The Silicon–Hydrogen Exchange Reaction: A Catalytic σ-Bond Metathesis Approach to the Enantioselective Synthesis of Enol Silanes

The use of chiral enol silanes in fundamental transformations such as Mukaiyama aldol, Michael, and Mannich reactions as well as Saegusa–Ito dehydrogenations has enabled the chemical synthesis of enantiopure natural products and valuable pharmaceuticals. However, accessing these intermediates in high enantiopurity has generally required the use of either stoichiometric chiral precursors or stoichiometric chiral reagents. We now describe a catalytic approach in which strongly acidic and confined imidodiphosphorimidates (IDPi) catalyze highly enantioselective interconversions of ketones and enol silanes. These “silicon–hydrogen exchange reactions” enable access to enantiopure enol silanes via tautomerizing σ-bond metatheses, either in a deprotosilylative desymmetrization of ketones with allyl silanes as the silicon source or in a protodesilylative kinetic resolution of racemic enol silanes with a carboxylic acid as the silyl acceptor.

After complete consumption of the starting material (~90 min), the orange mixture was acidified (2 M H2SO4) extracted with ether, dried over anhydrous Na2SO4 and the crude brown solid (3.6 g, 12.5 mmol, 63% crude yield) was used without purification for the next step.
Step 2. According to a known procedure 14 : N-chlorosuccinimide (5.6 g, 42 mmol, 4 equiv.) was added to a mixture of HCl:MeCN (2 M, 1:5, 12 mL) and then the mixture was cooled to 0 °C. The 1,3,4,5,6,7,8-heptafluoronaphthalene-2-thiol (3 g, 10.5 mmol, 1 equiv.) was added portion wise using a spatula into the mixture. Temperature of the reaction mixture was kept below 15 °C for 30 min. The cooling bath was removed and it was allowed to warm up to room temperature. Once the reaction mixture became orange homogeneous solution (~15 min, consumption of starting materials was confirmed by TLC: 20% EtOAc in hexanes), it was diluted with ethyl acetate (100 mL). The organic layer was washed with copious amount of aq. NaCl (5 x 50 mL) to remove excess NCS and dried over anhydrous Na2SO4, concentrated in vacuo to get the desired product as brown solid (3.2 g, 9.1 mmol, 86% crude yield). The crude product was used for the next step without purification.

S7
Step 3. According to a known procedure 15 : 1,3,4,5,6,7,8-Heptafluoronaphthalene-2-sulfonyl chloride (3.2 g, 9.1 mmol, 1 equiv.) was dissolved in newly-distilled THF and then the mixture was cooled to -10 °C. 0.5 M ammonia solution in dioxane (~30 mL, 14.6 mmol, 1.6 equiv.) was added dropwise to get a dark brown solution. The cooling bath was removed and it was allowed to attain room temperature. The reaction mixture was stirred for another 3 h (consumption of starting materials was confirmed by TLC: 30% EtOAc in hexanes). The volatiles were removed via vacuum and the crude product was directly subjected to silica gel flash column chromatography using 25% EtOAc in hexanes as eluents. The pure desired product was isolated as yellow solid (1.8 g, 5.4 mmol, 59% yield). Yield over three steps were 32% from octafluoronaphthalene.
Step 4. In a flame dried pre-weighed Schlenk flask (25 mL) under Ar equipped with a magnetic stirring bar, solid PCl5 (0.951 g, 4.57 mmol, 1.3 equiv.) was added and weighed directly inside the Schlenk flask. 1,3,4,5,6,7,8-heptafluoronaphthalene-2-sulfonamide (1.17 g, 3.15 mmol, 1.0 equiv.) were placed. 0.5 mL of dry toluene was added and the mixture was heated to 110 °C under Ar. The yellow solution was stirred for 30 min and then volatiles were carefully removed at 300 mbar until bubbling disappeared. The liquid mixture was then heated to 130 °C for 1 h at 10 mbar to remove the excess amount of PCl5 by sublimation. PCl5 that condensed in the top part of the Schlenk flask was removed by heating with hot gun (100 °C for 15 min). The mixture was then cooled to room temperature and the remaining traces of HCl were removed in vacuo to afford the desired product Rf-6 as a light brown solid (1.61 g, 98%).
Note: 13 C NMR spectrum could not be obtained due to very low signal intensity. General procedure for the preparation of compounds 4a-4f. To a mixture of the 3,3'-disubstituted BINOL (2.1 equiv.) and various (substituted sulfonyl)phosphorimidoyl trichlorides (2.1 equiv.) in toluene (0.1 M) was added diisopropylethylamine (16 equiv.) at room temperature under an argon atmosphere. After stirring for 10-30 min, HMDS (1.0 equiv.) was added. After an additional 10 min at room temperature, the reaction mixture was sealed and heated to 120 °C for 2-3 d. The mixture was diluted with ethyl acetate and insoluble solid was filtered off through a short pad of Celite. Then the solvent was removed under reduced pressure and the crude residue was purified by column chromatography on silica gel using ethyl acetate/hexanes mixtures. After evaporation of solvent, the collected solid was stirred in a biphasic solution (DCM/6 N HCl) for 15 min and extracted with DCM. Azeotropic removal of water using toluene gave catalysts 4a-4f as white solids in their acidic form (yield: 50-65%).

