A neutral reverse electron state carbene and a preparation method and application thereof

Abstract

This invention provides a neutral-electron-reversed carbene, its preparation method, and its applications, belonging to the fields of organic chemistry and organic catalysis. The neutral-electron-reversed carbene described in this invention has the structure shown in formula (I). This invention synthesizes the neutral-electron-reversed carbene in one step by reacting a diazo compound as a precursor with a rhodium complex, followed by nitrogen removal and COD (1,5-cyclooctadiene) removal processes. The reaction conditions of this invention are simple, and the yield is good. Stable separation of neutral-electron-reversed carbene is achieved for the first time.

Description

Technical Field

[0001] This invention relates to the fields of organic chemistry and organic catalysis, and provides a neutral reversed electron state carbene, its preparation method, and its application. Background Technology

[0002] Carbene (R₂C₂) is a class of divalent carbon compounds with a central carbon atom possessing a six-electron structure. The history of carbene can be traced back to 1835, when Dumas claimed to have dreamt of separating the (H₂C₂) species. Ann. Chim. Phys. 1835 , 58 In the following years, several research groups indirectly confirmed the existence of carbene species, until 1988 when Bertrand's group reported the first stable acyclic phosphine-based silicon carbene. J. Am. Chem. Soc 1988, 110 , 6463). Following this, in 1991, Arduengo's group reported the first single-crystal structure characterization of a nitrogen-containing heterocyclic carbene (NHC). J. Am. Chem. Soc. 1991, 113 , 361). From then on, carbene officially entered the research field of chemists and embarked on a new journey of exploration. In 1995-1996, Enders and Teles revealed the potential of triazole-derived NHC as an organocatalyst ( Angew. Chem. Int. Ed. Engl. 1995 , 34, 1021). Of particular note is that in 1999, Grubbs successfully developed a second-generation Grubbs catalyst using NHC. Tetrahedron Lett. 1999 , 40, (2247). These groundbreaking discoveries demonstrate that carbenes are not the transient compounds traditionally thought to be; they can be isolated and have broad application prospects. Currently, carbenes are widely used in numerous fields such as ligand modification, synthetic catalysis, materials science, and medicinal chemistry.

[0003] The carbon valence shell of a carbene contains four electrons (two of which are unbonded). Based on the different orbitals occupied by these two unbonded electrons, carbenes can be classified into four types. Currently, the most studied type is the classical singlet carbene (σ). 2 π 0 This includes, but is not limited to, NHC and CAAC (cyclic monoamino carbene). However, carbene (σ) has an opposite electron-occupying orbital configuration. 0 π 2 However, this type of anti-electronic carbene is rarely discussed; it is also known as the reverse-electronic carbene. Figure 1 ). σ 0 π 2The electronic carbene was first confirmed in 1995. Although its existence was computationally confirmed, stabilizing it experimentally remains a significant challenge. Theoretical calculations show that, with a ground state of σ... 1 π 1 The parent carbene H2C(:) is excited to σ 0 π 2 The electronic state requires 60.1 kcal / mol of energy; this huge energy difference indicates that the reversed electronic state carbene possesses extremely high reactivity. Faced with this challenge, several international research groups (Maier, Bertrand, Kusumoto, etc.) have attempted to stably separate it, but none have achieved satisfactory results. It is worth mentioning that recently, Liu's research group in China achieved the first stable separation of the reversed electronic state carbene, and further, combined with theoretical calculations and reactivity, fully confirmed the electronic state property of the carbene. Science 2024, 383 ,81).

[0004] It is worth noting that the application research of inverted electronic carbenes remains largely unexplored due to the difficulty and limitations of their synthesis. However, this does not hinder theoretical chemists' research and predictions. In 2024, Zhu's research group reported theoretical calculations predicting the use of this type of carbene for activating N2, H2, CH4, and HBPin, further elucidating the σ... 0 π 2 Carbene's unique reactivity and activation potential for small molecules ( Inorg. Chem. 2024, 63 (15931). Fast forward to 2021, Wagner et al. studied σ... 0 π 2 The reaction mechanism of carbene with hydrogen and olefins was theoretically studied, and the results showed that σ 0 π 2 Electronic carbene undergoes minimal configurational change and has a low activation energy when reacting with either of these substances. J. Org. Chem. 2021 , 86, 15247). This study also illustrates the potential advantages of reverse-electron carbenes in activating small molecules. The predictions of theoretical chemists fully reflect the high reactivity and unique chemical properties of reverse-electron carbenes. If a universally applicable method for synthesizing reverse-electron carbenes can be developed, it will greatly promote subsequent research on carbene reactivity and the exploration of its application potential, injecting new vitality into the development of synthetic catalysis, materials science, and medicinal chemistry. Due to the high reactivity of reverse-electron carbenes, most studies can only obtain their adducts by adding scavenging agents. Synthetic methods are scarce; currently, there is only one method for synthesizing cationic reverse-electron carbenes (…). Science 2024, 383(81). In summary, cationic carbenes have two main defects and shortcomings: 1. The synthetic route is relatively complex and needs to be completed step by step; 2. Cationic complexes have obvious shortcomings in terms of solubility and universality of reaction, and have specific requirements for reaction solvents, temperatures, etc., which increases the difficulty of popularization and application.

