Studies related to dihydro-1,4-thiazines. Part III. Transformations of methyl (6S)-7-hydroxy-5,5,9,9-tetramethyl-8-oxa-4-thia-1-azabicyclo-[4.3.0]non-2-ene-3-carboxylate

Abstract

Methyl (6S)-7-hydroxy-5,5,9,9-tetramethyl-8-oxa-4-thia-1 -azabicyclo[4.3.0]non-2-ene-3-carboxylate (2) is converted into methyl 5,5,9-trimethyl-4-thia-1 -azabicyclo[4.3.0]nona-2,6,8-triene-3-carboxylate (14) by lithium aluminium hydride–aluminium chloride in ether. The rearrangement is also induced by aluminium chloride in ether, toluene-p-sulphonyl chloride in pyridine. and methanesulphonyl chloride–triethylamine in dichloromethane.

Methanolic hydrogen chloride rapidly converts the lactol (2) into a mixture of acetals; the minor acetal is then isomerised under the reaction conditions to the thermodynamically preferred major acetal, which is considered to be the (7S)-isomer (12). Deuterium-incorporation studies suggest that the iminium ion (15) is involved in the transformation of derivative (2) into the acetal (12).

The lactol (2) affords the methylthio-derivative (6) with acidified methanethiol and the phenylthio-derivative (7) with acidified benzenethiol. Treatment of the former material with sodium periodate yields the sulphoxide (8), which is further oxidised to the disulphoxide (9). Raney nickel converts the sulphoxide (8) mainly into the oxazolidine (17), although complex reactions ensue when the thioacetals (6) and (7) and the disulphoxide (9) are treated with this reagent.