酮转换成酯wittig-type Reactions of 2-Lithio-2-trimethylsilyl- 1,3-dithian(Peterson-type reaction)

J. Chem. Soc., Chem. Commun., 1972, 526-526

2-[4-Cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexylidene]-1,3-dithiane (11):

To a solution of 2-(trimethylsilyl)-1,3-dithiane (9.25 mL, 48.7 mmol) in dry THF (80 mL) at 0 °C under an argon atmosphere was added rapidly n-butyllithium (2.5 M in hexanes, 19.2 mL, 48 mmol). After 10 min, the mixture was cooled to -78 °C and a solution of 10 (7.53 g, 23 mmol) in THF (40 mL) was added. After 10 min, aqueous NaCl was added, and the mixture was allowed to warm to room temperature and was diluted with water. This mixture was combined with the product of three substantially similar reactions conducted on 10 (3.04, 6.01, and 6.1 g, 48.3 mmol total), the combined mixture was extracted three times with CH₂Cl₂, the extract was dried (MgSO₄), and the solvent was evaporated. Purification by flash chromatography, eluting with 10% EtOAc/hexanes, provided 11 as a white solid (26 g, 87%).

Methyl cis-and trans-4-Cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexane-1-carboxylate (12 and 13):
Perchloric acid (70%, 13.8 mL, 160 mmol) and mercuric chloride (34.1 g, 126 mmol) were added to a solution of 11 (13 g, 31.3 mmol) in CH₃OH (0.5 L) under an argon atmosphere, and the mixture was heated at reflux for 2 h and then was allowed to stir at room temperature for 42 h. The mixture was diluted with CH₂Cl₂ and was filtered through Celite, and the filtrate was combined with that of a similar reaction conducted concurrently on the same scale. The mixture was neutralized with aqueous NaHCO₃ and was extracted three times with CH₂Cl₂. The organic extract was washed three times with aqueous sodium sulfite, was dried (MgSO₄), and was evaporated. Purification by flash chromatography, eluting with 15% EtOAc/hexanes, provided the cis ester (12) as a white solid (12.4 g, 56%), The trans ester (13) was also isolated from this mixture as a solid (1.04 g, 5%).

J. Med. Chem.1998, 41, 6, 821–835