Science of Synthesis

Masson, G.; Zhu, J., Science of Synthesis: Stereoselective Synthesis, (2011) 2, 735.

General Introduction

The Morita–Baylis–Hillman (MBH)[‌1‌,‌2‌] reaction has been recognized as one of the most effective C—C bond-forming processes. It generates densely functionalized compounds from simple starting materials under catalytic conditions without loss of atoms. This reaction involves the condensation of an electron-deficient alkene with an aldehyde in the presence of a catalytic amount of an organic nucleophilic base, such as a tertiary amine or phosphine. Imines can also participate in an analogous reaction, which is commonly referred to as the aza-Morita–Baylis–Hillman (aza-MBH) reaction (‌Scheme 1‌).[‌3‌] These operationally simple and atom-economic C—C bond-forming reactions afford α-methylene-β-hydroxycarbonyl or α-methylene-β-aminocarbonyl derivatives, respectively, which can serve as valuable building blocks for the synthesis of medicinally relevant compounds as well as complex natural products.[‌4‌–‌10‌] The synthetic potential of this reaction is illustrated by its application in industrial processes, such as the synthesis of tert-butyl 2-(hydroxymethyl)propenoate, a key intermediate in Pfizerʼs synthesis of the zinc-metallaprotease inhibitor Sampatrilat.[‌11‌]

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References