‘Hidden’ axial chirality as a stereodirecting element in reactions involving enol(ate) intermediates. Part 1. Cyclisation reactions of methyl (4R)-3-(2-diazo-3-oxobutanoyl)thiazolidine-4-carboxylate and related compounds

Abstract

Methyl (4R)-3-(2-diazo-3-oxobutanoyl)thiazolidine-4-carboxylate 1b underwent cyclisation, under a variety of basic conditions, to give methyl (6S)-2-oxo-8-thia-1.4,5-triazabicyclo[4.3.0]non-3-ene-6-carboxylate 2a in an enantiopure state. The absolute configuration of compound 2a was deduced by X-ray crystallography. Similar stereoselective cyclisations, proceeding with retention of configuration, were observed with methyl (4R)-3-[diazo(methoxycarbonyl)acetyl]thiazolidine-4-carboxylate 1g(to give compound 5a). methyl (4R)-3-(2-diazo-3-oxobutanoyl)-2,2-dimethylthiazolidine-4-carboxylate 20a(to give compound 21a) and methyl (2R,4R)-3-(2-diazo-3-oxobutanoyl)-2-methylthiazolidine-4-carboxylate 22a(to give compound 24). An X-ray crystallographic analysis of compound 22a revealed that the amide and diazo ketone units, although individually near planar, were twisted from each other by 35°; it was notable that the amide linkage adopted the (Z)-geometry required for the cyclisation reaction whereas the diazo moiety was incorrectly aligned. It is suggested that the cyclisation reactions proceed by way of planar enol(ate) intermediates, e.g. 6a, which possess axial chirality.