Nickel-Catalyzed Direct Stereoselective Alpha-Allylation of Ketones with Non-conjugated Dienes

The development of efficient, sustainable methods for the construction of carbon-carbon bonds with the simultaneous stereoselective generation of vicinal stereogenic centers is a longstanding goal in organic chemistry. In this respect, the carbonyl group is a particularly relevant due to its ability reacting either as electrophile or pro-nucleophile at the alpha-carbon in its enolized form. The transition from precious metals to catalysts based on earth-abundant metals made impressive progress, and especially nickel became a powerful tool due to its low-cost and unique reactivity profiles. Low-valent nickel(0) complexes promote reductive couplings carbonyl compounds exploiting the electrophilic nature of the carbonyl group. In stark contrast, complementary alpha-functionalization of carbonyls leveraging its pro-nucleophilic character in conjunction with olefin acceptors are very scarce despite their attractivity. We report a Ni(0)NHC catalyst which promotes the conversion of ketones and non-conjugated dienes that are both cheap and widely accessible starting materials to synthetically highly valuable alpha-allylated products in excellent yields under mild conditions without any additional base or additive. The catalyst directly activates the alpha-hydrogen atom of the carbonyl substrates transferring it the olefin acceptor. The complete process is redox neutral and fully atom-economic. This feature contrasts typical carbonyl -functionalizations with precious metals that require functionalized substrates like a pre-formed enolate nucleophile and allyl electrophile. The transformation creates adjacent quaternary and tertiary stereogenic centers in a highly diastereoselective manner. Moreover, we introduce a chiral bulky designer NHC ligand allowing to conduct the reaction in an enantioselective manner providing the functionalized products with up to 99:1 er and >20:1 dr. Mechanistic and computational studies indicate an initial LLHT process from the ketone substrate to the olefin substrate to set the selectivity of the whole transformation. A beta-hydride elimination chain walking events is triggered until a favorable pi-allyl intermediate is reached leading by reductive elimination to the targeted products. The shown facile and selective functionalization of alpha-C-H bond of carbonyl groups by Ni(0)NHC catalysts opens new opportunities to exploit sustainable 3d-metal catalysis for a stereoselective access to valuable chiral building blocks.