Sila spiro compound as well as preparation method and application thereof

Abstract

The invention discloses a silaspiro compound as well as a preparation method and application thereof. The silicon spiro compound is prepared from simple and cheap mono-o-substituted aryl bromide through C-silylation, hydrolysis, O-silylation and intramolecular asymmetric C-H dehydrogenation silylation in sequence, and a silicon spiro chiral disiloxane skeleton is obtained. Two key ligand platform molecules of silicon spiro chiral disiloxane diphenol and silicon spiro chiral disiloxane dibenzyl bromide are obtained through demethylation or benzyl bromination, and catalysts and ligands of alkyl monophosphine, diaryl phosphine, phosphoramidite, phosphite ester, phosphoric acid and the like of a silicon spiro ring skeleton can be obtained through subsequent derivatization. The silaspiro compound provided by the invention can directly catalyze various organic reactions. The chiral silaspiro catalyst / ligand provided by the invention has practical application value, and enriches a chiral ligand library.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of ligand catalysts, in particular to a silicon spiro compound and a preparation method and application thereof. BACKGROUND

[0002] Chirality is one of the important properties in nature, and many natural phenomena are related to chirality, from the macroscopic world to the microscopic molecules. In the material world, chiral compounds are important molecules indispensable to life, and are closely related to the survival and development of human beings. At present, the most efficient and most convenient method for synthesizing chiral compounds is asymmetric catalysis, which effectively reduces the waste of raw materials or chiral auxiliaries, and has the characteristics of short synthesis steps and high enantioselectivity. Asymmetric catalytic reaction is of great concern in synthetic chemistry, and the core is to develop diversified and controllable ligands or catalysts to achieve efficient and high enantioselective synthesis of target chiral compounds.

[0003] The main strategy for the diversified synthesis of the currently dominant chiral catalyst is to perform post-modification on the specific skeleton. Due to the particularity of the catalyst skeleton structure, there are few dominant chiral catalyst skeletons that can be widely used, such as binaphthol (BINOL) and spiro dihydroindene diol (SPINOL), which are currently recognized as dominant chiral catalyst skeletons. Among them, catalysts and ligands derived from the chiral SPINOL skeleton exhibit excellent catalytic activity and enantioselectivity in various types of reactions such as asymmetric hydrogenation, asymmetric carbon-carbon and carbon-heteroatom bond formation. When the central carbon atom of the chiral SPINOL skeleton is replaced by a silicon atom, the dihedral angle changes greatly, and the structure becomes more rigid, which further affects the chemical reactivity and enantioselectivity. It has been reported that phosphoramidite ligands derived from SPINOL have better chemical reactivity and higher enantioselectivity when the central atom is replaced by silicon in specific reactions. Currently, the chiral spiro catalyst skeleton has problems such as difficult synthesis, single structure, and insufficient modification space. Therefore, it is of great significance to develop diversified chiral spiro catalyst skeletons in an efficient and convenient manner.

[0004]

[0005] Chiral trivalent alkyl phosphine is widely used as a catalyst in small organic molecule catalysis and transition metal catalysis due to its strong Lewis basicity, good nucleophilicity, and suitable chiral pocket. Chiral alkyl phosphine SITCP derived from SPINOL exhibits excellent chemical activity and enantioselectivity in asymmetric catalysis. However, the current alkyl phosphine ligands derived from SPINOL and other chiral spiro skeletons have problems such as long synthesis route and low total yield. For example, it takes 14 steps to synthesize SITCP from the basic raw material, with a total yield of only 14% (as shown below).

[0006]

[0007] Therefore, it is crucial to develop new synthetic methods to greatly shorten the synthesis steps of such catalysts for mass production of such catalysts. It is worth mentioning that phosphine center chiral ligand has better enantioselectivity control because the phosphorus atom center coordinates with the transition metal, making the chiral pocket closer to the substrate. However, the current synthesis method of phosphine center chiral ligand mainly relies on chiral resolution, and the synthesis route is long, which causes a lot of raw material waste and is not conducive to mass production. Therefore, it is the urgent hope of scientists to obtain phosphine center chiral ligand with simple and convenient steps. SUMMARY

[0008] The purpose of the present application is to provide a kind of sila-spiro compound and its preparation method and application. The sila-spiro compound of the present application is started from simple and cheap mono-ortho-substituted aryl bromide, and sequentially undergoes C-silylation, hydrolysis, O-silylation, intramolecular asymmetric C-H dehydrogenation silylation to obtain a sila-spiro chiral disiloxane skeleton. Respective demethylation or benzyl bromination obtains two types of key ligand platform molecules, sila-spiro chiral disiloxane diphenol and sila-spiro chiral disiloxane dibenzyl bromide. Through subsequent derivatization, alkyl monophosphine, diaryl phosphine, phosphoramidite, phosphite, phosphoric acid and other catalysts and ligands with sila-spiro skeleton can be obtained. One of the alkyl phosphines can be separated by a simple column to obtain an alkyl phosphine with a phosphine center chirality. The above compounds can directly catalyze organic reactions, be used for asymmetric construction of C-N bond and [3+2] de- aromatization cycloaddition reaction, or be used as ligands to participate in transition metal catalyzed asymmetric construction of C-S and C-C bond, asymmetric hydrogenation, allyl substitution, [4+2] cycloaddition reaction, etc.

[0009] The three main technical problems solved by the present application are as follows: (1) asymmetric construction of spiro ring catalyst skeleton is difficult, synthesis steps are long, and skeleton structure is single. (2) The synthesis route of chiral spiro ring bisalkyl monophosphine ligand represented by SITCP is extremely long, the cost is extremely high, and the skeleton modification is extremely difficult. (3) The synthesis route of phosphine center chiral ligand is long, and often needs to be obtained by resolution method, causing waste of chiral raw materials.

[0010] In order to achieve the above purpose, the technical scheme adopted by the present application is as follows

[0011] The first aspect of the present application is to provide a kind of sila-spiro compound, the sila-spiro compound has the structure as shown in formula I, formula II, formula III, formula IV, formula V, and the corresponding racemate and optical isomer of formula I, formula II, formula III, formula IV, formula V:

[0012]

[0013] R in formula I, formula II, formula III 1 identically or differently each independently is C1-C8 alkyl, C1-C8 alkoxy, phenyl;

[0014] R in formula I, formula II, formula III, formula IV, formula V 3 , R 4 identically or differently each independently is hydrogen, C1-C8 alkyl, C1-C8 alkoxy, phenyl, phenyl substituted with 1-5 C1-C8 alkyl, phenyl substituted with 1-5 C1-C8 alkoxy, halogen, cyano, carboxyl, hydroxyl, 5-6 membered heteroaryl; the heteroatom in the heteroaryl is selected from one or more of N, O, S, and the number of heteroatoms is 1-4;

[0015] n1 and n2 in formula I, formula II, formula III, formula IV, formula V are the same or different and each independently is 0, 1, 2, 3;

[0016] * in formula I, formula II, formula III represents a chiral silicon center, which is independently S configuration silicon or R configuration silicon;

[0017] X and X' in formula I are the same or different and each independently is -CH2R a1 , -OH, -OR a2 , -OTf, -P(R a3 )2, -PO(R a6 )2;

[0018] R a1 is hydrogen, C1-C8 alkyl, halogen; R a2 is C1-C8 alkyl; R a3 is hydrogen, C1-C8 alkyl, C1-C8 alkoxy, phenyl, phenyl substituted with 1-5 C1-C8 alkyl, phenyl substituted with 1-5 C1-C8 alkoxy; R a6 is hydrogen, C1-C8 alkyl, C1-C8 alkoxy, phenyl, phenyl substituted with 1-5 C1-C8 alkyl, phenyl substituted with 1-5 C1-C8 alkoxy;

[0019] Y in formula II is -O- or -CH2; Z is -NR a4 R b4 , -R a5 ; A is present or absent, when A is present, A is O or S atom (in this case the phosphorus atom in formula II is pentavalent, or when A is absent, the phosphorus atom in formula II is trivalent);

[0020] R a4 , R b4each independently is hydrogen, C1-C8alkyl, C1-C8alkoxy, phenyl, phenyl substituted with 1-5 C1-C8alkyl, phenyl substituted with 1-5 C1-C8alkoxy;

[0021] said R a5 is hydrogen, C1-C8alkyl, C1-C8alkoxy, phenyl, phenyl substituted with 1-5 C1-C8alkyl, phenyl substituted with 1-5 C1-C8alkoxy.

[0022] As a preferred embodiment, R 1 each independently is hydrogen, C1-C6alkyl, C1-C6alkoxy, phenyl;

[0023] As a preferred embodiment, R 3 , R 4 each independently is hydrogen, C1-C6alkyl, C1-C6alkoxy, phenyl, phenyl substituted with 1-5 C1-C8alkyl, phenyl substituted with 1-5 C1-C8alkoxy, halogen, cyano, carboxyl, hydroxyl; the halogen is at least one selected from fluorine, chlorine, bromine, iodine;

[0024] X and X' in Formula I are the same or different, each independently -CH2R a1 , -OH, -OR a2 , -OTf, -P(R a3 )2, -PO(R a6 )2;

[0025] said R a1 is hydrogen, C1-C6alkyl, halogen, the halogen is at least one selected from fluorine, chlorine, bromine, iodine; said R a2 is C1-C6alkyl; said R a3 is hydrogen, C1-C6alkyl, C1-C6alkoxy, phenyl, phenyl substituted with 1-5 C1-C6alkyl, phenyl substituted with 1-5 C1-C6alkoxy; said R a6 is hydrogen, C1-C6alkyl, C1-C6alkoxy, phenyl, phenyl substituted with 1-5 C1-C6alkyl, phenyl substituted with 1-5 C1-C6alkoxy.

[0026] Y in Formula II is -O- or -CH2; Z is -NR a4 R b4 , -R a5 ; A is present or absent, when A is present, A is O or S atom; said R a4 , R b4each independently is hydrogen, C1-C6 alkyl, C1-C6 alkoxy, phenyl, phenyl substituted with 1-5 C1-C6 alkyl, phenyl substituted with 1-5 C1-C6 alkoxy; said R a5 is hydrogen, C1-C6 alkyl, C1-C6 alkoxy, phenyl, phenyl substituted with 1-5 C1-C6 alkyl, phenyl substituted with 1-5 C1-C6 alkoxy.

[0027] As a preferred embodiment, the silaspirocyclic compound is selected from the following compounds:

[0028]

[0029]

[0030] A second aspect of the present application is to provide a method for preparing the silaspirocyclic compound as described in the first aspect of the present application, comprising the following steps: Step One:

[0031]

[0032] (1-1) Under a protective atmosphere, a compound shown in formula IV, 4-dimethylaminopyridine (DMAP), imidizole, R 1 2HSiCl (preferably diethylchlorosilane) as a raw material, reacting in a solvent to form a compound shown in formula V;

[0033] wherein the structural formula of formula IV is wherein R 3 , R 4 , n1, n2 correspond to R 3 , R 4 , n1, n2 of the first aspect of the present application;

[0034] R 1 of 2HSiCl 1 correspond to R 1 of the first aspect of the present application;

[0035] The structural formula of formula V is wherein R 1 , R 3 , R 4 , n1, n2 correspond to R 1 , R 3 , R 4 , n1, n2 of the first aspect of the present application;

[0036]

[0037] (1-2) under a protective atmosphere, a compound shown as formula V is used as raw material, and is reacted in a solvent in the presence of rhodium catalyst, chiral ligand, and cyclopentene to generate a compound shown as formula I 1 and / or a compound shown as formula I 2 ;

[0038] wherein the structural formula of formula I 1 is wherein R 1 , R 3 , R 4 , n1, n2 correspond to R 1 , R 3 , R 4 , n1, n2 described in the first aspect of the present application; -OR 1 of formula I a2 is -OMe;

[0039] the structural formula of formula I 2 is wherein R 1 , R 3 , R 4 , n1, n2 correspond to R 1 , R 3 , R 4 , n1, n2 described in the first aspect of the present application; -CH2R 2 of formula I a1 is -CH3;

[0040] Step two,

[0041]

[0042] (2-1) under a protective atmosphere, a compound shown as formula I 1 , wherein -OR 1 of formula I a2 is -OMe, tri-pentafluorophenyl boron (BCF), HSiEt2Me is used as raw material, and is reacted in a solvent, and then is reacted with HCl to generate a compound shown as formula I 3 ;

[0043] wherein the structural formula of formula I 3 is wherein R 1 , R 3 , R 4 , n1, n2 correspond to R 1 , R 3 , R 4 , n1, n2 described in the first aspect of the present application;

[0044] or

[0045]

[0046] (2-1') under a protective atmosphere, a compound of formula I 2 , wherein formula I 2 -CH2R a1 is -CH3, N-halosuccinimide is reacted in the presence of azobisisobutyronitrile (AIBN) in a solvent to obtain a compound of formula I 2 , wherein formula I 2 -CH2R a1 is -halomethyl;

[0047] Step three,

[0048]

[0049] (3-1) a compound of formula I 3 , pyridine (Pyridine), trifluoromethanesulfonic anhydride (Tf20) as raw materials, in a solvent to react, to generate the compound shown in formula I 4 ;

[0050] wherein, formula I 4 structure is wherein, R 1 , R 3 , R 4 , n1, n2 and the first aspect of the present invention described in R 1 , R 3 , R 4 , n1, n2 corresponding to the same;

[0051] or

[0052]

[0053] (3-1') under a protective atmosphere, a compound of formula I 3 , triethylamine (Et3N), phosphorus oxychloride (POCl3) as raw materials, in a solvent to react, to generate the compound shown in formula III;

[0054] wherein, formula III structure is wherein, R 1 , R 3 , R 4 , n1, n2 and the first aspect of the present invention described in R 1 , R 3 , R 4 , n1, n2 corresponding to the same;

[0055] or

[0056]

[0057] (3-1") under a protective atmosphere, a compound of formula I 3 , triethylamine, R a4 R b4 NPC12 as raw material, reacting in a solvent to form a compound of formula II 1 ;

[0058] wherein R a4 R b4 R in NPC12 a4 , R b4 R in the first aspect of the present application a4 R b4 corresponding to the same;

[0059] formula II 1 formula II wherein R 1 , R 3 , R 4 , R a4 , R b4 R in the first aspect of the present application 1 , R 3 , R 4 , R a4 , R b4 R, n1, n2 corresponding to the same;

[0060] or

[0061]

[0062] (3-1'") under a protective atmosphere, a compound of formula I 2 -CH2R a1 -CH2Br, PR a5 H2, base as raw material, reacting in a solvent to form a compound of formula II 2 ;

[0063] wherein PR a5 R in H2 a5 R in the first aspect of the present application a5 corresponding to the same;

[0064] formula II 2 formula II wherein R 1 , R 3 , R 4 , R a5 R in the first aspect of the present application 1 , R 3 , R 4 , R a5n1 and n2 correspond to the same value;

[0065] Step Four

[0066]

[0067] (4-1) Under a protective atmosphere, using formula I 4 Using palladium catalyst, ligand, diisopropylethylamine (DIPEA), and HP(R) as raw materials, a3 In the presence of 2, it reacts in a solvent to produce formula I. 5 The compound shown;

[0068] HP(R a3 R in )2 a3 R as described in any one of claims 1-3 a3 The corresponding ones are the same;

[0069] Formula I 5 The structural formula is Among them, R 1 R 3 R 4 R a3 n1, n2 and R as described in the first aspect of the invention 1 R 3 R 4 R a3 n1 and n2 correspond to the same value;

[0070] Step 5

[0071]

[0072] (5-1) Under a protective atmosphere, using formula I 3 The compound shown, wherein R 1 For ethyl, R 3 R 4 All are methyl, triethylamine, Using it as a raw material, the reaction in a solvent produces the compound shown in Formula 28;

[0073] The compound shown in Formula 28 is

[0074] or,

[0075]

[0076] (5-1') Under a protective atmosphere, using formula I 3 The compound shown, wherein R 1 For ethyl, R 3 R 4each is hydrogen, in the presence of a palladium catalyst, a ligand, diisopropylethylamine (DIPEA), HPOPh2, in a solvent to form a compound of Formula 30;

[0077] The compound of Formula 30 is

[0078] As a preferred embodiment, the method for preparing Formula IV is as follows:

[0079]

[0080] In a protective atmosphere, using Formula VI, Formula VI', n-butyllithium, silicon tetrachloride as raw materials, reacting in a solvent, and then hydrolyzing to form a silanol compound of Formula IV;

[0081] G in Formula VI' is halogen, preferably Br;

[0082] wherein R 3 , R 4 , n1, n2 in Formula VI, Formula VI' correspond to R 3 , R 4 , n1, n2 in claim 1; the solvent is selected from at least one of diethyl ether, toluene, tetrahydrofuran, 1,2-dichloroethane, n-hexane, cyclohexane, n-heptane, n-octane;

[0083] The molar ratio of the compound VI, VI', nBuLi, SiCl4 = 1:1:2:1 is (0.8-1.5):(0.8-1.5):2:(0.8-1.5);

[0084] The temperature of the reaction is room temperature to 130°C; the time of the reaction is 12-48 hours.