[0005] Therefore, it is necessary to focus on the development of methods for synthesizing neutral reverse electronic states in order to broaden the application scope of carbene. Summary of the Invention

[0006] To address the problems mentioned in the background art, this invention develops a method for synthesizing neutral-electron-inverted carbenes, achieving for the first time the stable separation of neutral-electron-inverted carbenes. The synthesis method uses a diazo compound as a precursor, reacts with a rhodium complex, and completes the synthesis of neutral-electron-inverted carbenes in one step through a process of nitrogen removal and COD removal (1,5-cyclooctadiene). This reaction condition is simple, efficiently synthesizing carbon carbene compounds with a planar four-membered ring central framework stabilized by a rhodium complex, with good yields.

[0007] Firstly, a neutral inverted electronic state carbene is provided, with the structure shown in equation (I): .

[0008] Secondly, a method for preparing a neutral-electron-inverted carbene is provided, comprising: reacting a diazo compound of formula (II) with a rhodium complex of formula (III), and simultaneously removing nitrogen gas and COD to prepare a neutral-electron-inverted carbene as shown in formula (I). .

[0009] In some embodiments, the molar ratio of the diazo compound of formula (II) to the rhodium complex of formula (III) is 1:(0.5~5), preferably 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:2, 1:3, 1:3.2, 1:3.5, 1:3.8, 1:4, 1:5, and any two of the above values ​​constitute any one of the ranges.

[0010] In some embodiments, the first solvent for the reaction is dichloromethane or trichloromethane.

[0011] In some embodiments, the reaction is carried out at -50 to -10°C, preferably within a range of -50°C, -40°C, -30°C, -20°C, -10°C, or any two of the above values.

[0012] In some embodiments, the reaction time is 10 to 60 minutes, preferably 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, 60 minutes, or any two of the above values ​​forming a range.

[0013] Thirdly, an application of a neutral reversed electron state carbene is provided, wherein in a second solvent, the neutral reversed electron state carbene of formula (I) reacts with reactants to form a compound of formula (IV); ; The reactants are selected from hydrogen, deuterium, or hydrogen-deuterium. The R 1 and R 2 Each is either hydrogen or deuterium.

[0014] In some embodiments, the second solvent is benzene.

[0015] In some embodiments, the neutral reversed electron state carbene shown in formula (I) is dissolved in a second solvent, degassed by 3 to 5 cycles of freezing-evacuation-thawing at 0 to 10°C, and then reactants are introduced to carry out the reaction.

[0016] In some embodiments, the reaction temperature is 10~35°C and the reaction time is 20~30 hours.

[0017] On one hand, the present invention provides a compound of formula (IV), which is: ; The R 1 and R 2 Each is either hydrogen or deuterium.

[0018] In some embodiments, the specific structure of the compound of formula (IV) is selected from one of the following structures: , , .

[0019] Fourthly, an application of a neutral reversed electron state carbene is provided, in which an aldehyde substrate and pinacol borane are reacted to prepare a primary alcohol product under the catalysis of the neutral reversed electron state carbene shown in formula (I); ; R is hydrogen, alkyl, haloalkyl, cycloalkyl, heterocyclic, heteroaryl, cycloalkylalkyl, heterocyclic alkyl, heteroarylalkyl, aralkyl, or aryl; The R is further optionally each independently replaced by the same or different substituents R 0 Mono- or poly-substituted; The substituent R 0The following are possible meanings: hydrogen, -F, -Cl, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl group, -COOH, -(CH2). m -COOH, -O-SO3H, -SO3H, -(CH2) m -SO3H, alkyl-C(=O)-, aryl-C(=O)-, haloalkyl, amino, nitro, alkoxy, alkylthio, cycloalkyl, heterocyclic, aryl, heteroaryl or alkyl.

