Nickel-Catalyzed C-I-Selective C(sp2)-C(sp3) Cross-Electrophile Coupling of Bromo(iodo)arenes with Alkyl Bromides.

Abstract

Despite several methodologies established for C(sp2)-I selective C(sp2)-C(sp3) bond formations, achieving arene-flanked quaternary carbons by cross-coupling of tertiary alkyl precursors with bromo(iodo)arenes in a C(sp2)-I selective manner is rare. Here we report a general Ni-catalyzed C( sp2 )-I selective cross-electrophile coupling (XEC) reaction, in which, beyond 3° alkyl bromides (for constructing arene-flanked quaternary carbons), 2° and 1° alkyl bromides are also demonstrated to be viable coupling partners. Moreover, this mild XEC displays excellent C(sp2)-I selectivity and functional group compatibility. The practicality of this XEC is demonstrated in simplifying the routes to several medicinally relevant and synthetically challenging compounds. Extensive experiments show that the terpyridine-ligated NiI halide can exclusively activate alkyl bromides, forming a NiI-alkyl complex through a Zn reduction. Attendant density functional theory (DFT) calculations reveal two different pathways for the oxidative addition of the NiI-alkyl complex to the C(sp2)-I bond of bromo(iodo)arenes, explaining both the high C(sp2)-I selectivity and generality of our XEC.