[0085] As a preferred embodiment,

[0086] In steps (one) to step (five), the solvent is each independently selected from an organic solvent, preferably at least one of diethyl ether, toluene, tetrahydrofuran, 1,2-dichloroethane, n-hexane, cyclohexane, n-heptane, n-octane, dioxane, alcohol (preferably methanol, ethanol, isopropyl alcohol), carbon tetrachloride; and / or,

[0087] In step (1-1), the molar ratio of Formula IV, R 1 2HSiCl, imidazole, 4-dimethylaminopyridine is 1:(2.4-4.5):(2.4-4.5):(0.02-0.6); and / or,

[0088] The concentration of Formula IV in the solvent is 0.1-1.0 mol / L; and / or,

[0089] the temperature of the reaction is room temperature to 60℃; and / or,

[0090] the time of the reaction is 12-48 hours;

[0091] in step (1-2),

[0092] the rhodium catalyst is monovalent rhodium dimer, preferably [Rh(cod)OH]2; and / or,

[0093] the chiral ligand is selected from at least one of the following: wherein tBu represents tert-butyl; Cy represents cyclohexyl; Ad represents adamantyl; iPr represents isopropyl; further preferably the chiral ligand is dissolved in dioxane and added in the form of a solution; and / or,

[0094] the molar ratio of the compound V, the rhodium catalyst, the chiral ligand is 1:(0.01-0.1):(0.01-0.1); and / or,

[0095] the concentration of the compound V in the solvent is 0.1-0.5 mol / L; and / or,

[0096] the molar volume ratio of the compound V to cyclopentene is 1 mmol: 50-1000 μL; and / or,

[0097] the reaction temperature is 60℃ to 130℃; and / or,

[0098] the reaction time is 12-50 hours; and / or,

[0099] in step (2-1),

[0100] Formula I 1 the molar ratio of the compound V, the rhodium catalyst, the chiral ligand is 1:(0.01-0.1):(0.01-0.1); and / or,

[0101] Formula I 1 the concentration in the solvent is 0.1-0.5 mol / L; and / or,

[0102] the temperature of the reaction in the solvent is room temperature to 80℃; and / or,

[0103] the time of the reaction in the solvent is 12-48 hours; and / or,

[0104] the temperature of the reaction with HCl again is room temperature to 80℃; and / or,

[0105] the time of the reaction with HCl again is 12-48 hours; and / or,

[0106] In step (2-1'),

[0107] the N-halosuccinimide is N-bromosuccinimide; and / or,

[0108] the formula I 2 , the molar ratio of the N-halosuccinimide, azodiisobutyronitrile is 1 : (1.6-3.2) : (0.08-0.15);

[0109] the formula I 2 , the concentration in the solvent is 1-3 mol / L; and / or,

[0110] the reaction temperature is room temperature; and / or,

[0111] the reaction time is 12-48 hours.

[0112] as a preferred embodiment,

[0113] In step (3-1),

[0114] the formula I 3 , the molar ratio of the pyridine, Tf20 is 1 : (2.4-3.6) : (2.0-3.0); and / or,

[0115] the formula I 3 , the concentration in the solvent is 0.1-2.0 mol / L; and / or,

[0116] the reaction temperature is room temperature to 130°C; and / or,

[0117] the reaction time is 12-48 hours; and / or,

[0118] In step (3-1'),

[0119] the formula I 3 , the molar ratio of the triethylamine, phosphorus oxychloride is 1 : (4.8-7.2) : (3.2-4.8); and / or,

[0120] the formula I 3 , the concentration in the solvent is 0.1-2.0 mol / L; and / or,

[0121] the reaction temperature is room temperature; and / or,

[0122] the reaction time is 12-48 hours; and / or,

[0123] In step (3-1"),

[0124] the formula I 3 , the triethylamine, R a4 R b4the molar ratio of the NPCI2 is 1 : (2.4-3.6) : (0.6-2.4); and / or,

[0125] the formula I 3 the concentration in the solvent is 0.1-2.0 mol / L; and / or,

[0126] the reaction temperature is room temperature to 60°C; and / or,

[0127] the reaction time is 12-48 hours; and / or,

[0128] in step (3-1”’),

[0129] the base is at least one of an organic base and an inorganic base; preferably, the base is at least one of one or more of pyridine, triethylamine, tributylamine, N-methylmorpholine and diazabicyclo, potassium acetate, sodium acetate, potassium fluoride, sodium fluoride, cesium fluoride, potassium tert-butoxide, sodium tert-butoxide, n-butyllithium, potassium carbonate, sodium carbonate, cesium carbonate, cesium fluoride, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, sodium hexamethyldisilazide, potassium hexamethyldisilazide, lithium hexamethyldisilazide;

[0130] the formula II 2 , PR a5 the molar ratio of H2, the base is 1 : (0.8-1.5) : (1.6-3.2); and / or,

[0131] the formula II 2 the concentration in the solvent is 0.1-2.0 mol / L; and / or,

[0132] the reaction temperature is room temperature; and / or,

[0133] the reaction time is 12-48 hours.

[0134] as a preferred embodiment, step (4-1),

[0135] the palladium catalyst is at least one of palladium acetate, palladium trifluoromethanesulfonate, tris(dibenzylideneacetone)dipalladium, palladium trimethylacetate or palladium acetylacetonate;

[0136] the ligand is at least one of ;

[0137] the formula I 4 , diisopropylethylamine, HP(R a3 )2, a palladium catalyst, a ligand, the molar ratio is 1 : (2.4-4) : (2.4-3.6) : (0.05-0.2) : (0.1-0.4); and / or,

[0138] The formula I 4 The concentration in the solvent is 0.1-2.0 mol / L; and / or,

[0139] The reaction temperature is room temperature to 130℃; and / or,

[0140] The reaction time is 12-48 hours;

[0141] Step (5-1),

[0142] The formula I 3 triethylamine, The molar ratio of the formula I, the palladium catalyst, the ligand, diisopropylethylamine and HPOPh2 is 1:(2.4-3.6):(0.6-2.4):(2.4-4):(2.4-3.6); and / or,

[0143] The formula I 3 The concentration in the solvent is 0.1-2.0 mol / L; and / or,

[0144] The reaction temperature is room temperature to 60℃; and / or,

[0145] The reaction time is 12-48 hours;

[0146] Step (5-1),

[0147] The formula I 3 The molar ratio of the formula I, the palladium catalyst, the ligand, diisopropylethylamine and HPOPh2 is 1:(2.4-3.6):(0.6-2.4):(2.4-4):(2.4-3.6); and / or,

[0148] The formula I 3 The concentration in the solvent is 0.1-2.0 mol / L; and / or,

[0149] The reaction temperature is 60-150℃; and / or,

[0150] The reaction time is 12-48 hours.

[0151] The third aspect of the present application provides the application of the silicon spirocyclic compound according to the first aspect of the present application as a catalyst or a ligand in an asymmetric catalytic reaction.

[0152] As a preferred embodiment, the asymmetric catalytic reaction 1 is that the formula 33, the formula 34 reacts in a solvent under the action of a catalyst to obtain a compound shown in the formula 35;

[0153] The structure of the formula 33 is

[0154] The structure of the formula 34 is CF3CONH2;

[0155] The structure of the formula 35 is

[0156] Scheme 1

[0157]

[0158] Preferably,

[0159] the catalyst is at least one selected from compounds 17-28 shown in claim 3; and / or,

[0160] the molar ratio of the compound of formula 33, the compound of formula 34 and the catalyst is 1:(1-1.5):(0.05-0.5); and / or,

[0161] the concentration of the compound of formula 33 in the solvent is 0.1-0.5 mol / L; and / or,

[0162] the reaction temperature is room temperature to 60°C; and / or,

[0163] the reaction time is 12-48 hours;

[0164] or,

[0165] the asymmetric catalytic reaction 4 is that the compound of formula 41 and the compound of formula 42 react in the presence of a catalyst in a solvent to obtain a compound shown in formula 43;

[0166] wherein, formula 41 is formula 42 is formula 43 is

[0167] Scheme 4

[0168]

[0169] Preferably,

[0170] the catalyst is at least one selected from compounds 17-28 shown in claim 3; and / or,

[0171] the molar ratio of the compound of formula 41, the compound of formula 42 and the catalyst is 1:(1.2-2.0):(0.05-0.15); and / or,

[0172] the concentration of the molecular sieve in the solvent is 50-200 mg / mL; and / or,

[0173] the molecular sieve is at least one selected from molecular sieve, molecular sieve, molecular sieve; and / or,

[0174] The concentration of the formula 41 in the solvent is 0.1-0.5 mol / L; and / or,

[0175] The reaction temperature is room temperature to 80°C; and / or,

[0176] The reaction time is 12-48 hours.

[0177] As a preferred embodiment, the asymmetric catalytic reaction 2 is that the formula 36, the formula 37, the ligand, the additive react under the action of the palladium catalyst in the solvent to obtain the compound shown in the formula 38;

[0178] The formula 36 is The formula 37 is The formula 38 is

[0179] Scheme two

[0180]

[0181] The palladium catalyst is selected from at least one of palladium acetate, palladium triflate, tris(dibenzylideneacetone)dipalladium, palladium trimethylacetate, palladium acetylacetone; and / or,

[0182] The ligand is selected from at least one of the compounds shown in the compounds 17-28 in claim 3; and / or,

[0183] The additive is selected from at least one of phenyl phosphite, p-toluene sulfonic acid, acetic acid, potassium carbonate, triethylamine, diphenyl phosphate; and / or,

[0184] The molar ratio of the formula 36, the formula 37, the palladium catalyst, the ligand, the additive is (0.8-3.0):1:(0.05-0.15):(0.1-0.24):(0.2-1.0); and / or,

[0185] The concentration of the formula 36 in the solvent is 0.1-0.5 mol / L; and / or,

[0186] The reaction temperature is 40-120°C; and / or,

[0187] The reaction time is 12-48 hours;

[0188] Or,

[0189] The asymmetric catalytic reaction 3 is that the formula 36, the formula 39, the ligand react under the action of the palladium catalyst in the solvent to obtain the compound shown in the formula 40;

[0190] The formula 36 is The formula 39 is The formula 40 is

[0191] Scheme three

[0192]

[0193] the palladium catalyst is at least one selected from the group consisting of bis-tri-tert-butylphosphine palladium, tetra-triphenylphosphine palladium, palladium acetate, palladium triflate, tris(dibenzylideneacetone)dipalladium, palladium trimethylacetate, palladium acetylacetone; and / or,

[0194] the ligand is at least one selected from the group consisting of compounds 17-28 in claim 3; and / or,

[0195] the molar ratio of the formula 36, the formula 39, the palladium catalyst, the ligand is 1:(1.5-3.0):(0.05-0.15):(0.1-0.24); and / or,

[0196] the concentration of the formula 36 in the solvent is 0.1-0.5 mol / L; and / or,

[0197] the reaction temperature is 40-120℃; and / or,

[0198] the reaction time is 12-48 hours;

[0199] or,

[0200] the asymmetric catalytic reaction 5 is that the formula 44, the ligand is reacted in the solvent under the action of the rhodium catalyst to obtain the compound shown in the formula 45; wherein, the formula 44 is the formula 45 is

[0201] Scheme five

[0202]

[0203] the rhodium catalyst is at least one selected from the group consisting of dimeric hydroxy(1,5-cyclooctadiene)rhodium, bis(1,5-cyclooctadiene)-trifluoromethanesulfonate rhodium, bis(1,5-cyclooctadiene)-tetrafluoroborate rhodium; and / or,

[0204] the ligand is at least one selected from the group consisting of compounds 17-28 in claim 3; and / or,

[0205] the molar ratio of the formula 44, the rhodium catalyst, the ligand is 1:(0.01-0.1):(0.02-0.2); and / or,

[0206] the concentration of the formula 44 in the solvent is 0.1-0.5 mol / L; and / or,

[0207] the reaction temperature is room temperature to 80℃; and / or,

[0208] the reaction time is 12-48 hours;

[0209] or,

[0210] the asymmetric catalytic reaction 6 is that formula 46, formula 47, a ligand, and a base are reacted in the presence of a palladium catalyst in a solvent to obtain a compound shown in formula 48;

[0211] wherein formula 46 is formula 47 is formula 48 is

[0212] Scheme VI

[0213]

[0214] preferably,

[0215] the palladium catalyst is at least one selected from the group consisting of allylpalladium chloride dimer, palladium acetate, palladium trifluoromethanesulfonate, tris(dibenzylideneacetone)dipalladium, palladium trimethylacetate, and palladium acetylacetonate; and / or,

[0216] the ligand is at least one selected from the group consisting of compounds 17-28 shown in claim 3; and / or,

[0217] the base is at least one selected from the group consisting of N,O-bistrimethylsilylacetamide, triethylamine, diisopropylethylamine, potassium carbonate, and potassium phosphate; and / or,

[0218] the molar ratio of formula 46, formula 47, the palladium catalyst, the ligand, and the base is 1:(1.2-1.5):(0.02-0.1):(0.05-0.2):(1.0-3.0); and / or,

[0219] the concentration of formula 46 in the solvent is 0.1-0.5 mol / L; and / or,

[0220] the reaction temperature is -40-60℃; and / or,

[0221] the reaction time is 12-48 hours;

[0222] or,

[0223] the asymmetric catalytic reaction 7 is that formula 49, formula 50, and a ligand are reacted in the presence of a palladium catalyst in a solvent to obtain a compound shown in formula 51;

[0224] wherein formula 49 is formula 50 is formula 51 is Nap represents a naphthyl group;

[0225] Scheme seven

[0226]

[0227] Preferably,

[0228] The palladium catalyst is selected from at least one of palladium acetate, palladium triflate, tris(dibenzylideneacetone)dipalladium, palladium trimethylacetate, palladium acetylacetone; and / or,

[0229] The ligand is selected from at least one of the compounds shown in compounds 17-28 in claim 3; and / or,

[0230] The molar ratio of the formula 49, formula 50, palladium catalyst, ligand is 1:(1.5-3.0):(0.02-0.1):(0.05-0.2); and / or,

[0231] The concentration of the formula 49 in the solvent is 0.1-0.5 mol / L; and / or,

[0232] The reaction temperature is room temperature to 60℃; and / or,

[0233] The reaction time is 12-72 hours.

