(1R,3R)-2-Methylene-1,3-dithiolane 1,3-dioxide: a highly reactive and highly selective chiral ketene equivalent in cycloaddition reactions with a broad range of dienes

Abstract

The chiral ketene equivalent trans-2-methylene-1,3-dithiolane 1,3-dioxide has been prepared in racemic and enantiomerically pure form in four steps. The key step in the asymmetric synthesis utilised a Modena asymmetric oxidation of 2-benzyloxymethyl-1,3-dithiolane which gave the trans bis-sulfoxide with high diastereocontrol (91∶9 in favour of trans) and high enantiocontrol (>97% ee). The ketene equivalent shows high selectivity (>97∶3) in Diels–Alder reactions with a range of simple dienes (cyclopentadiene, furan, 1-methoxybutadiene, Danishefsky’s diene, 1-methoxycyclohexa-1,3-diene) and shows high reactivity as it is able to undergo cycloadditions with notoriously unreactive dienes (cyclohexa-1,3-diene, 90∶10 selectivity; 2H-pyran-2-one, 94∶6 selectivity). Dihydropyridines also participated in cycloaddition reaction but with only moderate selectivity (73∶27). The Diels–Alder adducts can be readily deprotected to return the carbonyl group using a two step sequence involving reduction followed by hydrolysis.