Temperature-Dependent Direct Enantioconvergent Silylation of a Racemic Cyclic Allylic Phosphate by Copper(I)-Catalyzed Allylic Substitution

Abstract

The near-quantitative transformation of a racemic cyclic allylic phosphate to a highly enantiomerically enriched allylic silane by allylic substitution with a silicon nucleophile is reported. The reaction is catalyzed by a chiral NHC–copper(I) complex. Experimental analysis revealed a rare case of a direct enantioconvergent transformation where the enantiomeric allylic phosphates converge to the same allylic silane by two distinctive S_N2′ pathways with opposite diastereofacial selectivity.

Biographical Sketches

Lukas B. Delvos (born in 1985 in Gießen, Germany) studied chemistry and biochemistry (2005–2011) at Ludwig-Maximilians­-Universität München where he completed his Bachelor thesis (2008) with Thomas Carell. During his Master studies he spent a five-month research stay with André Charette at the Université de Montréal (2009) and joined Corinne Gosmini at the École Polytechnique in Palaiseau (2011) for his Master’s thesis. He is currently pursuing graduate research with Martin Oestreich at the Technische Universität Berlin.

Martin Oestreich (born in 1971 in Pforzheim, Germany) is currently Professor of Organic Chemistry at the Technische Universität Berlin. He received his diploma degree with Paul Knochel (Marburg, 1996) and his doctoral degree with Dieter Hoppe (Münster, 1999). After a two-year postdoctoral stint with Larry E. Overman (Irvine, 1999–2001), he completed his habilitation with Reinhard Brückner (Freiburg, 2001–2005) and was appointed as Professor of Organic Chemistry at Westfälische Wilhelms-Universität Münster (2006–2011). He has also held visiting positions at Cardiff University in Wales (2005) and at The Australian National University in Canberra (2010).

The synthesis of chiral molecules in enantiomerically pure form from racemic starting materials is central to synthetic organic chemistry. Non-enzymatic kinetic resolution (KR) is a typical approach,[1] but it is intrinsically limited to 50% yield. As a consequence, significant efforts have been made to design new strategies that would transform both enantiomers of the racemic mixture into a single enantiomer of the target compound.[2] One successful way is dynamic kinetic resolution (DKR), which relies on rapid racemization of the slow-reacting enantiomer of the racemic mixture.[3] Another strategy is dynamic kinetic asymmetric transformation (DYKAT), where a chiral catalyst initially transfers both enantiomers into a common C ₂-symmetric or meso-configured intermediate before it controls the absolute configuration in a subsequent step.[4]

Recently, Ito, Sawamura, and co-workers introduced a fundamentally new approach to achieve high enantiocontrol in transition-metal catalysis, namely direct enantioconvergent transformation (DET).[5] [6] In such processes, both starting enantiomers are converted into one product enantiomer by two distinctive reaction pathways mediated by the same chiral catalyst. These reaction pathways must proceed with similar reaction rates to prevent classical kinetic resolution. As an example, these authors disclosed a copper(I)-catalyzed asymmetric allylic substitution of racemic cyclic allylic ethers and carbonates with a boron nucleo­phile.[7] By this method, allylic boronates become accessible with high enantiomeric purity and in excellent yields [e.g., rac-1 → (S)-2, Scheme [1], top]. Detailed mechanistic analysis revealed that the chiral copper(I) catalyst with L1 as ligand delivers the boron nucleophile in either syn-S_N2′ or anti-S_N2′ fashion depending on the absolute configuration of the allylic acceptor (I and II, Scheme [1], top). As a consequence, I and II lead to the same absolute configuration in the final product. Prior to this seminal work, Alexakis and co-workers had published an asymmetric allylic substitution of a racemic cyclic allylic bromide with a range of alkyl Grignard­ reagents in the presence of a copper(I) salt and chiral phosphoramidite L2 [8] as supporting ligand [e.g., rac-3a → (S)-4, Scheme [1], middle].[9] Near-quantitative conversions and excellent enantioselectivities were obtained, but the mechanism of this phenomenon was not fully understood at that time. Ito’s work[5] then prompted Alexakis and co-workers to reexamine their reaction.[10] Deuterium-labeling experiments and quantum-chemical calculations showed that the high enantiomeric excesses again emerge from enantiomers undergoing different reaction pathways with the same catalyst (III and IV, Scheme [1], middle). Oxidative addition of (S)-3a to the chiral copper(I) catalyst occurs in anti-S_N2 fashion whereas an anti-S_N2′ route is seen with (R)-3a, thereby converging to the same copper(III) intermediate (not shown). This mechanism is different from that described by Ito and co-workers, but it still satisfies the criteria for a direct enantioconvergent transformation.

We have been interested in copper(I)-catalyzed reactions involving Me₂PhSiBpin[11] as a silicon pronucleophile for some time.[12] [13] In this context, we recently described a highly regio- and enantioselective allylic silylation of linear allylic phosphates.[12b,d,14] The reaction is promoted by the NHC–copper(I) chloride complex L3·CuCl[15] which is converted into the active catalyst by ligand metathesis with sodium methoxide to form L3·CuOMe. Intrigued by the phenomenon of direct enantioconvergent transformation, we decided to apply this catalytic system to the asymmetric allylic substitution of racemic cyclic substrates [rac-3 → (S)-5, Scheme [1], bottom]. We report herein the full experimental analysis of this transformation that eventually culminates in the identification of a highly enantioselective allylic displacement at full conversion. Our work adds another example to the rare class of direct enantioconvergent transformations.

We began our investigation by testing typical leaving groups in the allylic displacement of cyclic substrate rac-3 [rac-3b–g → (S)-5, Table [1]].[16] We applied the standard procedure that we have described previously[12d] [13c] [precatalyst L3·CuCl (5 mol%), pronucleophile Me₂PhSiBpin (1.5 equiv), NaOMe (1.5 equiv), Et₂O]. Precursors rac-3b–e with carbamate, carbonate, and carboxylate leaving groups showed little or no conversion to allylic silane 5 (entries 1–4). Conversely, cyclohex-2-en-1-yl chloride (3f) yielded (S)-5 with 30% ee [using (S,S)-L3·CuCl] in moderate yield (entry 5). The low reactivity of 3f contrasts with the high reactivity of linear allylic chlorides.[12b] We were then delighted to find allylic phosphate 3g to be more reactive, affording (S)-5 with promising 82% ee and in 53% yield at 59% conversion (entry 6). Using less reagent/base (0.75 equiv) resulted in a deterioration not only in conversion and yield but also in the enantiomeric excess (entry 7). In turn, excess reagent/base (3.0 equiv) forced the reaction to completion, affording (S)-5 with 50% ee in 92% yield. This outcome indicates that the enantiomers of 3g partially convert into 5 with the same absolute configuration, corresponding to an enantioconvergent transformation.[17]

Table 1 Survey of Leaving Groups

Entry	Substrate	Leaving group	Conv.a (%)	eeb (%)	Yielda (%)
1	3b	OC(O)NHPh	–	–	–
2	3c	OCO2Me	8	–	<5
3	3d	OAc	8	–	<5
4	3e	OBz	<5	–	–
5	3f	Cl	n.d.	30	35
6	3g	OP(O)(OEt)2	59	82	53
7c	3g	OP(O)(OEt)2	50	78	38
8d	3g	OP(O)(OEt)2	99	50	92

^a Determined by ¹H NMR analysis with durol as internal standard.

^b Determined by HPLC analysis on a chiral stationary phase.

^c Reaction was performed with Me₂PhSiBpin (0.75 equiv) and NaOMe (0.75 equiv).

^d Reaction was performed with Me₂PhSiBpin (3.0 equiv) and NaOMe (3.0 equiv).