Development of suitable reaction conditions and catalyst identification.
General procedure for the optimization of the catalytic silylation of ketones with allylsilanes.
After the ketone was fully consumed, as monitored by TLC, the reaction mixture was treated with triethylamine. Volatiles were removed in vacuo and the yield of 3a was determined by NMR analysis with nitrobenzene as internal standard. The enantiomeric ratio was determined by HPLC after purification by prep. TLC. Table S1. Initial screening with commonly used Brønsted acid catalysts: S11 Table S2. Screening of different IDPi catalysts: a Reactions were conducted with ketone 1a (0.025 mmol), allyl silane 2a (2.0 equiv.), and catalyst 4a-4f (1.0 mol%) in toluene at rt. b All yields were determined by crude 1 H NMR analysis with nitrobenzene as internal standard. c The enantiomeric ratio (e.r.) was determined by HPLC analysis. S12 a Reactions were conducted with ketone 1a (0.025 mmol), silane source 2a (2.0 equiv.), and catalyst 4a (1.0 mol%) at 25 °C. b All yields were determined by crude 1 H NMR analysis with nitrobenzene as internal standard. c The enantiomeric ratio (e.r.) was determined by HPLC analysis. S13 a Reactions were conducted with ketone 1a (0.025 mmol), 2a (2.0 equiv.), and catalyst 4c (1.0 mol%) in combined solvent (toluene/dioxane = 2:1) at 25 °C. b All yields were determined from crude NMR analysis with newly distilled nitrobenzene as internal standard. c The enantiomeric ratio (e.r.) was determined by HPLC analysis. d with sole dioxane as solvent.

