Synthesis of a Fused β-Lactone via Pyridine-Assisted [2+2] Cycloaddition

Significance

The synthesis of pyrrolidinyl-fused β-lactones 5 and 6 by reaction of in situ generated acroyl pyridinium salt 2 with N-p-methoxybenzyl-substituted amino ketone 3 is reported. Compared to previous work by the same group (J. Am. Chem. Soc. 2005, 127, 8974-8976), which employed bulkier bases such as triisobutylamine or 2,6-di-tert-butylpyridine for the formation of acroyl ammonium species, the present method leads more effectively to the formation of 1,2- as opposed to 1,4-addition intermediates. The reaction is proposed to proceed via ketene 4 followed by a [2+2] cycloaddition process to give 5 and 6 favoring the formation of 5 in an 8:1 ratio.