As no optical rotation had been reported for allylic silane (S)-5, we decided to confirm its absolute configuration by chemical correlation (Scheme [2]). For this, we subjected an enantiomerically enriched sample of (S)-5 (86% ee) to hydroboration followed by oxidation with aqueous hydrogen peroxide [(S)-5 → anti-6 and anti-7].[18] The regio- and diastereoselectivity of the sequence were poor, yielding the desired anti-6 (dr 59:51) and its regioisomer anti-7 (dr 77:23) in a ratio of 74:26. The alcohols anti-6 and anti-7 were separated by flash chromatography on silica gel, and both diastereomers of 6 were subsequently oxidized[19] to the known β-silylated cyclic ketone (S)-8. The absolute configuration was assigned by comparison of its optical rotation with reported values[20] and based on similar HPLC characteristics.[21]

We then set out to determine the regioselectivity of the reaction and its solvent dependence. For this, we prepared deuterium-labeled allylic phosphate rac-3g-d ₁ and subjected it to the aforementioned standard protocol in different solvents (Table [2]). In tetrahydrofuran, rac-3g-d ₁ transformed into (S)-γ-5-d ₁ and α-5-d ₁ in 44% yield with little enantioinduction and poor regiocontrol (γ/α 68:32, entry 1). Toluene as solvent also lead to significant amounts of α-5-d ₁ (γ/α 88:12), but the overall enantiomeric excess of (S)-γ-5-d ₁ and α-5-d ₁ was higher (50% ee, entry 2). Good regio­selectivity (γ/α 94:6) was obtained in dichloromethane, but the enantiomeric excess of (S)-γ-5-d ₁ remained low (40% ee, entry 3). With these results in hand, we returned to diethyl ether (entries 4–6). Conversion and yield were in the same range as before, but the level of regioselection was excellent; (S)-γ-5-d ₁ was detected as the sole isotopomer in the ²H NMR spectrum (γ/α >95:5). To ensure that both enantiomers of rac-3g-d ₁ favor substitution in the γ position and to exclude that the high regioselectivity is a result of kinetic preference of one enantiomer over the other at incomplete conversion, we again increased the reagent/base amount from 1.5 to 3.0 equivalents to reach higher conversion (entry 5). At 91% yield, the enantiomeric excess declined from 77 to 51% ee (cf. Table [1], entries 6 and 8). Careful analysis of the crude reaction mixture showed a γ/α ratio of 94:6, but α substitution alone as a minor pathway cannot explain the lower level of enantioselection. At –15 °C (rather than 0 °C), the excellent γ/α ratio and 70% ee were re-established (entry 6). These above findings finally rule out that α substitution contributes to the stereochemical outcome of this allylic displacement. Moreover, the interconversion of enantiomeric η¹-allyl–copper(III) complexes through a common η³-allyl–copper(III) intermediate (DYKAT scenario) is equally unlikely as this would bring about formation of significant quantities of α-5-d ₁.

Table 2 Solvent Dependence of Regioselectivity^a

Entry	Solvent	Conv.b (%)	Ratioc γ/α	eed,e (%)	Yieldb (%)
1	THF	60	68:32	10	44
2	toluene	65	88:12	50	49
3	CH2Cl2	57	94:6	40	42
4	Et2O	67	>95:5	77	54
5f	Et2O	92	94:6	51	91
6g	Et2O	94	>95:5	70	93

^a Absolute configuration of α-5-d ₁ not assigned.

^b Determined by ¹H NMR analysis with durol as internal standard.

^c Determined by ²H NMR analysis prior to purification.

^d Determined by HPLC analysis on a chiral stationary phase.

^e Overall enantiomeric excess of isotopomers (S)-γ-5-d ₁ and α-5-d ₁.

^f Reaction was performed with Me₂PhSiBpin (3.0 equiv) and NaOMe (3.0 equiv).

^g Reaction was performed with Me₂PhSiBpin (3.0 equiv) and NaOMe (3.0 equiv) at –15 °C.

To learn more about the intrinsic diastereofacial preference of the chiral precatalyst L3·CuCl, we installed a methyl group at C5 of the cyclohex-2-en-1-yl phosphate rac-3g as a stereochemical probe (syn-9g-d ₁ and anti-9g, Scheme [3]). Complex L3·CuCl was used as a racemic mixture to compensate for its potential stereochemical bias toward either enantiomer of 9g. The deuterium-labeled allylic phosphate syn-9g-d ₁ underwent S_N2′ reaction highly anti-selectively to afford anti-10-d ₁ (Scheme [3], top). Unlabeled syn-9g converted into anti-10 the same way (not shown; see the Supporting Information for details). Remarkably, anti-9g reacted with good syn-selectivity to give the same allylic silane anti-10 (Scheme [3], bottom). anti-9g is in fact kinetically favored over its diastereomer syn-9g as reflected in the dia­stereomeric ratio of the remaining 9g (dr 50:50 from anti-9g with dr 84:16).

The anti/syn switch observed in the diastereoselective allylic substitutions prompted us to study matched/mismatched cases with enantioenriched (S)-3g and both enantiomers of McQuade’s catalyst L3·CuCl at various temperatures (Table [3]). Our evaluation commenced with (R,R)-L3·CuCl as precatalyst (entries 1–3). At –15 °C, (S)-3g was converted into (R)-5 in 25% yield at 38% conversion; the enantiomeric excess is high (91% ee), and the R configuration of 5 emerges from a syn-S_N2′ mechanism starting from S-configured 3g. Higher conversion and yield were seen at 0 °C, and the enantiomeric excess remained high (89% ee). A further increase in the reaction temperature revealed a strong temperature-dependence of this process, resulting in an almost racemic allylic silane at room temperature. We performed the same set of reactions for the precatalyst enantiomer (S,S)-L3·CuCl (entries 4–6). At –15 °C, the (S,S)-L3·CuCl complex catalyzed the allylic substitution faster than (R,R)-L3·CuCl. However, the S configuration of 5 proves that an anti-S_N2′ mechanism is operative for this substrate/catalyst combination; 54% ee indicates that the anti-selective reaction of (S)-3g in the presence of (S,S)-L3·CuCl is less enantioselective than the syn-selective displacement in (S)-3g using (R,R)-L3·CuCl. Again, higher temperatures lead to loss of enantiocontrol (4% ee for S at 0 °C), and inverted absolute configuration is even obtained at room temperature (36% ee for R). This temperature-dependent switch in enantioselectivity could be the result of α substitution (cf. Table [2], entry 5) and/or a competing syn-S_N2′ reaction pathway.

Table 3 Survey of Diastereofacial Selectivity at Various Temperatures

Entry	Catalyst	Temp ( °C)	Conv.a (%)	eeb (%)	Yielda (%)
1	(R,R)	–15	38	91 (R)	25
2	(R,R)	0	57	89 (R)	43
3	(R,R)	r.t.	71	10 (R)	50
4	(S,S)	–15	66	54 (S)	54
5	(S,S)	0	71	4 (S)	50
6	(S,S)	r.t.	64	36 (R)	57

^a Determined by ¹H NMR analysis with durol as internal standard.

^b Determined by HPLC analysis on a chiral stationary phase.

All of the above findings together allow for the following prediction: Allylic substitution of allylic phosphate rac-3g employing precatalyst (S,S)-L3·CuCl will produce allylic silane (S)-5 with high enantiomeric excess in diethyl ether as solvent at low temperature. Of the racemic mixture, (R)-3g will be converted enantioselectively into (S)-5 in a syn-S_N2′ fashion and (S)-3g will undergo the allylic displacement predominantly in an anti-S_N2′ fashion, also arriving at (S)-5. This scenario is in accordance with the related borylation presented by Ito and co-workers.[5] When putting this prediction to the test, we found that rac-3g indeed produces (S)-5 with 87% ee in near-quantitative yield [rac-3g → (S)-5, Scheme [4]]. Full conversion was achieved by using 3.0 equivalents of the silicon pronucleophile. The enantiomeric excess is slightly higher than expected from the previous data (Table [3], entries 1 and 4).

