High activation of carbonyl groups with bidentate Lewis acid catalysts

Carbonyl group is one of the most popular and yet ubiquitous functionality of organic compounds and often encountered in biomolecules such as peptides and lipids, playing a crucial role to organize three dimensional intermolecular associations. For organic chemists, it always appears as an extremely useful functional group to be manipulated and either Brønsted acids or Lewis acids are routinely employed for the activation of carbonyls in electrophilic substitution reactions, where the acids preferably coordinate to one of the two carbonyl lone pairs. Being close to the core of Lewis acid chemistry, we have been interested some time in the possibility of double electrophilic activation of carbonyl functionality by designing bidentate Lewis acid catalysts which could simultaneously coordinate to both of the carbonyl lone pairs with two metals. In this review, we describe the development of bidentate aluminum and titanium Lewis acids, and evaluation of their reactivity and selectivity in organic synthesis. Further, the applications of our concept to the elaboration of new synthetic methodologies are also discussed. Those include neutral allylation of carbonyls with bidentate tin compounds by using chelation-induced Lewis acidity, and activation of bidentate bis(silyl) compounds with a fluoride anion.