Double aza-Morita-Baylis-Hillman Domino Reaction to Access Amino Derived 1,6-Dienes

Aza-Morita-Baylis-Hillman reaction plays specific roles in the construction of C-C bond, and their applications in synthetic chemistry and pharmaceutical chemistry have also been well-documented. Herein, a novel 1,4-diazabicyclo-[2.2.2]octane (DABCO) mediated double aza-Morita-Baylis-Hillman cascade strategy toward synthetically important aza-MBH adducts is reported. Complementary to classical aza-MBH reaction, this protocol employs a wide variety of primary amines including benzyl, alkyl and aryl moieties as the reaction partners, giving an efficient alternative to produce amino derived 1,6-dienes in moderate to high yields in the presence of formaldehyde and alpha,beta-unsaturated carbonyl compounds. Rather surprisingly, using an aqueous medium has proven to be successful in promoting the reaction efficiency and achieving a higher yield of target products. One-pot operation, high chemoselectivity, short reaction time, and broad substrate scope of primary amines exemplified the significant advances and practicability of this protocol.

Automated summary

The Aza-Morita-Baylis-Hillman cascade strategy mediated by 1,4-diazabicyclo-[2.2.2]octane (DABCO) was utilized to efficiently produce amino derived 1,6-dienes using a variety of primary amines. Surprisingly, using an aqueous medium promoted reaction efficiency and increased product yield. The protocol demonstrated significant advances in synthetic chemistry and pharmaceutical chemistry with its one-pot operation, high chemoselectivity, and broad substrate scope.