[0020] In some embodiments, the amount of the neutral inverted electronic state carbene shown in formula (I) is 1 to 2 mol% of the aldehyde substrate, preferably 1 mol%, 1.1 mol%, 1.2 mol%, 1.3 mol%, 1.4 mol%, 1.5 mol%, 1.6 mol%, 1.7 mol%, 1.8 mol%, 1.9 mol, or 2 mol%.

[0021] In some embodiments, the reaction is carried out in tetrahydrofuran.

[0022] In some embodiments, the molar ratio of the aldehyde substrate to pinacol borane is 1:(1~2), preferably 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9 or 1:2.

[0023] In some embodiments, the reaction is carried out at 10-35°C for 2-4 hours.

[0024] In some embodiments, R is hydrogen, C 1-12 Alkyl, C 1-12 Haloalkyl, C 3-12 cycloalkyl, C 2-12 Heterocyclic group, C 1-12 heteroaryl, C 3-12 cycloalkyl C 1-12 Alkyl, C 2-12 Heterocyclic C 1-12 Alkyl, C 1-12 heteroaryl C 1-12 Alkyl, C 6-12 Fragrance C 1-12 Alkyl or C 6-12 Aryl.

[0025] In some embodiments, the substituent R 0 -Hydrogen, -F, -Cl, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl group, -COOH, -O-SO3H, -SO3H, C 1-12 Alkyl-C(=O)-, C 6-12 aryl-C(=O)-, amino, nitro, C 1-12 Haloalkyl, C1-12 Alkoxy, C 1-12 Alkylthio, C 3-12 cycloalkyl, C 2-12 Heterocyclic group, C 6-12 Aryl, C 1-12 heteroaryl or C 1-12 alkyl.

[0026] In some embodiments, the substituent R 0 -Hydrogen, -F, -Cl, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl group, -COOH, -O-SO3H, -SO3H, C 1-12 Alkyl-C(=O)-, C 6-12 Aryl-C(=O)-, amino, nitro, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butyloxy, phenyl, chloromethyl, dichloroethyl, chloro-n-propyl, trifluoromethyl, methyl, ethyl, n-propyl, isopropyl, n-butyl or tert-butyl.

[0027] In this invention, the alkyl group is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, or n-decyl, etc. The haloalkyl group is selected from chloromethyl, dichloroethyl, chloropropyl, trifluoromethyl, etc. The cycloalkyl group is selected from cyclobutyl, cyclopropyl, cyclohexyl, cyclopentyl, etc. The heterocyclic group is selected from 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothiophen-2-yl, tetrahydrothiophen-3-yl, 1-piperazinyl, 2-piperazinyl, dihydrofuranyl, dioxane, dithiaalkyl, piperazine, pyrrolidine, dihydropyranyl, oxothiacyclopentyl, dithiacyclopentane, oxothiophenyl, etc. The heteroaryl group is selected from 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), thiophene, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, tetrazolyl, etc. The aryl group is selected from phenyl or naphthyl. In this invention, the selection of arylalkyl or aralkyl groups can be based on the selection of aryl and alkyl groups, and can be combined accordingly. For example, if the aryl group is selected from phenyl and the alkyl group is selected from methyl, then the arylalkyl or aralkyl group is phenylmethyl. Another example is alkoxy, where the alkyl group is selected from methyl, then the alkoxy group is methoxy, and so on.

[0028] Compared with the prior art, the present invention has the following beneficial effects: Reversed electronic state carbene (σ 0 π2 The electron configuration of neutral-inverted carbene, which differs from that of classical carbenes (NHC, CAAC, etc.), has long been a focus of theoretical chemists. Meanwhile, experimental chemists are also eagerly anticipating its preparation and application prospects. In this invention, the preparation of neutral-inverted carbene offers the following advantages: (1) The first stable separation of neutral inverted electronic carbene was achieved; (2) The conditions are simple and the operation is easy; (3) Compared with cationic types, it has stronger practicality and application prospects.

[0029] In this invention, neutral carbenes are synthesized for the first time, demonstrating high efficiency in activation by hydrogen (the simplest σ single bond), deuterium, or hydrogen-deuterium, providing a theoretical and experimental basis for the activation of carbon-hydrogen and heteroatom hydrogen bonds of this type of carbene. Activation of multi-type atomic hydrogen bonds is an important chemical method in molecular modification and recombination, possessing significant atom economy advantages and representing a preferred strategy for drug synthesis and material preparation. Overall, currently σ... 0 π 2 Research on the application of carbene is still in its early stages, and its synthesis and stable separation remain the biggest challenges.