[0234] The beneficial effects of the present application relative to the prior art include:

[0235] (1) The 1,1-spiro-bis-indene skeleton of the silicon substitution variation catalyst skeleton provided by the present application exhibits more excellent catalytic performance and chiral induction in the above-mentioned many reaction types;

[0236] (2) The 1,1-spiro-bis-indene skeleton of the silicon substitution variation catalyst skeleton provided by the present application has a shorter synthesis route, lower raw material cost, simpler processing process and feasibility of large-scale production.

[0237] (3) The present application provides a preparation method of a chiral silicon-containing spiro ligand platform molecule and an asymmetric catalytic reaction developed. Compared with commercial chiral spiro catalysts / ligands, the asymmetric catalytic reaction has many advantages, such as greatly shortened synthesis route, greatly reduced cost, relatively stable intermediates, large-scale production, more excellent catalytic performance, novel structure, etc. Therefore, the preparation method of the chiral silicon-containing spiro ligand platform molecule and the catalyst / ligand provided by the present application is an industrialized route; the asymmetric catalytic application provided by the present application shows that the chiral silicon-containing spiro catalyst / ligand provided by the present application has practical application value and enriches the chiral ligand library. DETAILED DESCRIPTION

[0238] The present application will be further described in detail through specific embodiments.

[0239] Example 1

[0240] Synthesis of bis-aryl silane diols:

[0241]

[0242] To a 100 mL Schlenk flask was added aryl bromide (compound shown in Formula VI') (20.0 mmol, 2.0 eq) and 20.0 mL of diethyl ether under nitrogen protection. The solution was lowered to -78 °C with stirring. On the other side, a pear-shaped flask containing diethyl ether (20.0 mL) and silicon tetrachloride (10.0 mmol) was prepared for standby. Then, n-butyllithium (2.5 M in hexane, 20.0 mmol) was slowly added dropwise to the solution of aryl bromide under stirring at -78 °C. Then, the temperature was raised to room temperature and stirred for one hour. The mixture was re-cooled to -78 °C and added dropwise to the silicon tetrachloride solution in diethyl ether under stirring. The reaction was left to stir overnight at room temperature. Then, 10 mL of water was added to the reaction mixture and stirred at room temperature for three hours. Then, saturated sodium bicarbonate was added to adjust pH = 7. The solution was extracted with diethyl ether, concentrated, dried with anhydrous sodium sulfate, filtered. The yellow oil was recrystallized with diethyl ether and petroleum ether to obtain the silicon diol.

[0243] Compound 33-1

[0244]

[0245] White solid, yield 99%, 2.44 g. m.p. 133-134 °C. R f (PE / EA = 5:1): 0.4. 1 H NMR (400 MHz, CDC13) δ 7.70 (d, J = 7.3 Hz, 2H), 7.33 (t, J = 7.3 Hz, 2H), 7.19 - 7.11 (m, 4H), 3.32 (s, 2H), 2.32 (s, 6H). 13 C NMR (101 MHz, CDC13) δ 144.02 (s), 135.53 (s), 133.57 (s), 130.61 (s), 129.95 (s), 125.04 (s), 22.76 (s). HRMS (ESI) calcd. For C 14 H 16 02SiNa [M + Na] + : 267.0817. Found: 267.0814.

[0246] Compound 37-1

[0247]

[0248] White solid, yield 65%, 1.80 g. m.p. 133-134 °C. R f (PE / EA = 2:1): 0.3. 1 H NMR (400 MHz, CDC13) δ 7.54 (dd, J = 7.2, 1.6 Hz, 2H), 7.43 - 7.38 (m, 2H), 6.98 (t, J = 7.2 Hz, 2H), 6.88 (d, J = 8.3 Hz, 2H), 3.83 (s, 6H), 3.57 (s, 2H). 13 C NMR (101 MHz, CDC13) δ 163.79 (s), 136.36 (s), 132.03 (s), 122.87 (s), 121.00 (s), 109.81 (s), 55.46 (s). HRMS (ESI) calcd. For C 14 H 16 04SiNa [M + Na] + : 299.0716. Found: 299.0713.

[0249] Example 2

[0250] Synthesis of dihydrogen silyl ethers:

[0251]

[0252] Method A: To an oven-dried Schlenk flask was added the silanediol (10.0 mmol), DMAP (0.2 mmol), imidazole (30.0 mmol) and dichloromethane (20.0 mL) under nitrogen. Diethylchlorosilane (30.0 mmol) was added slowly with stirring and the reaction mixture was stirred at room temperature overnight. The solvent was then removed by rotary evaporation, n-pentane was added and the mixture was filtered. The filtrate was concentrated and purified by column chromatography on silica gel to give the corresponding silyl ether.

[0253] Alternatively, Method B: To an oven-dried Schlenk flask was added [Ir(cod)OMe]2(0.02 mmol), anhydrous diethyl ether (20.0 mL) and diethylsilane (30.0 mmol) under nitrogen. The silanediol (10.0 mmol) was then added with stirring. The reaction was stirred at room temperature overnight and the solvent was then removed by rotary evaporation. The product was purified by column chromatography on silica gel (PE / DCM 1 :0 to 5:1) to give the corresponding silyl ether.

[0254] Compound 40-1

[0255]

[0256] Prepared according to Method A above: colorless oil, yield 83%. Rf (PE): 0.8. 1 H NMR (400MHz, CDCl3) δ7.71(d,J=7.2Hz,2H),7.36–7.31(m,2H),7.22(t,J=7.3Hz,2H),7.14(d,J= 7.5Hz,2H),4.68–4.62(m,2H),2.29(s,6H),0.96(t,J=7.9Hz,12H),0.67(qd,J=7.8,2.1Hz,8H). 13 C NMR(101MHz, CDCl3)δ143.55(s),135.32(s),135.07(s),130.02(s),129.72(s),124.84(s),22.68(s),6.79(s),6.55(s).HRMS(EI)calcd.For C 20 H 31 O2Si3[M-C2H5] + :387.1632.Found:387.1628.

[0257] Compound 41-1

[0258]

[0259] Prepared according to method B above: colorless oil, yield 61%. f (PE:DCM=5:1):0.5. 1 H NMR (400MHz, CDCl3) δ7.84 (dd, J=6.6, 2.1Hz, 2H), 7.47 (t, J=7.3Hz, 4H), 7.43–7.33 (m,10H),4.83–4.74(m,2H),2.36(s,6H),1.06(t,J=7.9Hz,12H),0.83–0.74(m,8H). 13 C NMR(101MHz, CDCl3)δ142.65(s),142.29(s),140.73(s),136.57(s),134.52(s),131.85(s),12 9.46(s),128.11(s),126.74(s),125.05(s),21.03(s),6.93(s),6.67(s).HRMS(EI)calcd.ForC 34 H 44 O2Si3[M] + :568.2649.Found:568.2651.

[0260] Compound 42-1

[0261]

[0262] Prepared according to Method A above: colorless oil, yield 50%. R f (PE:DCM = 5:1): 0.6. 1 H NMR (400 MHz, CDC13) δ 7.30 (d, J = 7.3 Hz, 2H), 7.21 (t, J = 7.7 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 4.68 - 4.59 (m, 2H), 3.82 (s, 6H), 2.20 (s, 6H), 0.96 (t, J = 7.9 Hz, 12H), 0.66 (qd, J = 7.8, 2.2 Hz, 8H). 13 C NMR (101 MHz, CDC13) δ 157.28 (s), 137.18 (s), 131.95 (s), 127.01 (s), 126.02 (s), 111.75 (s), 55.25 (s), 15.90 (s), 6.77 (s), 6.54 (s). HRMS (EI) calcd. For C 24 H 40 O4Si3[M] + : 476.2234. Found: 476.2230.

[0263] Compound 43-1

[0264]

[0265] Prepared according to Method A above: colorless oil, yield 38%. R f (PE:DCM = 5:1): 0.6. 1 H NMR (400 MHz, CDC13) δ 7.30 (d, J = 7.3 Hz, 2H), 7.21 (t, J = 7.7 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 4.68 - 4.59 (m, 2H), 3.82 (s, 6H), 2.20 (s, 6H), 0.96 (t, J = 7.9 Hz, 12H), 0.66 (qd, J = 7.8, 2.2 Hz, 8H). 13C NMR (101 MHz, CDC13) δ 157.29 (s), 143.49 (s), 136.97 (s), 135.50 (s), 134.98 (s), 131.98 (s), 129.92 (s), 129.67 (s), 127.05 (s), 126.02 (s), 124.79 (s), 111.80 (s), 55.25 (s), 22.69 (s), 15.84 (s), 6.76 (s), 6.51 (s). HRMS (EI) calcd. For C 21 H 33 O3Si3[M-C2H5] + : 417.1737. Found: 417.1751.

[0266] Compound 44-1

[0267]

[0268] Prepared according to Method B above: white solid, yield 51%, m.p. 43-45 °C. R f (PE:DCM = 10:1): 0.6. 1 HNMR (400 MHz, CDC13) δ 7.45 (dd, J = 7.2, 1.6 Hz, 2H), 7.41 - 7.33 (m, 2H), 6.92 (td, J = 7.3, 0.7 Hz, 2H), 6.80 (d, J = 8.2 Hz, 2H), 4.54 (dt, J = 4.5, 2.2 Hz, 2H), 3.68 (s, 6H), 0.92 (t, J = 7.9 Hz, 12H), 0.61 (qd, J = 7.6, 1.9 Hz, 8H). 13 C NMR (101 MHz, CDC13) δ 164.11 (s), 136.33 (s), 131.33 (s), 124.56 (s), 120.13 (s), 109.26 (s), 54.66 (s), 6.70 (s), 6.54 (s). HRMS (EI) calcd. For C 22 H 35 O4Si3[M-H] + : 447.1843. Found: 447.1836.

[0269] Compound 45-1

[0270]

[0271] Prepared according to Method B above: colorless oil, yield 45%. R f (PE:DCM = 5:1): 0.4.1 H NMR (400 MHz, CDC13) δ 7.53 (d, J = 7.1 Hz, 2H), 7.21 (d, J = 7.3 Hz, 2H), 7.06 (t, J = 7.3 Hz, 2H), 4.63 - 4.55 (m, 2H), 3.33 (s, 6H), 2.23 (s, 6H), 0.93 (t, J = 7.9 Hz, 12H), 0.65 (tt, J = 8.1, 4.1 Hz, 8H). 13 CNMR (101 MHz, CDC13) δ 163.71 (s), 133.69 (s), 133.44 (s), 130.12 (s), 129.68 (s), 123.57 (s), 60.14 (s), 16.40 (s), 6.79 (s), 6.56 (s). HRMS (EI) calcd. For C 24 H 39 O4Si3[M-H] + : 475.2156. Found: 475.2148.

[0272] Compound 46-1

[0273]

[0274] Prepared according to the above method A: colorless oil, yield 42%. R f (PE:DCM = 10:1): 0.4. 1 H NMR (400 MHz, CDC13) δ 7.68 (dt, J = 7.2, 1.9 Hz, 2H), 7.54 - 7.49 (m, 4H), 7.40 - 7.35 (m, 6H), 7.30 (dd, J = 10.5, 4.1 Hz, 2H), 7.20 (td, J = 7.4, 1.6 Hz, 2H), 4.67 (dd, J = 4.5, 2.3 Hz, 2H), 2.90 (d, J = 1.9 Hz, 6H), 0.99 (td, J = 7.8, 1.7 Hz, 12H), 0.76 - 0.68 (m, 8H). 13 CNMR (101 MHz, CDC13) δ 162.63 (s), 139.08 (s), 134.90 (s), 133.46 (s), 133.19 (s), 130.89 (s), 128.74 (s), 128.34 (s), 126.94 (s), 123.76 (s), 59.93 (s), 6.89 (s), 6.66 (s). HRMS (EI) calcd. For C 32 H 39 O4Si3[M-C2H5] +:571.2156.Found:571.2155.

[0275] Example 3

[0276] Asymmetric catalytic C-H dehydrogenative silylation reaction:

[0277]

[0278] In a glove box under nitrogen, an oven-dried 8 ml sealed tube was charged with [Rh(cod)OH]2(1.3 mg, 0.003 mmol), Phox (3.0 mg, 0.006 mmol) and anhydrous dioxane (0.5 mL). After stirring at room temperature for 0.5 h, the substrate compound V (0.1 mmol) and cyclopentene (50.0 μL) were added. The sealed tube was capped with a stopper and removed from the glove box. The resulting mixture was stirred in a preheated (130 °C) aluminum block for 48 h. The reaction mixture was then concentrated and purified by column chromatography on silica gel to give the silylated target product. The ee value was determined by chiral HPLC.

[0279] Compound 1

[0280]

[0281] White solid, melting point: 99-100 °C, yield 75%, 98% ee, 31.0 mg. R f (PE:DCM = 5:1): 0.5. 1 HNMR (400 MHz, CDC13) δ 7.45 (d, J = 7.2 Hz, 2H), 7.37 (t, J = 7.4 Hz, 2H), 7.17 (d, J = 7.5 Hz, 2H), 2.14 (s, 6H), 1.09 (t, J = 7.8 Hz, 6H), 1.02 (t, J = 7.6 Hz, 6H), 0.95 - 0.84 (m, 8H). 13 C NMR (101 MHz, CDC13) δ 148.06 (s), 142.80 (s), 142.61 (s), 130.28 (s), 130.19 (s), 129.11 (s), 22.38 (s), 6.99 (s), 6.90 (s), 6.79 (s), 6.48 (s). HRMS (EI) calcd. For C 22 H 32 O2Si3[M] + :412.1710.Found:412.1715.

[0282] Compound 2

[0283]

[0284] White solid, melting point: 103-104 °C, yield 84% 87% ee, 47.5 mg. R f (PE:DCM = 5: 1): 0.4. 1 HNMR (400 MHz, CDC13) δ 7.53 (d, J = 7.4 Hz, 2H), 7.41 - 7.36 (m, 5H), 7.33 (dd, J = 8.5, 6.8 Hz, 7H), 2.18 (s, 6H), 1.11 (q, J = 7.8 Hz, 12H), 0.99 - 0.90 (m, 8H). 13 C NMR (101 MHz, CDC13) δ 147.00 (s), 144.07 (s), 142.91 (s), 141.92 (s), 139.91 (s), 132.08 (s), 129.41 (s), 129.29 (s), 128.05 (s), 126.83 (s), 20.95 (s), 7.01 (s), 6.99 (s), 6.85 (s), 6.56 (s). HRMS (EI) calcd. For C 34 H 40 O2Si3[M] + : 564.2336. Found: 564.2336.

