ABSTRACT
Herein, we report a Kumada cross-coupling reaction of benzylic sulfonamides. The scope of the transformation includes acyclic and cyclic sulfonamide precursors that cleanly produce highly substituted acyclic fragments. Preliminary data are consistent with a stereospecific mechanism that allows for a diastereoselective reaction.
ABSTRACT
The application of amine derivatives as coupling partners is rare due to the inherent strength of the C-N bond. Herein, we report the first cross-electrophile coupling reaction of unstrained benzylic sulfonamides. Nickel-catalyzed intramolecular cross-electrophile coupling reactions of acyclic and cyclic benzylic sulfonamides with pendant alkyl chlorides generate cyclopropane products. Mechanistic experiments and DFT calculations are consistent with initiation of the reaction by magnesium iodide accelerated oxidative addition of the benzylic sulfonamide. This work establishes neutral and unstrained amine derivatives as XEC partners, furnishes structural rearrangement of benzylic sulfonamides, and provides valuable information regarding catalyst design for the development of new cross-electrophile coupling reactions of carbon-heteroatom bonds.
ABSTRACT
A nickel-catalyzed intramolecular conjunctive cross-electrophile coupling reaction has been established. This method enables the synthesis of 3,5-vicinal carbocyclic rings found in numerous biologically active compounds and natural products. We provide mechanistic experiments that indicate this reaction proceeds through alkyl iodides formed in situ, initiates at the secondary electrophilic center, and proceeds through radical intermediates.