[0030] Terminology Explanation Certain embodiments of the invention will now be described in detail, examples of which are illustrated by the accompanying structural and chemical formulas. The invention is intended to cover all alternatives, modifications, and equivalents, all of which are included within the scope of the invention as defined in the claims. Those skilled in the art will recognize that many similar or equivalent methods and materials can be used to practice the invention. The invention is by no means limited to the methods and materials described herein. In the event that one or more of the incorporated documents, patents, and similar materials differ from or contradict this application (including, but not limited to, defined terminology, application of terminology, described techniques, etc.), this application shall prevail.

[0031] It should be further appreciated that certain features of the invention, for clarity, have been described in multiple independent embodiments, but may also be provided in combination in a single embodiment. Conversely, various features of the invention, for brevity, have been described in a single embodiment, but may also be provided individually or in any suitable sub-combination.

[0032] Unless otherwise stated, all technical terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art. All patents and publications related to this invention are incorporated herein by reference in their entirety.

[0033] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0034] In the following content, all numbers disclosed herein, whether or not they use words such as "approximately" or "about," are approximate values. The value of each number may vary by 1%, 2%, 5%, 7%, 8%, 10%, 15%, or 20%. Whenever a number with a value of N is disclosed, any numbers with values ​​of N+ / -1%, N+ / -2%, N+ / -3%, N+ / -5%, N+ / -7%, N+ / -8%, N+ / -10%, N+ / -15%, or N+ / -20% will be explicitly disclosed, where "+ / -" indicates addition or subtraction. Attached Figure Description

[0035] Figure 1 This is the X-ray single-crystal diffraction structure of the neutral inverted electronic state of carbene 3.

[0036] Figure 2 For neutral inverted electronic state carbene 3 1 H NMR (600 MHz, d 8-THF spectrum.

[0037] Figure 3 For neutral inverted electronic state carbene 3 13 C NMR (151 MHz, d 8-THF spectrum.

[0038] Figure 4 For neutral inverted electronic state carbene 3 31 P NMR (243 MHz, d 8-THF spectrum.

[0039] Figure 5 The image shows the HRMS spectrum of the neutral inverted electronic state of carbene 3.

[0040] Figure 6 This is the X-ray single-crystal diffraction structure of compound 4.

[0041] Figure 7For compound 4 1 H NMR (400 MHz, d 8-THF spectrum.

[0042] Figure 8 For compound 4 13 C NMR (151 MHz, d 8-THF spectrum.

[0043] Figure 9 For compound 4 31 P NMR (162 MHz, d 8-THF spectrum.

[0044] Figure 10 The image shows the HRMS spectrum of compound 4.

[0045] Figure 11 For compound 5 1 H NMR (400 MHz, d 8-THF spectrum.

[0046] Figure 12 For compound 5 13 C NMR (151 MHz, d 8-THF spectrum.

[0047] Figure 13 For compound 5 2 H NMR (92 MHz, d 8-THF spectrum.

[0048] Figure 14 For compound 5 31 P NMR (162 MHz, d 8-THF spectrum.

[0049] Figure 15 The image shows the HRMS spectrum of compound 5.

[0050] Figure 16 For compound 6 1 H NMR (600 MHz, d 8-THF spectrum.

[0051] Figure 17 For compound 6 13 C NMR (151 MHz, d 8-THF spectrum.

[0052] Figure 18 For compound 6 2 H NMR (92 MHz,d 8-THF spectrum.

[0053] Figure 19 For compound 6 31 P NMR (243 MHz, d 8-THF spectrum.

[0054] Figure 20 The image shows the HRMS spectrum of compound 6.

[0055] Figure 21 These are the four main electronic configurations of the carbene. Detailed Implementation

[0056] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. The specific embodiments described herein are for illustrative purposes only and are not intended to limit the invention in any way. Furthermore, descriptions of well-known structures and techniques are omitted in the following description to avoid unnecessarily obscuring the concepts of this disclosure. Such structures and techniques have also been described in many publications.

[0057] Generally, the compounds of the present invention can be prepared by the methods described herein. The following examples are provided to further illustrate the content of the present invention.

[0058] Those skilled in the art will recognize that the chemical reactions described herein can be suitably used to prepare many other compounds of the present invention, and that other methods for preparing the compounds of the present invention are considered to be within the scope of the present invention. For example, the synthesis of those non-illustrative compounds according to the present invention can be successfully accomplished by those skilled in the art through modification methods, such as appropriate changes to ligand substituents, by utilizing other known reagents besides those described herein, or by making some conventional modifications to the reaction conditions. Furthermore, the reactions disclosed in this invention or the known reaction conditions are also generally accepted to be applicable to the preparation of other compounds of the present invention.