The preparation and characterization of cyclic ketones
The 4-aryl substituted ketones were prepared according to the methods reported in the literature with minor modifications. 1c, 1e, 1j, 1k and 1n are known compounds and the spectra are in accordance with the reported structures. 1 Step 1: To a flame dried two-neck round-bottom flask with a condenser, magnesium turnings (0.60 g, 49.6 mmol) and a small portion of iodine as initiator was added. After the first 5 mL of R 1 -Br (23.5 mmol) solution in THF (40 mL) was added in one portion, the suspension was heated till the color changed from dark brown to clear (which indicates the formation of the Grignard reagent). Then the remaining solution of R 1 -Br was slowly added via a funnel and the reaction mixture was heated to reflux for 2 h. After the flask was cooled to room temperature, a solution of 1,4-cyclohexanedione monoethylene ketal (3.50 g, 22.4 mmol) in THF (40 mL) was added dropwise, and the reaction mixture was heated to reflux for 12 h. The mixture was treated with a saturated aqueous NH4Cl solution (50 mL), and the resultant mixture was extracted with ethyl acetate (3 x 50 mL). The organic layers were dried (MgSO4), filtered, and concentrated under reduced pressure to give the crude product. This material was purified directly by column chromatography on silica gel to afford the desired alcohols.
Step 2: To a solution of alcohols (15.0 mmol) in pyridine (85 mL) at 0 °C was added DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) (4.5 mL, 30.0 mmol) followed by POCl3 (2.7 mL, 29.5 mmol) dropwise. The resultant orange solution was stirred at room temperature for 1 h and at 80 °C for 90 min during which time the orange color darkened. The solution was cooled to 0 °C and carefully treated with ethyl acetate (100 mL) and H2O (100 mL). The organic phase was washed with H2O and brine, dried (MgSO4), and evaporated in vacuo to give the alkenes as orange-brown oil. The crude products were purified by column chromatography on silica gel to afford the desired pure alkenes.
Step 3: The pure alkenes from the above reactions were dissolved in 1:1 MeOH/ethyl acetate (25 mL) and Palladium (10% on carbon, 0.3 g) was added. The mixture was stirred for 5 h under hydrogen (4 MPa) and filtered through a pad of Celite ® . The solvent was S14 removed under reduced pressure to afford the crude ketals. The crude products were purified directly by column chromatography on silica gel to afford the desired pure ketals.
Step 4: The ketals were dissolved in a mixture of THF, water, and concentrated sulfuric acid (4:2:1, 70 mL). The mixture was stirred for 90 min, diluted with brine (50 mL), and extracted with ethyl acetate (3 x 50 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated. Column chromatography of the residue over silica gel gave the desired pure 4-substituted cyclohexanones. 1 1

4,4'-disubstituted cyclohexanone 1s was prepared according to a literature report with minor revisions 2
Step 1: To a 25 mL round-bottom flask with a condenser, 2-phenylpropanal (20 mmol, 2 g, 1.0 equiv.), but-3-en-2-one (30 mmol, 2.4 mL, 1.5 equiv.), p-toluenesulfonic acid monohydrate (4 mmol, 0.76 g, 0.2 equiv.), and toluene (6 mL) were added subsequently. Then the reaction mixture was stirred in an oil bath at 80 °C for 12 h till completion (as monitored by TLC). After the reaction mixture cooled down to room temperature, the solvent was removed in vacuo. Then 1M aqueous sodium hydroxide solution was added to the residue and the mixture extracted with ethyl acetate (3 x 10 mL). The combined organic phase was washed by brine, dried over NaSO4, and filtered. The crude product was purified by column chromatography on silica gel to afford the desired pure unsaturated ketone.
Step 2: To a solution of the aforementioned unsaturated ketone (9.1 mmol, 1.7 g) in ethyl acetate (17 mL) at rt was added Palladium (10% on carbon, 0.3 g). The resultant suspension was stirred for 5 h under hydrogen (8 bar) and filtered through a pad of Celite ® . The crude products were purified by column chromatography on silica gel to afford the desired pure ketone 1s. Biscyclopentanone 1u and 1w were prepared according to reported methods 3 Step 1. To a solution of cis-bicyclo [3.3.0]octan-3,7-dione (25 g, 181.06 mmol) in toluene (300 mL) was added 2,2-dimethyl-1,propanediol (18.9 g, 181.06 mmol) and p-toluenesulfonic acid monohydrate (5%). The resultant solution was stirred at room temperature overnight. After completion of the reaction (as monitored by TLC), the mixture was evaporated in vacuo and the crude residue was subjected to column chromatography to give the mono-protected ketone 1w.

