Nickel-Catalyzed Regio- and Diastereoselective Arylamination of Unactivated Alkenes

Abstract

An intermolecular syn-1,2-arylamination of unactivated alkenes with arylboronic acids and O-benzoylhydroxylamine electrophiles has been developed with Ni(II) catalyst. The cleavable bidentate picolinamide directing group facilitated formation of stabilized 4-, 5- or 6-membered nickelacycles and enabled the difunctionalization of diverse alkenyl amines with high levels of regio-, chemo- and diastereocontrol. This general and practical protocol was compatible with broad substrate scope and high functional group tolerance. The utility of this method was further demonstrated by the site-selective late-stage modification of pharmaceutical agents.

Directed Nickel-Catalyzed Diastereoselective Reductive Difunctionalization of Alkenyl Amines

“…Catalytic difunctionalization of alkenyl amines is an attractive alternative to prepare branched amines with up to two stereocenters, which is difficult to prepare by means of C­(sp 3 )–H functionalizations or other conventional protocols. However, the development of methods for the difunctionalization of alkenyl amines in this area is grievously lagging . Very recently, our group described an arylalkylation of alkenyl amines with arylboronic acids and alkyl halides but achieved poor diastereoselectivities when using internal alkene substrates…”

Nickel-Catalyzed 1,2-Carboamination of Alkenyl Alcohols

“…Such transformations have historically been fraught with issues, including competitive two-component coupling, difficulty in controlling regioselectivity, and formation of undesired side products that arise from unstable alkylmetal or alkyl radical intermediates. Thus, three-component carboamination has been limited to conjugated alkenes, , strained cyclopropenes, or alkenes bearing directing auxiliary groups. − For instance, in 2019 our lab developed a nickel-catalyzed umpolung 1,2-carboamination that unites alkenes bearing the strongly coordinating 8-aminoquinoline (AQ) directing auxiliary with electrophilic aminating reagents and alkylzinc nucleophiles (Figure B). Although this system offered high regio- and stereoselectivity, the method has an intrinsic limitation in requiring two additional steps for auxiliary installation and removal.…”