To recap, we described herein the transformation of a racemic cyclic allylic acceptor to a highly enantioenriched cyclic allylic silane at full conversion and in near-quantitative yield. Deuterium-labeling showed that the substitution is highly γ-selective. Hence, the contribution of α-substitution to the overall enantioselectivity is negligible, and interconversion of enantiomeric η¹-allyl–copper(III) complexes through a common η³-allyl–copper(III) intermediate is not occurring. Based on matched/mismatched substrate/catalyst combinations, we found that both enantiomers react in S_N2′ fashion, but with opposite diastereofacial selectivity. By this, the enantiomeric allylic phosphates converge to the same allylic silane by two distinctive reaction pathways, qualifying this reaction as a direct enantioconvergent transformation. It is interesting to note that this phenomenon seems to be particularly prevalent for cyclic acceptors, and our work adds copper(I)-catalyzed carbon–silicon bond formation to the carbon–boron and carbon–carbon bond-forming reactions reported by Ito[5] and Alexakis[10] (Scheme [1], top and middle).

All reactions were performed in flame-dried glassware using Schlenk techniques under a static pressure of N₂. Liquids and solutions were transferred with syringes. Solvents were purified and dried following standard procedures: Et₂O and CH₂Cl₂ were distilled from CaH₂ and THF and toluene from K metal prior to use. Technical grade solvents for extraction and chromatography (cyclohexane, n-pentane, EtOAc­, and t-BuOMe) were distilled prior to use. Me₂PhSiBpin[11a] and L3·CuCl[15b] were prepared according to reported procedures. Cyclohex-2-en-1-ol and 1-deuteriocyclohex-2-en-1-ol were prepared from cyclohex-2-en-1-one by a reported procedure.[22] Enantiomerically enriched (S)-cyclohex-2-en-1-ol was synthesized by the method developed by Lüssem and Gais[23] and subsequently derivatized to the corresponding benzoate for HPLC analysis. The allylic alcohol for the synthesis of syn-9g was prepared according to the literature;[24] anti-9g was made from the same starting material after Mitsunobu inversion of the alcohol and reductive cleavage of the resulting benzoate.[25] [26] Allylic substrates 3b,[26] 3c,[27] 3d,[28] and 3f [29] were prepared by standard protocols. Authentic samples of all racemic allylic silanes for HPLC analysis were obtained by our established method.[12a] Analytical TLC was performed on silica gel SIL G-25 glass plates from Macherey-Nagel­. Flash column chromatography was performed on silica gel 60 (40–63 μm, 230–400 mesh, ASTM) by Merck using the indicated solvents. ¹H, ²H, ¹³C, ²⁹Si DEPT, and ³¹P NMR spectra were recorded in CDCl₃­ on Bruker AV 400 and Bruker AV 500 instruments referenced to the residual solvent resonance as the internal standard [CHCl₃: δ = 7.26 (¹H) and CDCl₃: δ = 77.16 (¹³C)]. Yields and conversion were determined by ¹H NMR spectroscopy with a relaxation time of 32 s for each scan to ensure precise integration. Durol was used as internal standard. Infrared spectra were recorded on an Agilent Technologies Cary 630 FT-IR spectrophotometer equipped with an ATR unit. GLC was performed on an Agilent Technologies 7820A gas chromatograph equipped with a FS-SE-54 capillary column (30 m × 0.32 mm, 0.25 μm film thickness) by CS-Chromatographie Service. Optical rotations were measured on a Schmidt & Haensch Polatronic H532 polarimeter with [α]_λ values reported in 10^–1 (cm²·g^–1); concentration c was in g/100 mL and λ as indicated. Enantiomeric excesses were determined by analytical HPLC analysis on an Agilent Technologies 1290 Infinity instrument with a chiral stationary phase using a Daicel Chiralcel OJ-RH­ column (MeCN–H₂O) or Daicel Chiralcel AD-H column (n-heptane–i-PrOH). HRMS analysis was performed by the Analytical Facility at the Institut für Chemie, Technische Universität Berlin.

Cyclohex-2-en-1-yl Benzoate (rac-3e)

A flame-dried Schlenk flask was successively charged with CH₂Cl₂ (3 mL), cyclohex-2-en-1-ol[22] (0.20 g, 2.0 mmol, 1.0 equiv), Et₃N (0.32 mL, 2.2 mmol, 1.1 equiv), and DMAP (50 mg, 0.41 mmol, 0.20 equiv). The mixture was cooled to 0 °C and Bz₂O (0.51 g, 2.2 mmol, 1.1 equiv) was added portionwise to the solution. The mixture was allowed to warm up to r.t. and maintained for a further 5 h at this temperature. After completion (TLC monitoring), the reaction was carefully quenched with sat. aq NH₄Cl solution, and the aqueous phase was extracted with CH₂Cl₂ (3 × 5 mL). The combined organic phases were washed with water and dried (anhyd Na₂SO₄). After evaporation of the solvent under reduced pressure, the residue was purified by flash column chromatography (silica gel, cyclohexane–t-BuOMe, 40:1) to give rac-3e (0.30 g, 73%) as a clear oil; R_f = 0.27 (cyclohexane–t-BuOMe, 40:1).

HPLC (Daicel Chiralcel AD-H column; 20 °C; n-heptane–i-PrOH, 99:1; 0.8 mL/min; λ = 230 nm): t _R = 7.9 [(R)-3e], 8.3 min [(S)-3e].

IR (ATR): 706, 914, 1006, 1067, 1108, 1174, 1264, 1313, 1450, 1708, 2935, 3032 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 1.66–1.76 (m, 1 H), 1.79–1.93 (m, 2 H), 1.94–2.09 (m, 2 H), 2.10–2.20 (m, 1 H), 5.49–5.54 (m, 1 H), 5.84 (ddt, J = 10.4, 3.5, 2.3 Hz, 1 H), 6.00 (dtd, J = 10.4, 3.9, 1.1 Hz, 1 H), 7.40–7.46 (m, 2 H), 7.52–7.57 (m, 1 H), 8.04–8.08 (m, 2 H).

¹³C NMR (126 MHz, CDCl₃): δ = 19.1, 25.1, 28.6, 68.4, 125.9, 128.4, 129.7, 131.0, 132.9, 133.0, 166.4.

HRMS (EI): m/z [M]⁺ calcd for C₁₃H₁₄O₂: 202.0988; found: 202.0991.

syn-1-Deuterio-5-methylcyclohex-2-en-1-ol (syn-11-d ₁)

A flame-dried Schlenk flask was charged with LiAlD₄ (0.17 g, 4.1 mmol, 0.50 equiv) suspended Et₂O (20 mL) and cooled to –78 °C. 5-Methylcyclohex-2-en-1-one[24] (0.90 g, 8.2 mmol, 1.00 equiv) was added dropwise and the mixture was stirred for a further 1 h at –78 °C. The reaction was allowed to warm up to r.t. and then carefully quenched with aq NH₄Cl; the aqueous phase was extracted with Et₂ O (3 × 20 mL). The combined organic phases were washed with water and dried (anhyd Na₂SO₄) to give syn-11-d ₁ (0.72 g, 78%, dr 96:4) without further purification as a colorless oil; R_f = 0.31 (cyclohexane–t-BuOMe, 65:35).