[0059] In the examples described below, all temperatures are set to Celsius unless otherwise stated. Reagents were purchased from commercial suppliers such as Aldrich Chemical Company and were not further purified before use. Generally, reagents were purchased from companies such as Anhui Zesheng Technology Co., Ltd., Beijing Bailingwei Technology Co., Ltd., and Shanghai Bide Pharmaceutical Technology Co., Ltd., unless otherwise stated.

[0060] Anhydrous tetrahydrofuran, toluene, and diethyl ether are used after reflux distillation with LiAlH4 followed by molecular sieve filtration. n-Hexane and n-pentane are used after drying with a sodium / potassium alloy followed by molecular sieve filtration. Anhydrous dichloromethane and acetonitrile are used after drying with molecular sieve filtration.

[0061] The following reactions are generally carried out in a glove box or on a double-row tube under positive pressure of nitrogen or argon (unless otherwise indicated). All reaction flasks are sealed with suitable rubber stoppers, and the substrate is injected using a syringe. Glassware is used only after it has been dried.

[0062] The NMR spectrum was obtained using a Bruker 600 MHz ( 1 H: 600 MHz, 13 C: 151 MHz, 31 Recorded by a nuclear magnetic resonance spectrometer (P: 342 MHz). 1 H NMR spectrum and d 8-THF is used as the solvent (in ppm). d 8-THF (3.58, 1.72 ppm) was used as the reference standard. When multiplets are observed, the following abbreviations will be used: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), dd (doublet of doublets), dt (doublet of triplets), td (triplet of doublets). Coupling constant. J It is represented by Hertz (Hz).

[0063] High-resolution mass spectrometry (HRMS) analysis was performed using a Q-Exactive liquid chromatography-quadrupole orbital trap mass spectrometer. Crystal data were collected on a Bruker D8 Venture diffractometer, Ga Kα (λ = 1.34139).

[0064] The following examples further illustrate the present invention; however, these examples should not be construed as limiting the scope of the invention. In cases where the structure and name of the compounds of the present invention differ, the structure of the compound shall prevail.

[0065] Example 1: Preparation of Neutral Inverted Electronic Carbene

[0066] Weigh out 50.0 mg (0.07 mmol) of diazo compound 1, dissolve it in 2.0 mL of dichloromethane, and bring the solution to -30°C. o In a low-temperature reaction vessel of C, another 17.6 mg (0.07 mmol) of rhodium complex 2 was dissolved in 1.0 mL of dichloromethane. The reaction was carried out at a low temperature (-30 °C). oC) The dichloromethane solvent containing the rhodium complex was added dropwise in three batches to the dichloromethane solution of the diazo compound, and the mixture was stirred at the same temperature for 30 minutes. After the reaction was complete, the solution was concentrated under reduced pressure until no fraction remained, then extracted with n-hexane (2 × 3.0 mL), and the n-hexane solution phase was collected. Finally, the solution was concentrated under reduced pressure until no fraction remained to give an orange-yellow solid 3 (49 mg, 85%). At room temperature, orange-yellow crystals of compound 3 grew in a saturated solution of n-hexane.

[0067] 1 H NMR (600 MHz, THF- d 8) δ (ppm) 6.51 (d, J = 6.0 Hz, 8H, Mes Ar-H), 4.36 – 4.28 (m, 1H, allyl C H ), 3.50 – 3.47 (m, 6H, C H 2 and allyl C H 2 ), 3.42 – 3.38 (m, 4H, C) H 2 ), 2.21 (s, 12 H, Mes C H 3 ), 2.15 (s, 12 H, Mes C H 3 ), 2.07 (s, 12 H, Mes C H 3 ), 1.86 – 1.83 (m, 2H, allyl C H 2 ). 13 C{ 1 H} NMR (151 MHz, THF- d 8) δ (ppm) 139.6, 138.9, 137.5 (d, J = 3.0Hz), 137.48 (d, J = 3.0 Hz), 135.7, 129.8, 129.2, 100.0 – 99.9 (m, allyl C H), 50.2 – 50.0 (m, allyl C H2), 48.0 (d,J = 4.5 Hz, C H2), 47.98 (d, J = 4.5 Hz, C H2), 21.5, 19.4, 19.3, -22.7 (d, 2 J Rh-C = 10.6 Hz, P C P). 31 P NMR (243 MHz, THF- d 8) δ (ppm) 88.3 (d, 1 J Rh-P = 194.4 Hz). HRMS (ESI): m / z calcd for [C 44 H 58 N4P2Rh] + 807.3186 found 807.3183. Example 2: Reactivity of neutral-flipped carbene 3 – Synthetic steps of compound 4