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Cyclobutanone 1v was prepared according to a literature method with minor modification 4 Step 1. To a stirred suspension of freshly-prepared Zn-Cu couple (1.60 g, 25 mmol) and styrene (10 mmol) in dry Et2O (20 mL) was added a solution of trichloroacetic chloride (2.2 mL, 20 mmol) and phosphorus oxychloride (1.9 mL, 20 mmol) in Et2O (10 mL) dropwise through an addition funnel, after 2 h at reflux. The mixture was cooled to room temperature and then filtered through a pad of Celite.
The residue was extracted with Et2O (3 × 15 mL). The organic phase was concentrated under reduced pressure to give a crude product, which was carefully purified through column chromatography with silica gel.
Step 2. The solution of the obtained product from the above-mentioned step in acetic acid (10 mL) was added dropwise to a vigorously stirred suspension of zinc dust (2.6 g, 40 mmol) in acetic acid (8 mL) at 0 °C. After the addition, the reaction mixture was heated to 70 °C for 2 h. The mixture was allowed to cool to room temperature and then evacuated to remove most of the acetic acid. The residue was dissolved in Et2O (20 mL) and then poured into a separation funnel containing water (20 mL) and Et2O (20 mL). The organic layer was washed with water (3 × 10 mL), saturated sodium bicarbonate solution (2 × 10 mL), brine (50 mL) and dried over MgSO4. The solution was then filtered and concentrated, followed by purification by flash chromatography to afford the desired pure cyclobutanone 1v as a light yellow liquid. (Notes: the mono-chlorine substituted 3-ph cyclobutanone byproduct from the first step, which is inseparable from the desired product, can be further reduced with fine Zn powder, thus furnishing the desired product that can be used without purification)

3-phenyl cyclopentanone 1ac was prepared according to a literature method 5
To a stirred solution of [Rh(cod)Cl]2 (1 mol%) and PhB(OH)2 (1.37 g, 11.3 mmol) in degassed aqueous 1,4-dioxane was added a solution of 2-cyclopentene-1-one (0.63 mL, 7.5 mmol) in aqueous 1,4-dioxane and degassed Et3N (1.0 equiv.). The resulting solution was stirred at 50 °C for 6 h, then cooled to rt and concentrated under reduced pressure. The crude product was purified via column chromatography and the desired brown oil 1ac was obtained.

Substrate scope for the deprotosilylation of ketones 1 with allylsilane reagents 2a or 2b
General procedure for the catalytic desymmetrization of ketones with allylsilanes.
Allyl silane 2a or 2b (80 μL, 0.4 mmol, 2.0 equiv.) was placed in a flame-dried Schlenk flask, equipped with a teflon-coated magnetic stirring bar. IDPi 4a-4f (0.01 equiv.) and a solvent mixture of toluene with 1,4-dioxane (2:1 v/v 0.08 M, 2.4 mL) were added at 25 °C and stirred for 30 min. The resultant mixture was cooled to 20 °C for 10 min, and ketones 1a-1w (0.2 mmol, 1.0 equiv.) were slowly added. Then the reaction was stirred for 1-5 d at 20 °C. After the ketone was fully consumed as monitored by TLC, the reaction was treated with one drop of triethylamine. All volatiles were removed in vacuo and the crude residue was purified by column chromatography with silica gel to afford the desired enol silanes 3a-3w.

S21
The reaction was performed according to the general procedure and catalyzed by IDPi 4c. The titled product was purified by column chromatography with hexanes as eluent to afford 3e as a colorless oil (60.7 mg, 99% yield). 1  [ ] = 26.7 (c 0.42, CH3CN).

S24
The titled product was purified by column chromatography with hexanes as eluent to afford 3m as a colorless oil (67.0 mg, 99% yield). 1

Gram scale reaction and derivatizations of the enol silane 3a
i. Gram scale catalytic deprotosilylative desymmetrization of ketone 1a with allylsilane 2a.

S28
To a solution of compound 3a (57.7 mg, 0.2 mmol) in THF (0.1 M), N-Bromosuccinimide was added at 0 °C. The reaction mixture was stirred for 1.5 h at this temperature. After the reaction was completed (monitored by TLC), the reaction mixture was quenched with water (1 mL) and extracted with ethyl acetate (3 × 5 mL). The organic layers were combined, dried over anhydrous Na2SO4 and filtered through celite. The volatile components were removed under reduced pressure, and purified by column chromatography (hexanes) affording the brominated enol silane 5 as a colorless oil (68.3 mg, 93% yield). 1
The reaction mixture was stirred for 1 h at this temperature. After the reaction was completed (monitored by TLC), the reaction mixture quenched with water (1 mL) and extracted with ethyl acetate (3 × 5 mL). The organic layers were combined, dried over Na2SO4 and filtered through celite. The volatile components were removed under reduced pressure, and purified by column chromatography (ethyl acetate/hexanes 1:9) affording the fluorinated cyclic ketone 6 as a colorless oil (31.1 mg, 81% yield).