[0285] Compound 3

[0286]

[0287] White solid, melting point: 103-104 °C, yield 51% 97% ee, 24.1 mg. R f (PE:DCM = 5: 1): 0.4. 1 HNMR (400 MHz, CDC13) δ 7.46 (d, J = 7.9 Hz, 2H), 6.97 (d, J = 7.9 Hz, 2H), 3.83 (s, 6H), 2.06 (s, 6H), 1.04 (dt, J = 21.3, 7.7 Hz, 12H), 0.91 - 0.84 (m, 8H). 13 C NMR (101 MHz, CDC13) δ 158.65 (s), 144.89 (s), 137.85 (s), 131.36 (s), 130.80 (s), 112.38 (s), 55.30 (s), 16.27 (s), 7.17 (s), 7.14 (s), 6.79 (s), 6.51 (s). HRMS (EI) calcd. For C 24 H 36 O4Si3[M] +:472.1921.Found:472.1912.

[0288] Compound 4

[0289]

[0290] Colorless oil, yield 73%, 81% ee, 32.3 mg. f (PE:DCM=5:1):0.5. 1 H NMR (400MHz, CDCl3) δ7.49–7.44(m,2H),7.38(t,J=7.4Hz,1H),7.18(d,J=7.4Hz,1H),6.99(d,J=7.9Hz,1H ),3.84(s,3H),2.19(s,3H),2.05(s,3H),1.09(t,J=7.8Hz,6H),1.03(t,J=7.7Hz,6H),0.95–0.87(m,8H). 13 C NMR(101MHz, CDCl3)δ158.66(s),147.95(s),144.62(s),142.90(s),142 .80(s),137.95(s),131.37(s),130.81(s),130.26(s),130.17(s),129.1 1(s),112.39(s),55.29(s),22.45(s),16.19(s),7.25(s),7.13(s),6.95(s),6.93(s),6.83(s),6.77(s),6.53(s),6.49(s).HRMS(EI)calcd.For C 21 H 29 O3Si3[M-C2H5] + :413.1424.Found:413.1414.

[0291] Compound 9

[0292]

[0293] White solid, melting point: 117-118℃, yield 82%, 98% ee, 36.5 mg. f (PE:DCM=5:1):0.4. 1HNMR (400 MHz, CDC13) δ 7.47 - 7.40 (m, 2H), 7.20 (d, J = 7.1 Hz, 2H), 6.80 (d, J = 8.2 Hz, 2H), 3.59 (s, 6H), 1.11 (t, J = 7.8 Hz, 6H), 1.03 (t, J = 7.7 Hz, 6H), 0.97 - 0.85 (m, 8H). 13 C NMR (101 MHz, CDC13) δ 163.34 (s), 150.20 (s), 132.10 (s), 131.06 (s), 123.99 (s), 110.43 (s), 54.62 (s), 6.85 (s), 6.64 (s), 6.55 (s). HRMS (EI) calcd. For C 20 H 27 O2Si3[M-C2H5] + : 415.1217. Found: 415.1203.

[0294] Compound 10

[0295]

[0296] Colorless oil, yield 84%, 84% ee, 39.7 mg. R f (PE:DCM = 5:1): 0.5. 1 H NMR (400 MHz, CDC13) δ 7.29 (s, 4H), 3.33 (s, 6H), 2.24 (s, 6H), 1.13 (t, J = 7.8 Hz, 6H), 1.00 (t, J = 7.7 Hz, 6H), 0.96 - 0.84 (m, 8H). 13 C NMR (101 MHz, CDC13) δ 162.91 (s), 147.58 (s), 136.17 (s), 134.52 (s), 131.49 (s), 127.82 (s), 60.61 (s), 16.07 (s), 6.84 (s), 6.81 (s), 6.69 (s), 6.50 (s). HRMS (EI) calcd. For C 24 H 36 O4Si3[M] + : 472.1921. Found: 472.1919.

[0297] Compound 11

[0298]

[0299] White solid, melting point: 80-81 °C, yield 68%, 94% ee, 40.6 mg. Rf (PE:DCM = 5: 1): 0.5. 1 HNMR (400 MHz, CDC13) δ 7.44 (d, J = 7.3 Hz, 4H), 7.39 - 7.31 (m, 4H), 7.26 (t, J = 7.3 Hz, 4H), 7.21 - 7.16 (m, 2H), 2.91 (s, 6H), 1.06 (t, J = 7.7 Hz, 6H), 0.98 (t, J = 7.6 Hz, 6H), 0.94 - 0.81 (m, 8H). 13 C NMR (101 MHz, CDC13) δ 161.77 (s), 149.60 (s), 138.60 (s), 137.18 (s), 134.66 (s), 134.21 (s), 128.90 (s), 128.37 (s), 128.01 (s), 127.21 (s), 60.43 (s), 6.89 (s), 6.72 (s), 6.65 (s). HRMS (EI) calcd. For C 34 H 40 O4Si3[M] + : 596.2234. Found: 596.2240.

[0300] Compound 12

[0301]

[0302] White solid, melting point: >200 °C, yield 97%, 99% ee, 58.2 mg. R f (PE / DCM = 5: 1): 0.5. 1 H NMR (400 MHz, CDC13) δ 7.49 (d, J = 8.6 Hz, 2H), 6.67 (d, J = 8.6 Hz, 2H), 3.56 (s, 6H), 1.10 - 1.02 (m, 10H), 1.02 - 0.97 (m, 10H). 13 C NMR (101 MHz, CDC13) δ 162.41 (s), 151.55 (s), 135.13 (s), 134.10 (s), 118.03 (s), 113.00 (s), 54.99 (s), 6.62 (s), 6.59 (s), 6.27 (s). HRMS (EI) calcd. For C 22 H 30 Br2O4Si3[M] + : 599.9819. Found: 599.9812.

[0303] Example 4

[0304] De-methylation:

[0305] Into a 25 mL Schlenk flask, under nitrogen protection, was added sequentially compound of Formula I 1 spirocyclic silyl ether (0.1 mmol), tris-pentafluorophenyl boron (2.6 mg, 0.005 mmol), dissolved in dichloromethane (1.0 mL), ethyldimethylsilane (40 μL, 0.3 mmol) was added slowly with stirring at room temperature and stirred for 1-12 hours. The reaction mixture was concentrated by rotary evaporation to remove the solvent, and the remaining crude product was added sequentially with stirring isopropanol or ethanol (1.0 mL), hydrogen chloride (80 μL, 4 M in EtOH), followed by stirring at 0 °C to room temperature for 0.7 hours. The reaction mixture was added to 20 mL water and 20 mL diethyl ether, the organic layer was separated, and the remaining inorganic layer was extracted with diethyl ether three times. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation to remove the solvent to obtain the target product.

[0306] Compound 13

[0307]

[0308] White solid, melting point: 129-130 °C, yield 80%, 99% ee, 33.3 mg. R f (PE / EA = 10:1): 0.4. 1 HNMR (400 MHz, CDC13) δ 7.37 - 7.30 (m, 2H), 7.19 (d, J = 7.0 Hz, 2H), 6.66 (d, J = 8.0 Hz, 2H), 4.73 (s, 2H), 1.03 (dt, J = 13.3, 7.9 Hz, 12H), 0.94 - 0.85 (m, 8H). 13 C NMR (101 MHz, CDC13) δ 159.57 (s), 150.27 (s), 132.64 (s), 128.02 (s), 124.59 (s), 115.79 (s), 6.82 (s), 6.71 (s), 6.55 (s), 6.45 (s). HRMS (APCI) calcd. For C 20 H 29 O4Si3[M + H] + : 417.1374. Found: 417.1369.

[0309] Compound 14

[0310]

[0311] White solid, melting point: 158-160 °C, yield 75%, 94% ee, 33.3 mg. Rf (PE / EA = 10:1): 0.6. 1 HNMR (400 MHz, CDC13) δ 7.25 (d, J = 6.8 Hz, 2H), 7.12 (d, J = 7.0 Hz, 2H), 4.55 (s, 2H), 2.18 (s, 6H), 1.07 (t, J = 7.7 Hz, 6H), 1.00 (t, J = 7.6 Hz, 6H), 0.90 (dt, J = 23.1, 7.6 Hz, 8H). 13 C NMR (101 MHz, CDC13) δ 158.11 (s), 147.39 (s), 134.45 (s), 127.67 (s), 124.82 (s), 124.05 (s), 15.59 (s), 6.90 (s), 6.89 (s), 6.64 (s), 6.46 (s). HRMS (APCI) calcd. For C 22 H 33 O4Si3[M + H] + : 445.1687. Found: 445.1680.

[0312] Compound 15

[0313]

[0314] White solid, melting point: 117-118 °C, yield 76%, 93% ee, 43.2 mg. R f (PE / EA = 20:1): 0.5. 1 HNMR (400 MHz, CDC13) δ 7.29 - 7.24 (m, 8H), 7.21 - 7.19 (m, 1H), 7.17 (d, J = 7.2 Hz, 3H), 7.08 (s, 1H), 7.07 (d, J = 3.9 Hz, 1H), 5.14 (s, 2H), 0.90 (q, J = 7.8 Hz, 12H), 0.82 - 0.72 (m, 8H). 13 CNMR (101 MHz, CDC13) δ 156.23 (s), 150.08 (s), 136.92 (s), 133.15 (s), 129.33 (s), 129.13 (s), 128.80 (s), 128.26 (s), 127.92 (s), 124.55 (s), 6.80 (s), 6.72 (s), 6.67 (s), 6.58 (s). HRMS (APCI) calcd. For C 32 H 36 O4Si3[M] + : 568.1921. Found: 568.1915.

[0315] Compound 16

[0316]

[0317] White solid, melting point: >200 °C, yield 98%, 98% ee, 56.3 mg. R f (DCM): 0.6. 1 H NMR (400 MHz, Acetone) δ 8.76 (s, 2H), 7.50 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.5 Hz, 2H), 1.18 - 1.03 (m, 20H). 13 C NMR (101 MHz, Acetone) δ 160.61 (s), 150.81 (s), 134.99 (s), 132.56 (s), 118.08 (s), 116.24 (s), 6.18 (s), 6.12 (s), 6.04 (s), 5.89 (s). HRMS (ESI) calcd. For C 20 H 26 Br2O4Si3Na [M + Na] + : 596.9383. Found: 596.9390.

[0318] Example 5

[0319] Palladium catalyzed C-phosphination reaction:

[0320] Under nitrogen protection, into 8 mL reaction bottle in glove box was added bis(dibenzylideneacetone)palladium (5.7 mg, 0.01 mmol), tris-(o-methylphenyl)phosphine (6.0 mg, 0.02 mmol), Formula I 4 Silaspirocyclic bistriflate (68.0 mg, 0.1 mmol), diisopropylethylamine (70 μί), dissolved with dioxane (0.5 mL), diphenylphosphine (0.3 mmol) was added with stirring. The mixture was heated to 120 °C, stirred for 48 hours. Subsequently, the reaction mixture was concentrated, and column purified on silica gel to obtain the bisphosphine product.

[0321] Compound 31

[0322]

[0323] White solid, melting point: 168-169 °C, yield 20%, 15.0 mg. R f (PE / EA = 20: 1): 0.5. 1H NMR (400 MHz, CDC13) δ 7.65 (d, J = 7.1 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.18 (dt, J = 7.6, 4.4 Hz, 10H), 7.06 (t, J = 7.4 Hz, 4H), 6.98 - 6.89 (m, 4H), 6.79 (t, J = 7.6 Hz, 4H), 1.00 (t, J = 7.5 Hz, 6H), 0.93 - 0.80 (m, 14H). 13 C NMR (101 MHz, CDC13) δ 153.77 (d, J = 3.2 Hz), 153.27 (d, J = 3.2 Hz), 149.14 (d, J = 2.4 Hz), 149.01 (d, J = 1.9 Hz), 141.45 (d, J = 11.8 Hz), 139.22 (d, J = 12.3 Hz), 137.17 (d, J = 12.7 Hz), 134.98 (s), 134.96 (s), 134.07 (d, J = 20.4 Hz), 132.70 (s), 132.60 (s), 132.22 (d, J = 16.1 Hz), 129.86 (s), 128.38 (s), 128.12 (d, J = 7.2 Hz), 127.98 (d, J = 5.3 Hz), 127.30 (s), 6.98 (s), 6.77 (s), 6.76 (s), 6.60 (s), 6.30 (s), 6.24 (s). 31 P NMR (162 MHz, CDC13) δ -10.03 (s). HRMS (ESI) calcd. For C 44 H 47 O2P2Si3[M + H] + : 753.2359. Found: 753.2345.

[0324] Example 6

[0325] Synthesis of chiral phosphonic acid:

[0326] In a dry Schlenk flask, the silaspirocyclic diphemol (41.7 mg, 0.1 mmol), triethylamine (83 μL, 0.6 mmol) were dissolved in anhydrous dichloromethane (1.0 mL). After stirring for ten minutes at room temperature, phosphorous oxychloride (38 μL, 0.4 mmol) was slowly added. After stirring for 6 hours, triethylamine (28 μL, 0.2 mmol), water (0.7 mL) and tetrahydrofuran (0.7 mL) were added. Stirring was continued for 8 hours at room temperature, the mixture was diluted with water (15 mL), acidified with 2 M hydrochloric acid to pH = 2-3 and extracted with 20 mL of dichloromethane. The organic layer was washed with 2 M hydrochloric acid and concentrated. Purification was performed by flash column chromatography on silica gel eluted with dichloromethane / methanol. The resulting product was dissolved in 20 mL of dichloromethane, washed with 2 M hydrochloric acid and concentrated to the desired product.

[0327] Compound 32

[0328]

[0329] Off-white solid, melting point: 151-152 °C, yield 50%, 23.9 mg. R f (DCM / MeOH / AcOH = 12:6:1): 0.4. 1 H NMR (400 MHz, Acetone) δ 8.17 (s, 1H), 7.30 (s, 4H), 7.23 (d, J = 5.2 Hz, 2H), 0.92 (t, J = 7.3 Hz, 6H), 0.86 - 0.78 (m, 10H), 0.77 - 0.69 (m, 4H). 13 C NMR (101 MHz, Acetone) δ 155.39 (d, J = 5.8 Hz), 150.30 (s), 133.66 (d, J = 7.7 Hz), 132.25 (s), 127.94 (s), 120.11 (s), 6.35 (s), 6.09 (s), 6.06 (s), 5.94 (s). 31 P NMR (162 MHz, Acetone) δ -5.85 (s). HRMS (APCI) calcd. For C 20 H 26 O6PSi3[M-H] - : 477.0775. Found: 477.0778.

[0330] Example 7

[0331] Synthesis of chiral phosphoramidites:

[0332] Into a 25 mL Schlenk flask under nitrogen protection was added formula I 3Chiral silaspirocyclic diphenol (0.2 mmol, 1.0 eq), triethylamine (83 μL, 0.6 mmol, 3.0 eq), dissolved in dichloromethane (1.0 mL), added to a solution of dialkylphosphine dichloride R a4 R b4 NPC12 (0.24 mmol, 1.2 eq) in dichloromethane (0.5 mL). The remaining mixture was stirred at room temperature to 60 °C for 16 h. Subsequently filtered over silica gel (previously wetted with PE / EA / Et3N 20:2:1, v / v / v) and PE / EA / Et3N (20:2:1, v / v / v) as eluent. The remaining crude was concentrated and purified by reverse phase preparative column (C18 (ODS)) with acetonitrile as eluent.

