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A New and Efficient Access to Thiazoline‐4‐carboxylates and Cysteine Derivatives Incorporating Cyclopropyl Groups
Author(s) -
Nötzel Marcus W.,
Labahn Thomas,
EsSayed Mazen,
de Meijere Armin
Publication year - 2001
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200108)2001:16<3025::aid-ejoc3025>3.0.co;2-k
Subject(s) - chemistry , thiazoline , cysteine , combinatorial chemistry , stereochemistry , organic chemistry , enzyme
Under basic conditions (NaHCO 3 , MeCN), thiocarboxamides 2 , including N,N ‐thioureas, cleanly undergo Michael addition onto 2‐chloro‐2‐cyclopropylideneacetates 1 , attacking through the sulfur, and this is followed by an intramolecular substitution to afford 5‐spirocyclopropane‐annelated thiazoline‐4‐carboxylates 4 in 37−92% yields. The thiazolines 4 are cysteine derivatives that possess a cyclopropyl or substituted cyclopropyl group in place of the gem ‐dimethyl‐substituted β‐carbon atom of penicillamine; they can be hydrolyzed to the hydrochloride salt of the amino acid 5 by heating in acid. Under acidic conditions (CH 2 Cl 2 , HCl), the Michael adducts 7 of thioamides 2 onto 1 are formed in high to virtually quantitative yields. When treated with NaHCO 3 in MeCN, the adducts 7 cyclize to thiazolinecarboxylates 4 (51−82%), but in the presence of Ti(O i Pr) 4 they form spirocyclopropane‐annelated thiazinones 8 (19−88%).