[0068] Compound 3 (50.0 mg, 0.06 mmol) was dissolved in benzene (2.0 mL), and degassed at 10 °C through 3–5 freeze-evacuation-thawing cycles, followed by the introduction of 1 atm hydrogen gas. The reaction system was then slowly heated to room temperature and stirred for 24 hours, during which the solution gradually turned brown. All volatile components were removed under reduced pressure to obtain a dark brown solid. The resulting mixture was extracted three times with n-hexane (3 × 2 mL), and the extracts were filtered through a diatomaceous earth filter. The n-hexane solution was concentrated to 2 mL and allowed to evaporate at room temperature to give orange-yellow crystalline product 4, with a mass of 32 mg (0.04 mmol, yield 67%). At room temperature, saturated solutions of n-hexane produced orange-yellow crystals of compound 4.

[0069] 1 H NMR (400 MHz, THF- d 8) δ (ppm) 6.69 (br, 2H, Mes Ar- H ), 6.66 – 6.63(m, 6H, Mes Ar- H ), 4.18 (td, J = 8.8 Hz, 1H, PC H2 P), 3.98 – 3.87 (m, 2H, allyl C H and PC H 2 P), 3.43 – 3.34 (m, 4H, C H 2 ), 3.32 – 3.26 (m, 4H, C H 2 ), 3.11 (dd, J =7.2, 3.2 Hz, 2H, allyl C H 2 ), 2.39 (s, 6H, Mes C H 3 ), 2.37 (s, 6H, Mes C H 3 ), 2.26 (s,6H, Mes C H 3 ), 2.23 (s, 6H, Mes C H 3 ), 1.98 (s, 6H, Mes C H 3 ), 1.89 (s, 6H, Mes C H 3 ),1.23 (dd, J = 13.6, 8.0 Hz, 2H, allyl C H 2 ). 13 C{ 1 H} NMR (151 MHz, THF- d 8) δ (ppm) 140.9 (d, J = 9.1 Hz), 140.88,140.42 (d, J = 9.1 Hz), 140.4, 139.6, 139.4, 139.0, 138.6, 135.6, 135.4,130.1, 130.0, 129.9, 129.6, 114.5 (br, allyl C H), 81.6 (d, 2J Rh-C = 15.1 Hz, P C H2P), 55.8 (dd, 1 J Rh-C = 34.7, 2 J P-C = 6.0 Hz, allyl C H2), 51.3, 51.1, 21.66 (d, J = 3.0 Hz), 21.64 (d, J = 3.0 Hz), 21.4, 21.3, 21.2, 19.6, 19.5. 31 P NMR (162 MHz, THF- d 8) δ (ppm) 71.0 (d, 1 J Rh-P = 251.1 Hz). HRMS [M-allyl] + C 41 H 54 N4P2Rh + calc. 767.2873 m / z , found 767.2868 m / z . Example 3: Reactivity of neutral-flipped carbene 3 – Synthetic steps of compound 5

[0070] Compound 3 (40.0 mg, 0.05 mmol) was dissolved in benzene (2.5 mL), and degassed at 10 °C through 3–5 freeze-evacuation-thawing cycles, followed by the introduction of 1 atm deuterium gas. The reaction system was then slowly heated to room temperature and stirred for 24 hours, during which the solution gradually turned brown. All volatile components were removed under reduced pressure to obtain a dark brown solid. The resulting mixture was extracted three times with n-hexane (3 × 2 mL), and the extracts were filtered through a diatomaceous earth filter. The n-hexane solution was concentrated to 2 mL and allowed to evaporate at room temperature to give orange-yellow crystalline product 5, weighing 24 mg (0.03 mmol, yield 60%).

