 7.9 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 3.99 - 3.80 (m, 1H), 3.39 - 3.18 (m, 1H), 2.91 - 2.73 (m, 1H), 2.32 (s, 3H), 2.22 - 2.10 (m, 1H), 2.10 - 1.98 (m, 1H), 1.96 - 1.65 (m, 6H), 0.97 - 0.86 (m, 6H).

[0371] Validation data for compound 3v: 1 H NMR (400 MHz, CDC13) δ 8.36 (d, J = 8.9 Hz, 2H), 8.08 (d, J = 8.8 Hz, 2H), 7.13 (d, J = 7.9 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 3.99 - 3.80 (m, 1H), 3.39 - 3.18 (m, 1H), 2.91 - 2.73 (m, 1H), 2.32 (s, 3H), 2.22 - 2.10 (m, 1H), 2.10 - 1.98 (m, 1H), 1.96 - 1.65 (m, 6H), 0.97 - 0.86 (m, 6H).

[0372] Validation data for compound 3w: 1 H NMR (400 MHz, CDC13) δ 8.36 (d, J = 8.9 Hz, 2H), 8.08 (d, J = 8.8 Hz, 2H), 7.13 (d, J = 7.9 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 3.99 - 3.80 (m, 1H), 3.39 - 3.18 (m, 1H), 2.91 - 2.73 (m, 1H), 2.32 (s, 3H), 2.22 - 2.10 (m, 1H), 2.10 - 1.98 (m, 1H), 1.96 - 1.65 (m, 6H), 0.97 - 0.86 (m, 6H).

[0373] Validation data for compound 3x: 1H NMR (400 MHz, CDC13) δ 8.36 (d, J = 8.9 Hz, 2H), 8.07 (d, J = 8.9 Hz, 2H), 7.27 (d, J = 8.5 Hz, 2H), 7.10 (d, J = 8.5 Hz, 2H), 4.05 - 3.85 (m, 1H), 3.38 - 3.20 (m, 1H), 2.96 - 2.78 (m, 1H), 2.26 - 2.11 (m, 1H), 2.11 - 1.98 (m, 1H), 1.95 - 1.81 (m, 2H), 1.79 - 1.72 (m, 2H), 1.71 - 1.58 (m, 2H), 1.00 - 0.80 (m, 6H).

[0374] Validation data for compound 3y: 1 H NMR (400 MHz, CDC13) δ 8.36 (d, J = 8.9 Hz, 2H), 8.07 (d, J = 8.9 Hz, 2H), 7.27 (d, J = 8.5 Hz, 2H), 7.10 (d, J = 8.5 Hz, 2H), 4.05 - 3.85 (m, 1H), 3.38 - 3.20 (m, 1H), 2.96 - 2.78 (m, 1H), 2.26 - 2.11 (m, 1H), 2.11 - 1.98 (m, 1H), 1.95 - 1.81 (m, 2H), 1.79 - 1.72 (m, 2H), 1.71 - 1.58 (m, 2H), 1.00 - 0.80 (m, 6H).

[0375] Validation data for compound 3z: 1 H NMR (400 MHz, CDC13) δ 8.36 (d, J = 8.9 Hz, 2H), 8.07 (d, J = 8.9 Hz, 2H), 7.27 (d, J = 8.5 Hz, 2H), 7.10 (d, J = 8.5 Hz, 2H), 4.05 - 3.85 (m, 1H), 3.38 - 3.20 (m, 1H), 2.96 - 2.78 (m, 1H), 2.26 - 2.11 (m, 1H), 2.11 - 1.98 (m, 1H), 1.95 - 1.81 (m, 2H), 1.79 - 1.72 (m, 2H), 1.71 - 1.58 (m, 2H), 1.00 - 0.80 (m, 6H).

[0376] Validation data for compound 3aa: 1H NMR(400MHz, CDCl3)δ8.36(d,J=8.7Hz,2H),8.08(d,J=8.8Hz,2H),7.38-7 .33(m,1H),7.30(d,J=1.9Hz,1H),7.22-7.14(m,1H),7.13-7.04(m,1H),3. 98-3.82(m,1H),3.38-3.22(m,1H),2.92-2.71(m,1H),2.27-2.11(m,1H),2 .10-1.99(m,1H),1.95-1.81(m,2H),1.80-1.61(m,4H),0.97-0.85(m,6H).

[0377] Validation data for compound 3ab: 1 H NMR (400MHz, CDCl3) δ8.37(d,J=8.9Hz,2H),8.09(d,J=8.9Hz,2H),7.25-7.01(m,4H),4.00-3.82(m,1H),3.39-3.26 (m,1H),3.18-3.01(m,1H),2.33(s,3H),2.16-2.08(m,2H),1.96-1.76(m,3H),1.76-1.63(m,3H),1.03-0.81(m,6H).

[0378] Validation data for compound 3ac: 1 H NMR (400MHz, CDCl3) δ8.36(d,J=8.8Hz,2H),8.09(d,J=8.8Hz,2H),7.63-7.49(m,1H),7.36-7.25(m,1H),7.24-7.15(m,1H),7.14 -7.01(m,1H),4.04-3.80(m,1H),3.50-3.21(m,2H),2.25-2.01(m,2H),2.00-1.74(m,4H),1.73-1.61(m,2H),1.08-0.82(m,6H).

[0379] Example 22 Cycloaddition reaction of azacyclic butane with alkynes

[0380]

[0381] Compound 5 was prepared by reacting compounds 1-1 (0.2 mmol), 4 (0.6 mmol), and CB16 (10 mol%) in dichloromethane (8 mL) at a certain temperature for a certain period of time.

[0382] Optimization of reaction conditions:

[0383]

[0384] Table 6. Optimum conditions

[0385]

[0386]

[0387] [a] Unless otherwise stated, compound 1a-1c (0.1 mmol), compound 4a (0.3 mmol) and catalyst (10 mol%) were reacted in solvent (1 mL) for 12 h. [b] Determined by 1 H NMR analysis. [c] 2 mL of CH2Cl2. [d] 4 mL of CH2Cl2. [e] Reaction for 24 h. [f] Reaction for 36 h. [g] Compound 1a (0.2 mmol), compound 4a (0.6 mmol) and CB16 (10 mol%) were reacted in CH2Cl2(8 mL) at 70 °C for 36 h.

[0388] Given the success of this ditelluride catalytic system in the cycloaddition of azetidine with olefins, we attempted to incorporate alkynes into this reaction system to provide an alternative method for the construction of 1,2-tetrahydropyridine structures. Subsequently, we used the synthetic organotellurium BArF4 - salt as catalyst to study the reaction of azetidine 1a with phenylacetylene 4a. Again, only CB15 and CB16 were able to catalyze this reaction, with CB16 being relatively more effective. Subsequent optimization confirmed that the conditions developed by us for the cycloaddition of azetidine with olefins were equally applicable (and performed excellently) for this reaction, ultimately affording the target tetrahydropyridine 5a in 82% isolated yield.

[0389] Reaction substrate expansion:

[0390]

[0391] Azetidine (1, 0.2 mmol, 1.0 equiv.) and CB16 (10 mol%) were dissolved in CH2Cl2(8 mL), and an alkyne (4, 0.6 mmol, 3.0 equiv.) was added to the mixture. After the mixture was stirred at 70 °C for 36 h, the reaction solution was concentrated by evaporation, and the target product 5 was obtained by purification on a silica gel column (V(ethyl acetate) / V(petroleum ether) = 20 / 1).