S29
According to a known procedure with minor modification 19 To a solution of compound 3a (57.7 mg, 0.2 mmol) in CH3CN (0.1 M), Pd(OAc)2 (49.4 mg, 0.22 mmol, 1.1 equiv.) was slowly added at 0 °C. The reaction mixture was stirred for 12 h at this temperature. After the reaction was completed (monitored by TLC), the reaction mixture was quenched with water (1 mL) and extracted with ethyl acetate (3 × 5 mL). The organic layers were combined, dried over Na2SO4 and filtered through celite. The volatile components were removed under reduced pressure, and purified by column chromatography (ethyl acetate/hexanes 1:9) affording the aldehyde 7 as a white solid (29.2 mg, 85% yield). 1  The configuration of the enolsilane product 3a could be deduced by analogy to be R.

S30
According to a known procedure with minor modification 22 To a solution of compound 3a (57.7 mg, 0.2 mmol) in DCM (0.1 M), ZnCl2 (1.0 equiv.) and BnBr (3 equiv.) was added at rt. The reaction mixture was stirred for 4 h at this temperature. After the reaction completed (monitored by TLC), the reaction mixture quenched with water (1 mL) and extracted with ethyl acetate (3 × 5 mL). The organic layers were combined and dried over Na2SO4, then filtered through celite. The volatile components were removed under vacuo and purified by column chromatography (ethyl acetate/hexanes 1:10) affording the ketone 9 as a white solid (29.1 mg, 55% yield).

Recycling of catalyst 4c recovered from the gram-scale reaction:
Allyl silane 2a (80 μL, 0.4 mmol, 2.0 equiv.) was placed in a flame-dried Schlenk flask, equipped with a Teflon-coated magnetic stirring bar. Recovered IDPi 4c (0.01 equiv.) and solvent mixture toluene with 1,4-dioxane (2:1 v/v 0.08 M, 2.4 mL) were added at 25 °C and stirred for 30 min. The resultant mixture was cooled to 20 °C for 10 min, and ketones 1a (0.2 mmol, 1.0 equiv.) was slowly added. After stirring at 20 °C for 2 d, till the ketone was fully consumed monitored by TLC, the reaction was quenched with one drop of triethylamine added via pipet. Organic volatiles were evaporated in vacuo and the crude residue was purified by column chromatography with silica gel to afford the desired enol silanes 3a (99%, 97:3 e.r.).

S31
Triethyl(2-methylallyl)silane 2b (79 μL, 0.4 mmol, 2.0 equiv.) was placed in a flame-dried Schlenk flask, equipped with a teflon-coated magnetic stirring bar. IDPi 4f (0.01 equiv.) in solvent mixture toluene (0.08 M, 2.4 mL) was added at 25 °C and stirred for 10 min. The reaction mixture was cooled to 20 °C for 10 min, and ketone 1w (0.2 mmol, 1.0 equiv.) was slowly added. The resultant solution was stirred at 20 °C. After the ketone was fully consumed monitored by TLC, the reaction was quenched by one drop of trimethylamine through pipet. Organic volatiles were evaporated in vacuo and the crude residue was purified by column chromatography with silica gel to afford the desired enol silane 3w as light yellow oil (66.4 mg, 98%, 97:3 er).  And the absolute configuration of the titled product was confirmed to be 3aR, 6aS according to the reported data.lit 23 [ ] = 2.1 (c 9.8, THF).