[0333] Compound 22

[0334]

[0335] Colorless oil, yield 90%, 88.1 mg. R f (PE / EA = 20:1): 0.7. 1 H NMR (400 MHz, CDC13) δ 7.52 (t, J = 7.5 Hz, 1H), 7.45 (dd, J = 15.5, 7.7 Hz, 2H), 7.39 (d, J = 7.0 Hz, 1H), 7.14 (d, J = 7.9 Hz, 1H), 6.86 (d, J = 7.9 Hz, 1H), 2.30 (d, J = 9.1 Hz, 6H), 1.17 (t, J = 7.8 Hz, 6H), 1.02 (t, J = 7.7 Hz, 4H), 0.80 - 0.67 (m, 10H). 13 C NMR (101 MHz, CDC13) δ 157.29 (d, J = 7.9 Hz), 155.29 (d, J = 9.4 Hz), 150.90 (s), 150.03 (s), 137.59 (s), 136.55 (s), 132.95 (s), 132.88 (s), 128.24 (d, J = 1.7 Hz), 127.60 (s), 123.33 (s), 122.91 (d, J = 5.4 Hz), 35.29 (d, J = 19.8 Hz), 6.97 (s), 6.85 (s), 6.83 (s), 6.80 (s), 6.69 (s), 6.10 (s), 5.95 (s). 31 P NMR (162 MHz, CDC13) δ 129.76 (s). HRMS (APCI) calcd. For C 22 H 33 NO4PSi3 [M+H] +:490.1455.Found:490.1448.

[0336] Compound 23

[0337]

[0338] White solid, melting point: 179-180 °C, yield 52% 53.8 mg. R f (PE / EA = 20:1): 0.6. 1 HNMR (400 MHz, CDC13) δ 7.33 (ddd, J = 27.5, 12.6, 5.8 Hz, 4H), 2.36 (s, 3H), 2.31 (d, J = 7.2 Hz, 6H), 2.27 (s, 3H), 1.16 (t, J = 7.8 Hz, 6H), 1.00 (ddd, J = 9.2, 7.3, 2.4 Hz, 4H), 0.88 - 0.79 (m, 6H), 0.79 - 0.64 (m, 4H). 13 C NMR (101 MHz, CDC13) δ 155.58 (d, J = 5.6 Hz), 153.96 (d, J = 10.3 Hz), 147.57 (s), 146.37 (s), 137.28 (d, J = 3.3 Hz), 136.25 (s), 134.57 (s), 134.50 (s), 131.23 (s), 131.20 (s), 128.12 (s), 127.51 (s), 16.80 (d, J = 8.9 Hz), 16.34 (s), 7.04 (s), 6.96 (s), 6.90 (s), 6.77 (s), 6.25 (s), 6.13 (s). 31 P NMR (162 MHz, CDC13) δ 127.80 (s). HRMS (APCI) calcd. For C 24 H 37 NO4PSi3[M + H] + :518.1768.Found:518.17.

[0339] Compound 24

[0340]

[0341] White solid, melting point: 86-87 °C, yield 49% 62.9 mg. R f (PE / EA = 20:1): 0.7. 1H NMR (400 MHz, CDC13) δ 7.73 - 7.65 (m, 4H), 7.61 (d, J = 7.4 Hz, 2H), 7.56 (dd, J = 7.3, 1.0 Hz, 1H), 7.51 (d, J = 7.3 Hz, 1H), 7.38 (td, J = 7.6, 5.3 Hz, 4H), 7.30 (dd, J = 9.4, 5.1 Hz, 2H), 1.72 (d, J = 9.2 Hz, 6H), 1.27 (td, J = 7.7, 3.4 Hz, 6H), 1.16 - 1.08 (m, 4H), 1.00 (t, J = 7.6 Hz, 3H), 0.97 - 0.82 (m, 7H). 13 C NMR (101 MHz, CDC13) δ 154.51 (d, J = 6.5 Hz), 152.73 (d, J = 9.9 Hz), 150.09 (d, J = 1.6 Hz), 148.99 (s), 138.65 (d, J = 3.2 Hz), 138.44 (s), 137.95 (s), 137.80 (s), 135.50 (d, J = 4.8 Hz), 135.35 (s), 133.58 (s), 133.53 (s), 129.81 (d, J = 1.3 Hz), 129.33 (s), 128.66 (s), 128.10 (s), 127.99 (s), 127.93 (s), 127.19 (s), 127.06 (s), 34.50 (d, J = 24.0 Hz), 7.06 (s), 7.02 (s), 6.99 (s), 6.90 (s), 6.81 (s), 6.80 (s), 6.30 (s), 6.24 (s). 31 P NMR (162 MHz, CDC13) δ 129.92 (s). HRMS (APCI) calcd. For C 34 H 41 NO4PSi3[M + H] + : 642.2081. Found: 642.2070.

[0342] Compound 25

[0343]

[0344] Colorless oil, yield 90%, 88.1 mg. R f (PE / EA = 20:1): 0.7. 1H NMR (400 MHz, CDC13) δ 7.52 (t, J = 7.5 Hz, 1H), 7.45 (dd, J = 15.5, 7.7 Hz, 2H), 7.39 (d, J = 7.0 Hz, 1H), 7.14 (d, J = 7.9 Hz, 1H), 6.86 (d, J = 7.9 Hz, 1H), 2.30 (d, J = 9.1 Hz, 6H), 1.17 (t, J = 7.8 Hz, 6H), 1.02 (t, J = 7.7 Hz, 4H), 0.80 - 0.67 (m, 10H). 13 C NMR (101 MHz, CDC13) δ 157.29 (d, J = 7.9 Hz), 155.29 (d, J = 9.4 Hz), 150.90 (s), 150.03 (s), 137.59 (s), 136.55 (s), 132.95 (s), 132.88 (s), 128.24 (d, J = 1.7 Hz), 127.60 (s), 123.33 (s), 122.91 (d, J = 5.4 Hz), 35.29 (d, J = 19.8 Hz), 6.97 (s), 6.85 (s), 6.83 (s), 6.80 (s), 6.69 (s), 6.10 (s), 5.95 (s). 31 P NMR (162 MHz, CDC13) δ 129.76 (s). HRMS (APCI) calcd. For C 22 H 33 NO4PSi3[M + H] + : 490.1455. Found: 490.1448.

[0345] Compound 26

[0346]

[0347] White solid, melting point: 140-141 °C, yield 95%, 103.7 mg. R f (PE / EA = 20:1): 0.7. 1 H NMR (400 MHz, CDC13) δ 7.51 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.5 Hz, 1H), 7.38 (dd, J = 14.5, 7.1 Hz, 2H), 7.11 (d, J = 7.9 Hz, 1H), 7.05 (d, J = 7.9 Hz, 1H), 3.05 (s, 2H), 1.16 (dd, J = 14.7, 7.6 Hz, 12H), 1.06 - 0.93 (m, 10H), 0.80 - 0.66 (m, 10H). 13C NMR (101 MHz, CDC13) δ 158.75 (d, J = 8.9 Hz), 156.18 (d, J = 12.1 Hz), 150.65 (s), 149.03 (s), 136.81 (s), 135.94 (s), 132.97 (s), 132.58 (s), 127.94 (s), 127.45 (s), 123.84 (s), 122.99 (d, J = 6.0 Hz), 45.28 (d, J = 12.5 Hz), 24.36 (s), 7.04 (s), 6.87 (s), 6.80 (s), 6.72 (s), 6.71 (s), 5.97 (s), 5.81 (s). 31 PNMR (162 MHz, CDC13) δ 141.09 (s). HRMS (APCI) calcd. For C 26 H 41 NO4PSi3[M + H] + : 546.2081. Found: 546.2066.

[0348] Compound 27

[0349]

[0350] Colorless oil, yield 31%, 41.5 mg. R f (PE / EA = 20:1): 0.6. 1 H NMR (400 MHz, CDC13) δ 8.30 (d, J = 2.0 Hz, 1H), 7.41 - 7.32 (m, 2H), 7.24 - 7.14 (m, 7H), 7.04 (d, J = 7.0 Hz, 3H), 7.01 (d, J = 7.0 Hz, 1H), 6.74 - 6.64 (m, 1H), 5.86 (d, J = 8.1 Hz, 1H), 4.86 (dd, J = 11.4, 6.9 Hz, 2H), 1.86 (d, J = 7.1 Hz, 6H), 1.20 (t, J = 7.8 Hz, 3H), 1.10 - 0.75 (m, 17H). 13C NMR (101 MHz, CDC13) δ 154.38 (d, J = 6.2 Hz), 151.08 (d, J = 2.7 Hz), 147.86 (s), 140.91 (s), 138.75 (s), 130.53 (d, J = 2.5 Hz), 129.39 (d, J = 5.3 Hz), 129.16 (s), 127.33 (s), 126.54 (d, J = 2.0 Hz), 126.10 (s), 126.02 (s), 125.24 (s), 124.27 (s), 120.59 (d, J = 2.7 Hz), 120.07 (d, J = 9.6 Hz), 51.12 (d, J = 11.6 Hz), 20.14 (d, J = 9.8 Hz), 4.77 (s), 4.74 (s), 4.59 (s), 4.53 (s), 4.41 (s), 4.37 (s), 3.99 (s), 3.60 (s). 31 P NMR (162 MHz, CDC13) δ 141.82 (s). HRMS (APCI) calcd. for C 36 H 47 NO5PSi3[M + H3O] + : 688.2500. Found: 688.2488.

[0351] Compound 28

[0352]

[0353] White solid, melting point: 170-171 °C, yield 46%, 51.5 mg. R f (PE / EA = 20:1): 0.5. 1 H NMR (400 MHz, CDC13) δ 7.31 (t, J = 7.9 Hz, 2H), 7.22 (dd, J = 12.7, 5.5 Hz, 2H), 3.38 (d, J = 50.1 Hz, 4H), 2.76 (s, 2H), 2.66 - 2.39 (m, 2H), 2.27 (d, J = 36.0 Hz, 6H), 1.07 (t, J = 7.7 Hz, 6H), 0.90 (dd, J = 14.9, 7.8 Hz, 4H), 0.77 - 0.58 (m, 10H). 13C NMR (101MHz, CDCl3) δ155.37 (d, J = 4.8Hz), 153.79 (d, J = 10.4Hz), 147.69 (s), 146.40(s),137.12(d,J=4.1Hz),136.16(s),134.70(s),134.58(s),131.15(s ),131.03(d,J=3.8Hz),128.25(s),127.78(s),68.06(s),16.80(d,J=8.7Hz) ,16.72(s),7.05(s),6.93(s),6.90(s),6.84(s),6.72(s),6.18(s),6.09(s). 31 P NMR(162MHz,CDCl3)δ125.05(s).HRMS(ESI)calcd.For C 26 H 39 NO5PSi3[M+H] + :560.1874.Found:560.1861.

[0354] Example 8

[0355] benzylic bromination:

[0356]

[0357] Under nitrogen protection, add formula I sequentially to a 25 mL Schlenk flask. 2 Spirocyclic silyl ether (1.0 mmol), N-bromosuccinimide (373.8 mg, 2.1 mmol), and azobisisobutyronitrile (16.4 mg, 0.1 mmol) were dissolved in degassed carbon tetrachloride (0.5 mL). The mixture was then reacted at 70–80 °C for 16 hours with stirring. The mixture was subsequently cooled to room temperature, the solid was filtered off with diatomaceous earth, eluted with dichloromethane, concentrated, and the solvent was removed by rotary evaporation. The remaining crude product was purified by column chromatography on silica gel to give the benzylic brominated product.

[0358] Compound 5

[0359]

[0360] White solid, melting point: 131-132℃, yield 84%, 99% ee, 477.1 mg. f (PE / DCM = 5:1): 0.4. 1HNMR (400 MHz, CDC13) δ 7.59 (dd, J = 5.7, 2.6 Hz, 2H), 7.54 - 7.47 (m, 4H), 4.27 (q, J = 10.4 Hz, 4H), 1.13 (t, J = 7.8 Hz, 6H), 1.04 - 0.99 (m, 8H), 0.98 - 0.87 (m, 6H). 13 C NMR (101 MHz, CDC13) δ 148.49 (s), 144.54 (s), 144.19 (s), 140.38 (s), 140.26 (s), 133.09 (s), 131.98 (s), 129.02 (s), 128.11 (s), 127.43 (s), 33.00 (s), 7.14 (s), 6.81 (s), 6.79 (s), 6.49 (s). HRMS (APCI) calcd. For C 22 H 29 Br2O2Si3[M-H] + : 568.9999. Found: 568.9993.

[0361] Compound 6

[0362]

[0363] White solid, melting point: 118-120 °C, yield 84%, 99% ee, 604.6 mg. R f (PE / DCM = 5: 1): 0.5. 1 HNMR (400 MHz, CDC13) δ 7.63 (d, J = 7.4 Hz, 2H), 7.43 - 7.35 (m, 12H), 4.31 (dd, J = 27.7, 10.1 Hz, 4H), 1.14 (dd, J = 12.3, 4.9 Hz, 6H), 1.10 - 1.03 (m, 8H), 1.02 - 0.93 (m, 6H). 13 C NMR (101 MHz, CDC13) δ 148.49 (s), 144.54 (s), 144.19 (s), 140.38 (s), 140.26 (s), 133.09 (s), 131.98 (s), 129.02 (s), 128.11 (s), 127.43 (s), 33.00 (s), 7.14 (s), 6.81 (s), 6.79 (s), 6.49 (s). HRMS (APCI) calcd. For C 34 H 37 Br2O2Si3[M-H] - : 719.0468. Found: 719.0463.

[0364] Compound 7

[0365]

[0366] White solid, melting point: 151-152 °C, yield 99%, 97% ee, 621.5 mg. R f (PE / DCM = 2: 1): 0.6. 1 HNMR (400 MHz, CDC13) δ 7.59 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.1 Hz, 2H), 4.32 (dd, J = 26.2, 9.6 Hz, 4H), 3.91 (s, 6H), 1.11 (t, J = 7.7 Hz, 6H), 1.00 (dd, J = 14.5, 6.8 Hz, 8H), 0.96 - 0.82 (m, 6H). 13 C NMR (101 MHz, CDC13) δ 159.23 (s), 144.88 (s), 138.90 (s), 134.00 (s), 131.06 (s), 113.62 (s), 55.72 (s), 29.66 (s), 7.35 (s), 6.90 (s), 6.80 (s), 6.47 (s). HRMS (APCI) calcd. For C 24 H 35 Br2O4Si3[M+H] + : 629.0210. Found: 629.0197.

