Studies related to dihydro-1,4-thiazines. Part IV. Stereochemical consequences of 1,3-sulphur migrations

Abstract

Methyl (6S,7R)-5,5-dimethyl-4-thia-1-aza[7-²H]bicyclo[4.1.0]hept-2-ene-3-carboxylate (2) is thermally isomerised in boiling toluene to methyl (2R,3R)-3,4-dihydro-3-isopropenyl-2H-[2-²H]1,4-thiazine-6-carboxylate (4), indicating that the new carbon–sulphur bond is formed with retention of configuration. The latter derivative is also produced when methyl (3R)-3,4-dihydro-3-{(S)-iodo[²H]methyl}-2,2-dimethyl-2H-1,4-thiazine-6-carboxylate (15), obtained from the reaction of the aziridine (2) with hydriodic acid, is heated in boiling ethyl methyl ketone; in this case the new carbon–sulphur bond is formed with inversion of configuration.

Derivative (2) was synthesised by way of methyl (3R)-3,4-dihydro-3-{(S)-hydroxy[²H]methyl}-2,2-dimethyl-2H-1,4-thiazine-6-carboxylate (13), obtained from the reaction of 6α-chloro-[(S)-3-methylene-²H]penicillanyl alcohol (28) with sodium methoxide. The last-named alcohol is prepared by reduction of 6α-chloro[formyl-²H]-penicillanal (23) with actively fermenting yeast. 6α-Chloropenicillanoylmethanol (25), available from the reaction of the diazo-ketone (24) with dilute sulphuric acid, affords the aldehyde (23) by reduction with sodium borodeuteride followed by oxidation with sodium periodate.