Studies related to dihydro-1,4-thiazines. Part II. Reduction of methyl (6S)-7-hydroxy-5,5,9,9-tetramethyl-8-oxa-4-thia-1-azabicyclo[4,3,0]non-2-ene-3-carboxylate and its 4-oxide

Abstract

Reduction of methyl (6S)-5,5,9,9-tetramethyl-7-oxo-8-oxa-4-thia-1-azabicyclo[4,3,0]non-2-ene-3-carboxylate (12) with sodium aluminium hydride gives the 7-hydroxy-analogue (11). Little stereoselectivity is observed in the conversion of compound (11) into the monodeuteriated alcohol (5) with lithium or sodium borodeuteride, lithium aluminium deuteride, or lithium deuteridotri-t-butoxyaluminate, and of the hemiacetal sufphoxides (13) into the monodeuteriated alcohol sulphoxides (15) with sodium borodeuteride.

The alcohol sulphoxides (14) react with acetyl chloride to give methyl (1R,5S)-2-chloro-4,4-dimethyl-7-oxa-3-thia-8-azabicyclo[3,2,1]octane-2-carboxylate (16), which affords the amide (17). The derivative (17) is reduced to the alcohol (4) by iron(II) chloride in methanolic hydrochloric acid and to methyl (1R,5S)-8-acetyl-4,4-dimethyl-7-oxa-3-thia-8-azabicyclo[3,2,1]octane-2-carboxylate (20) by zinc in acetic acid. It also reacts with silver perchlorate in methanol to yield the methoxy-derivative (19).