Pyrazine Alkylation with Aldehydes and Haloalkanes Using N,N’‐Bis(trimethylsilyl)‐1,4‐dihydropyrazine Derivatives

Abstract

N,N'-Bis(trimethylsilyl)-1,4-dihydropyrazines are useful starting materials for synthesizing alkylpyrazines upon combination with aldehydes and tetra(n-butyl)ammonium fluoride. Various aryl, heteroaryl, and alkyl aldehydes are utilized as sources of the alkyl substituents; reactions with electron-rich aldehydes afford the corresponding alkylpyrazines in good yields. The overall reaction sequence was clarified by DFT calculations; in this reaction, activation of the N-trimethylsilyl moiety by fluoride, forming the electron-rich silicate intermediate Int-1, is the key step for the subsequent CÀ C bond formation with aldehydes, and the following 1,3-proton transfer from Int-3 to Int-4 is the rate-determining step. In addition, treatment of N,N'-bis(trimethylsilyl)-2,5-dimethyl-1,4-dihydropyrazines (1 a) with electron-deficient alkyl halides under fluoride-free conditions affords the corresponding alkylated pyrazines.

Chromium-catalyzed olefination of arylaldehydes with haloforms assisted by 2,3,5,6-tetramethyl-N,N′-bis(trimethylsilyl)-1,4-dihydropyrazine

“…In contrast, 2-formylpyridine was not applicable in this olefination reaction; the corresponding pinacol coupling product was obtained in quantitative yields by 1a even in the absence of CrCl 2 (see ESI†). 12…”