化学
对映选择合成
亚胺离子
吡嗪
二嗪
炔烃
杂原子
非对映体
有机化学
对映体
组合化学
催化作用
烷基
作者
Devin R. Ketelboeter,Mukesh Pappoppula,Aaron Aponick
摘要
Despite much progress in the area of dearomatization, the enantioselective dearomatization of heterocycles is limited to those with a single heteroatom. Here we report a highly enantioselective copper-catalyzed dearomatization of pyrazine, a diazine, leading to chiral C-substituted piperazines. When exposed to a chloroformate and an alkyne in the presence of a catalyst derived from a copper salt and the chiral ligand StackPhos, pyrazine is readily dearomatized to provide a 2,3-disubstituted dihydropyrazine as single diastereomer in high enantiomeric excess. Mechanistic studies support a noninnocent involvement of chloride ion preventing a second iminium alkynylation, thus enabling subsequent functionalization at the second reactive site. The synthetically useful dihydropyrazine products, obtained in up to 95% yield and 99% ee, can be further manipulated to form optically active C-substituted piperazines and C1-symmetric 1,2-diamines.
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