Compound 8a

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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

Procedure A:α-Silyl benzoate ester 32 (1.84 g, 4.1 mmol, 1.0 equiv) in a Schlenk reaction vessel was dissolved in anhydrous Et₂O (6 mL) under an atmosphere of nitrogen. The reaction mixture was cooled to –78 °C. s-BuLi (1.5-1.6 M in hexanes, 1.0 equiv) was added dropwise to the reaction mixture at –78 °C and stirred for 10 min. Phenethylboronic ester 6a (1.2 g, 4.9 mmol, 1.2 equiv) in Et₂O (6 mL) was then added dropwise to the reaction mixture at –78 °C. The reaction mixture was stirred at this temperature for 10 min and warmed to room temperature for 1 h. The reaction was diluted with Et₂O (15 mL) and water (15 mL). The aqueous layer was extracted with Et₂O (2×25 mL) and the combined organic layers were washed with brine, dried over anhydrous MgSO₄ and concentrated. The crude boronic ester was purified by flash column chromatography (SiO₂, CH₂Cl₂:MeOH:NH₄OH, 100:2.5:0.5 → 100:5:1) to afford the corresponding boronic ester 8a (1.55 g, 88% yield, 99:1 d.r.) as a pale yellow oil.

Procedure B: An oven-dried Schlenk tube under nitrogen was charged with chiral α-chlorosilane (S)-12 (141.6 mg, 0.52 mmol, 1.3 equiv) in anhydrous Et₂O (2 mL). The suspension was degassed by three freeze/pump/thaw cycles under nitrogen before cooling down to –78 °C. s-BuLi (1.3 M in hexanes, 0.7 mL, 0.96 mmol, 2.4 equiv) was slowly added dropwise to the reaction mixture at –78 °C and stirred (500 rotations per minute) for 1 h. A solution of phenethylboronic ester 6a (92.9 mg, 0.4 mmol, 1.0 equiv) in anhydrous Et₂O (2 mL) was then added dropwise at a rate of approximately 0.16 mL•min^-1 to the reaction mixture at –78 °C. The reaction mixture was stirred (600-700 rotations per minute) at this temperature for 1 h and warmed to room temperature for 1 h. The reaction was diluted with Et₂O (5 mL) and water (5 mL). The aqueous layer was extracted with Et₂O (2×10 mL) and the combined organic layers were washed with brine, dried over anhydrous MgSO₄ and concentrated. The crude product was purified by flash column chromatography (SiO₂, CH₂Cl₂:MeOH:NH₄OH, 100:2.5:0.5 → 100:5:1) to give the corresponding boronic ester 8a (0.16 g, 92% yield, 97:3 d.r.) as a pale yellow oil. : –55.2 (c 1.0, CHCl₃) ¹H NMR (400 MHz, CDCl₃): δ 7.29–7.23 (m, 2H, Ar-H), 7.20–7.12 (m, 3H, Ar-H), 3.46–3.36 (m, 1H, 2-CHH), 3.31 (s, 3H, OCH₃), 3.18 (dd, J = 8.3 Hz, 1H, 2-CHH), 3.09–2.95 (m, 1H, 6-CHH), 2.71 (ddd, J = 14.4, 9.9, 5.0 Hz, 1H, 12-CHH), 2.58–2.42 (m, 2H, 12-CHH, 7-CHH), 2.41–2.26 (m, 1H, 3-CH), 2.16–1.99 (m, 1H, 6-CHH), 1.93–1.78 (m, 2H, 4-CHH, 11-CHH), 1.78–1.61 (m, 4H, 7-CHH, 5-CH₂, 11-CHH), 1.66–1.47 (m, 1H, 4-CHH), 1.26 (s, 12H, CH₃ of Bpin), 0.51 (dd, J = 12.1, 3.1 Hz, 1H, 10-CH), 0.10 (s, 3H, CH₃-Si), 0.06 (s, 3H, CH₃-Si). ¹³C NMR (101 MHz, CDCl₃): δ 142.8 (C), 128.5 (2×CH), 128.2 (2×CH), 125.5 (CH), 82.7 (2×C-O of Bpin), 76.5 (2-CH₂), 67.5 (3-CH), 59.1 (OCH₃), 57.4 (6-CH₂), 44.8 (7-CH₂), 39.6 (12-CH₂), 28.5 (4-CH₂), 27.9 (11-CH₂), 25.3 (CH₃, of Bpin), 24.8 (CH₃, of Bpin), 23.2 (5-CH₂), 13.4 (10-CH), –2.6 (CH₃-Si), –2.8 (CH₃-Si). HRMS (ESI⁺): calculated for C₂₄H₄₃BNO₃Si [M+H⁺]: 432.3104; found 432.3111 IR (v_max/cm^-1, neat): 2975, 2925, 1603, 1453, 1350, 1304, 1247, 1143, 1109, 846, 746, 698 The absolute stereochemistry and diastereomeric purity of (S,S)-8a was determined by HPLC analysis of the corresponding allylic alcohol (R)-36, obtained by Zweifel olefination¹² followed by Tamao oxidation of C–Si bond.