IR (ATR): 667, 720, 880, 942, 1043, 1084, 1107, 1279, 1374, 1454, 2114, 2829, 2873, 2906, 2950, 3025, 3312 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 0.97 (d, J = 6.7 Hz, 3 H), 1.09–1.15 (m, 1 H), 1.58–1.66 (m, 2 H), 1.68–1.78 (m, 1 H), 1.99–2.06 (m, 2 H), 5.61–5.66 (m, 1 H), 5.73 (ddd, J = 10.4, 5.0, 2.0 Hz, 1 H).

¹³C NMR (126 MHz, CDCl₃): δ = 22.1, 28.3, 33.9, 41.5, 67.8 (t, J = 22.6 Hz), 129.0, 131.1.

²H NMR (77 MHz, CDCl₃): δ = 4.29.

HRMS (APCI): m/z [M + H]⁺ calcd for C₇H₁₂DO: 114.1029; found: 114.1024.

Allylic Phosphates; General Procedure

A flame-dried Schlenk flask was successively charged with CH₂Cl₂ (0.1–0.2 M), the corresponding allylic alcohol (1.0 equiv), Et₃N (1.5 equiv), and DMAP (0.20 equiv). The mixture was cooled to 0 °C and diethyl chlorophosphate (1.5 equiv) was added dropwise to the solution. The resulting suspension was allowed to warm to r.t. and stirred for a further 5 h at this temperature. After completion (TLC monitoring), the reaction was carefully quenched with sat. aq NH₄Cl solution, and the aqueous phase was extracted with CH₂Cl₂ (3 ×). The combined organic phases were washed with water and dried (anhyd Na₂SO₄­). After evaporation of the solvent under reduced pressure, the residue was purified by flash column chromatography (silica gel, cyclohexane, EtOAc, and Et₃N mixtures). Allylic phosphates were obtained as colorless oils.

Cyclohex-2-en-1-yl Diethyl Phosphate (rac-3g)

Prepared from cyclohex-2-en-1-ol[22] (1.5 g, 15 mmol, 1.0 equiv), Et₃N (3.3 mL, 23 mmol, 1.5 equiv), DMAP (0.37 g, 3.3 mmol, 0.21 equiv), and diethyl chlorophosphate (3.3 mL, 23 mmol, 1.5 equiv) according to the general procedure. Purification of the crude product by flash column chromatography (silica gel, cyclohexane–EtOAc–Et₃N, 65:32:2) afforded rac-3g (2.8 g, 79%) in analytically pure form as a colorless oil; R_f = 0.21 (cyclohexane–EtOAc, 50:50).

An enantiomerically enriched sample of (S)-cyclohex-2-en-1-yl diethyl phosphate (95% ee) was synthesized from the corresponding allylic alcohol obtained by the method of Lüssem and Gais:[23] [α]_D ²⁰ –86 (c 1.00, CHCl₃).

IR (ATR): 754, 806, 892, 967, 1258, 1394, 2935 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 1.29–1.33 (m, 6 H), 1.53–1.63 (m, 1 H), 1.70–1.80 (m, 1 H), 1.83–2.00 (m, 3 H), 2.01–2.10 (m, 1 H), 4.08 (dq, J = 7.4, 7.2 Hz, 4 H), 4.80–4.88 (m, 1 H), 5.76 (ddt, J = 10.3, 3.4, 2.5 Hz, 1 H), 5.92 (dt, J = 10.1, 3.7 Hz, 1 H).

¹³C NMR (101 MHz, CDCl₃): δ = 16.2 (d, J = 6.9 Hz), 18.6, 24.9, 30.0 (d, J = 4.7 Hz), 63.6 (d, J = 6.0 Hz), 63.6 (d, J = 6.0 Hz), 72.2 (d, J = 5.8 Hz), 126.4 (d, J = 5.5 Hz), 132.8.

³¹P NMR (202 MHz, CDCl₃): δ = –1.3.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₀H₁₉NaO₄P: 257.0913; found: 257.0906.

1-Deuteriocyclohex-2-en-1-yl Diethyl Phosphate (rac-3g-d ₁)

Prepared from 1-deuteriocyclohex-2-en-1-ol[22] (0.31 g, 3.1 mmol, 1.0 equiv), Et₃N (0.65 mL, 4.7 mmol, 1.5 equiv), DMAP (77 mg, 0.63 mmol, 0.20 equiv), and diethyl chlorophosphate (0.68 mL, 4.7 mmol, 1.5 equiv) according to the general procedure. Purification of the crude product by flash column chromatography (silica gel, cyclohexane–EtOAc–Et₃N, 50:50:2) afforded rac-3g-d ₁ (0.54 g, 71%) in analytically pure form as a colorless oil; R_f = 0.21 (cyclohexane–EtOAc, 50:50).

IR (ATR): 724, 816, 889, 964, 1027, 1165, 1261, 1392, 1441, 2935, 2982 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 1.30–1.35 (m, 6 H), 1.54–1.65 (m, 1 H), 1.70–1.81 (m, 1 H), 1.82–2.00 (m, 3 H), 2.02–2.12 (m, 1 H), 4.09 (dq, J = 7.2, 7.1 Hz, 4 H), 5.75–5.80 (m, 1 H), 5.90–5.96 (m, 1 H).

¹³C NMR (126 MHz, CDCl₃): δ = 16.2 (d, J = 7.1 Hz), 18.6, 24.9, 29.9 (d, J = 4.7 Hz), 63.6 (d, J = 5.9 Hz), 63.6 (d, J = 5.9 Hz), 71.9 (td, J = 24.5, 5.9 Hz), 126.4 (d, J = 5.9 Hz), 132.9.

³¹P NMR (202 MHz, CDCl₃): δ = –1.2.

²H NMR (77 MHz, CDCl₃): δ = 4.87.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₀H₁₈DNaO₄P: 258.0976; found: 258.0969.

syn-(1-Deuterio-5-methylcyclohex-2-en-1-yl) Diethyl Phosphate (syn-9g-d ₁)

Prepared from syn-1-deuterio-5-methylcyclohex-2-en-1-ol (syn-11-d ₁; 0.30 g, 2.6 mmol, 1.0 equiv, dr 96:4), Et₃N (0.55 mL, 4.0 mmol, 1.5 equiv), DMAP (63 mg, 0.52 mmol, 0.20 equiv), and diethyl chlorophosphate (0.57 mL, 4.0 mmol, 1.5 equiv) according to the general procedure. Purification of the crude product by flash column chromatography (silica gel, cyclohexane–EtOAc–Et₃N, 50:50:2) afforded syn-9g-d ₁ (0.34 g, 52%, dr 96:4) as a colorless oil; R_f = 0.44 (cyclohexane–EtOAc, 50:50).

IR (ATR): 661, 725, 755, 799, 879, 906, 990, 1027, 1165, 1262, 1390, 1456, 2907, 2952, 2980 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 0.98 (d, J = 7.0 Hz, 3 H), 1.30–1.41 (m, 7 H), 1.66 (ddd, J = 17.5, 10.5, 2.7 Hz, 1 H), 1.71–1.81 (m, 1 H), 2.04–2.08 (m, 1 H), 2.12–2.16 (m, 1 H), 4.06–4.13 (m, 4 H), 5.66–5.70 (m, 1 H), 5.82 (ddd, J = 10.2, 5.1, 2.2 Hz, 1 H).

¹³C NMR (126 MHz, CDCl₃): δ = 16.3 (d, J = 6.6 Hz), 21.9, 28.0, 33.5, 38.6 (d, J = 4.1 Hz), 63.7 (d, J = 6.0 Hz), 74.5 (td, J = 23.5, 5.6 Hz), 127.6 (d, J = 5.9 Hz), 130.8.

³¹P NMR (202 MHz, CDCl₃): δ = –1.1.

²H NMR (77 MHz, CDCl₃): δ = 5.00.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₁H₂₀DNaO₄P: 272.1132; found: 272.1127.

