Triple Cascade Reaction Leading to Tetra-Substituted Cyclohexenes

Key words

cascade reaction - Michael reaction - aldol reaction

Significance

A novel 3-component organocatalytic cascade reaction is reported that generates cyclohexene derivatives 5 with four contiguous stereogenic centers in good diastereoselectivities (from 2.1:1 to 99:1) and high enantioselectivities (>99%). A large variety of substrates can be used: aldehyde 2 can be aliphatic or highly functionalized; the α,β-unsaturated aldehyde 4 tolerates aromatics as well as aliphatics. However, nitro­olefin 3 is limited to aromatic substrates. Surprisingly, the product itself did not react further with the catalyst, possibly due to steric hindrance.

Comment

Construction of several stereogenic centers in complex molecules in a single step is one of the most challenging and desirable processes in synthetic chemistry. Herein the authors present a remarkably broad substrate scope for such a cascade reaction, which allows for building blocks that can be used in natural product synthesis. Moreover, the easy access to both enantio­mers of the catalyst gives rise to a large diversity of products. One advantage of this transformation is that it can be employed to combinatorial processes without the need of any protecting groups.