[0392] The specific values of each substituent in azetidine 1-1, alkyne 4 and target product 5 are shown in Table 7 below:

[0393] Table 7. Values of each substituent

[0394]

[0395]

[0396] The product obtained was shown as the following structure:

[0397]

[0398] Subsequently, the substrate scope of this reaction was investigated. As shown in the above structure, the protecting group on the nitrogen atom had a significant impact on the reaction outcome: when p-toluenesulfonyl and benzenesulfonyl were used, the yield dropped to 65% (5b) and 66% (5c), respectively. Next, the influence of the substituent on the azetidine benzene ring was studied. For meta-substitution: the introduction of a methyl group led to a significant drop in yield (5d, 50%), while the introduction of a bromine atom almost restored the yield to a good level (5e, 78%). Substrates with ortho- or para-substitution also showed similar trends (5f, 55% vs 5g, 89%; 5h, 62% vs 5i, 86%). As expected, the reaction outcome of azetidine with other electron-donating groups (5j) was worse than that with halogen atoms (5k and 5l). Unfortunately, the synthesis yield of tetrahydropyridine 5m with a para-trifluoromethyl substituent was only 47% (Table 2A). The next study shifted to exploring the suitability of phenylacetylene derivatives (Table 2B). The yields of cyclization products 5n-5x with different substituents at the ortho- or meta-position were 38-90%, but no clear pattern could be observed from these results. In addition, 2-naphthyl and heteroaryl-derived acetylenes were also suitable for the reaction, giving the target products 5y-5aa in moderate yields. In addition, the application also tried internal alkyne participation in the reaction, and the results showed that the introduction of an alkyl substituent at the end had limited impact on high yield (5ab-5ad).

[0399] Verification data of compound 5a: 1 H NMR (400 MHz, CD2Cl2) δ 8.31 (d, J = 8.4 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H), 7.54-7.38 (m, 2H), 7.38-7.28 (m, 3H), 7.28-7.12 (m, 3H), 7.03-6.80 (m, 2H), 5.58 (d, J = 3.5 Hz, 1H), 4.23-4.01 (m, 1H), 3.94-3.71 (m, 1H), 3.64-3.43 (m, 1H), 2.04-1.81 (m, 1H), 1.54-1.40 (m, 1H).

[0400] Verification data of compound 5b: 1H NMR (400 MHz, CDC13) δ 7.64 (d, J = 8.3 Hz, 2H), 7.58 - 7.47 (m, 2H), 7.40 - 7.30 (m, 5H), 7.28 - 7.17 (m, 3H), 6.96 - 6.81 (m, 2H), 5.51 (d, J = 3.4 Hz, 1H), 4.20 - 4.08 (m, 1H), 3.78 - 3.65 (m, 1H), 3.56 - 3.42 (m, 1H), 2.47 (s, 3H), 1.95 - 1.78 (m, 1H), 1.54 - 1.37 (m, 1H).

[0401] Validation data for compound 5c: 1 H NMR (400 MHz, CDC13) δ 7.64 (d, J = 8.3 Hz, 2H), 7.58 - 7.47 (m, 2H), 7.40 - 7.30 (m, 5H), 7.28 - 7.17 (m, 3H), 6.96 - 6.81 (m, 2H), 5.51 (d, J = 3.4 Hz, 1H), 4.20 - 4.08 (m, 1H), 3.78 - 3.65 (m, 1H), 3.56 - 3.42 (m, 1H), 2.47 (s, 3H), 1.95 - 1.78 (m, 1H), 1.54 - 1.37 (m, 1H).

[0402] Validation data for compound 5c: 1 H NMR (400 MHz, CDC13) δ 7.64 (d, J = 8.3 Hz, 2H), 7.58 - 7.47 (m, 2H), 7.40 - 7.30 (m, 5H), 7.28 - 7.17 (m, 3H), 6.96 - 6.81 (m, 2H), 5.51 (d, J = 3.4 Hz, 1H), 4.20 - 4.08 (m, 1H), 3.78 - 3.65 (m, 1H), 3.56 - 3.42 (m, 1H), 2.47 (s, 3H), 1.95 - 1.78 (m, 1H), 1.54 - 1.37 (m, 1H).

[0403] Validation data for compound 5c: 1H NMR (400 MHz, CDC13) δ 8.31 (d, J = 8.8 Hz, 2H), 7.82 (d, J = 8.8 Hz, 2H), 7.43 - 7.26 (m, 6H), 7.18 - 7.06 (m, 1H), 7.03 - 6.90 (m, 2H), 5.49 (d, J = 3.5 Hz, 1H), 4.25 - 4.06 (m, 1H), 3.84 - 3.70 (m, 1H), 3.62 - 3.45 (m, 1H), 2.08 - 1.93 (m, 1H), 1.57 - 1.41 (m, 1H).

[0404] Validation data for compound 5f: 1 H NMR (400 MHz, CDC13) δ 8.29 (d, J = 8.9 Hz, 2H), 7.82 (d, J = 8.8 Hz, 2H), 7.43 - 7.37 (m, 2H), 7.35 - 7.27 (m, 3H), 7.15 - 7.08 (m, 2H), 7.07 - 6.97 (m, 1H), 6.86 - 6.69 (m, 1H), 5.53 (d, J = 3.5 Hz, 1H), 4.16 - 4.03 (m, 1H), 3.90 - 3.71 (m, 2H), 2.29 (s, 3H), 2.09 - 1.95 (m, 1H), 1.53 - 1.40 (m, 1H).

[0405] Validation data for compound 5g: 1 H NMR (400 MHz, CDC13) δ 8.27 (d, J = 8.9 Hz, 2H), 7.80 (d, J = 8.9 Hz, 2H), 7.59 - 7.44 (m, 1H), 7.42 - 7.23 (m, 5H), 7.22 - 7.14 (m, 1H), 7.12 - 7.03 (m, 1H), 6.91 (dd, J = 7.6, 1.8 Hz, 1H), 5.51 (d, J = 3.6 Hz, 1H), 4.14 - 3.96 (m, 2H), 3.92 - 3.76 (m, 1H), 2.21 - 2.05 (m, 1H), 1.55 - 1.40 (m, 1H).

[0406] Validation data for compound 5h: 1H NMR (400 MHz, CDC13) δ 8.29 (d, J = 8.8 Hz, 2H), 7.83 (d, J = 8.8 Hz, 2H), 7.46 - 7.24 (m, 5H), 7.05 (d, J = 7.7 Hz, 2H), 6.85 (d, J = 8.1 Hz, 2H), 5.56 (d, J = 3.5 Hz, 1H), 4.19 - 4.04 (m, 1H), 3.88 - 3.73 (m, 1H), 3.61 - 3.49 (m, 1H), 2.31 (s, 3H), 2.06 - 1.91 (m, 1H), 1.61 - 1.46 (m, 1H).