Diethyl syn-(5-Methylcyclohex-2-en-1-yl) Phosphate (syn-9g)

Prepared from syn-5-methylcyclohex-2-en-1-ol[24] (0.12 g, 1.0 mmol, 1.0 equiv, dr 95:5), Et₃N (0.22 mL, 1.5 mmol, 1.5 equiv), DMAP (25 mg, 0.20 mmol, 0.20 equiv), and diethyl chlorophosphate (0.23 mL, 1.5 mmol, 1.5 equiv) according to the general procedure. Purification of the crude product by flash column chromatography (silica gel, cyclohexane–EtOAc–Et₃N, 50:50:2) afforded syn-9g (0.14 g, 55%, dr 95:5) as a colorless oil; R_f = 0.36 (cyclohexane–EtOAc, 50:50).

IR (ATR): 667, 739, 800, 912, 970, 998, 1166, 1259, 1392, 1454, 2952, 2982 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 0.98 (d, J = 6.6 Hz, 3 H), 1.30–1.43 (m, 7 H), 1.61–1.70 (m, 1 H), 1.71–1.81 (m, 1 H), 2.01–2.08 (m, 1 H), 2.12–2.18 (m, 1 H), 4.06–4.13 (m, 4 H), 4.95–5.02 (m, 1 H), 5.67–5.71 (m, 1 H), 5.79–5.85 (m, 1 H).

¹³C NMR (126 MHz, CDCl₃): δ = 16.3 (d, J = 6.4 Hz), 21.9, 28.0, 33.5, 38.8 (d, J = 4.2 Hz), 63.7 (d, J = 5.7 Hz), 74.8 (d, J = 5.8 Hz), 127.7 (d, J = 6.0 Hz), 130.7.

³¹P NMR (202 MHz, CDCl₃): δ = –1.1.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₁H₂₁NaO₄P: 271.1070; found: 271.1064.

Diethyl anti-(5-Methylcyclohex-2-en-1-yl) Phosphate (anti-9g)

Prepared from anti-5-methylcyclohex-2-en-1-ol[25] (60 mg, 0.53 mmol, 1.0 equiv, dr 84:16), Et₃N (0.11 mL, 0.80 mmol, 1.5 equiv), DMAP (13 mg, 0.11 mmol, 0.20 equiv), and diethyl chlorophosphate (0.12 mL, 0.80 mmol, 1.5 equiv) according to the general procedure. Purification of the crude product by flash column chromatography (silica gel, cyclohexane–EtOAc–Et₃N, 50:50:2) afforded anti-9g (77 mg, 58%, dr 84:16) as a colorless oil; R_f = 0.44 (cyclohexane–EtOAc, 50:50).

IR (ATR): 733, 764, 797, 896, 963, 1028, 1165, 1259, 1393, 1456, 2907, 2951 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 0.97 (d, J = 6.7 Hz, 3 H), 1.30–1.36 (m, 6 H), 1.39–1.74 (m, 1 H), 1.56–1.64 (m, 1 H), 1.89–2.01 (m, 2 H), 2.12–2.20 (m, 1 H), 4.06–4.12 (m, 4 H), 4.83–4.87 (m, 1 H), 4.80–4.85 (m, 1 H), 5.98 (ddd, J = 10.1, 5.4, 2.7 Hz, 1 H).

¹³C NMR (126 MHz, CDCl₃): δ = 16.2 (d, J = 6.5 Hz), 16.3 (d, J = 6.6 Hz), 21.5, 23.5, 33.7, 37.9 (d, J = 4.8 Hz), 63.6 (d, J = 6.0 Hz), 63.6 (d, J = 6.0 Hz), 71.8 (d, J = 6.2 Hz), 125.0 (d, J = 4.2 Hz), 133.7.

³¹P NMR (202 MHz, CDCl₃): δ = –1.3.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₁H₂₁NaO₄P: 271.1070; found: 271.1065.

Allylic Silanes; General Procedure

A flame-dried Schlenk tube was charged with L3·CuCl (5 mol%) and the indicated amount of durol as internal standard. The solids were dissolved in Et₂O (0.5 mL), and the yellow solution was brought to the desired reaction temperature. The indicated amount of NaOMe was added, and the wall of the vessel was rinsed with Et₂O (0.5 mL). The corresponding allylic phosphate (1.0 equiv) was added followed by the indicated amount of Me₂PhSiBpin. The suspension slowly turned brownish; it was stirred until analysis of aliquots by GLC showed no further formation of the allylic silane or otherwise for 16 h. The reaction was diluted with EtOAc (5 mL) and filtered through a short silica plug that was rinsed with EtOAc (3 × 5 mL). The solvents were evaporated under reduced pressure. Conversion, yield, and, if necessary, diastereoselectivity were determined by ¹H NMR analysis. If desired, the crude allylic silane was passed through a short column of silica gel (cyclohexane). A sample of this solution was analyzed by HPLC on a chiral stationary phase to determine the enantiomeric excess.

(S)-Cyclohex-2-en-1-yldimethyl(phenyl)silane [(S)-5]

Prepared at –15 °C from cyclohex-2-en-1-yl diethyl phosphate (rac-3g, 18 mg, 0.075 mmol, 1.0 equiv), NaOMe (12 mg, 0.23 mmol, 3.0 equiv), and Me₂PhSiBpin (60 mg, 0.23 mmol, 3.0 equiv) in Et₂O (1 mL) in the presence of (S,S)-L3·CuCl (2 mg, 4 μmol, 5 mol%) and durol (21 mg) as internal standard according to the general procedure. ¹H NMR analysis of the crude product showed full conversion of the substrate and (S)-5 (97% yield). Purification of the crude allylic silane by filtration through silica gel (cyclohexane) afforded a sample of (S)-5 (87% ee) suitable for HPLC analysis on a chiral stationary phase. For the preparation of an analytically pure sample, the reaction was performed without the internal standard; R_f = 0.55 (cyclohexane); [α]_D ²⁰ –40 (c 0.90, CHCl₃).

Enantiomeric excess determined by HPLC (Daicel Chiralcel OJ-RH column; 20 °C; MeCN–H₂O, 70:30; 0.35 mL/min, λ = 230 nm): t _R = 26.6 [(R)-5], 30.2 min [(S)-5].

An enantiomerically enriched sample of (R)-cyclohex-2-en-1-yldimethyl(phenyl)silane (89% ee) was synthesized accordingly (see Table [3] for stoichiometry and temperature) from enantiomerically enriched (S)-cyclohex-2-en-1-yl diethyl phosphate in the presence of (R,R)-L3·CuCl: [α]_D ²⁰ +38 (c 0.3, CHCl₃).

IR (ATR): 695, 727, 774, 806, 890, 987, 1029, 1068, 1113, 1189, 1247, 2851, 2925, 3013 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 0.28 (s, 3 H), 0.29 (s, 3 H), 1.41–1.53 (m, 2 H), 1.62–1.72 (m, 1 H), 1.74–1.82 (m, 2 H), 1.86–2.04 (m, 2 H), 5.61–5.68 (m, 2 H), 7.33–7.38 (m, 3 H), 7.50–7.55 (m, 2 H).

¹³C NMR (126 MHz, CDCl₃): δ = –4.7, –4.5, 22.7, 24.0, 25.2, 25.8, 126.1, 127.7, 127.8, 129.0, 134.1, 138.4.

²⁹Si NMR (DEPT, 99 MHz, CDCl₃): δ = –2.5.

HRMS (EI): m/z [M]⁺ calcd for C₁₄H₂₀Si: 216.1329; found: 216.1328.