Development of a catalytic asymmetric protodesilylation of racemic enol silanes.
General procedure for the optimization of catalytic kinetic resolution of racemic silyl enol ethers with different proton sources.
IDPi 4c-d (0.01 equiv.) in toluene (0.1 M, 2 mL) was added at 25 °C, after 5 min, the reaction mixture was cooled to a certain temperature for 10 min, then proton source (0.5 equiv., with H2O: 0.25 equiv.) was added. After calibration with triphenylmethane as internal standard, the resultant solution was stirred at this temperature for proper time and monitored by GC or NMR analysis. Then the reaction was quenched by one drop of triethylamine through pipet. Organic volatiles were evaporated under vacuo and the crude residue was purified by prep. TLC, and the enantiomeric ratio (e.r.) was determined by HPLC. with triphenylmethane as internal standard, and NMR yields were determined with triphenylmethane as internal standard). When the conversion of the racemic enol silane was around 50%, the reaction was quenched by one drop of triethylamine through pipet. Organic volatiles were evaporated under reduced pressure and the crude product was purified by column chromatography (starting with sole hexanes with eluent to obtain the recovered silyl enol ethers, then with ethyl acetate : hexanes = 1:20-1:10 as eluent to get the ketone byproducts) or prep. TLC, then the enantiomeric ratio was determined by HPLC analysis. ((1,2,3,6-tetrahydro-[1,1

oxy)silane 3aa
The titled product was purified by column chromatography (sole hexanes to ethyl acetate : hexanes = 1 : 20) to afford 3aa as a colorless oil. 1

Mechanistic study
Procedure of reactivity comparison between Tf2NH (Bistriflimide) and confined IDPi catalysts 4c: Figure S1. ESI-MS spectrum of the reaction mixture catalyzed by Tf2NH. 11-5 was isolatable and the structure was confirmed by NMR analysis.
Procedure: allyl(tert-butyl)dimethylsilane 2a (20 μL, 0.1 mmol, 2.0 equiv.) was placed in a flame-dried Schlenk flask, equipped with a teflon-coated magnetic stirring bar. IDPi 4c (0.01 equiv.) and toluene-d8/dioxane-d8 = 2:1 (0.08 M, 0.6 mL) were added at 25 °C and stirred for 5 min. The reaction mixture was cooled to 20 °C for 10 min, ketone 1a (8.7 mg, 0.05 mmol, 1.0 equiv.) was added afterwards, then the resultant solution was transferred to a 5mm NMR tube and reaction was performed at this temperature for 3 d. Conclusion: during the first 10 h of NMR monitoring of the reaction, no product formation was observed. Instead, only the conversion of TBSOH accompanied by the formation of TBSOTBS. Till all the TBSOH was consumed fully, the formation of the desired product starts to be observed. In sharp contrast, the reaction in toluene-d8 had a ~0.5 h dormant period, which was detected via NMR studies.

Determination of reaction order of IDPi catalyst 4c.
The catalyst order was determined by time normalization analysis reported by the Bures group. [24][25][26][27][28][29] When comparing conversion plots normalized to different catalyst orders (Figure S4), the curves were found to overlap nicely when a first order with respect to the catalyst S39 was used, implying no significant influence from off-cycle equilibria or synergistic effects. The model reaction was conducted with 0.6, 1.2 and 2.4 mol% of catalyst 4c under standard reaction conditions. Figure S4. Conversion plots obtained from NMR measurements with time scales normalized to different catalyst orders: a) zero-order reaction; b) half-order reaction; c) first-order reaction and d) second-order reaction.

Determination of reaction order of ketone 1a and allylsilane 2a
The order of the ketone 1a was also determined by variable time normalisation analysis (VTNA). Reaction plots normalized to different reaction order of ketone can be found in Figure S5. By comparing the outcome of different orders, the reactions were found to in accordance with the zeroth order in ketone 1a ( Figure S5).
Note: we have observed this zeroth order dependence of aldehyde in the cyanosilylation of aldehyde catalyzed by disulfonimide. 30 S40 Figure S5. Conversion plots obtained from NMR measurements with time scales normalized to the catalyst concentration and different orders of ketone 1a: a) zero-order reaction; b) half-order reaction; c) first-order reaction and d) second-order reaction.
The reaction order with respect to the silane source was also determined by VTNA. Concentration plots obtained from NMR normalized to different orders of silane 2a can be found in Figure S6. Figure S6. Product concentrations obtained from NMR measurements with time scales normalized to the catalyst concentration and different orders of ketone 1aa: a) zero-order reaction; b) half-order reaction; c) first-order reaction and d) second-order reaction.

