Exploiting 3-Oxidopyraziniums toward Diazabicyclo[3.2.1]octanes and Their Conversion into Diazabicyclo[2.2.2]octanes and Tricyclic Lactone-Lactams.

Abstract

3-Oxidopyraziniums are azomethine ylides derived from 2(1H)-pyrazinones that can undergo 1,3-dipolar cycloadditions with acrylate and acrylic acid derivatives. The cycloaddition of 1-(4-methoxybenzyl)-5,6-dimethyl-3-oxidopyrazinium with methyl and tert-butyl acrylate and with methyl crotonate afforded a 3,8-diazabicyclo[3.2.1]octane in 51-73% yield together with traces of the 2,5-diazabicyclo[2.2.2]octane. In contrast, cycloaddition of this 3-oxidopyrazinium with methyl 2-phenyl acrylate provided the [2.2.2] product in 40% yield. Herein, we show that the 2,5-diazabicyclo[2.2.2]octanes were formed from the [3.2.1] compounds via a Wagner-Meerwein rearrangement. Remarkably, when acrylic acid and 2-phenylacrylic acid were employed as dipolarophiles, novel tricyclic fused lactone-lactam systems were obtained in 71% and 50% yields, respectively. The formation of these tricyclic compounds can be rationalized via the mechanism described above followed by lactonization of the 2,5-diazabicyclo[2.2.2]octane.