Spectral data matched those reported in the literature.[25]

(S)-(3-Deuteriocyclohex-2-en-1-yl)dimethyl(phenyl)silane [(S)-γ-5-d ₁] (Table [2,] Entry 4)

Prepared at 0 °C from 1-deuteriocyclohex-2-en-1-yl diethyl phosphate (rac-3g-d ₁, 34 mg, 0.15 mmol, 1.0 equiv), NaOMe (6 mg, 0.23 mmol, 1.5 equiv), and Me₂PhSiBpin (30 mg, 0.23 mmol, 1.5 equiv) in Et₂O (1 mL) in the presence of (S,S)-L3·CuCl (2 mg, 4 μmol, 5 mol%) and durol (21 mg) as internal standard according to the general procedure. ¹H NMR analysis of the crude mixture showed 67% conversion of rac-3g-d ₁ and (S)-γ-5-d ₁ (54% yield). Purification of the crude allylic silane by filtration through silica gel (cyclohexane) afforded a sample of (S)-γ-5-d ₁ (77% ee) suitable for HPLC analysis on a chiral stationary phase. For the preparation of an analytically pure sample, the reaction was performed without the internal standard; R_f = 0.55 (cyclohexane); [α]_D ²⁰ –43 (c 0.6, CHCl₃).

Enantiomeric excess determined by HPLC (Daicel Chiralcel OJ-RH column; 20 °C; MeCN–H₂O, 70:30; 0.35 mL/min; λ = 230 nm): t _R = 27.2 [(R)-γ-5-d ₁], 30.6 min [(S)-γ-5-d ₁].

IR (ATR): 696, 729, 771, 807, 955, 986, 1031, 1110, 1246, 1426, 2850, 2925 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 0.28 (s, 3 H), 0.29 (s, 3 H), 1.41–1.52 (m, 2 H), 1.62–1.71 (m, 1 H), 1.73–1.82 (m, 2 H), 1.87–2.02 (m, 2 H), 5.64 (s, 1 H), 7.35–7.38 (m, 3 H), 7.50–7.55 (m, 2 H).

¹³C NMR (101 MHz, CDCl₃): δ = –4.7, –4.5, 22.7, 24.0, 25.0, 25.7, 125.7 (t, J = 23.4 Hz), 127.5, 127.8, 129.0, 134.1, 138.4.

²⁹Si NMR (DEPT, 99 MHz, CDCl₃): δ = –2.5.

²H NMR (77 MHz, CDCl₃): δ = 5.66.

HRMS (EI): m/z [M]⁺ calcd for C₁₄H₁₉DSi: 217.1392; found: 217.1396.

anti-(3-Deuterio-5-methylcyclohex-2-en-1-yl)dimethyl(phenyl)silane (anti-10-d ₁)

Prepared at 0 °C from diethyl syn-(1-deuterio-5-methylcyclohex-2-en-1-yl) phosphate (syn-9g-d ₁, 18 mg, 0.075 mmol, 1.5 equiv), NaOMe (6.0 mg, 0.11 mmol, 1.5 equiv), and Me₂PhSiBpin (30 mg, 0.11 mmol, 1.5 equiv) in Et₂O (1 mL) in the presence of rac-L3·CuCl (2 mg, 4 μmol, 5 mol%) and durol (22 mg) as internal standard according to the general procedure. ¹H NMR analysis of the crude mixture showed 61% conversion of syn-9g-d ₁ and anti-10-d ₁ (60% yield, dr 97:3). For the preparation of an analytically pure sample, the reaction was performed without the internal standard.

IR (ATR): 697, 729, 770, 820, 1030, 1110, 1246, 1426, 1453, 1656, 2869, 2902, 2950 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 0.29 (s, 3 H), 0.30 (s, 3 H), 0.88 (d, 3 H), 1.41–1.49 (m, 1 H), 1.58–1.72 (m, 3 H), 1.82–1.87 (m, 1 H), 2.01–2.07 (m, 1 H), 5.63 (s, 1 H), 7.33–7.37 (m, 3 H), 7.50–7.55 (m, 2 H).

¹³C NMR (126 MHz, CDCl₃): δ = –4.1, –4.1, 21.2, 24.8, 26.2, 31.2, 32.8, 124.0 (t, J = 22.9 Hz), 127.1, 127.7, 128.9, 133.9, 138.5.

²⁹Si NMR (DEPT, 99 MHz, CDCl₃): δ = –2.6.

²H NMR (77 MHz, CDCl₃): δ = 5.62.

HRMS (EI): m/z [M]⁺ calcd for C₁₅H₂₁DSi: 231.1548; found: 231.1562.

Spectral data matched those previously reported.[30]

anti-Dimethyl(5-methylcyclohex-2-en-1-yl)(phenyl)silane (anti-10)

Prepared at 0 °C from diethyl syn-(5-methylcyclohex-2-en-1-yl) phosphate (syn-9g, 18 mg, 0.075 mmol, 1.5 equiv), NaOMe (6.0 mg, 0.11 mmol, 1.5 equiv), and Me₂PhSiBpin (30 mg, 0.11 mmol, 1.5 equiv) in Et₂O (1 mL) in the presence of rac-L3·CuCl (2 mg, 3.8 μmol, 5 mol%) and durol (22 mg) as internal standard according to the general procedure. ¹H NMR analysis of the crude mixture showed 73% conversion of syn-9g and anti-10 (69% yield, dr 97:3). For the preparation of an analytically pure sample, the reaction was performed without the internal standard.

IR (ATR): 697, 728, 787, 828, 1045, 1117, 1252, 1427, 1668, 1723, 2956 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 0.29 (s, 3 H), 0.30 (s, 3 H), 0.88 (d, J = 6.5 Hz, 3 H), 1.41–1.48 (m, 1 H), 1.58–1.72 (m, 3 H), 1.82–1.87 (m, 1 H), 2.01–2.07 (m, 1 H), 5.55–5.59 (m, 1 H), 5.61–5.65 (m, 1 H), 7.33–7.37 (m, 3 H), 7.49–7.54 (m, 2 H).

¹³C NMR (126 MHz, CDCl₃): δ = –4.0, –3.9, 21.3, 25.1, 26.4, 31.3, 33.1, 124.4, 127.4, 127.8, 129.0, 134.0, 138.7.

²⁹Si NMR (DEPT, 99 MHz, CDCl₃): δ = –2.6.

HRMS (APCI): m/z [M]⁺ calcd for C₁₅H₂₂Si: 230.1491; found: 230.1492.

Spectral data matched those reported in the literature.[26]

The reaction starting from diethyl anti-(5-methylcyclohex-2-en-1-yl) phosphate (anti-9g, 18 mg, 0.075 mmol, 1.5 equiv) was performed according to the above procedure with NaOMe (6.0 mg, 0.11 mmol, 1.5 equiv) and Me₂PhSiBpin (30 mg, 0.11 mmol, 1.5 equiv) in Et₂O (1 mL) in the presence of rac-L3·CuCl (2 mg, 3.8 μmol, 5 mol%) and durol (25 mg) as internal standard. ¹H NMR analysis of the crude mixture showed 66% conversion of anti-9g and anti-10 (65% yield, dr 89:11).

