Nickel-Catalyzed [4 + 4] Cycloaddition of Diene-Vinylcyclobutanones

Reported here is a Ni(0)-catalyzed [4 + 4] cycloaddition of diene-vinylcyclobutanones to access trans-5/8 bicyclic structure with a bridgehead quaternary carbon center, which is found in natural products but cannot be accessed by existing transition metal cata-lyzed cycloadditions. This [4+4] reaction has broad scope and the catalyst used is the earth-abundant Ni complex. Key to the suc-cess of the [4+4] cycloaddition is utilizing the vinyl group in the substrates to activate the cyclobutanone (substrate with an alkyl group failed to realize the [4+4] reaction). Of the same importance, the vinyl group in the final [4+4] cycloadducts can be trans-formed into other functional groups so that 5/8 products with various substituents at bridgehead position can be pursued. DFT calcu-lations have been applied to reveal how the vinyl-group assisted C-C cleavage, diene insertion (via an unexpected endo-metal-insertion mode), ligand dissociation, and reductive elimination take place consecutively. Among them, the ligand dissociation pro-cess, benefiting from a higher reaction temperature (80 °C), is critical to favor the [4+4] reaction and suppress the competing vinyl-cyclobutanone rearrangement and Diels-Alder reaction.