[0407] Verification data for compound 5i: 1 H NMR (400 MHz, CDC13) δ 8.29 (d, J = 8.8 Hz, 2H), 7.83 (d, J = 8.8 Hz, 2H), 7.46 - 7.24 (m, 5H), 7.05 (d, J = 7.7 Hz, 2H), 6.85 (d, J = 8.1 Hz, 2H), 5.56 (d, J = 3.5 Hz, 1H), 4.19 - 4.04 (m, 1H), 3.88 - 3.73 (m, 1H), 3.61 - 3.49 (m, 1H), 2.31 (s, 3H), 2.06 - 1.91 (m, 1H), 1.61 - 1.46 (m, 1H).

[0408] Verification data for compound 5j: 1 H NMR (400 MHz, CDC13) δ 8.29 (d, J = 8.8 Hz, 2H), 7.83 (d, J = 8.8 Hz, 2H), 7.46 - 7.24 (m, 5H), 7.05 (d, J = 7.7 Hz, 2H), 6.85 (d, J = 8.1 Hz, 2H), 5.56 (d, J = 3.5 Hz, 1H), 4.19 - 4.04 (m, 1H), 3.88 - 3.73 (m, 1H), 3.61 - 3.49 (m, 1H), 2.31 (s, 3H), 2.06 - 1.91 (m, 1H), 1.61 - 1.46 (m, 1H).

[0409] Verification data for compound 5k: 1 H NMR (400 MHz, CDC13) δ 8.29 (d, J = 8.8 Hz, 2H), 7.83 (d, J = 8.8 Hz, 2H), 7.46 - 7.24 (m, 5H), 7.05 (d, J = 7.7 Hz, 2H), 6.85 (d, J = 8.1 Hz, 2H), 5.56 (d, J = 3.5 Hz, 1H), 4.19 - 4.04 (m, 1H), 3.88 - 3.73 (m, 1H), 3.61 - 3.49 (m, 1H), 2.31 (s, 3H), 2.06 - 1.91 (m, 1H), 1.61 - 1.46 (m, 1H).

[0410] Verification data for compound 5k: 1 H NMR (400 MHz, CDC13) δ 8.26 (d, J = 8.8 Hz, 2H), 7.78 (d, J = 8.8 Hz, 2H), 7.43 - 7.20 (m, 5H), 7.09 - 6.77 (m, 4H), 5.51 (d, J = 3.5 Hz, 1H), 4.12 - 3.98 (m, 1H), 3.94 - 3.73 (m, 1H), 3.62 - 3.20 (m, 1H), 2.10 - 1.88 (m, 1H), 1.72 - 1.49 (m, 1H).

[0411] Verification data for compound 5m: 1 H NMR (400 MHz, CDC13) δ 8.25 (d, J = 8.7 Hz, 2H), 7.76 (d, J = 8.8 Hz, 2H), 7.53 (d, J = 8.0 Hz, 2H), 7.36 - 7.15 (m, 7H), 5.52 (d, J = 3.5 Hz, 1H), 4.15 - 4.02 (m, 1H), 3.90 - 3.72 (m, 1H), 3.71 - 3.51 (m, 1H), 2.17 - 2.01 (m, 1H), 1.76 - 1.62 (m, 1H).

[0412] Verification data for compound 5n: 1 H NMR (400 MHz, CDC13) δ 8.31 (d, J = 8.9 Hz, 2H), 7.86 (d, J = 8.9 Hz, 2H), 7.40 - 7.19 (m, 5H), 7.13 (d, J = 7.8 Hz, 2H), 7.02 - 6.93 (m, 2H), 5.56 (d, J = 3.5 Hz, 1H), 4.27 - 4.05 (m, 1H), 3.95 - 3.73 (m, 1H), 3.66 - 3.51 (m, 1H), 2.40 (s, 3H), 2.11 - 1.94 (m, 1H), 1.66 - 1.44 (m, 1H).

[0413] Verification data for compound 5o: 1H NMR (400 MHz, CDC13) δ 8.29 (d, J = 8.9 Hz, 2H), 7.83 (d, J = 8.8 Hz, 2H), 7.34 - 7.22 (m, 5H), 7.16 - 7.08 (m, 2H), 7.06 - 6.89 (m, 2H), 5.57 (d, J = 3.5 Hz, 1H), 4.23 - 4.06 (m, 1H), 3.92 - 3.77 (m, 1H), 3.66 - 3.48 (m, 1H), 2.68 (q, J = 7.6 Hz, 2H), 2.12 - 1.97 (m, 1H), 1.70 - 1.54 (m, 1H), 1.28 (t, J = 7.6 Hz, 3H).

[0414] Verification data for compound 5p: 1 H NMR (400 MHz, CDC13) δ 8.25 (d, J = 8.9 Hz, 2H), 7.80 (d, J = 8.9 Hz, 2H), 7.32 - 7.21 (m, 7H), 7.12 - 6.91 (m, 2H), 5.57 (d, J = 3.6 Hz, 1H), 4.27 - 4.03 (m, 1H), 4.00 - 3.79 (m, 1H), 3.71 - 3.54 (m, 1H), 2.18 - 1.98 (m, 1H), 1.76 - 1.54 (m, 1H), 1.34 (s, 9H).

[0415] Verification data for compound 5q: 1 H NMR (400 MHz, CDC13) δ 8.28 (d, J = 8.9 Hz, 2H), 7.81 (d, J = 8.9 Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H), 7.25 - 7.17 (m, 3H), 7.02 - 6.90 (m, 2H), 6.85 - 6.75 (m, 2H), 5.48 (d, J = 3.5 Hz, 1H), 4.21 - 4.04 (m, 1H), 3.84 - 3.72 (m, 4H), 3.62 - 3.48 (m, 1H), 2.06 - 1.92 (m, 1H), 1.60 - 1.51 (m, 1H).

[0416] Verification data for compound 5r: 1H NMR (400 MHz, CDC13) δ 8.33 (d, J = 8.8 Hz, 2H), 7.85 (d, J = 8.8 Hz, 2H), 7.36 (d, J = 8.5 Hz, 2H), 7.29 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 6.6 Hz, 3H), 6.95 - 6.84 (m, 2H), 5.56 (d, J = 3.5 Hz, 1H), 4.18 - 4.03 (m, 1H), 3.83 - 3.70 (m, 1H), 3.59 - 3.44 (m, 1H), 2.00 - 1.82 (m, 1H), 1.54 - 1.36 (m, 1H).

[0417] Verification data for compound 5s: 1 H NMR (400 MHz, CDC13) δ 8.33 (d, J = 8.8 Hz, 2H), 7.85 (d, J = 8.8 Hz, 2H), 7.36 (d, J = 8.5 Hz, 2H), 7.29 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 6.6 Hz, 3H), 6.95 - 6.84 (m, 2H), 5.56 (d, J = 3.5 Hz, 1H), 4.18 - 4.03 (m, 1H), 3.83 - 3.70 (m, 1H), 3.59 - 3.44 (m, 1H), 2.00 - 1.82 (m, 1H), 1.54 - 1.36 (m, 1H).

[0418] Verification data for compound 5t: 1 H NMR (400 MHz, CDC13) δ 8.33 (d, J = 8.8 Hz, 2H), 7.85 (d, J = 8.8 Hz, 2H), 7.36 (d, J = 8.5 Hz, 2H), 7.29 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 6.6 Hz, 3H), 6.95 - 6.84 (m, 2H), 5.56 (d, J = 3.5 Hz, 1H), 4.18 - 4.03 (m, 1H), 3.83 - 3.70 (m, 1H), 3.59 - 3.44 (m, 1H), 2.00 - 1.82 (m, 1H), 1.54 - 1.36 (m, 1H).