3-[Dimethyl(phenyl)silyl]cyclohexan-1-ol (6) and 2-[Dimethyl(phenyl)silyl]cyclohexan-1-ol (7)

A flame-dried Schlenk flask was charged with enantiomerically enriched cyclohex-2-en-1-yldimethyl(phenyl)silane [(S)-5, 86% ee, 22 mg, 0.10 mmol, 1.0 equiv]. The flask was cooled to 0 °C, and 1 M BH₃·THF in THF (0.30 mL, 3.0 equiv) was added. After stirring for 2 h at 0 °C, the reaction had reached completion (TLC monitoring); the mixture was successively treated with H₂O (50 μL, slow addition), aq 3 M NaOH (0.10 mL, 3.0 equiv), and aq 1 M H₂O₂ (0.10 mL, 1.0 equiv). The mixture was heated to 50 °C and maintained at this temperature for an additional 1 h. The mixture was cooled to r.t. and extracted with t-BuOMe (3 × 5 mL); the organic phase was dried (Na₂SO₄). The ratio of the four regio- and diastereomers was determined by GLC and ¹H NMR analysis (anti-6/syn-6/anti-7/syn-7, 44:30:20:6). Regioisomers anti-6 and anti-7 were separated by flash column chromatography (silica gel, cyclohexane–t-BuOMe, 9:1). The desired regioisomer anti-6 (12 mg, 51%, dr 59:41) was obtained as a colorless oil.

anti-3-[Dimethyl(phenyl)silyl]cyclohexan-1-ol (anti-6)

R_f = 0.23 (cyclohexane–t-BuOMe, 4:1).

IR (ATR): 696, 730, 766, 809, 851, 967, 1110, 1245, 1425, 2842, 2920, 3337 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 0.25 (s, 3 H), 0.26 (s, 3 H), 1.10 (dddd, J = 12.6, 12.6, 12.6, 3.3 Hz, 1 H), 1.26 (dddd, J = 12.6, 12.6, 3.5, 3.5 Hz, 1 H), 1.36–1.56 (m, 4 H), 1.56–1.76 (m, 4 H), 3.99–4.03 (m, 1 H), 7.32–7.35 (m, 3 H), 7.46–7.51 (m, 2 H).

¹³C NMR (126 MHz, CDCl₃): δ = –5.0, –5.0, 18.3, 21.3, 26.8, 33.0, 33.8, 66.2, 127.8, 129.0, 134.1, 138.2.

²⁹Si NMR (DEPT, 99 MHz, CDCl₃): δ = –1.1.

syn-3-[Dimethyl(phenyl)silyl]cyclohexan-1-ol (syn-6)

R_f = 0.18 (cyclohexane–t-BuOMe, 4:1).

¹H NMR (500 MHz, CDCl₃): δ = 0.26 (s, 3 H), 0.26 (s, 3 H), 0.84 (dddd, J = 13.1, 13.1, 2.8, 2.8 Hz, 1 H), 0.95 (dddd, J = 12.7, 12.7, 12.7, 3.6 Hz, 1 H), 1.00–1.07 (m, 1 H), 1.09–1.17 (m, 1 H), 1.21–1.31 (m, 1 H), 1.46–1.63 (m, 2 H), 1.77–1.83 (m, 1 H), 1.89–2.00 (m, 2 H), 3.5 (dddd, J = 6.4, 6.4, 4.3, 4.3, 4.3 Hz, 1 H), 7.33–7.37 (m, 3 H), 7.46–7.50 (m, 2 H).

¹³C NMR (126 MHz, CDCl₃): δ = –5.1, –5.0, 24.3, 26.3, 26.8, 36.2, 36.7, 72.2, 127.8, 129.1, 134.1, 138.1.

²⁹Si NMR (DEPT, 99 MHz, CDCl₃): δ = –1.8.

Spectral data matched those reported in the literature.[31]

anti-2-[Dimethyl(phenyl)silyl]cyclohexan-1-ol (anti-7)

R_f = 0.50 (cyclohexane–t-BuOMe, 4:1).

IR (ATR): 697, 733, 768, 816, 834, 894, 961, 1043, 1083, 1110, 1180, 1245, 1425, 1444, 2849, 2921, 3354 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 0.34 (s, 3 H), 0.35 (s, 3 H), 0.83–0.91 (m, 1 H), 1.05–1.31 (m, 5 H), 1.56–1.78 (m, 3 H), 1.89–1.91 (m, 1 H), 3.39–3.46 (m, 1 H), 7.33–7.37 (m, 3 H), 7.53–7.58 (m, 2 H).

¹³C NMR (126 MHz, CDCl₃): δ = –3.3, –3.5, 25.3, 26.9, 35.0, 38.0, 73.1, 127.9, 129.0, 134.2, 139.1.

²⁹Si NMR (DEPT, 99 MHz, CDCl₃): δ = –2.0.

Spectral data matched those reported in the literature.[18]

Characterization data matched those obtained for the racemic series of the synthesis. Assignment of spectral data was done for the racemic compounds.

(S)-3-[Dimethyl(phenyl)silyl]cyclohexan-1-one [(S)-8]

A N₂-flushed sample vial was charged with 3-[dimethyl(phenyl)silyl]cyclohexan-1-ol (anti-6, 10 mg, 42 μmol, 1.0 equiv, dr 59:41). CH₂Cl_2­ (300 μL) was added followed by PDC (32 mg, 84 μmol, 2.0 equiv). After 24 h, conversion had reached over 95% (GLC analysis), and the mixture was diluted with t-BuOMe and filtered over a short silica plug; (S)-8 (8 mg, 82%, 84% ee) was obtained as a colorless oil. Spectral data matched with those of a racemic sample, and the absolute configuration was assigned by comparison of the optical rotation and the HPLC characteristics with reported data;[20] [21] R_f = 0.21 (cyclohexane–t-BuOMe, 19:1); [α]_D ²⁰ –73 (c 0.8, CDCl₃).

Enantiomeric excess determined by HPLC (Daicel Chiralcel AD-H column; 20 °C; n-heptane–i-PrOH, 99:1; 0.8 mL/min; λ = 230 nm): t _R = 9.9 [(S)-8], 11.2 min [(R)-8].

¹H NMR (500 MHz, CDCl₃): δ = 0.30 (s, 3 H), 0.31 (s, 3 H), 1.29 (dddd, J = 13.6, 13.6, 3.0, 3.0 Hz, 1 H), 1.42 (dddd, J = 13.1, 13.1, 13.1, 3.5 Hz, 1 H), 1.65–1.75 (m, 1 H), 1.79–1.85 (m, 1 H), 2.06–2.17 (m, 2 H), 2.22–2.39 (m, 3 H), 7.34–7.40 (m, 3 H), 7.46–7.50 (m, 2 H).

¹³C NMR (126 MHz, CDCl₃): δ = –5.3, –5.1, 26.2, 27.8, 29.9, 42.0, 42.6, 128.0, 129.4, 134.1, 136.8, 212.8.

²⁹Si NMR (DEPT, 99 MHz, CDCl₃): δ = –1.5.

Spectral data matched those reported in the literature.[20] [21]

Acknowledgment

M.O. is indebted to the Einstein Foundation (Berlin) for an endowed professorship.

