Highly selective nickel-catalyzed gem-difluoropropargylation of unactivated alkylzinc reagents

• DOI: 10.1038/s41467-017-01540-1
• Publication Date: 2017-11-07T16:45:37Z
• Authors: Lun An; Chang Xu; Xingang Zhang
• Keywords: Catalytic cycle

In spite of the important applications difluoroalkylated molecules in medicinal chemistry, to date, reaction difluoroalkylating reagents with unactivated, aliphatic substrates through a controllable manner remains challenging and has not been reported. Here we describe an efficient nickel-catalyzed cross-coupling unactivated alkylzinc reagen\ts gem-difluoropropargyl bromides. The proceeds under mild conditions high efficiency excellent regiochemical selectivity. Transformations resulting alkanes lead variety biologically active molecules, providing facile route for drug discovery development. Preliminary mechanistic studies reveal that alkyl nickel intermediate [Ni(tpy)alkyl] (tpy, terpyridine) is involved catalytic cycle.