[0419] Verification data for compound 5u: 1H NMR (400 MHz, CDC13) δ 8.26 (d, J = 8.8 Hz, 2H), 7.79 (d, J = 8.7 Hz, 2H), 7.30 - 7.13 (m, 5H), 7.13 - 7.06 (m, 2H), 7.04 - 6.96 (m, 2H), 5.55 (d, J = 3.5 Hz, 1H), 4.18 - 4.03 (m, 1H), 3.89 - 3.71 (m, 1H), 3.64 - 3.41 (m, 1H), 2.27 (s, 3H), 2.10 - 1.91 (m, 1H), 1.75 - 1.53 (m, 1H).

[0420] Verification data for compound 5v: 1 H NMR (400 MHz, CDC13) δ 8.34 (d, J = 8.5 Hz, 2H), 7.88 (d, J = 8.5 Hz, 2H), 7.39 - 7.18 (m, 5H), 7.14 - 6.84 (m, 4H), 5.64 (d, J = 3.5 Hz, 1H), 4.21 - 4.02 (m, 1H), 3.94 - 3.69 (m, 1H), 3.65 - 3.35 (m, 1H), 2.14 - 1.90 (m, 1H), 1.61 - 1.50 (m, 1H).

[0421] Verification data for compound 5w: 1 H NMR (400 MHz, CDC13) δ 8.47 - 8.15 (m, 2H), 7.88 - 7.71 (m, 2H), 7.33 - 7.16 (m, 7H), 7.07 - 6.82 (m, 2H), 5.60 (d, J = 3.5 Hz, 1H), 4.18 - 3.97 (m, 1H), 3.85 - 3.68 (m, 1H), 3.63 - 3.48 (m, 1H), 2.14 - 1.93 (m, 1H), 1.67 - 1.59 (m, 1H).

[0422] Verification data for compound 5x: 1 H NMR (400 MHz, CDC13) δ 8.30 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.9 Hz, 2H), 7.46 - 7.38 (m, 1H), 7.38 - 7.30 (m, 2H), 7.29 - 7.14 (m, 4H), 7.04 - 6.95 (m, 2H), 5.59 (d, J = 3.5 Hz, 1H), 4.19 - 4.01 (m, 1H), 3.91 - 3.70 (m, 1H), 3.68 - 3.45 (m, 1H), 2.13 - 1.95 (m, 1H), 1.78 - 1.60 (m, 1H).

[0423] Verification data for compound 5y:1 H NMR (400 MHz, CDC13) δ 8.16 (d, J = 8.5 Hz, 2H), 7.82 - 7.68 (m, 6H), 7.52 - 7.43 (m, 3H), 7.27 - 7.19 (m, 3H), 7.00 (d, J = 6.7 Hz, 2H), 5.68 (d, J = 3.5 Hz, 1H), 4.28 - 4.07 (m, 1H), 3.90 - 3.70 (m, 1H), 3.67 - 3.45 (m, 1H), 2.13 - 1.98 (m, 1H), 1.70 - 1.56 (m, 1H).

[0424] Verification data for compound 5z: 1 H NMR (400 MHz, CDC13) δ 8.29 (d, J = 8.9 Hz, 2H), 7.88 (d, J = 8.9 Hz, 2H), 7.27 - 7.17 (m, 4H), 7.08 - 7.02 (m, 1H), 7.01 - 6.95 (m, 2H), 6.94 - 6.87 (m, 1H), 5.70 (d, J = 3.6 Hz, 1H), 4.14 - 3.98 (m, 1H), 3.85 - 3.69 (m, 1H), 3.63 - 3.47 (m, 1H), 2.17 - 2.00 (m, 1H), 1.75 - 1.61 (m, 1H).

[0425] Verification data for compound 5aa: 1 H NMR (400 MHz, CDC13) δ 8.29 (d, J = 8.9 Hz, 2H), 7.88 (d, J = 8.9 Hz, 2H), 7.27 - 7.17 (m, 4H), 7.08 - 7.02 (m, 1H), 7.01 - 6.95 (m, 2H), 6.94 - 6.87 (m, 1H), 5.70 (d, J = 3.6 Hz, 1H), 4.14 - 3.98 (m, 1H), 3.85 - 3.69 (m, 1H), 3.63 - 3.47 (m, 1H), 2.17 - 2.00 (m, 1H), 1.75 - 1.61 (m, 1H).

[0426] Verification data for compound 5ab: 1 H NMR (400 MHz, CDC13) δ 8.08 (d, J = 8.9 Hz, 2H), 7.58 - 7.39 (m, 4H), 7.23 - 6.92 (m, 7H), 4.40 - 4.20 (m, 1H), 3.76 - 3.54 (m, 1H), 3.42 (t, J = 8.5 Hz, 1H), 2.44 - 2.21 (m, 1H), 2.11 - 1.88 (m, 1H), 1.37 (s, 3H).

[0427] Verification data for compound 5ac:1 H NMR (400 MHz, CDC13) δ 8.05 (d, J = 8.6 Hz, 2H), 7.60-7.31 (m, 4H), 7.24-6.75 (m, 7H), 4.30-4.10 (m, 1H), 3.76-3.53 (m, 2H), 2.42-2.26 (m, 1H), 2.11-1.86 (m, 2H), 1.57-1.44 (m, 1H), 0.72 (t, J = 7.5 Hz, 3H).

[0428] Verification data of compound 5ad: 1 H NMR (400 MHz, CDC13) δ 8.05 (d, J = 8.6 Hz, 2H), 7.60-7.31 (m, 4H), 7.24-6.75 (m, 7H), 4.30-4.10 (m, 1H), 3.76-3.53 (m, 2H), 2.42-2.26 (m, 1H), 2.11-1.86 (m, 2H), 1.57-1.44 (m, 1H), 0.72 (t, J = 7.5 Hz, 3H).

[0429] Example 23 Aziridine with olefin or alkyne cycloaddition reaction

[0430]

[0431] Compound 1-1 (0.1 mmol), compound 2 (0.3 mmol) and catalyst (10 mol%) were reacted in solvent (1 mL) at room temperature (r.t.) for 12 hours to obtain compound 3-1.

[0432] General reaction process C:

[0433] Olefin addition reaction:

[0434] A solution of aziridine 6 (0.2 mmol, 1.0 eq) and CB16 (10 mol%) in dichloromethane (8 mL) was added to olefin 2a (0.6 mmol, 3.0 eq) and the mixture was stirred at 70 °C for 36 hours. The reaction solution was concentrated by evaporation and then purified by silica gel column chromatography (V (ethyl acetate) / V (petroleum ether) = 20 / 1) to obtain the target product 7.

[0435] General reaction process D:

[0436] Alkyne addition reaction:

[0437] A solution of aziridine 6 (0.2 mmol, 1.0 eq) and CB16 (10 mol%) in dichloromethane (8 mL) was added to a mixture of alkyne 4a (0.6 mmol, 3.0 eq) and the mixture was stirred at 70 °C for 36 h. The reaction mixture was concentrated by evaporation and purified by silica gel column chromatography (V(acetone) / V(petroleum ether) = 20 / 1) to give the target product 8.