[0367] Compound 8

[0368]

[0369] Colorless oil, yield 99%, 81% ee, 592.1 mg. R f (PE / DCM = 5: 1): 0.5. 1 H NMR (400 MHz, CDC13) δ 7.61 (dd, J = 10.1, 5.9 Hz, 2H), 7.55 - 7.50 (m, 2H), 7.08 (d, J = 8.1 Hz, 1H), 4.38 (dd, J = 9.8, 8.3 Hz, 2H), 4.27 (dd, J = 13.0, 10.1 Hz, 2H), 3.92 (s, 3H), 1.14 (t, J = 7.7 Hz, 6H), 1.03 (t, J = 7.5 Hz, 8H), 0.99 - 0.86 (m, 6H). 13C NMR (101 MHz, CDC13) δ 159.24 (s), 148.74 (s), 144.91 (s), 143.00 (s), 142.14 (s), 138.92 (s), 134.07 (s), 131.81 (s), 131.31 (s), 131.14 (s), 130.96 (s), 113.70 (s), 55.73 (s), 34.16 (s), 29.39 (s), 7.35 (s), 7.14 (s), 6.93 (s), 6.82 (s), 6.78 (s), 6.77 (s), 6.47 (s), 6.44 (s). HRMS (APCI) calcd. For C 23 H 31 Br2O2Si3[M-H] - : 596.9948. Found: 596.9946.

[0370] Example 9

[0371] Synthesis of chiral alkyl phosphines:

[0372] A mixture of spiro siloxane (1.0 mmol) and phenyl phosphine (110 μL, 1.0 mmol) in tetrahydrofuran (10 ml) was added to a base (2.0 mmol) at -78 °C (lithium hexamethyldisilazide). The mixture was gradually raised to room temperature and stirred for 48 hours. The solvent was removed in vacuum and the residue was purified on a silica gel column to give the desired product.

[0373] Compound 17

[0374]

[0375] White solid, melting point: 117-120 °C, yield 54%, 280.2 mg. R f (PE / EA = 20:1): 0.5. 1HNMR (400 MHz, CDC13) δ 7.45 (dd, J = 8.1, 5.1 Hz, 2H), 7.39 - 7.34 (m, 1H), 7.31 (d, J = 7.1 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.14 (dd, J = 7.8, 7.1 Hz, 2H), 6.92 (t, J = 7.4 Hz, 1H), 6.77 (t, J = 6.9 Hz, 2H), 5.95 (d, J = 7.6 Hz, 1H), 3.23 (dd, J = 12.4, 2.7 Hz, 1H), 2.98 (dd, J = 14.3, 5.9 Hz, 1H), 2.86 (dd, J = 12.4, 7.7 Hz, 1H), 2.76 (dd, J = 14.3, 11.5 Hz, 1H), 1.10 (dd, J = 14.3, 7.6 Hz, 6H), 0.99 - 0.92 (m, 4H), 0.87 (dd, J = 8.9, 3.3 Hz, 4H), 0.81 - 0.73 (m, 6H). 13 CNMR (101 MHz, CDC13) δ 148.00 (d, J = 2.1 Hz), 146.51 (s), 144.03 (d, J = 3.7 Hz), 143.14 (d, J = 1.3 Hz), 142.03 (d, J = 8.1 Hz), 138.77 (d, J = 5.7 Hz), 135.48 (d, J = 18.6 Hz), 132.62 (s), 132.43 (s), 131.34 (d, J = 2.6 Hz), 130.15 (d, J = 5.5 Hz), 129.95 (d, J = 1.0 Hz), 129.91 (s), 129.67 (d, J = 2.9 Hz), 128.92 (d, J = 5.4 Hz), 127.88 (d, J = 6.6 Hz), 32.00 (d, J = 30.0 Hz), 30.04 (d, J = 20.0 Hz), 7.13 (s), 7.07 (s), 7.02 (s), 7.00 (s), 6.68 (s), 6.67 (s), 6.54 (s), 6.35 (s). 31 P NMR (162 MHz, CDC13) δ -6.97 (s). HRMS (ESI) calcd. For C 28 H 35 O2PSi3[M + H] + : 519.1761. Found: 519.1755.

[0376] Compound 18

[0377]

[0378] White solid, melting point: 59-62 °C, yield 35% 202.6 mg. R f (PE / EA = 10:1): 0.5. 1 H NMR (400 MHz, CDC13) δ 7.48 (d, J = 7.6 Hz, 1 H), 7.36 (d, J = 7.9 Hz, 1 H), 7.22 (t, J = 7.2 Hz, 1 H), 7.14 (t, J = 7.3 Hz, 2 H), 7.06 (d, J = 7.9 Hz, 1 H), 6.87 (t, J = 7.2 Hz, 2 H), 6.60 (d, J = 7.9 Hz, 1 H), 3.88 (s, 3 H), 3.54 - 3.44 (m, 1 H), 3.25 (dd, J = 12.2, 5.5 Hz, 1 H), 3.11 (d, J = 12.3 Hz, 1 H), 2.92 (s, 3 H), 2.60 (dd, J = 14.2, 4.5 Hz, 1 H), 1.14 (t, J = 7.7 Hz, 6 H), 0.97 (dd, J = 12.8, 6.7 Hz, 8 H), 0.85 - 0.71 (m, 6 H). 13 C NMR (101 MHz, CDC13) δ 158.20 (d, J = 4.2 Hz), 157.59 (d, J = 1.2 Hz), 146.16 (d, J = 4.1 Hz), 145.02 (d, J = 1.1 Hz), 137.51 (d, J = 2.2 Hz), 136.46 (d, J = 18.5 Hz), 135.87 (s), 133.15 (d, J = 21.0 Hz), 131.34 (d, J = 2.9 Hz), 130.34 (s), 130.26 (d, J = 7.4 Hz), 128.62 (s), 128.43 (d, J = 5.3 Hz), 127.25 (d, J = 7.2 Hz), 113.54 (d, J = 2.0 Hz), 112.40 (s), 55.64 (s), 54.17 (s), 24.53 (d, J = 29.9 Hz), 24.09 (d, J = 19.4 Hz), 7.40 (s), 7.32 (s), 7.24 (s), 7.22 (s), 6.72 (s), 6.61 (s), 6.37 (s). 31 P NMR (162 MHz, CDC13) δ -14.63 (s). HRMS (ESI) calcd. For C 30 H 40 O4PSi3[M + H] + : 579.1972. Found: 579.1967.

[0379] Compound 19

[0380]

[0381] White solid, melting point: 126-128 °C, yield 24% 131.7 mg. R f (PE / EA = 20:1): 0.4. 1 HNMR (400 MHz, CDC13) δ 7.48 (d, J = 5.6 Hz, 2H), 7.38 (d, J = 7.9 Hz, 2H), 7.23 (t, J = 7.2 Hz, 1H), 7.14 (t, J = 7.4 Hz, 2H), 6.82 (t, J = 7.2 Hz, 2H), 6.61 (d, J = 7.9 Hz, 1H), 3.50 - 3.42 (m, 1H), 3.38 (d, J = 12.5 Hz, 1H), 2.91 (s, 3H), 2.84 (dd, J = 12.3, 8.3 Hz, 1H), 2.55 (dd, J = 14.3, 4.4 Hz, 1H), 1.14 (t, J = 7.9 Hz, 6H), 1.02 - 0.93 (m, 8H), 0.86 - 0.74 (m, 6H). 13 C NMR (101 MHz, CDC13) δ 156.63 (s), 146.78 (d, J = 1.2 Hz), 143.88 (s), 143.23 (d, J = 3.3 Hz), 141.29 (d, J = 8.5 Hz), 135.08 (s), 134.92 (d, J = 5.5 Hz), 132.11 (d, J = 21.0 Hz), 130.25 (s), 129.40 (s), 129.02 (d, J = 4.4 Hz), 128.50 (d, J = 2.2 Hz), 127.80 (s), 127.29 (d, J = 6.0 Hz), 126.26 (d, J = 7.3 Hz), 111.46 (s), 53.09 (s), 29.87 (d, J = 20.8 Hz), 22.96 (d, J = 31.7 Hz), 6.34 (s), 6.27 (s), 5.99 (s), 5.96 (s), 5.66 (s), 5.64 (s), 5.57 (s), 5.28 (s). 31 P NMR (162 MHz, CDC13) δ -7.19 (s). HRMS (ESI) calcd. For C 29 H 38 O3PSi3[M + H] + : 549.1866. Found: 549.1860.

[0382] Compound 20

[0383]

[0384] White solid, melting point: 80-82 °C, yield 16%, 87.8 mg. R f (PE / EA = 20:1): 0.4. 1 H NMR (400 MHz, CDC13) δ 7.39 (d, J = 7.4 Hz, 1H), 7.23 (d, J = 6.9 Hz, 1H), 7.15 (d, J = 7.0 Hz, 1H), 7.07 (t, J = 6.8 Hz, 2H), 6.96 (d, J = 7.8 Hz, 1H), 6.83 (t, J = 7.2 Hz, 1H), 6.75 (t, J = 6.3 Hz, 2H), 5.87 (d, J = 7.4 Hz, 1H), 3.77 (s, 3H), 3.22 (dd, J = 11.8, 4.8 Hz, 1H), 2.95 (dd, J = 14.1, 5.8 Hz, 1H), 2.87 (d, J = 11.8 Hz, 1H), 2.72 (t, J = 12.7 Hz, 1H), 1.09 - 0.97 (m, 6H), 0.94 - 0.85 (m, 4H), 0.81 - 0.60 (m, 10H). 13 C NMR (101 MHz, CDC13) δ 157.14 (d, J = 4.3 Hz), 145.28 (s), 144.93 (d, J = 4.5 Hz), 142.18 (s), 137.84 (d, J = 5.5 Hz), 136.62 (d, J = 2.3 Hz), 135.00 (d, J = 19.2 Hz), 131.40 (d, J = 19.1 Hz), 130.37 (d, J = 3.1 Hz), 128.97 (d, J = 7.5 Hz), 128.71 (d, J = 12.1 Hz), 127.66 (d, J = 9.6 Hz), 126.77 (d, J = 6.3 Hz), 112.50 (d, J = 1.9 Hz), 54.57 (s), 31.42 (d, J = 29.6 Hz), 22.16 (d, J = 19.8 Hz), 6.19 (s), 6.16 (s), 6.10 (s), 6.03 (s), 5.67 (s), 5.62 (s), 5.45 (s), 5.33 (s). 31 P NMR (162 MHz, CDC13) δ -14.06 (s). HRMS (ESI) calcd. For C 29 H 38 O3PSi3[M + H] + : 549.1866. Found: 549.1864.

[0385] Compound 21

[0386]

[0387] White solid, melting point: 93-95℃, yield 41%, 275.1 mg. f (PE / EA = 20:1): 0.4. 1 H NMR (400MHz, CDCl3) δ7.51 (dd, J=7.4, 1.6Hz, 1H), 7.43 (t, J=7.5Hz, 3H), 7.34 (d, J=7.4Hz,1H),7.29–7.16(m,4H),7.07–6.92(m,6H),6.33(t,J=7.2Hz,4H),3.45( t,J=13.9Hz,1H),3.33(d,J=12.9Hz,1H),2.93(dd,J=14.6,3.3Hz,1H),2.86(dd, J=12.8,7.0Hz,1H),1.15(t,J=7.7Hz,6H),1.05–0.98(m,7H),0.97–0.83(m,7H). 13 C NMR (101MHz, CDCl3) δ146.48 (d, J = 2.1Hz), 145.39 (s), 145.01 (d, J = 3.8Hz), 144.49 (d, J = 1.2Hz), 143.34 (s), 143.07 (d, J = 4.2H z),141.24(s),140.85(s),139.35(d,J=7.3Hz),137.75(d,J=5.1Hz),135.07(d,J=18.5Hz),134.10(s),133.88(s),133.44(d,J =1.9Hz),132.82(s),129.56(d,J=4.5Hz),129.28(s),129.11(s),128.75(s),128.02(s),127.71(d,J=7.9Hz),127.62(s),126. 95(s),126.37(s),29.92(d,J=22.1Hz),27.30(d,J=32.7Hz),7.26(s),7.22(s),7.15(s),7.05(s),6.78(s),6.73(s),6.60(s). 31 PNMR(162MHz,CDCl3)δ-6.62(s).HRMS(ESI)calcd.For C 40 H 44 O2PSi3[M+H] + :671.2387.Found:671.2383.

[0388] Example 10

[0389] Asymmetric C-N bond construction:

[0390] Scheme 1

[0391]

[0392] In a nitrogen purged glovebox, catalyst (compound 17, i.e. compound 17 prepared in Example 9, 0.01 mmol), 2,2,2-trifluoroacetamide (11.3 mg, 0.1 mmol) and diallyl carbonate (12.6 mg, 0.1 mmol) in dioxane (0.5 mL) were sequentially added to a dry 8 mL reaction vial. The reaction vial was sealed and removed from the glovebox, and stirred at room temperature for 16 h. The reaction mixture was then concentrated and the residue was purified by column chromatography.

[0393] Compound 49

[0394]

[0395] Colorless oil, yield 66% (15.8 mg), 87% ee. R f (PE:EA = 10:1): 0.4. 1 H NMR (400 MHz, CDC13) δ 6.84 (dd, J = 15.7, 5.4 Hz, 1H), 6.53 (s, 1H), 5.92 (d, J = 15.7 Hz, 1H), 4.75 (dd, J = 13.0, 6.5 Hz, 1H), 4.20 (q, J = 7.1 Hz, 2H), 1.40 (d, J = 6.9 Hz, 3H), 1.29 (t, J = 7.1 Hz, 3H). 13 CNMR (101 MHz, CDC13) δ 166.01 (s), 156.63 (q, J = 37.4 Hz), 145.99 (s), 121.82 (s), 115.72 (q, J = 287.8 Hz), 60.82 (s), 46.56 (s), 19.36 (s), 14.09 (s). 19 FNMR (376 MHz, CDC13) δ -75.78 (s).

[0396] Example 11: Asymmetric C-S bond construction

[0397] Scheme 2

[0398]

[0399] In a glove box under nitrogen, a dry vial was charged with a stir bar, catalyst precursor palladium acetate (1.7 mg, 0.0075 mmol), ligand (compound 17, 0.012 mmol), 1,3-diene (26.0 mg, 0.20 mmol), 4-methylbenzenesulfonylhydrazide (18.6 mg, 0.10 mmol), and diphenyl phosphate (12.5 mg, 0.05 mmol), ethylene glycol dimethyl ether (0.5 mL). After the reaction vial was sealed, it was removed from the glove box, stirred at room temperature for ten minutes, heated at 80 °C for 24 hours, and after cooling to room temperature, the solvent was removed in vacuo and the residue was purified by column chromatography to give the target product.

[0400] Compound 52

[0401]

[0402] White solid, yield 79% (22.6 mg), 89% ee. R f (PE:EA = 10:1): 0.4. 1 H NMR (400 MHz, CDC13) δ 7.72 (d, J = 8.2 Hz, 2H), 7.34 - 7.25 (m, 7H), 6.34 (d, J = 15.9 Hz, 1H), 6.08 (dd, J = 15.9, 8.2 Hz, 1H), 3.84 (p, J = 7.1 Hz, 1H), 2.42 (s, 3H), 1.53 (d, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 144.75 (s), 136.40 (s), 136.03 (s), 134.09 (s), 129.60 (s), 129.43 (s), 128.75 (s), 128.45 (s), 126.70 (s), 122.38 (s), 64.18 (s), 21.75 (s), 13.74 (s).

[0403] Example 12: Asymmetric C-C bond construction

[0404] Scheme Three

[0405]

[0406] A sealed tube was charged with di-tert-butylphosphine palladium (5.1 mg, 0.01 mmol), ligand (0.02 mmol) (compound 20, prepared in example 9) and ethylene glycol dimethyl ether (0.5 mL) under a nitrogen atmosphere. After stirring for 30 minutes, 2-naphthol (21.6 mg, 0.15 mmol) and 1,3-diene (13.0 mg, 0.1 mmol) were added. The reaction vessel was sealed and stirred at 60 °C for 48 hours, cooled to room temperature and the residue purified by column chromatography to give the desired product.

