posted on 2004-04-16, 00:00authored byDallas K. Bates, Xiaofen Li, Parag V. Jog
A new protocol for synthesis of 2-heterocylylacetic acid derivatives involving conjugate addition of
allyl mercaptan to an acrylate containing a tethered olefinic site followed by RCM (ring-closing
metathesis) is described. In this series, sulfanyl derivatives were unreactive, while sulfoxide and
sulfone analogues provided the corresponding thiazocines in fair to excellent yields. Use of the
sulfoxide oxidation state as a protecting group for sulfides inert to RCM is demonstrated also.
Thus, oxidation of sulfide 9 [N-allyl-N-[2-(allylthio)-4-(1H-indol-1-yl)-4-oxobutyl]-4-methylbenzenesulfonamide] followed by cyclization yielded the corresponding thiazocine sulfoxide 12. Deprotection (deoxygenation) of 12 was accomplished using Lawesson's reagent, producing 1-[[4-[4-(methylphenyl)sulfonyl]-3,4,5,8-tetrahydro-2H-1,4-thiazocin-2-yl]acetyl]-1H-indole (21) in 67%
unoptimized yield.