Regiodivergent Dearomatization of N-Alkyl Pyrazinium Salts

Abstract

The first chapter contains a review of the methods for the synthesis of piperazines. These methods can be grouped into two categories: cyclization and dearomatization methods. Cyclization as a means for piperazine synthesis has been well developed and there are many examples. Dearomatization of pyrazines to obtain piperazines is not as developed with only a handful of established methods, however, has recently gained more attention. We discuss advantages and limitations of each of these methods.

The second chapter proceeds with a brief introduction to dearomatization of N-alkyl pyrazinium salts toward the synthesis of piperazines. Following, we discuss the regiodivergent nucleophilic dearomatization reaction of such pyrazinium salts with aryl boronic acids which produced a dimeric tetrahydropyrazine. We then report that the dimer can be reduced at the NC aminal bonds to yield tetrahydropyrazines and further reduced to obtain substituted piperazines. Finally, we show that for these dearomatization reaction alternative regioselectivity to that of aryl boronic acids can be obtained using Grignard reagents as nucleophiles.