Asymmetric organocatalysis involving double activation

Asymmetric organocatalysis contributed tremendously to the field of organic synthesis since year 2000. Considering the diversity of organocatalysts and their activation modes, chemists developed the double activation strategy, in which two distinct catalysts simultaneously interact with a single substrate, thus enabling effective transformations that might be too challenging or even unattainable under a sole catalytic system. This review summarized the asymmetric reactions via double activation catalysis involving different Lewis bases (aminocatalysts, N-heterocyclic carbenes, isothioureas, N,N-dimethyl-4-aminopyridine, tertiary amines/phosphines, or even thiols), Brønsted bases (including phase transfer catalysts), Brønsted acids, and a few examples combining organocatalysts and metal catalysts or photocatalysts were also discussed. In most cases, compared to those with a single catalyst, better reactivity and stereoselectivity, or even completely different regioselectivity or chemoselectivity were observed under double activation catalysis, demonstrating the power and superiority of this promising strategy. Some key intermediates as well as the mechanisms have been presented to provide insights into the activation processes, which might inspire the development of new double activation systems and more interesting work in the future.