Convergent Catalytic Asymmetric Synthesis of Esters of Chiral Dialkyl Carbinols

Abstract

The yields have not been optimized.General Procedure 1 (GP-1): Preparation of the electrophile. 2 An oven-dried 100 mL round-bottom flask was charged with a magnetic stir bar and either ZnCl2 or ZnBr2 (0.050 equiv), and then it was sealed with a rubber septum cap. The flask was placed under a nitrogen atmosphere by evacuating and backfilling the flask (three cycles), followed by the addition of DCM and the acyl bromide (1.2 equiv). The resulting solution was cooled to -10 °C, and the mixture was stirred for 10 min. At this temperature, the aldehyde (1.0 equiv) was added via syringe pump over 30 min, and the resulting mixture was stirred for 2 h. Then, the reaction mixture was filtered through a short column of neutral aluminium oxide, with a DCM washing. The filtrate was concentrated under reduced pressure. The residue was either purified by vacuum distillation to afford the pure product, or used directly after the determination of its purity by 1 H NMR (CH2Br2 as the internal standard).1-Bromoethyl benzoate. The title compound was synthesized according to GP-1 from ZnCl2 (544 mg, 4.0 mmol), BzBr (11.3 mL, 96.0 mmol), acetaldehyde (4.5 mL, 80 mmol), and DCM (10 mL). The product was purified by vacuum distillation (b.p. = 75-79 °C, 1.2 Torr). 9.6 g (42.1 mmol, 53% yield). Colorless oil. 1 H NMR (400 MHz, CDCl3) δ 8.12 -8.04 (m, 2H), 7.65 -7.56 (m, 1H), 7.52 -7.42 (m, 2H), 6.97 (q, J = 5.9 Hz, 1H), 2.14 (d, J = 5.9 Hz, 3H). cm -1 .1-Bromopropyl benzoate. The title compound was synthesized according to GP-1 from ZnCl2 (870 mg, 6.4 mmol), BzBr (18.0 mL, 154 mmol), propionaldehyde (9.2 mL, 128 mmol), and DCM (20 mL). The product was purified by vacuum distillation (b.p. = 88-90 °C, 0.5 Torr). 22.4 g (92.6 mmol, 72% yield). Colorless oil. ZnCl 2 or ZnBr 2 DCM, -10 °C R O Br Br R 1 O R 1 O H R O S-4 1 H NMR (500 MHz, CDCl3) δ 8.10 -8.05 (m, 2H), 7.65 -7.58 (m, 1H), 7.50 -7.43 (m, 2H), 6.85 (t, J = 5.7 Hz, 1H), 2.36 -2.23 (m, 2H), 1.15 (t, J = 7.3 Hz, 3H). , 961, 908, 716 cm -1 . 1-Bromopentyl benzoate. The title compound was synthesized according to GP-1 from ZnCl2 (544 mg, 4.0 mmol), BzBr (11.3 mL, 96.0 mmol), valeraldehyde (8.5 mL, 80 mmol), and DCM (10 mL). The product was purified by vacuum distillation (b.p. = 103-108 °C, 0.7 Torr). 8.4 g (31.1 mmol, 39% yield). Yellow oil. 1 H NMR (400 MHz, CDCl3) δ 8.10 -8.04 (m, 2H), 7.66 -7.57 (m, 1H), 7.52 -7.44 (m, 2H), 6.89 (t, J = 5.9 Hz, 1H), 2.37 -2.21 (m, 2H), 1.61 -1.49 (m, 2H), 1.48 -1.35 (m, 2H), 0.95 (t, J = 7.3 Hz, 3H). cm -1 .1-Bromo-3-methylbutyl benzoate. The title compound was synthesized according to GP-1 from ZnBr2 (888 mg, 4.0 mmol), BzBr (11.3 mL, 96.0 mmol), isovaleraldehyde (8.6 mL, 80 mmol), and DCM (10 mL). The product was purified by vacuum distillation (b.p. = 95-98 °C, 0.7 Torr). 14.3 g (53.0 mmol, 66% yield). Colorless oil. 1 H NMR (400 MHz, CDCl3) δ 8.12 -8.04 (m, 2H), 7.65 -7.57 (m, 1H), 7.53 -7.42 (m, 2H), 6.95 (dd, J = 7.6, 5.6 Hz, 1H), 2.28 (ddd, J = 14.2, 7.6, 6.6 Hz, 1H), 2.16 (ddd, J = 14.3, 7.3, 5.6 Hz, 1H), 1.99 -1.86 (m, 1H), 0.99 (d, J = ...

Enantio‐ and Regioselective NiH‐Catalyzed Reductive Hydroarylation of Vinylarenes with Aryl Iodides

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Catalytic asymmetric reductive hydroalkylation of enamides and enecarbamates to chiral aliphatic amines

“…Our group devoted efforts to develop olefin reductive alkylation reactions 26 – 30 . Nowadays, olefin reductive hydroalkylation has been one of the most appealing methods for alkyl–alkyl formation 31 – 35 . In the elegant work from Fu’s group at Caltech 32 , enantioconvergent coupling of a broad scope of racemic alkyl electrophiles with olefins was achieved.…”

NiH-catalyzed asymmetric hydroarylation of N-acyl enamines to chiral benzylamines

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