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1.1.16 (Aza)-Morita–Baylis–Hillman Reactions

DOI: 10.1055/sos-SD-204-00330

Hatakeyama, S.Science of Synthesis: Asymmetric Organocatalysis, (20121673.

General Introduction

The MoritaBaylisHillman (MBH) reaction is essentially a three-component procedure involving the coupling of the α-position of an activated alkene, such as an acrylate, with a carbon electrophile, such as an aldehyde, under nucleophilic amine or phosphine catalysis thereby producing synthetically useful multifunctional products. When an imine is used as the carbon electrophile, the procedure is called the aza-MoritaBaylisHillman (aza-MBH) reaction (Scheme 1). The MoritaBaylisHillman reaction was discovered in 1967 when Morita and co-workers disclosed the phosphine-catalyzed reaction of an aldehyde with an activated alkene in a French patent.[‌1‌,‌2‌] In 1972, Baylis and Hillman subsequently reported a basically similar amine-catalyzed reaction in a German patent.[‌3‌] However, since these discoveries were not followed by substantial journal publications, the MoritaBaylisHillman reaction did not attract much attention at the time. It was only in the early 1980s that organic chemists started realizing the enormous synthetic advantages of the MoritaBaylisHillman reaction and the first reports of aza-MoritaBaylisHillman reactions appeared in the literature. Thus, it was found that aromatic N-tosylimines undergo a MoritaBaylisHillman-type reaction with ethyl acrylate under 1,4-diazabicyclo[2.2.2]octane-catalyzed conditions.[‌4‌] Now the MoritaBaylisHillman reaction, including the aza version, is regarded as one of the most promising CC bond-forming reactions in terms of synthetic utility, atom economy, and operational simplicity, an importance evidenced by a quantum jump in the number of publications dealing with these reactions since the late 1990s.[‌5‌‌12‌]

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References