S41
The best overlap was found, when a first order dependence in silane concentration was assumed ( Figure S6c).
Taking all the measurements into account, this data supports the hypothesis that the silylation of the catalyst is the overall rate determining step of the reaction.

Study of racemization process of unsymmetric ketones
During the substrate screening of the catalytic asymmetric protodesilylative kinetic resolution of racemic enol silanes with 2-biphenyl carboxylic acid, we found that under the reaction conditions the chiral ketone byproducts partially racemize. This may due to the tautomerization between ketone and enol, and also caused by the kinetic equilibrium among enol silane regiomers and the relevant ketone.

S42
In order to verify the tautomerization, reactions of both enantiomers of 2-phenylcyclohexanone with IDPi 4d were conducted, and the ee was checked by HPLC analysis.

Figure S7. Study of keto-enol tautomerization
With the data in hand, we confirmed one reason is tautomerization, which causes ketone racemization. However, under lower temperature, this tautomerization effect could be slower.
Since the rate of tautomerization is quite slow, there may be another reason. In order to verify our hypothesis, the kinetic resolution between racemic enolsilane 3aa and biphenyl carboxylic acid 10 under standard condition were performed in toluene-d8, and the reaction was monitored by reaction progress kinetic analysis ( Figure S8). From the kinetic plot, the racemic enolsilane 3aa keep decreasing, accompanied by increasing of the ketone 1aa. It is quite clear that there is equilibrium between 3aa and 1aa in the reaction system, which possibly cause the racemization of 1aa. The starting racemic enolsilane 3aa was a mixture of kinetic product and thermodynamic product (isomer) (95:5), and the ratio of isomer remains the same throughout the entire reaction process. To 2-substituted enol silane, there presumed to be no equilibrium between the kinetic product and the thermodynamic product under acidic atmosphere. ArCOOTBS keeps increasing till the conversion was ~ 50%, after that, TBSOTBS starts to be observed from the hydrolysis of 3aa with less reactive adventitious water. Finally, the reaction end up with ~55% conversion.

P NMR analysis of the reaction solution:
The hypothesis that the silylation of the catalyst is the rate-determining step can be further confirmed by 31 P NMR spectra taken at different time points (Figure S9). At the beginning of the reaction, only the protonated form of the catalyst is observed (δ31P= -16.9 ppm). After 12 h, two new signals at -11.3 and -20.0 ppm with a characteristic coupling 1 JPP=134 Hz appeared. At early stage of the reaction, most of the catalyst remained in the protonated form and when it started to be silylated, the enolsilane product was immediately generated. At a later stage, the amount of ketone presumed to be prominent in terms of rate limiting factors, while the silylated catalyst can also be observed in the reaction mixture. If the silylation of the ketone turned out to be the rate determining step instead of the catalyst silylation, we would expect to observe the only presence of the Cat-TBS in the reaction. In contrary, both of the Cat-TBS (silylated catalyst) and Cat-H (initial protonated catalyst) exist till the end of the reaction.   From 1 H- 29 Si HMBC NMR spectrum of the activated catalyst 4c-TBS, the correlation of the TBS moiety to the 29 Si signal appears at 54.9 ppm. Other signals in the mixture can be assigned to the side products from the silylation process and grease. The red box shows the chemical exchange between the diastereotopic Si-Me groups.

S48
The spectrum was acquired with a spin-lock time of 300 ms. The exchange peaks in the ROESY show that there is an internal silicon transfer within the catalyst observable at a 0.3 s timescale (see the scheme below), which is much quicker than the reaction rates observed during the reaction.

S168
The forward asymmetric silylation was conducted with IDPi 4c to afford (R)-3x under standard reaction conditions, and the e.r. of (R)-3x was determined to be 74:26.