Angewandte Chemie International Edition ( IF 12.102 ) Pub Date : 2017-12-28 , DOI: 10.1002/anie.201710676 Gang Li, Andrew K. Dilger, Peter T. Cheng, William R. Ewing, John T. Groves
The selective C−H functionalization of aliphatic molecules remains a challenge in organic synthesis. While radical chain halogenation reactions provide efficient access to many halogenated molecules, the use of typical protocols for the selective halogenation of electron-deficient and strained aliphatic molecules is rare. Herein, we report selective C−H chlorination and fluorination reactions promoted by an electron-deficient manganese pentafluorophenyl porphyrin catalyst, Mn(TPFPP)Cl. This catalyst displays superior properties for the aliphatic halogenation of recalcitrant, electron-deficient, and strained substrates with unique regio- and stereoselectivity. UV/Vis analysis during the course of the reaction indicated that an oxo-MnV species is responsible for hydrogen-atom abstraction. The observed stereoselectivity results from steric interactions between the bulky porphyrin ligand and the intermediate substrate radical in the halogen rebound step.
A deficiency that's a bonus: A highly electron-deficient manganese porphyrin was found to effectively catalyze the radical halogenation of strained, electron-deficient aliphatic substrates under mild conditions (see scheme). The bulkiness of the catalyst resulted in unique stereo- and regioselectivity.