A new and efficient access to thiazoline-4-carboxylates and cysteine derivatives incorporating cyclopropyl groups

Under basic conditions (NaHCO3, MeCN), thiocarboxamides 2, including NN-thi oureas, cleanly undergo Michael addition onto 2-chloro-2-cyclopropylideneac etates 1, attacking through the sulfur, and this is followed by an intramol ecular substitution to afford 5-spirocyclopropane-annelated thiazoline-4-ca rboxylates 4 in 37-92% yields. The thiazolines 4 are cysteine derivatives t hat possess a cyclopropyl or substituted cyclopropyl group in place of the gem-dimethyl-substituted beta -carbon atom of penicillamine; they can be hy drolyzed to the hydrochloride salt of the amino acid 5 by heating in acid. Under acidic conditions (CH2Cl2, HCl), the Michael adducts 7 of thioamides 2 onto 1 are formed in high to virtually quantitative yields. When treated with NaHCO3 in MeCN, the adducts 7 cyclize to thiazolinecarboxylates 4 (51- 82%), but in the presence of Ti(OiPr)(4) they form spirocyclopropane-annela ted thiazinones 8 (19-88%).