[0407] Compound 54

[0408]

[0409] Yellow oil, 76% yield (20.8 mg), 87% ee. R f (PE:EA = 20:1): 0.4. 1 H NMR (400 MHz, CDC13) δ 8.09 (d, J = 8.7 Hz, 1H), 7.85 (d, J = 8.1 Hz, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.57 - 7.51 (m, 1H), 7.45 (d, J = 7.6 Hz, 2H), 7.42 - 7.33 (m, 3H), 7.28 (dd, J = 9.5, 4.9 Hz, 1H), 7.12 (d, J = 8.8 Hz, 1H), 6.80 (s, 2H), 4.69 (q, J = 7.1 Hz, 1H), 1.68 (d, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 152.32 (s), 136.65 (s), 133.60 (s), 132.54 (s), 130.57 (s), 129.68 (s), 128.97 (s), 128.82 (s), 128.72 (s), 127.77 (s), 126.59 (s), 126.41 (s), 123.12 (s), 122.44 (s), 121.25 (s), 119.31 (s), 33.53 (s), 17.29 (s).

[0410] Example 13

[0411] Asymmetric [3+2] cycloaddition:

[0412] Scheme Four

[0413]

[0414] A sealed tube was charged with cyclopropenone (30.9 mg, 0.15 mmol), catalyst (compound 20, 0.01 mmol), ligand (0.02 mmol) and ethylene glycol dimethyl ether (0.5 mL) under a nitrogen atmosphere. After stirring for 30 minutes, 2-naphthol (21.6 mg, 0.15 mmol) and 1,3-diene (13.0 mg, 0.1 mmol) were added. The reaction vessel was sealed and stirred at 60 °C for 48 hours, cooled to room temperature and the residue purified by column chromatography to give the desired product. Molecular sieves (100 mg), dry toluene (0.5 mL) and N-methylbenzimidazole (13.2 mg, 0.1 mmol). The mixture was stirred at 40 °C for 24 h, quenched with water (0.5 mL). The aqueous phase was extracted with dichloromethane (10 mL x 3), and the combined organic layers were washed with brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was then purified by silica gel column chromatography to give the target product.

[0415] Compound 57

[0416]

[0417] Yellow solid, yield 80%, 27.0 mg, 91% ee. R f (PE / DCM = 1 : 1): 0.5. 1 H NMR (400 MHz, CDC13) δ 7.45 (d, J = 7.5 Hz, 1H), 7.42 - 7.35 (m, 5H), 7.34 - 7.26 (m, 5H), 7.02 (t, J = 7.7 Hz, 1H), 6.85 (t, J = 7.6 Hz, 1H), 6.54 (d, J = 7.7 Hz, 1H), 6.11 (s, 1H), 2.59 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 172.21 (s), 152.96 (s), 147.92 (s), 133.61 (s), 131.57 (s), 130.17 (s), 129.15 (s), 128.49 (s), 128.24 (s), 127.87 (s), 127.39 (s), 127.17 (s), 124.31 (s), 118.81 (s), 115.01 (s), 107.21 (s), 85.74 (s), 34.56 (s). HRMS (ESI) calcd. For C 23 H 19 N2O [M+H] + : 339.1497. Found: 339.1500.

[0418] Example 14

[0419] Asymmetric hydrogenation:

[0420] Scheme Five

[0421]

[0422] Into a sealed tube was added [Rh(cod)2]BF4(0.9 mg, 0.002 mmol), ligand (compound 22, 0.0044 mmol), substrate (21.9 mg, 0.1 mmol) and anhydrous dichloromethane (0.5 mL). After the mixture was stirred for 10 min, it was removed from the glove box, evacuated and purged with hydrogen 3 times. The mixture was stirred at room temperature under a hydrogen atmosphere for 16 h. The solution was concentrated in vacuo and the residue was purified by preparative thin layer chromatography to give the hydrogenated product.

[0423] Compound 59

[0424]

[0425] White solid, yield 99%, 21.9 mg, 97% ee. R f (PE:EA = 1 : 1): 0.4. 1 H NMR (400 MHz, CDC13) δ 7.27 (dt, J = 8.6, 6.9 Hz, 3H), 7.09 (d, J = 6.8 Hz, 2H), 5.98 (d, J = 5.9 Hz, 1H), 5.00 - 4.82 (m, 1H), 3.72 (s, 3H), 3.12 (qd, J = 13.9, 5.8 Hz, 2H), 1.98 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 172.10 (s), 169.59 (s), 135.82 (s), 129.25 (s), 128.60 (s), 127.16 (s), 53.11 (s), 52.34 (s), 37.86 (s), 23.16 (s).

[0426] Example 15

[0427] Asymmetric allyl substitution:

[0428] Scheme Six

[0429]

[0430] Into a sealed tube was added [Rh(cod)2]BF4(0.9 mg, 0.002 mmol), ligand (compound 22, 0.0044 mmol), substrate (21.9 mg, 0.1 mmol) and anhydrous dichloromethane (0.5 mL). After the mixture was stirred for 10 min, it was removed from the glove box, evacuated and purged with hydrogen 3 times. The mixture was stirred at room temperature under a hydrogen atmosphere for 16 h. The solution was concentrated in vacuo and the residue was purified by preparative thin layer chromatography to give the hydrogenated product.

[0431] Compound 62

[0432]

[0433] Colorless oil, 95% yield, 30.8 mg, 83% ee. f (PE:EA=20:1):0.4. 1 H NMR (400MHz, CDCl3) δ7.33–7.17(m,10H),6.48(d,J=15.8Hz,1H),6.33(dd,J=15.7,8.6 Hz,1H),4.27(dd,J=10.8,8.7Hz,1H),3.96(d,J=10.9Hz,1H),3.71(s,3H),3.52(s,3H). 13 C NMR(101MHz, CDCl3)δ168.34(s),167.92(s),140.29(s),136.94(s),131.96(s),129.23(s),128.86(s) ,128.61(s),127.99(s),127.71(s),127.31(s),126.51(s),57.77(s),52.77(s),52.59(s),49.33(s).

[0434] Example 16: Asymmetric Si–C bond breaking

[0435]

[0436] Under nitrogen protection at room temperature, palladium acetate (2.2 mg, 0.01 mmol, 5 mol%), ligand (compound 22, 0.015 mmol, 7.5 mol%), and anhydrous trimethylbenzene (1.0 mL) were added to a sealed tube. After stirring the mixture for 10 minutes, silane (0.2 mmol, 1.0 equiv.) and allene (0.4 mmol, 2.0 equiv.) were added. The mixture was stirred at 30 °C for 72 hours. The solution was concentrated under vacuum, and the remaining crude product was purified by reverse-phase preparative column chromatography (C18(ODS)) using acetonitrile as the eluent to obtain the target product.

[0437] Compound 65

[0438]

[0439] Colorless oil, yield 70% (22.6 mg), 80% ee. f (PE:DCM=1:1):0.5. 1H NMR (400 MHz, CDC13) δ 8.11 - 8.05 (m, 1H), 7.89 (dd, J = 12.5, 6.5 Hz, 2H), 7.72 (d, J = 6.6 Hz, 1H), 7.54 - 7.44 (m, 3H), 6.09 (s, 1H), 4.17 (qd, J = 7.0, 1.8 Hz, 2H), 3.34 (dd, J = 11.2, 8.3 Hz, 1H), 2.91 (t, J = 10.9 Hz, 1H), 1.98 - 1.75 (m, 3H), 1.67 (dt, J = 13.2, 9.4 Hz, 1H), 1.59 - 1.49 (m, 1H), 1.28 (t, J = 7.1 Hz, 3H), 1.02 (ddd, J = 14.3, 9.5, 4.6 Hz, 1H), 0.57 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 165.66 (s), 164.95 (s), 137.07 (s), 134.93 (s), 133.50 (s), 133.10 (s), 130.49 (s), 129.15 (s), 128.15 (s), 125.94 (s), 125.91 (s), 125.58 (s), 125.19 (s), 59.78 (s), 32.58 (s), 30.40 (s), 24.20 (s), 15.10 (s), 14.31 (s), -3.38 (s). HRMS (ESI) calcd. For C 20 H 24 O2SiNa[M + Na] + : 347.1447. Found: 347.1440.

[0440] The above examples are merely illustrative of the present application and are not intended to limit the scope of the application. Other variations and modifications can be made to the above-described embodiments consistent with the principles of the present application. Any such variations and modifications are intended to be part of this disclosure, and are within the scope of the application as defined by the appended claims.

Claims

1. A silaspirocyclic compound characterized by, The silicon heterospirocyclic compounds have structures as shown in Formulas I, II, III, IV, and V, as well as racemates and optical isomers corresponding to Formulas I, II, III, IV, and V: wherein R in Formula I, Formula II, and Formula III is 1 each independently of the others is C1-C8 alkyl, C1-C8 alkoxy, phenyl; R in formula I, formula II, formula III, formula IV, formula V 3 , R 4 are each independently hydrogen, C1-C8alkyl, C1-C8alkoxy, phenyl, phenyl substituted with 1-5 C1-C8alkyl groups, phenyl substituted with 1-5 C1-C8alkoxy groups, halogen, cyano, carboxyl, hydroxyl, 5-6 membered heteroaryl; the heteroatoms in the heteroaryl are selected from one or more of N, O, S, the number of heteroatoms is 1-4; In Equations I, II, III, IV, and V, n1 and n2 are either the same or different, and each is independently 0, 1, 2, or 3. In Formulas I, II, and III, * represents a chiral silicon center, which is independently either S-configuration silicon or R-configuration silicon; X and X' in formula I are the same or different and each independently -CH2R a1 , -OH, -OR a2 , -OTf, -P(R a3 )2, -PO(R a6 )2; The R a1 The R is hydrogen, C1-C8 alkyl, or halogen; a2 It is a C1-C8 alkyl group; the R a3 The molecule is hydrogen, C1-C8 alkyl, C1-C8 alkoxy, phenyl, phenyl substituted with 1-5 C1-C8 alkyl groups, or phenyl substituted with 1-5 C1-C8 alkoxy groups. The R a6 The molecule is hydrogen, C1-C8 alkyl, C1-C8 alkoxy, phenyl, phenyl substituted with 1-5 C1-C8 alkyl groups, or phenyl substituted with 1-5 C1-C8 alkoxy groups. Y in Formula II is -O- or -CH2; Z is -NR a4 R b4 、 -R a5 ; A is present or absent, and when present, A is an O or S atom; R a4 , R b4 each independently is hydrogen, C1-C8alkyl, C1-C8alkoxy, phenyl, phenyl substituted with 1-5 C1-C8alkyl, phenyl substituted with 1-5 C1-C8alkoxy; R1is hydrogen, C1-C8alkyl, C1-C8alkoxy, phenyl, phenyl substituted with 1-5 C1-C8alkyl, phenyl substituted with 1-5 C1-C8alkoxy. a5 R1is hydrogen, C1-C8alkyl, C1-C8alkoxy, phenyl, phenyl substituted with 1-5 C1-C8alkyl, phenyl substituted with 1-5 C1-C8alkoxy.

2. The silicon heterospirocyclic compound according to claim 1, characterized in that, R in formula I, formula II, formula III 1 X and Y are each independently hydrogen, C1-C6alkyl, C1-C6alkoxy, phenyl; R in formula I, formula II, formula III, formula IV, formula V 3 , R 4 are each independently hydrogen, C1-C6alkyl, C1-C6alkoxy, phenyl, phenyl substituted with 1-5 C1-C8alkyl, phenyl substituted with 1-5 C1-C8alkoxy, halogen, cyano, carboxyl, hydroxyl; the halogen is selected from at least one of fluorine, chlorine, bromine, iodine; X and X' in formula I are the same or different and each independently -CH2R a1 , -OH, -OR a2 , -OTf, -P(R a3 )2, -PO(R a6 )2; said R a1 is hydrogen, C1-C6alkyl, halogen, said halogen being at least one selected from the group consisting of fluorine, chlorine, bromine, iodine; said R a2 is C1-C6alkyl; said R a3 is hydrogen, C1-C6alkyl, C1-C6alkoxy, phenyl, phenyl substituted with 1-5 C1-C6alkyl, phenyl substituted with 1-5 C1-C6alkoxy; said R a6 is hydrogen, C1-C6alkyl, C1-C6alkoxy, phenyl, phenyl substituted with 1-5 C1-C6alkyl, phenyl substituted with 1-5 C1-C6alkoxy; Y in Formula II is -O- or -CH2; Z is -NR a4 R b4 、 -R a5 ; A is present or absent, and when present, A is an O or S atom; R a4 , R b4 each independently is hydrogen, C1-C6 alkyl, C1-C6 alkoxy, phenyl, phenyl substituted with 1-5 C1-C6 alkyl groups, phenyl substituted with 1-5 C1-C6 alkoxy groups; R a5 is hydrogen, C1-C6 alkyl, C1-C6 alkoxy, phenyl, phenyl substituted with 1-5 C1-C6 alkyl groups, phenyl substituted with 1-5 C1-C6 alkoxy groups.