[0438] Specific values of each substituent R in aziridine 6, target product 7 and target product 8 4 are shown in Table 8 below:

[0439] Specific values of each substituent R in aziridine 6, target product 7 and target product 8

[0440]

[0441]

[0442] To further expand the scope of this method, as demonstrated in the above olefin addition and alkyne addition reactions, we attempted to use aziridine 6 as a substrate for a cycloaddition reaction. Preliminary studies showed that under standard conditions, aziridine 6a reacted with olefin 2a to give the expected [3+2] cycloaddition product 7a, albeit in a low yield (26%).

[0443]

[0444] Subsequently, we evaluated the effect of para-substituents on the benzene ring of aziridine: the introduction of electron-donating groups had negligible effect on the reaction outcome (7b, 30%), while halogen-substituted olefins gave significantly improved yields (52-64%, 7c-7e). Similarly, the yield of 6f with a meta-methyl substituent was much lower than its meta-bromine-substituted analogue 6g. Aziridine 6h with an ortho-bromine-substituted benzene ring also participated effectively in the reaction to give product 7h in 57% yield (Table 3A). We also evaluated the reactivity of aziridine 6a with phenylacetylene 4a to give product 8a in 70% yield. Unfortunately, the yield dropped to 38% when para-methyl-substituted phenylacetylene 6b was used. Fortunately, the yield returned to a good level (70-78%, 8c-8e) when para-halogen-substituted phenylacetylenes were used. The beneficial effect of halogen substitution was still present when the substitution was meta (8f, 43% vs 8g, 71%). In addition, ortho-bromine-substituted 6h could undergo the cycloaddition smoothly to give product 8h in 76% yield.

[0445] Verification data for compound 7a: 1H NMR (400 MHz, CDC13) δ 7.75 (d, J = 8.3 Hz, 2H), 7.29 (td, J = 8.3, 2.0 Hz, 4H), 7.25 - 7.20 (m, 1H), 7.18 - 7.04 (m, 2H), 3.89 - 3.73 (m, 1H), 3.37 - 3.15 (m, 2H), 2.42 (s, 3H), 2.19 - 2.11 (m, 1H), 2.07 - 1.80 (m, 5H), 0.96 (q, J = 7.6 Hz, 6H).

[0446] Verification data for compound 7b: 1 H NMR (400 MHz, CDC13) δ 7.75 (d, J = 8.3 Hz, 2H), 7.29 (td, J = 8.3, 2.0 Hz, 4H), 7.25 - 7.20 (m, 1H), 7.18 - 7.04 (m, 2H), 3.89 - 3.73 (m, 1H), 3.37 - 3.15 (m, 2H), 2.42 (s, 3H), 2.19 - 2.11 (m, 1H), 2.07 - 1.80 (m, 5H), 0.96 (q, J = 7.6 Hz, 6H).

[0447] Verification data for compound 7c: 1 H NMR (400 MHz, CDC13) δ 7.75 (d, J = 8.3 Hz, 2H), 7.29 (td, J = 8.3, 2.0 Hz, 4H), 7.25 - 7.20 (m, 1H), 7.18 - 7.04 (m, 2H), 3.89 - 3.73 (m, 1H), 3.37 - 3.15 (m, 2H), 2.42 (s, 3H), 2.19 - 2.11 (m, 1H), 2.07 - 1.80 (m, 5H), 0.96 (q, J = 7.6 Hz, 6H).

[0448] Verification data for compound 7d: 1 H NMR (400 MHz, CDC13) δ 7.75 (d, J = 8.3 Hz, 2H), 7.29 (td, J = 8.3, 2.0 Hz, 4H), 7.25 - 7.20 (m, 1H), 7.18 - 7.04 (m, 2H), 3.89 - 3.73 (m, 1H), 3.37 - 3.15 (m, 2H), 2.42 (s, 3H), 2.19 - 2.11 (m, 1H), 2.07 - 1.80 (m, 5H), 0.96 (q, J = 7.6 Hz, 6H).

[0449] Verification data for compound 7e: 1H NMR (400 MHz, CD2Cl2) δ 7.76 (d, J = 8.3 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.1 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 3.89-3.77 (m, 1H), 3.37-3.23 (m, 1H), 3.24-3.06 (m, 1H), 2.46 (s, 3H), 2.27-2.14 (m, 1H), 2.10-1.79 (m, 5H), 1.05-0.83 (m, 6H).

[0450] Verification data for compound 7f: 1 H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.22-7.13 (m, 1H), 7.04 (s, 1H), 6.97 (d, J = 6.6 Hz, 2H), 3.89-3.74 (m, 1H), 3.34-3.12 (m, 2H), 2.41 (s, 3H), 2.32 (s, 3H), 2.21-1.76 (m, 6H), 1.05-0.88 (m, 6H).

[0451] Verification data for compound 7g: 1 H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.22-7.13 (m, 1H), 7.04 (s, 1H), 6.97 (d, J = 6.6 Hz, 2H), 3.89-3.74 (m, 1H), 3.34-3.12 (m, 2H), 2.41 (s, 3H), 2.32 (s, 3H), 2.21-1.76 (m, 6H), 1.05-0.88 (m, 6H).

[0452] Verification data for compound 7h: 1 H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.22-7.13 (m, 1H), 7.04 (s, 1H), 6.97 (d, J = 6.6 Hz, 2H), 3.89-3.74 (m, 1H), 3.34-3.12 (m, 2H), 2.41 (s, 3H), 2.32 (s, 3H), 2.21-1.76 (m, 6H), 1.05-0.88 (m, 6H).

[0453] Verification data for compound 8a: 1H NMR (400 MHz, CD2Cl2) δ 7.76 - 7.64 (m, 2H), 7.54 (d, J = 8.2 Hz, 2H), 7.51 - 7.42 (m, 3H), 7.32 (d, J = 8.0 Hz, 2H), 7.26 - 7.12 (m, 3H), 7.01 - 6.81 (m, 2H), 5.52 (d, J = 2.6 Hz, 1H), 4.49 (dd, J = 12.5, 9.7 Hz, 1H), 3.86 (dd, J = 12.5, 8.2 Hz, 1H), 3.78 - 3.61 (m, 1H), 2.50 (s, 3H).

[0454] Verification data for compound 8b: 1 H NMR (400 MHz, CD2Cl2) δ 7.69 - 7.57 (m, 2H), 7.48 (d, J = 8.3 Hz, 2H), 7.41 (dd, J = 5.0, 2.0 Hz, 3H), 7.27 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 7.8 Hz, 2H), 6.74 (d, J = 8.1 Hz, 2H), 5.46 (d, J = 2.6 Hz, 1H), 4.40 (dd, J = 12.5, 9.6 Hz, 1H), 3.77 (dd, J = 12.5, 8.3 Hz, 1H), 3.69 - 3.56 (m, 1H), 2.45 (s, 3H), 2.28 (s, 3H).

[0455] Verification data for compound 8c: 1 H NMR (400 MHz, CD2Cl2) δ 7.74 - 7.64 (m, 2H), 7.55 - 7.39 (m, 5H), 7.30 (d, J = 7.9 Hz, 2H), 6.97 - 6.78 (m, 4H), 5.48 (d, J = 2.7 Hz, 1H), 4.46 (dd, J = 12.4, 9.6 Hz, 1H), 3.82 (dd, J = 12.4, 7.6 Hz, 1H), 3.78 - 3.62 (m, 1H), 2.49 (s, 3H).