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  CrossrefSearch in Google Scholar
• 13b Imines, racemic: Vyas DJ, Fröhlich R, Oestreich M. Org. Lett. 2011; 13: 2094
  CrossrefSearch in Google Scholar
• 13c Imines, asymmetric: Hensel A, Nagura K, Delvos LB, Oestreich M. Angew. Chem. Int. Ed. 2014; 53: 4964
  Search in Google Scholar

Hayashi and co-workers reported a related enantioselective allylic substitution (cf. refs. 12b and 12d):
• 14a Takeda M, Shintani R, Hayashi T. J. Org. Chem. 2013; 78: 5007
  CrossrefSearch in Google Scholar

For a comparison of both methods and indirect synthesis of α-chiral silanes by asymmetric copper(I) catalysis, see:
• 14b Delvos LB, Oestreich M. Chim. Oggi 2013; 31: 74
  Search in Google Scholar
• 15a Park J, McQuade D. Synthesis 2012; 44: 1485
  Thieme ConnectSearch in Google Scholar

For B–B bond activation for asymmetric 1,4-addition, see:
• 15b Park JK, Lackey HH, Rexford MD, Kovnir K, Shatruk M, McQuade DT. Org. Lett. 2010; 12: 5008
  Search in Google Scholar

For allylic substitution with boron nucleophiles catalyzed by a closely related complex, see:
• 15c Park JK, Lackey HH, Ondrusek BA, McQuade DT. J. Am. Chem. Soc. 2011; 133: 2410
  CrossrefSearch in Google Scholar
• 15d Park JK, McQuade DT. Angew. Chem. Int. Ed. 2012; 51: 2717
  CrossrefSearch in Google Scholar
• 16 For a palladium(0)-catalyzed silylation of 3f with moderate enantioselectivity, see: Hayashi T, Ohno A, Lu S.-j, Matsumoto Y, Fukuyo E, Yanagi K. J. Am. Chem. Soc. 1994; 116: 4221
  Search in Google Scholar
• 17 We note here that we used the term enantioconvergent incorrectly in ref. 12b. It is a stereoconvergent allylic substitution.
• 18 Fleming I, Lawrence NJ. J. Chem. Soc., Perkin Trans. 1 1992; 3309
• 19 Sarakinos G, Corey EJ. Org. Lett. 1999; 1: 811
  CrossrefSearch in Google Scholar
• 20 Lee K.-s, Hoveyda AH. J. Am. Chem. Soc. 2010; 132: 2898
  CrossrefSearch in Google Scholar
• 21 Walter C, Auer G, Oestreich M. Angew. Chem. Int. Ed. 2006; 45: 5675
  CrossrefSearch in Google Scholar
• 22 Hayashi T, Yamasaki K, Mimura M, Uozomi Y. J. Am. Chem. Soc. 2004; 126: 3036
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• 23 Lüssem BJ, Gais H.-J. J. Am. Chem. Soc. 2003; 125: 6066
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• 24 Liotta D, Zima G, Saindane M. J. Org. Chem. 1982; 47: 1258
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• 25 Fleming I, Higgins D, Lawrence NJ, Thomas AP. J. Chem. Soc., Perkin Trans. 1 1992; 3331
• 26 Oestreich M, Auer G. Adv. Synth. Catal. 2005; 347: 637
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• 27 Ramadhar TR, Kawakima J.-I, Lough AJ, Batey RA. Org. Lett. 2010; 12: 4446
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• 28 Qian X, Auffrant A, Felouat A, Gosmini C. Angew. Chem. Int. Ed. 2011; 50: 10402
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• 29 Renaud P, Fox MA. J. Org. Chem. 1988; 53: 3745
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• 30 Schmidtmann ES, Oestreich M. Chem. Commun. 2006; 3643
• 31 Ochiai M, Iwaki S, Takaoka Y, Nagao Y. Organometallics 1989; 8: 1751
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• References

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For allylic substitution, see:
• 12a Racemic: Vyas DJ, Oestreich M. Angew. Chem. Int. Ed. 2010; 49: 8513
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• 12b Enantioselective: Delvos LB, Vyas DJ, Oestreich M. Angew. Chem. Int. Ed. 2013; 52: 4650
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• 12c Diastereoselective: Hazra CK, Irran E, Oestreich M. Eur. J. Org. Chem. 2013; 4903
• 12d Enantioselective: Delvos LB, Hensel A, Oestreich M. Synthesis 2014; 46: 2957
  Thieme ConnectSearch in Google Scholar

For our work on 1,2-addition, see:
• 13a Aldehydes, racemic: Kleeberg C, Feldmann E, Hartmann E, Vyas DJ, Oestreich M. Chem. Eur. J. 2011; 17: 13538
  CrossrefSearch in Google Scholar
• 13b Imines, racemic: Vyas DJ, Fröhlich R, Oestreich M. Org. Lett. 2011; 13: 2094
  CrossrefSearch in Google Scholar
• 13c Imines, asymmetric: Hensel A, Nagura K, Delvos LB, Oestreich M. Angew. Chem. Int. Ed. 2014; 53: 4964
  Search in Google Scholar

Hayashi and co-workers reported a related enantioselective allylic substitution (cf. refs. 12b and 12d):
• 14a Takeda M, Shintani R, Hayashi T. J. Org. Chem. 2013; 78: 5007
  CrossrefSearch in Google Scholar

For a comparison of both methods and indirect synthesis of α-chiral silanes by asymmetric copper(I) catalysis, see:
• 14b Delvos LB, Oestreich M. Chim. Oggi 2013; 31: 74
  Search in Google Scholar
• 15a Park J, McQuade D. Synthesis 2012; 44: 1485
  Thieme ConnectSearch in Google Scholar

For B–B bond activation for asymmetric 1,4-addition, see:
• 15b Park JK, Lackey HH, Rexford MD, Kovnir K, Shatruk M, McQuade DT. Org. Lett. 2010; 12: 5008
  Search in Google Scholar

For allylic substitution with boron nucleophiles catalyzed by a closely related complex, see:
• 15c Park JK, Lackey HH, Ondrusek BA, McQuade DT. J. Am. Chem. Soc. 2011; 133: 2410
  CrossrefSearch in Google Scholar
• 15d Park JK, McQuade DT. Angew. Chem. Int. Ed. 2012; 51: 2717
  CrossrefSearch in Google Scholar
• 16 For a palladium(0)-catalyzed silylation of 3f with moderate enantioselectivity, see: Hayashi T, Ohno A, Lu S.-j, Matsumoto Y, Fukuyo E, Yanagi K. J. Am. Chem. Soc. 1994; 116: 4221
  Search in Google Scholar
• 17 We note here that we used the term enantioconvergent incorrectly in ref. 12b. It is a stereoconvergent allylic substitution.
• 18 Fleming I, Lawrence NJ. J. Chem. Soc., Perkin Trans. 1 1992; 3309
• 19 Sarakinos G, Corey EJ. Org. Lett. 1999; 1: 811
  CrossrefSearch in Google Scholar
• 20 Lee K.-s, Hoveyda AH. J. Am. Chem. Soc. 2010; 132: 2898
  CrossrefSearch in Google Scholar
• 21 Walter C, Auer G, Oestreich M. Angew. Chem. Int. Ed. 2006; 45: 5675
  CrossrefSearch in Google Scholar
• 22 Hayashi T, Yamasaki K, Mimura M, Uozomi Y. J. Am. Chem. Soc. 2004; 126: 3036
  CrossrefSearch in Google Scholar
• 23 Lüssem BJ, Gais H.-J. J. Am. Chem. Soc. 2003; 125: 6066
  CrossrefSearch in Google Scholar
• 24 Liotta D, Zima G, Saindane M. J. Org. Chem. 1982; 47: 1258
  CrossrefSearch in Google Scholar
• 25 Fleming I, Higgins D, Lawrence NJ, Thomas AP. J. Chem. Soc., Perkin Trans. 1 1992; 3331
• 26 Oestreich M, Auer G. Adv. Synth. Catal. 2005; 347: 637
  CrossrefSearch in Google Scholar
• 27 Ramadhar TR, Kawakima J.-I, Lough AJ, Batey RA. Org. Lett. 2010; 12: 4446
  CrossrefSearch in Google Scholar
• 28 Qian X, Auffrant A, Felouat A, Gosmini C. Angew. Chem. Int. Ed. 2011; 50: 10402
  CrossrefPubMedSearch in Google Scholar
• 29 Renaud P, Fox MA. J. Org. Chem. 1988; 53: 3745
  CrossrefSearch in Google Scholar
• 30 Schmidtmann ES, Oestreich M. Chem. Commun. 2006; 3643
• 31 Ochiai M, Iwaki S, Takaoka Y, Nagao Y. Organometallics 1989; 8: 1751
  CrossrefSearch in Google Scholar

• Supplementary Material