3. The silaspirocyclic compound according to claim 1, characterized by The silane-heterocyclic compounds are selected from the following compounds:

4. A process for the preparation of a silaspirocyclic compound according to any one of claims 1 to 3, characterized in that, Includes the following steps: Step 1: (1-1) Under a protective atmosphere, a compound represented by Formula IV, 4-dimethylaminopyridine, imidazole, R 1 2HSiCl is reacted in a solvent to form a compound represented by Formula V; wherein the structural formula of formula IV is wherein R 3 , R 4 , n1, n2 correspond to the same as described in any one of claims 1-3 3 , R 4 , n1, n2 correspond to the same as described in any one of claims 1-3 R 1 2HSiCl in R 1 R of any one of claims 1-3 1 corresponding to the same; The structural formula of formula V is wherein R 1 , R 3 , R 4 , n1, n2 and R 1 , R 3 , R 4 , n1, n2 correspond to the same as described in any one of claims 1-3. (1-2) under a protective atmosphere, a compound represented by the formula V is used as a raw material, and reacted in the presence of a rhodium catalyst, a chiral ligand, and cyclopentene in a solvent to produce a compound represented by the formula I 1 and / or a compound represented by the formula I 2 ​ wherein the structural formula of formula I 1 is wherein R 1 , R 3 , R 4 , n1, n2 correspond to R 1 , R 3 , R 4 , n1, n2 of any one of claims 1-3; -OR 1 of formula I a2 is -OMe; Formula I 2 Formula I wherein R 1 , R 3 , R 4 , n1, n2 correspond to R 1 , R 3 , R 4 , n1, n2 of any one of claims 1-3; Formula I 2 -CH2R a1 is -CH3; Step Two (2-1) A compound shown as formula I 1 wherein formula I 1 -OR a2 is -OMe, tris-pentafluorophenylboron, HSiEt2Me as starting material, reaction in solvent, and then reaction with HCl to form a compound shown as formula I 3 ​ wherein the structural formula of formula I 3 wherein R 1 , R 3 , R 4 , n1, n2 correspond to R 1 , R 3 , R 4 , n1, n2 of any one of claims 1-3;​ or, (2-1') under a protective atmosphere, a compound of formula I 2 wherein formula I 2 -CH2R a1 is -CH3, N-halosuccinimide is reacted in the presence of azobisisobutyronitrile (AIBN) in a solvent to give a compound of formula I 2 wherein formula I 2 -CH2R a1 is -halomethyl; Step 3 (3-1) reacting a compound of formula II 3 with a compound of formula III 4 in a solvent to form a compound of formula I wherein the structural formula of formula I 4 wherein R 1 , R 3 , R 4 , n1, n2 correspond to the same as R 1 , R 3 , R 4 , n1, n2 of any one of claims 1-3.​ or (3-1') under a protective atmosphere, reacting a compound of formula I 3 , triethylamine, phosphorus oxychloride as raw materials, in a solvent to generate a compound of formula III; wherein the structural formula of formula III is wherein R 1 , R 3 , R 4 , n1, n2 and R 1 , R 3 , R 4 , n1, n2 correspond to the same; or (3-1") under a protective atmosphere, a compound of formula I 3 , triethylamine, R a4 R b4 NPC12 as a starting material, in a solvent, to form a compound of formula II 1 as shown in the scheme. wherein R a4 R b4 R a4 R b4 R a4 R b4 correspond; Formula II 1 Formula II wherein R 1 , R 3 , R 4 , R a4 , R b4 , n1, n2 correspond to R 1 , R 3 , R 4 , R a4 , R b4 , n1, n2 correspond to the same; or (3-1' ') under protective atmosphere, a compound of formula I 2 -CH2R a1 is -CH2Br, PR a5 H2, a base, in a solvent, to form a compound of formula II 2 ​ wherein PR a5 R in H2 a5 R in any one of claims 1-3 a5 correspond; Formula II 2 Formula II wherein R 1 , R 3 , R 4 , R a5 , n1, n2 correspond to R 1 , R 3 , R 4 , R a5 , n1, n2 of any one of claims 1-3. Step Four (4-1) reacting a starting material of formula I 4 in the presence of a palladium catalyst, a ligand, diisopropylethylamine, HP(R a3 )2 in a solvent under a protective atmosphere to form a compound of formula I 5 ; HP(R a3 R in )2 a3 R as described in any one of claims 1-3 a3 The corresponding ones are the same; Formula I 5 Formula I wherein R 1 , R 3 , R 4 , R a3 , n1, n2 correspond to R 1 , R 3 , R 4 , R a3 , n1, n2 of any one of claims 1-3. Step 5 (5-1) under a protective atmosphere, a compound represented by the formula I 3 wherein R 1 is ethyl, R 3 , R 4 are each methyl, triethylamine, is reacted in a solvent to form a compound represented by the formula 28; The compound represented by formula 28 is or, (5-1') under a protective atmosphere, reacting a compound of the formula I 3 in which R 1 is ethyl, R 3 , R 4 are each hydrogen, in the presence of a palladium catalyst, a ligand, diisopropylethylamine (DIPEA), HPOPh2, in a solvent, to form a compound of the formula 30; The compound represented by formula 30 is 5. The method for preparing the silicon heterospirocyclic compound according to claim 4, characterized in that: In steps (i) to (v), each solvent is independently selected from organic solvents, preferably from at least one of diethyl ether, toluene, tetrahydrofuran, 1,2-dichloroethane, n-hexane, cyclohexane, n-heptane, n-octane, dioxane, alcohols, and carbon tetrachloride; and / or, In step (1-1), the molar ratio of the formula IV, R 1 2HSiCl, imidazole, 4-dimethylaminopyridine is 1 : (2.4-4.5) : (2.4-4.5) : (0.02-0.6); and / or, Formula IV has a concentration of 0.1–1.0 mol / L in the solvent; and / or, The reaction temperature is from room temperature to 60°C; and / or, The reaction time is 12-48 hours; In steps (1-2), The rhodium catalyst is a monovalent rhodium dimer, preferably [Rh(cod)OH]2; and / or, The chiral ligand is selected from at least one of the following: wherein tBu represents a tert-butyl group; Cy represents a cyclohexyl group; Ad represents an adamantyl group; iPr represents an iso-propyl group; further preferred the chiral ligand is dissolved in dioxane and added as a solution; and / or, The molar ratio of compound V, rhodium catalyst, and chiral ligand is 1:(0.01–0.1):(0.01–0.1); and / or, The concentration of compound V in the solvent is 0.1–0.5 mol / L; and / or, The molar volume ratio of compound V to cyclopentene is 1 mmol: 50-1000 μL; and / or, The reaction temperature is between 60°C and 130°C; and / or, The reaction time is 12-50 hours; and / or, In step (2-1), Formula I 1 , HSiEt2Me, tri-pentafluorophenylboron, HC1 in a molar ratio of 1 : (2.4-3.6) : (0.02-0.1) : (2.4-3.6); and / or, Formula I 1 a concentration of 0.1 to 0.5 mol / L in a solvent; and / or, The reaction temperature in the solvent is from room temperature to 80°C; and / or, The reaction time in the solvent is 12-48 hours; and / or, The reaction with HCl can be carried out at temperatures ranging from room temperature to 80°C; and / or, The reaction time with HCl is 12-48 hours; and / or, In step (2-1'), The N-halosuccinimide is N-bromosuccinimide; and / or, said formula I 2 the molar ratio of the azo initiator, the free radical initiator and the N-halosuccinimide is 1 : (1.6-3.2) : (0.08-0.15); said formula I 2 at a concentration of 1-3 mol / L in a solvent; and / or, The reaction temperature is room temperature; and / or, The reaction time is 12-48 hours.

6. The method for preparing the silicon heterospirocyclic compound according to claim 4, characterized in that: In step (3-1), said formula I 3 a molar ratio of the pyridine, Tf20 is 1 : (2.4-3.6) : (2.0-3.0); and / or, said formula I 3 a concentration of 0.1 to 2.0 mol / L in a solvent; and / or, The reaction temperature is from room temperature to 130°C; and / or, The reaction time is 12-48 hours; and / or, In step (3-1'), said formula I 3 a molar ratio of triethylamine, phosphorus oxychloride is 1 : (4.8-7.2) : (3.2-4.8); and / or, said formula I 3 a concentration of 0.1 to 2.0 mol / L in a solvent; and / or, The reaction temperature is room temperature; and / or, The reaction time is 12-48 hours; and / or, In step (3-1”), said formula I 3 , triethylamine, R a4 R b4 the molar ratio of NPCl2 is 1 : (2.4-3.6) : (0.6-2.4); and / or, said formula I 3 a concentration of 0.1 to 2.0 mol / L in a solvent; and / or, The reaction temperature is from room temperature to 60°C; and / or, The reaction time is 12-48 hours; and / or, In step (3-1”'), The base is at least one of an organic base and an inorganic base; preferably, the base is at least one of one or more of pyridine, triethylamine, tributylamine, N-methylmorpholine and diazabicyclo, potassium acetate, sodium acetate, potassium fluoride, sodium fluoride, cesium fluoride, potassium tert-butoxide, sodium tert-butoxide, n-butyllithium, potassium carbonate, sodium carbonate, cesium carbonate, cesium fluoride, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, sodium hexamethyldisilazide, potassium hexamethyldisilazide, lithium hexamethyldisilazide; said formula II 2 , PR a5 H2, the molar ratio of the base is 1 : (0.8-1.5) : (1.6-3.2); and / or, said formula II 2 a concentration of 0.1-2.0 mol / L in a solvent; and / or, The reaction temperature is room temperature; and / or, The reaction time is 12-48 hours.

7. The method of claim 4, wherein: step (4-1), The palladium catalyst is at least one of palladium acetate, palladium triflate, tris(dibenzylideneacetone)dipalladium, palladium trimethylacetate or palladium acetylacetonate; The reaction temperature is room temperature to 130°C; and / or, The ligand is selected from at least one of said formula I 4 diisopropylethylamine, HP(R a3 )2, a molar ratio of the palladium catalyst, the ligand is 1 :(2.4-4):(2.4-3.6):(0.05-0.2):(0.1-0.4); and / or, said formula I 4 a concentration of 0.1 to 2.0 mol / L in a solvent; and / or, The reaction time is 12-48 hours; Step (5-1), The reaction temperature is room temperature to 60°C; and / or, Formula I 3 triethylamine, in a molar ratio of 1 : (2.4-3.6) : (0.6-2.4); and / or, said formula I 3 a concentration of 0.1 to 2.0 mol / L in a solvent; and / or, The reaction time is 12-48 hours; Step (5-1), The reaction temperature is 60-150°C; and / or, Formula I 3 a molar ratio of palladium catalyst, ligand, diisopropylethylamine, HPOPh2 is 1 : (0.05-0.2) : (0.1-0.4) : (2.4-4) : (2.4-3.6); and / or, said formula I 3 a concentration of 0.1-2.0 mol / L in a solvent; and / or, The reaction time is 12-48 hours.

8. Use of the silaspirocyclic compound of any one of claims 1-3 as a catalyst or ligand in an asymmetric catalytic reaction.

9. The use of claim 8, wherein: The asymmetric catalytic reaction 1 is: formula 33, formula 34 reacts in a solvent under the action of a catalyst to obtain a compound represented by formula 35; The structure of formula 34 is CF3CONH2; wherein the structure of formula 33 is Preferably, The structure of Formula 35 is The catalyst is at least one of the compounds represented by compounds 17-28 in claim 3; and / or, The molar ratio of formula 33, formula 34, catalyst is 1:(1-1.5):(0.05-0.5); and / or, The concentration of formula 33 in the solvent is 0.1-0.5 mol / L; and / or, The reaction temperature is room temperature to 60°C; and / or, The reaction time is 12-48 hours; Alternatively, The asymmetric catalytic reaction 4 is: formula 41, formula 42 reacts in a solvent under the action of a catalyst to obtain a compound represented by formula 43; Preferably, wherein, formula 41 is Formula 42 is Formula 43 is The catalyst is at least one of the compounds represented by compounds 17-28 in claim 3; and / or, The molar ratio of formula 41, formula 42, catalyst is 1:(1.2-2.0):(0.05-0.15); and / or, The concentration of the molecular sieve in the solvent is 50-200 mg / mL; and / or, The concentration of formula 41 in the solvent is 0.1-0.5 mol / L; and / or, The molecular sieve is selected from molecular sieve, molecular sieve, molecular sieve, and / or, The reaction temperature is room temperature to 80°C; and / or, The reaction time is 12-48 hours.

10. The use of claim 8, wherein: The asymmetric catalytic reaction 2 is: formula 36, formula 37, ligand, additive reacts in a solvent under the action of a palladium catalyst to obtain a compound represented by formula 38; ​ wherein, formula 36 is Formula 37 is Formula 38 is The palladium catalyst is selected from at least one of palladium acetate, palladium triflate, tris(dibenzylideneacetone)dipalladium, palladium trimethylacetate, palladium acetylacetonate; and / or, The ligand is selected from at least one of compounds 17-28 shown in claim 3; and / or, The additive is selected from at least one of phenyl phosphite, p-toluenesulfonic acid, acetic acid, potassium carbonate, triethylamine, diphenyl phosphate; and / or, The molar ratio of the formula 36, formula 37, palladium catalyst, ligand, additive is (0.8-3.0):1:(0.05-0.15):(0.1-0.24):(0.2-1.0); and / or, The concentration of the formula 36 in the solvent is 0.1-0.5 mol / L; and / or, The reaction temperature is 40-120°C; and / or, The reaction time is 12-48 hours; Alternatively, The asymmetric catalytic reaction 3 is that the formula 36, formula 39, ligand react in the solvent under the action of the palladium catalyst to obtain the compound shown in the formula 40; wherein, formula 36 is Formula 39 is Formula 40 is The palladium catalyst is selected from at least one of bis-tri-tert-butylphosphine palladium, tetra-triphenylphosphine palladium, palladium acetate, palladium triflate, tris(dibenzylideneacetone)dipalladium, palladium trimethylacetate, palladium acetylacetonate; and / or, The ligand is selected from at least one of compounds 17-28 shown in claim 3; and / or, The molar ratio of the formula 36, formula 39, palladium catalyst, ligand is 1:(1.5-3.0):(0.05-0.15):(0.1-0.24); and / or, The concentration of the formula 36 in the solvent is 0.1-0.5 mol / L; and / or, The reaction temperature is 40-120°C; and / or, The reaction time is 12-48 hours; Alternatively, The asymmetric catalytic reaction 5 is: the reaction of formula 44, a ligand, under the action of a rhodium catalyst, in a solvent, to obtain a compound shown in formula 45; wherein, formula 44 is Formula 45 is The rhodium catalyst is selected from at least one of dimeric hydroxy(1,5-cyclooctadiene)rhodium, bis(1,5-cyclooctadiene)-trifluoromethanesulfonate rhodium, bis(1,5-cyclooctadiene)-tetrafluoroborate rhodium; and / or, The ligand is selected from at least one of compounds 17-28 shown in claim 3; and / or, The molar ratio of the formula 44, rhodium catalyst, ligand is 1:(0.01-0.1):(0.02-0.2); and / or, The concentration of the formula 44 in the solvent is 0.1-0.5 mol / L; and / or, The reaction temperature is room temperature to 80°C; and / or, The reaction time is 12-48 hours; Alternatively, The asymmetric catalytic reaction 6 is that the formula 46, formula 47, ligand, base react in the solvent under the action of the palladium catalyst to obtain the compound shown in the formula 48; wherein, formula 46 is Formula 47 is Formula 48 is Preferably, The palladium catalyst is selected from at least one of allyl palladium chloride dimer, palladium acetate, palladium triflate, tris(dibenzylideneacetone)dipalladium, palladium trimethylacetate, palladium acetylacetonate; and / or, The ligand is selected from at least one of compounds 17-28 shown in claim 3; and / or, the base is at least one selected from the group consisting of N, O-bistrimethylsilylacetamide, triethylamine, diisopropylethylamine, potassium carbonate, potassium phosphate; and / or, the molar ratio of the formula 46, the formula 47, the palladium catalyst, the ligand, the base is 1: (1.2-1.5): (0.02-0.1): (0.05-0.2): (1.0-3.0); and / or, the concentration of the formula 46 in the solvent is 0.1-0.5 mol / L; and / or, the reaction temperature is -40-60℃; and / or, the reaction time is 12-48 hours; or, the asymmetric catalytic reaction 7 is that the formula 49, the formula 50, the ligand react under the action of the palladium catalyst in the solvent to obtain the compound shown in the formula 51; wherein Formula 49 is Formula 50 is Formula 51 is Nap represents a naphthyl group; preferably, the palladium catalyst is at least one selected from the group consisting of palladium acetate, palladium triflate, tris(dibenzylideneacetone)dipalladium, palladium trimethylacetate, palladium acetylacetone; and / or, the ligand is at least one selected from the group consisting of the compounds shown in the formulae 17-28 in claim 3; and / or, the molar ratio of the formula 49, the formula 50, the palladium catalyst, the ligand is 1: (1.5-3.0): (0.02-0.1): (0.05-0.2); and / or, the concentration of the formula 49 in the solvent is 0.1-0.5 mol / L; and / or, the reaction temperature is room temperature to 60℃; and / or, the reaction time is 12-72 hours.

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