[0456] Verification data for compound 8d: 1 H NMR (400 MHz, CD2Cl2) δ 7.60 - 7.47 (m, 2H), 7.44 - 7.25 (m, 5H), 7.12 (d, J = 8.0 Hz, 2H), 7.08 - 6.94 (m, 2H), 6.79 - 6.57 (m, 2H), 5.34 (d, J = 2.7 Hz, 1H), 4.32 (dd, J = 12.6, 9.8 Hz, 1H), 3.70 (dd, J = 12.5, 7.2 Hz, 1H), 3.64 - 3.49 (m, 1H), 2.34 (s, 3H).

[0457] Validation data for compound 8e: 1 H NMR (400 MHz, CD2CI2) δ 7.70 - 7.57 (m, 2H), 7.49 - 7.36 (m, 5H), 7.28 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.73 (d, J = 8.4 Hz, 2H), 5.46 (d, J = 2.8 Hz, 1H), 4.44 (dd, J = 12.6, 9.8 Hz, 1H), 3.82 (dd, J = 12.6, 7.2 Hz, 1H), 3.74 - 3.59 (m, 1H), 2.46 (s, 3H).

[0458] Validation data for compound 8f: 1 H NMR (400 MHz, CD2CI2) δ 7.68 - 7.60 (m, 2H), 7.50 (d, J = 8.3 Hz, 2H), 7.42 (dd, J = 5.0, 2.0 Hz, 3H), 7.28 (d, J = 8.0 Hz, 2H), 7.06 (t, J = 7.5 Hz, 1H), 6.99 (d, J = 7.6 Hz, 1H), 6.73 - 6.59 (m, 2H), 5.46 (d, J = 2.6 Hz, 1H), 4.42 (dd, J = 12.5, 9.7 Hz, 1H), 3.78 (dd, J = 12.5, 8.6 Hz, 1H), 3.66 - 3.48 (m, 1H), 2.45 (s, 3H), 2.24 (s, 3H).

[0459] Validation data for compound 8g: 1 H NMR (400 MHz, CD2CI2) δ 7.63 (dd, J = 6.7, 2.9 Hz, 2H), 7.52 - 7.38 (m, 5H), 7.28 (dd, J = 23.3, 8.1 Hz, 3H), 7.11 - 7.03 (m, 1H), 7.02 - 6.93 (m, 1H), 6.82 (d, J = 7.7 Hz, 1H), 5.45 (d, J = 2.7 Hz, 1H), 4.44 (dd, J = 12.5, 9.9 Hz, 1H), 3.82 (dd, J = 12.6, 7.6 Hz, 1H), 3.74 - 3.62 (m, 1H), 2.44 (s, 3H).

[0460] Validation data for compound 8h: 1H NMR (400 MHz, CD2Cl2) δ 7.81 - 7.64 (m, 2H), 7.60 - 7.38 (m, 6H), 7.22 (d, J = 8.0 Hz, 2H), 7.02 (s, 2H), 6.72 (d, J = 7.4 Hz, 1H), 5.53 (d, J = 2.8 Hz, 1H), 4.59 (dd, J = 12.8, 9.8 Hz, 1H), 4.13 - 3.94 (m, 1H), 3.78 (dd, J = 12.8, 7.1 Hz, 1H), 2.44 (s, 3H).

[0461] Example 24 Mechanism verification test

[0462] 1) Standard reaction condition

[0463]

[0464] A solution of azetidine 1a (63.6 mg, 0.2 mmol) and CB16 (60.4 mg, 0.02 mmol) in dichloromethane (8 mL) was added to the mixture of alkyne 4a (61.2 mg, 0.6 mmol) and stirred at 70 °C for 36 h. The reaction mixture was concentrated by evaporation and purified by silica gel column chromatography (V(acetic ether) / V(petroleum ether) = 20 / 1) to give the target product 5a in 82% yield.

[0465] 2) Add CaH2

[0466] A solution of azetidine 1a (63.6 mg, 0.2 mmol), CaH2(10.1 mg, 0.24 mmol) and CB16 (60.4 mg, 0.02 mmol) in dichloromethane (8 mL) was added to the mixture of alkyne 4a (61.2 mg, 0.6 mmol) and stirred at 70 °C for 36 h. The reaction mixture was concentrated by evaporation and purified by silica gel column chromatography (V(acetic ether) / V(petroleum ether) = 20 / 1) to give the target product 5a in 80% yield.

[0467] 3) Add tetrahydrothiophene

[0468] A solution of azetidine 1a (63.6 mg, 0.2 mmol), tetrahydrothiophene (4.1 mg, 0.04 mmol) and CB16 (60.4 mg, 0.02 mmol) in dichloromethane (8 mL) was added to the mixture of alkyne 4a (61.2 mg, 0.6 mmol) and stirred at 70 °C for 36 h. No target product 5a was obtained.

[0469] 4) Add Ph3PO

[0470] A solution of azetidine la (63.6 mg, 0.2 mmol), Ph3PO (11.1 mg, 0.04 mmol) and CB16 (60.4 mg, 0.02 mmol) in dichloromethane (8 mL) was added to a mixture of alkyne 4a (61.2 mg, 0.6 mmol) and the mixture was stirred at 70 °C for 36 h. No target product 5a was obtained.

[0471] 5) Effect of azetidine protecting group

[0472] The difference from "1) Standard reaction condition" is that "azetidine la" is replaced by other azetidine derivatives, and the rest of the reaction conditions are consistent. Details are shown in Table 9 as follows:

[0473] Table 9 Azetidine replacement

[0474]

[0475] Verification data of compound 5ae: 1 H NMR (400 MHz, CDC13) δ 7.49-7.41 (m, 2H), 7.41-7.17 (m, 8H), 5.53 (d, J = 3.5 Hz, 1H), 3.93-3.79 (m, 1H), 3.77-3.61 (m, 2H), 2.89 (q, J = 7.4 Hz, 2H), 2.42-2.23 (m, 1H), 2.10-1.94 (m, 1H), 1.35 (t, J = 7.4 Hz, 3H).

[0476] To verify the reaction mechanism, the present application carried out a number of control experiments. Under standard conditions, the reaction of azetidine la and 4a produced 5a with a yield of 82%; when strong base calcium hydride (CaH2) was added, the yield was almost the same (80%). This ruled out the possibility that the "organic tellurium catalyst decomposes to produce a proton acid and promotes the reaction". Subsequently, the present application added 20 mol% of Lewis base (such as tetrahydrothiophene or Ph3PO), and found that the reaction was completely inhibited. This indicates that there is a weak interaction between the tellurium catalyst and the substrate through chalcogen bond (ChB). To study the activation mode of the bidentate telluronium catalyst and azetidine, the present application evaluated other types of nitrogen protecting groups on azetidine. The results showed that when the phenyl group on the sulfonyl group was replaced by an ethyl group, the corresponding product 5ae could still be obtained with a yield of 52%; while using tert-butyloxycarbonyl (t-butyloxycarbonyl) or phenyl-protected azetidine, the reaction did not occur. It is speculated that the bidentate telluronium dication may achieve the activation of the azetidine substrate by interacting with the two oxygen atoms of the sulfonyl group.

