Simple thiazocine-2-acetic acid derivatives via ring-closing metathesis

Dallas K Bates; Xiaofen Li; Parag V Jog

doi:10.1021/jo035692z

Simple thiazocine-2-acetic acid derivatives via ring-closing metathesis

J Org Chem. 2004 Apr 16;69(8):2750-4. doi: 10.1021/jo035692z.

Authors

Dallas K Bates¹, Xiaofen Li, Parag V Jog

Affiliation

¹ Department of Chemistry, Michigan Technological University, 1400 Townsend Drive, Houghton, Michigan 49931, USA. dbates@mtu.edu

PMID: 15074923
DOI: 10.1021/jo035692z

Abstract

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.