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Organocatalysts are also useful for the addition of carbonyl compounds to electron‐deficient alkenes, known as the Michael reaction. The reaction of aldehydes and nitroalkenes catalyzed by organocatalyst is a well‐investigated reaction. In 2005, diphenylprolinol silyl ether was applied to this reaction, which afforded a Michael product with excellent diastereo‐ and enantioselectivity (Eq. 1.12) [9]. It was also found that an acid additive accelerates the reaction, and the effect of the acid has been investigated in detail (Scheme 1.2) [27]. An enamine and a nitroalkene react to afford cyclobutane A and dihydro‐oxazine N oxide B as initial products, which were converted into the Michael product, and acid affects this conversion step.

(1.12)

As a Michael acceptor, not only nitroalkene but also vinyl sulfones [28], β‐substituted α‐nitroacrylates [29], dicyanoalkenes [30], and β‐substituted α‐cyano α,β‐unsaturated esters [31] can be successfully employed to afford the Michael products with excellent diastereo‐ and enantioselectivity (Eq. 1.13).

(1.13)

Scheme 1.2. The reaction mechanism of the Michael reaction of aldehyde and nitroalkene.

Source: Based on [27].

Low catalyst loading and the development of a reactive catalyst are important issues for the asymmetric synthesis of chiral molecules. For the Michael reaction of aldehydes and nitroalkenes, Wennemers reported a very active tripeptide catalyst H‐D‐Pro‐Pro‐Glu‐NH₂, which catalyzes the Michael reaction of butanal and nitrostyrene in the presence of only 0.1 mol% of the catalyst (Eq. 1.14) [32]. This catalyst is a bifunctional catalyst, possessing a secondary amine moiety and an acid moiety.

(1.14)