[0071] 1 H NMR (400 MHz, THF- d 8) δ (ppm) 6.69 (br, 2H, Mes Ar-H ), 6.66 – 6.63(m, 6H, Mes Ar- H ), 3.98 – 3.87 (m, 1H, allyl C H ), 3.43 – 3.36 (m, 4H, C H 2 ), 3.35 –3.24 (m, 4H, C H 2 ), 3.11 (dd, J = 7.2, 3.2 Hz, 2H, allyl C H 2 ), 2.39 (s, 6H, Mes C H 3 ), 2.37 (s, 6H, Mes C H 3 ), 2.26 (s, 6H, Mes C H 3 ), 2.23 (s, 6H, Mes C H 3 ), 1.98(s, 6H, Mes C H 3 ), 1.89 (s, 6H, Mes C H 3 ), 1.23 (dd, J = 16.0, 8.0 Hz, 2H, allyl C H 2 ). 13 C{ 1 H} NMR (151 MHz, THF- d 8) δ (ppm) 140.9 (d, J = 9.1 Hz), 140.89,140.44 (d, J = 7.6 Hz), 140.3, 139.6, 139.4, 139.0, 138.6, 135.6, 135.4,130.1, 130.0, 129.9, 129.6, 114.5 (br, allyl CH), 81.7 – 81.0 (m, P C D2P), 55.8(dd, 1 J Rh-C = 34.7, 2 J P-C = 6.0 Hz, allyl C H2), 51.3, 51.1, 21.65 (d, J = 3.0 Hz), 21.63 (d, J = 3.0 Hz), 21.4, 21.3, 21.1, 19.6, 19.5. 2 H NMR (92 MHz, THF- d 8) δ (ppm) 4.14 (br, 1D, PC D 2 P), 3.90 (br, 1D, PC D 2 P). 31 P NMR (162 MHz, THF- d 8) δ (ppm) 68.7 (d, 1 J Rh-P = 247.9 Hz). HRMS [M-allyl] + C 41 H 52 D2N4P2Rh + calc. 769.2999 m / z , found 769.2974 m / z . Example 4: Reactivity of Neutral Inverted Electronic State Carbene 3 – Synthetic Steps of Compound 6

[0072] Compound 3 (40.0 mg, 0.05 mmol) was dissolved in benzene (2.5 mL), and degassed at 10 °C through 3–5 freeze-evacuation-thawing cycles. Then, 1 atm of deuterium hydrogen gas was introduced. The reaction system was then slowly heated to room temperature and stirred for 24 hours, during which the solution gradually turned brown. All volatile components were removed under reduced pressure to obtain a dark brown solid. The resulting mixture was extracted three times with n-hexane (3 × 2 mL), and the extracts were filtered through a diatomaceous earth filter. The n-hexane solution was concentrated to 2 mL and allowed to evaporate at room temperature to give orange-yellow crystalline product 6, 25 mg (0.03 mmol, yield 63%).

[0073] 1 H NMR (600 MHz, THF- d 8) δ (ppm) 6.69 (br, 2H, Mes Ar -H ), 6.66–6.63 (m,6H, Mes Ar -H ), 4.20 – 4.15 (m, 0.47H, PC H DP), 3.96 – 3.89 (m, 1.53H, allyl C H and PC H DP), 3.45 – 3.35 (m, 4H, C H 2 ), 3.33 – 3.26 (m, 4H, C H 2 ), 3.11 (dd, J = 7.2, 2.4 Hz, 2H, allyl C H 2 ), 2.39 (s, 6H, Mes C H 3 ), 2.37 (s, 6H, Mes C H 3 ), 2.26 (s, 6H, Mes C H 3 ), 2.23 (s, 6H, Mes C H 3 ), 1.98 (s, 6H, Mes C H 3 ), 1.89 (s, 6H, MesC H 3 ), 1.23(dd, J = 13.6, 7.8 Hz, 2H, allyl C H 2 ). 13 C{ 1 H} NMR (151 MHz, THF- d 8) δ (ppm) 140.9 (d, J = 9.1 Hz), 140.44(d, J = 9.1 Hz), 140.4, 139.6, 139.4, 139.0, 138.6, 135.6, 135.4, 130.1,130.0, 129.9, 129.6, 114.5 (br, allyl C H), 81.7 – 81.2 (m, P C HDP), 55.8 (dd, 1 J Rh-C = 34.7, 2 J P-C = 6.0 Hz, allyl C H2), 51.3, 51.1, 21.65 (d, J = 3.0 Hz), 21.63(d, J = 4.5 Hz), 21.4, 21.3, 21.1, 19.6, 19.5. 2 H NMR (92 MHz, THF- d 8) δ (ppm) 4.15 (br, 0.47D, PCH D P), 3.90 (br,0.53D, PCH D P). 31 P NMR (243 MHz, THF- d 8) δ (ppm) 70.3 (d, 1 J Rh-P = 250.3 Hz). HRMS [M-allyl] + C 41 H 53DN4P2Rh + calc. 768.2936 m / z , found 768.2921 m / z . Example 5: Application of neutral reversed electron state carbene 3 in the catalytic reduction of aldehydes to primary alcohols

