Studies related to penicillins. Part XV. Reactions of 2-oxa-4,7-diazabicyclo[3.2.0]hept-3-en-6-ones with thiols

Abstract

(1R,5S)-3-Benzyl-7-(2-methylprop-1-enyl)-2-oxa-4,7-diazabicyclo[3.2.0]hept-3-en-6-one (2) is converted, probably by way of the azetinium ion (27), into a mixture of (3R,4R)-1-(2-methylprop-1-enyl)-4-methylthio-3-phenylacetamidoazetidin-2-one (7) and the (3R,4S)-isomer (17) by methanethiol in the presence of a Lewis acid. Corresponding reactions occur when the oxazoline (2) is similarly treated with ethanethiol, butane-1-thiol, butane-2-thiol, 2-methylpropane-2-thiol, prop-2-ene-1-thiol, ethane-1,2-dithiol, 2-mercaptoethyl acetate, methyl mercaptoacetate, and methyl 3-mercaptopropionate.

(1R,5S)-7-(2-Methylprop-1-enyl)-3-phenoxymethyl-2-oxa-4,7-diazabicyclo[3.2.0]hept-3-en-6-one (3) and methyl 2-{(1R,5S)-3-benzyl-6-oxo-2-oxa-4,7-diazabicyclo[3.2.0]hept-3-en-7-yl}-3-methylbut-2-enoate (4) also react with methanethiol to give mixtures of the corresponding cis-and trans-4-methylthioazetidin-2-ones.

The methylpropenyl substituents of derivatives (7) and (17) and of (3R,4R)-4-allylthio-1-(2-methylprop-1-enyl)-3-phenylacetamidoazetidin-2-one (12) and the (3R,4S)-isomer (22) are removed by treatment with either ozone–ammonium hydroxide or N-bromoacetamide–triethylamine.