| Transition metal-catalyzed cross-coupling reactions have emerged as the preeminent carbon-carbon disconnection for both medicinal and process chemistry. Given the usefulness of transition metal-catalyzed Csp 2-Csp2 cross-coupling reactions, it is unfortunate that the closely related Csp3-Csp2 cross-coupling involving Csp3-halides remain relatively rare. To address this shortcoming, the development of three distinct Csp3-Csp 2 palladium and iron-catalyzed cross couplings with alkyl halides will be presented: (1) A tethered intramolecular alkyne has been used to intercept a presumptive alkylpalladium species prior to beta-hydride elimination. Following migratory insertion of the alkyne, a vinyl carbopalladium intermediate provided an opportunity for a Suzuki coupling to form tetrasubstituted olefins; (2) To expand the utility of alkyne capture, tandem insertion events on an intramolecular alkyne and olefin were demonstrated on homoallylic iodides. Preliminary reactions did not provide the expected double insertion beta-hydride elimination products., but rather an iodide-transfer reaction to produce diquinane rings; (3) Finally, we sought to replace the transmetallation or insertion event with C-H activation. Thus though iron-catalyzed C-H activation/alkylation the ability to ortho alkylate Csp2 carbons with a variety of benzylic, primary, and secondary halides were demonstrated. Thus through this research we have been able to expand the scope and applicability of Csp3-Csp2 cross-couplings in the synthetic community. |