[0477] Based on the above research of the present application, the inventors of the present application propose a possible reaction pathway of the catalytic reaction, as shown in Scheme 1: azetidine 1a binds to CB16 through a bidentate activation mode to form intermediate Int-1. The activated intermediate can undergo electrophilic addition with olefin 2 or alkyne 4 to form intermediate Int-2. Finally, cyclization reaction occurs through intermediate Int-3 to form the target product piperidine 3 or tetrahydropyridine 5, while CB16 is regenerated. Figure 8

[0478] The method of the present application has been described by preferred embodiments, and the relevant personnel can obviously make changes or appropriate changes and combinations to the methods and applications described herein within the content, spirit and scope of the present application to realize and apply the present application technology. Those skilled in the art can refer to the content herein to appropriately improve the process parameters for implementation. It is particularly pointed out that all similar substitutions and changes are obvious to those skilled in the art, and they are considered to be included in the present application.​

Claims

1. A bidentate organotellurium salt catalyst and enantiomers or diastereomers thereof or a pharmaceutically acceptable salt thereof, characterized in that, having a structure as shown in formula (I): wherein m is selected from 0, 1, 2, 3 or 4; n is selected from 0, 1, 2, 3, 4 or 5; each R is independently H, -F, -Cl, -Br, -I, -NH2, -CN, -CHO, -COOH, -SO3H, alkyl-C(=O)-, aryl-C(=O)-, aryl-SO2-, -CONH2, -NHCOOH, -B(OH)2, -boronic pinacol ester, nitro, alkoxy, alkylthio, haloalkyl, haloalkenyl, haloalkynyl, haloalkoxy, haloalkenyloxy, haloalkynyloxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl or alkyl; X is BF 4 - or BArF 4 -; A is absent, a bond, -Z-, -N(R 1 ) y -; -C(=Z)-, -((C(R 2 ) p ) q -; -S(=O) y -; -NR 1 -C(=O)-, -NR 1 -C(=O)-NR 1 -; -C(=O)-NR 1 -; -((C(R 2 ) p ) q -Z) x -(C(R 2 ) p ) q -; each Y is independently absent, a bond, -N(R 1 ) y -, -C(=Z)-, -((C(R 2 ) p ) q -, -S(=O) y -, -NR 1 -C(=O)-, -NR 1 -C(=O)-NR 1 -, -C(=O)-NR 1 -, -((C(R 2 ) p ) q -Z) x -(C(R 2 ) p ) q - ; each Z is independently selected from O or S; each p is independently selected from 0, 1 or 2; each y is independently selected from 0 or 1; q and x are each independently selected from an integer from 0 to 30, for example from 0 to 20 or 0 to 10 or 0, 1, 2, 3, 4, 5, 6, 7 or 8; each R is independently H, cycloalkyl or alkyl; 1 independently H, cycloalkyl or alkyl; Each R 2 Independently, it is H, -F, -Cl, -Br, -I, -NH2, -CN, -CHO, -COOH, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkenyl, alkynyl or alkyl; The R, R 1 R 2 A and A are further optionally and independently replaced by the same or different substituents R. 0 Mono- or poly-substituted; the substituent R 0 It can be hydrogen, -F, -Cl, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -alkyl-COOH, -SO3H, -alkyl-SO3H, alkyl-C(=O)-, aryl-C(=O)-, aryl-SO2-, amino, nitro, alkoxy, alkylthio, haloalkyl, -Si(alkyl)2H, cycloalkyl, heterocyclic, aryl, heteroaryl, alkenyl, alkynyl, or alkyl.

2. The bidentate organotellurium salt catalyst according to claim 1, and its enantiomers or diastereomers or pharmaceutically acceptable salts thereof, characterized in that, said substituents R 0 are hydrogen, -F, -CI, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -C 1-12 alkyl-COOH, -SO3H, -C 1-12 alkyl-SO3H, C 1-12 alkyl-C(=O)-, C 6-12 aryl-C(=O)-, C 6-12 aryl-SO2-, amino, nitro, C 1-12 alkoxy, C 1-12 alkylthio, C 1-12 haloalkyl, -Si(C 1-12 alkyl)2H, C 3-12 cycloalkyl, C 2-12 heterocyclyl, C 6-12 aryl, C 1-12 heteroaryl, C 2-12 alkenyl, C 2-12 alkynyl or C 1-12 alkyl; and / or each R is independently H, -F, -Cl, -Br, -I, -NH2, -CN, -CHO, -COOH, -SO3H, C 1-6 alkyl-C(=O)-, C 6-12 aryl-C(=O)-, C 6-12 aryl-SO2-, -CONH2, -NHCOOH, -B(OH)2, -boronic pinacol ester, nitro, C 1-12 alkoxy, C 1-12 alkylthio, C 1-12 haloalkyl, C 2-12 haloalkenyl, C 2-12 haloalkynyl, C 1-12 haloalkoxy, C 2-12 haloalkenyloxy, C 2-12 haloalkynyloxy, C 3-12 cycloalkyl, C 2-12 heterocycloalkyl, C 6-12 aryl, C 1-12 heteroaryl, C 2-12 alkenyl, C 2-12 alkynyl or C 1-12 alkyl; which can be further mono- or polysubstituted by the same or different substituents R 0 substituted; and / or, each R 1 independently H, C 3-12 cycloalkyl or C 1-12 alkyl; which can be further substituted by the same or different substituents R 0 monosubstituted or polysubstituted; and / or, each R 2 independently H, -F, -CI, -Br, -I, -NH2, -CN, -CHO, -COOH, C 1-12 haloalkyl, C 2-12 haloalkenyl, C 2-12 haloalkynyl, C 3-12 cycloalkyl, C 2-12 heterocycloalkyl, C 6-12 aryl, C 1-12 heteroaryl, C 2-12 alkenyl, C 2-12 alkynyl or C 1-12 alkyl; which can be further mono- or polysubstituted by the same or different substituents R 0 substituted or polysubstituted.

3. The bidentate organic tellurium catalyst according to claim 1, its enantiomers or diastereomers, or pharmaceutically acceptable salts thereof, is characterized in that... each R is independently H, -F, -CI, -Br, -I, -NH2, -CN, -CHO, -COOH, -SO3H, -CONH2, -NHCOOH, -B(OH)2nitro, methoxy, methylthio, trifluoromethyl, monofluoromethyl, difluoromethyl, chloroethyl, methyl, ethyl, isopropyl, n-propyl, n-butyl, t-butyl, or n-hexyl; which can be further substituted by the same or different substituents R 0 monosubstituted or polysubstituted; and / or, each R 1 independently H, C 3-6 cycloalkyl or C 1-6 alkyl; can be further substituted by the same or different substituents R 0 monosubstituted or polysubstituted; and / or the substituents R 0 are hydrogen, -F, -CI, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -methyl-COOH, -SO3H, -methyl-SO3H, methyl-C(=O)-, C 6-12 aryl-C(=O)-, C 6-12 aryl-SO2-, amino, nitro, methoxy, methylthio, trifluoromethyl, -Si(methyl)2H, phenyl, naphthyl, methyl, ethyl, isopropyl, n-propyl, n-butyl or t-butyl; And / or, each R 2 Independently, it can be H, -F, -Cl, -Br, -I, -NH2, -CN, -CHO, -COOH, methyl, ethyl, isopropyl, n-propyl, n-butyl, tert-butyl, phenyl, naphthyl, 4-methoxyphenyl, or 4-fluorophenyl.

