Synlett 2006(11): 1715-1716  
DOI: 10.1055/s-2006-944223
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

David Díez*, Marta G. Nuñez, R. F. Moro, A. B. Antón, N. M. Garrido, I. S. Marcos, P. Basabe
Departamento de Química Orgánica, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain
Fax: +34(923)294574; e-Mail: ddm@usal.es;
Further Information

Publication History

Received 13 February 2006
Publication Date:
04 July 2006 (online)

Abstract

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

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(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.