[0074] In an inert atmosphere glove box, aldehyde substrate 7 (0.2 mmol, 1.0 eq.), carbene catalyst 3 (0.002–0.004 mmol), and tetrahydrofuran (2 mL) were added sequentially to the reaction flask and mixed thoroughly. Pinarylborane (HBPin) (0.22 mmol, 1.1 eq.) was slowly added dropwise under stirring. The reaction flask was then removed from the glove box and the reaction was stirred at room temperature for 2–4 h. After the reaction was complete, a quenching agent was added, and stirring was continued for 15 min. The reaction mixture was separated by rapid silica gel column chromatography, using ethyl acetate as eluent, and the solvent was removed under reduced pressure to obtain the target primary alcohol product. The structure of the compound was determined by... 1 H NMR and 13 C NMR characterization confirmed the findings.

[0075] Table 1 Results of 3-carbene catalytic reduction of aldehydes ; The results in Table 1 show that the catalyst of the present invention has excellent yield in the catalytic reduction of aldehydes to primary alcohols.

[0076] The method of this invention has been described through preferred embodiments. Those skilled in the art will readily be able to modify or appropriately alter and combine the methods and applications described herein within the scope, spirit, and context of this invention to implement and apply the technology of this invention. Those skilled in the art can refer to the content herein to appropriately improve process parameters. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included within the scope of this invention.

Claims

1. A neutral inverted electronic state carbene, characterized in that, The structure is shown in equation (I): 。 2. A method for preparing the neutral inverted electronic state carbene according to claim 1, characterized in that, include: The reaction of the diazo compound of formula (II) with the rhodium complex of formula (III), with simultaneous departure of nitrogen and COD, yields the neutral-inverted carbene shown in formula (I). 。 3. The preparation method according to claim 2, characterized in that, The molar ratio of the diazo compound of formula (II) to the rhodium complex of formula (III) is 1:(0.5~5); Alternatively, the first solvent in the reaction is dichloromethane or trichloromethane; Alternatively, the reaction is carried out at -50 to -10°C; Alternatively, the reaction time is 10 to 60 minutes.

4. An application of the neutral inverted electronic state carbene as described in claim 1, characterized in that, In a second solvent, the neutral-inverted-electron carbene of formula (I) reacts with the reactants to form a compound of formula (IV); ； The reactants are selected from hydrogen, deuterium, or hydrogen-deuterium. The R 1 and R 2 Each is either hydrogen or deuterium.

5. The application according to claim 4, characterized in that, The neutral reversed electron state carbene shown in formula (I) is dissolved in a second solvent, and after being degassed by 3 to 5 cycles of freezing-evacuation-thawing at 0 to 10°C, reactants are introduced to carry out the reaction.

6. The application according to any one of claims 4 or 5, characterized in that, The second solvent is benzene; Alternatively, the reaction temperature is 10~35℃ and the reaction time is 20~30 hours.

7. A compound of formula (IV), characterized in that, It is: ； The R 1 and R 2 Each is either hydrogen or deuterium.

8. The compound of formula (IV) according to claim 7, characterized in that, The specific structure of the compound of formula (IV) is selected from one of the following structures: , , .

9. An application of the neutral inverted electronic state carbene according to claim 1, characterized in that, Under the catalysis of the neutral inverted electronic state carbene shown in formula (I), aldehyde substrates and pinacol borane are reacted to prepare primary alcohol products; ； R is hydrogen, alkyl, haloalkyl, cycloalkyl, heterocyclic, heteroaryl, cycloalkylalkyl, heterocyclic alkyl, heteroarylalkyl, aralkyl, or aryl; The R is further optionally replaced by the same or different substituents R 0 Mono- or poly-substituted; The substituent R 0 The following are possible meanings: hydrogen, -F, -Cl, -Br, -I, -CN, -CHO, -B(OH)2, hydroxyl group, -COOH, -(CH2). m -COOH, -O-SO3H, -SO3H, -(CH2) m -SO3H, alkyl-C(=O)-, aryl-C(=O)-, haloalkyl, amino, nitro, alkoxy, alkylthio, cycloalkyl, heterocyclic, aryl, heteroaryl or alkyl.

10. The application according to claim 9, characterized in that, The amount of the neutral-inverted electronic carbene shown in formula (I) is 1-2 mol% of the aldehyde substrate. Alternatively, the reaction may be carried out in tetrahydrofuran; Alternatively, the molar ratio of aldehyde substrate to pinacol borane is 1:(1~2); Alternatively, the reaction may be carried out at 10-35°C for 2-4 hours.

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