4. The bidentate organotellurium salt catalyst according to claim 1, and enantiomers or diastereomers thereof, or a pharmaceutically acceptable salt thereof, wherein, having one of the following structures:

5. The bidentate organotellurium salt catalyst according to claim 1, and enantiomers or diastereomers thereof, or a pharmaceutically acceptable salt thereof, wherein, which is selected from one of the following structural formulae: ​ 6. A process for the preparation of a bidentate organotelluride salt catalyst of the formula (I) as claimed in any one of claims 1 to 5, and enantiomers or diastereomers thereof, or pharmaceutically acceptable salts thereof, characterized in that, comprising the following steps: Step 1): a diaryl tellurium compound (3.S1) is reacted with NFSI and cesium fluoride to form a difluorodiaryl tellurium compound (3.S2); Step 2): the difluorodiaryl tellurium compound (3.S2) and a bis-aryl boronic acid (3.S3) are reacted in the presence of boron trifluoride etherate solution and sodium tetrafluoroborate to obtain the bidentate organotellurium salt catalyst of formula (I); R, n, Y, A have the definitions as described in claim 1.

7. The preparation method according to claim 6, characterized in that, In step 1), the molar ratio of the diaryl tellurium compound (3.S1) to cesium fluoride is 1:1-5; and / or, in step 1), the molar ratio of the diaryl tellurium compound (3.S1) to NFSI is 1:1-5; and / or, in step 1), the solvent used is selected from one of toluene, chlorobenzene, dichloromethane, ethyl acetate, anisole, diethyl ether, methanol, ethanol, propanol, acetone and butanol; and / or, in step 2), the molar ratio of the difluorodiaryl tellurium compound (3.S2) to bis-aryl boronic acid is 1-5:1-5; and / or the bis-aryl boronic acid is selected from and / or, in step 2), the molar ratio of the bis-aryl boronic acid to boron trifluoride etherate solution is 1-5:1-5; and / or, in step 2), the molar ratio of the bis-aryl boronic acid to sodium tetrafluoroborate is 1-5:10-55; and / or, in step 2), the solvent used is selected from one of toluene, chlorobenzene, dichloromethane, ethyl acetate, anisole, diethyl ether, methanol, ethanol, propanol, acetone and butanol.

8. Use of the bidentate organotellurium salt catalyst of any one of claims 1-5 or any one of claims 6-7 or an enantiomer or diastereomer thereof or a pharmaceutically acceptable salt thereof, comprising use in the synthesis of a piperidine derivative.

9. Use according to claim 8, characterized in that, The synthesis of the piperidine derivative comprises: reacting compound 1, compound 2 and the bidentate organotellurium salt catalyst of formula (I) in a solvent to obtain compound 3, wherein z is 0 or 1; M is Ts-, Ns-, -SO2-Et, Boc, Ph- or Ph-SO2-; Each R 4 It can be independently a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group; R 5 , R 6 , R 7a , R 7b each independently is H, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkenyl, alkynyl, or alkyl; R 5 and R 7a together with the carbon atom to which they are attached form an E ring; R 6 and R 7b together with the carbon atom to which they are attached form an F ring; the E ring and the F ring each independently is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 7b and R 7a together with the carbon atom to which they are attached form a chemical bond; The R 4 R 5 R 6 R 7a R 7b The E and F rings are further optionally and independently substituented by the same or different substituents R. a Mono- or poly-substituted; the substituent R a It can be hydrogen, =O, -F, -Cl, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -alkyl-COOH, -SO3H, -alkyl-SO3H, alkyl-C(=O)-, aryl-C(=O)-, aryl-SO2-, amino, nitro, alkoxy, alkylthio, haloalkyl, -Si(alkyl)2H, cycloalkyl, heterocyclic, aryl, heteroaryl, alkenyl, alkynyl, or alkyl.

10. Use according to claim 8, characterized in that, said substituents R a are hydrogen, =0, -F, -CI, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -C 1-12 alkyl-COOH, -SO3H, -C 1-12 alkyl-SO3H, C 1-12 alkyl-C(=0)-, C 6-12 aryl-C(=0)-, C 6-12 aryl-SO2-, amino, nitro, C 1-12 alkoxy, C 1-12 alkylthio, C 1-12 haloalkyl, -Si(C 1-12 alkyl)2H, C 3-12 cycloalkyl, C 2-12 heterocyclyl, C 6-12 aryl, C 1-12 heteroaryl, C 2-12 alkenyl, C 2-12 alkynyl or C 1-12 alkyl; and / or the substituents R a are hydrogen, =0, -F, -CI, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl, -COOH, -methyl-COOH, -SO3H, -methyl-SO3H, methyl-C(=0)-, C 6-12 aryl-C(=0)-, C 6-12 aryl-SO2-, amino, nitro, methoxy, methylthio, trifluoromethyl, -Si(methyl)2H, phenyl, naphthyl, methyl, ethyl, isopropyl, n-propyl, n-butyl or t-butyl; and / or, each R 4 independently C 3-12 cycloalkyl, C 2-12 heterocycloalkyl, C 6-20 aryl or C 1-20 heteroaryl; can be further substituted by the same or different substituents R a monosubstituted or polysubstituted; And / or, each R 4 Independently phenyl, and / or, R 5 , R 6 , R 7a , R 7b are each independently H, C 1-12 haloalkyl, C 2-12 haloalkenyl, C 2-12 haloalkynyl, C 3-20 cycloalkyl, C 2-20 heterocycloalkyl, C 6-20 aryl, C 1-20 heteroaryl, C 2-12 alkenyl, C 2-12 alkynyl or C 1-12 alkyl; the E and F rings are each independently C 3-20 cycloalkyl, C 2-20 heterocycloalkyl, C 6-20 aryl or C 1-20 heteroaryl; R 5 , R 6 , R 7a , R 7b , E ring and F ring can be further mono- or poly-substituted with the same or different substituents R a ; and / or, R 5 , R 6 , R 7a , R 7b each independently is H, methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, the E and F rings are each independently cyclobutane, cyclopentane, or cyclohexane; R 5 , R 6 , R 7a , R 7b , the E and F rings can be further mono- or poly-substituted with the same or different substituents R a ; and / or, the structural formula of compound 1 includes and / or, the structural formula of compound 2 includes and / or, the structural formula of compound 3 includes and / or, R 7aa , R 7ba each independently is H, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkenyl, alkynyl, or alkyl; R 5 and R 7aa together with the carbon atom to which they are attached form an E ring; R 6 and R 7ba together with the carbon atom to which they are attached form an F ring; R 7aa , R 7ba may be further mono- or poly-substituted by said same or different substituents R a ; and / or, R 7aa , R 7ba each independently is H, C 3-6 cycloalkyl, C 2-6 heterocycloalkyl, C 6-20 aryl, C 1-12 heteroaryl or C 1-6 alkyl; and / or, the structural formula of compound 3 is selected from one of the following structures:

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