ASYMMETRIC TRANSFER HYDROGENATIONS AND ALPHA ALLYLATIONS USING FLEXIBLE OR RACEMIC PHOSPHORIC ACIDS VIA COUNTERION-ENHANCED CATALYSIS

Abstract

Forging new C-C stereocenters is one of the major challenges in modern organic chemistry. In this field, classical iminium and enamine catalysis became indispensable tools, enabling tremendous advancements for the asymmetric functionalization of both saturated and unsaturated carbonyl species. [1,2]As an add-on to classical aminocatalysis, B. List et al. pioneered the field of Asymmetric Counteranion Directed Catalysis (ACDC),providing remarkable examples for the β-functionalization of enals and enones by relying on catalyst salts of chiral/achiral amines and enantiomerically pure phosphoric acids.[3] While these elegant protocols provided indeed excellent yields and enantioselectivities, the catalyst synthesis often suffered from multi-step synthesis and tedious separations, resulting in rather expensive catalytic systems. As a conceptional spin-off of the aforementioned ACDC, we envisioned of using readily available chiral amines in combination with flexible or racemic phosphoric acids for asymmetric catalytic purposes. With both catalyst counterparts being natural-derived, such a “counterion enhanced catalytic” strategy would have the advantage of cheap and simple catalyst synthesis and therefore could provide a valuable alternative to current state-of-the-art methodologies. Using a thymol-derived racemic phosphoric acid in combination with chiral amines, we have developed efficient organocatalysts for the asymmetric transfer hydrogenation of enones and for the direct asymmetric α-allylation of aldehydes, respectively. For both reactions, excellent yields and enantioselectivities were obtained. These results showed that such a concept can be successfully adapted both to iminium– and enamine-catalytic reactions. Moreover, we also showed that sterically demanding, but simple flexible or racemic phosphoric acids might provide a good alternative to the field of ACDC.