Progress in catalytic asymmetric α-functionalization of vinylogous nucleophilic species

In conjugated pi systems, pi-extended enolates generated in situ from unsaturated pronucleophiles through suitable HOMO-raising strategies tend to proceed via stereoselective vinylogous reactions that sterically favored remote functionalization (gamma-, epsilon-, and omega-positions of the carbonyl group). In contrast, proximal functionalization (alpha-position) of bench-stable unsaturated pronucleophiles has historically remained underdeveloped or has not existed. To counter these obstacles, new synthetic methods and efficient catalytic systems have been developed in the last few years. This review focuses on the recent exciting achievements in the proximal functionalization of unsaturated pronucleophiles, such as unsaturated aldehydes, ketones, carboxylic acids, and their derivatives and analogs. Mechanistic insights, transition states, and some synthetic applications are summarized. The challenges and opportunities of this field are also discussed.