The development of two divergent and complementary Lewis acid catalyzed additions of bicyclobutanes to imines is described. Microscale high‐throughput experimentation was integral to the discovery and optimization of both reactions. N‐arylimines undergo formal (3+2) cycloaddition with bicyclobutanes to yield azabicyclo[2.1.1]hexanes in a single step; in contrast, N‐alkylimines undergo an addition/elimination sequence to generate cyclobutenyl methanamine products with high diastereoselectivity. These new products contain a variety of synthetic handles for further elaboration, including many functional groups relevant to pharmaceutical synthesis. The divergent reactivity observed is attributed to differences in basicity and nucleophilicity of the nitrogen atom in a common carbocation intermediate, leading to either nucleophilic attack (N‐aryl) or E1 elimination (N‐alkyl).

We report an easily prepared and bench-stable mononuclear Pd(0) source stabilized by a chelating N,N'-diaryldiazabutadiene ligand and maleic anhydride: DMP DAB-Pd-MAH. Phosphine ligands of all types, including bidentate phosphines and large cone angle biarylphosphines, rapidly and completely displace the diazabutadiene ligand at room temperature to give air-stable Pd(0) phosphine complexes. DMP DAB-Pd-MAH itself is readily soluble and stable in several organic solvents, making it an ideal Pd source for in situ catalyst preparation during reaction screening, as well as solution-dispensing to plate-based reaction arrays for high-throughput experimentation. Evaluation of DMP DAB-Pd-MAH alongside other common Pd(0) and Pd(II) sources in microscale reaction screens reveals that DMP DAB-Pd-MAH is superior at identifying hits across six different C-N, C-C, and C-O coupling reactions. DMP DAB-Pd-MAH, and the phosphine precatalysts derived therefrom, are also effective in preparative-scale cross couplings at low Pd loadings. ASSOCIATED CONTENTDetailed experimental procedures, full tables of screening data, characterization data, and XRD details. This material is available free of charge via the Internet at http://pubs.acs.org. CIFs for complexes 1, 3-5, 8 and 12 are deposited with the CCDC with deposition numbers 2056595-2056600.

We present recent advances in prominent organotransition metal-catalysed reactions in which Lewis acid cocatalysts are employed to increase catalyst activity or selectivity. The roles of Lewis acids are discussed.