Use of Nitriles in Synthesis. First Total Synthesis of ent-Sachalinol A

Abstract

The total synthesis of ent-sachalinol A, has been achieved by utilizing a Sharpless epoxidation and nitrile substitution as the key reactions.

sachalinol A - Sharpless epoxidation - nitriles - mono­terpenes

References and Notes

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For unsaturated nitriles, see also:

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9

(2 E ,4 S )-4,7-Dihydroxy-3,7-dimethyloct-2-enenitrile ( 2): NaCN (605 mg, 12.36 mmol) was added to a solution of 1 (1.7 g, 4.12 mmol) in HMPA (8 mL). After stirring for 3 h, the mixture was diluted with H₂O (150 mL). The aqueous layer was extracted with EtOAc (5 × 100 mL) and the combined organic extracts were washed with 10% aq HCl (3 × 50 mL), 5% aq NaHCO₃ (3 × 50 mL), and brine (3 × 50 mL). The aqueous acidic layer was extracted with EtOAc (100 mL) and the combined organic extracts washed again with 5% aq NaHCO₃ (3 × 10 mL) and brine (3 × 10 mL). The organic solution was dried and the filtrate was concentrated to give 1.6 g of the crude product, which was dissolved in MeOH (20 mL). Then, a catalytic amount of p-TsOH (75 mg, 0.41 mmol) was added and, after stirring for 2 h, the reaction was quenched by the addition of NaHCO₃ (100 mg). The MeOH was evaporated and the mixture was dissolved in EtOAc, filtered, and concentrated to give nitrile 2 (605 mg, 80%), which was used in the next step without further purification; [α]_D ²⁰ -27.0 (c 2.0, CHCl₃). IR (film): 3400 (br), 2970-2870, 2222, 1632, 1441, 1381, 1215, 1152, 1090, 910 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 5.55 (1 H, s, H-2), 4.18 (1 H, m, H-4), 2.01 (3 H, s, H-10), 1.9-1.2 (4 H, m, H-5, H-6), 1.24 (6 H, s, H-8, H-9). ¹³C NMR (100 MHz, CDCl₃): δ = 17.71 (C-10), 29.35 (C-5), 29.53 (C-9), 29.57 (C-8), 38.36 (C-6), 70.76 (C-7), 74.43 (C-4), 94.95 (C-2), 117.27 (C-1), 166.07 (C-3). HRMS-EI: m/z calcd for C₁₀H₁₇O₂N [M]⁺: 183.1259; found: 183.1237.

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