Stereoselective Synthesis of Trisubstituted Alkenes through Sequential Iron‐Catalyzed Reductive anti‐Carbozincation of Terminal Alkynes and Base‐Metal‐Catalyzed Negishi Cross‐Coupling

Abstract

The stereoselective synthesis of trisubstituted alkenes is challenging. Here, we show that an iron‐catalyzed anti‐selective carbozincation of terminal alkynes can be combined with a base‐metal‐catalyzed cross‐coupling to prepare trisubstituted alkenes in a one‐pot reaction and with high regio‐ and stereocontrol. Cu‐, Ni‐, and Co‐based catalytic systems are developed for the coupling of sp‐, sp2‐, and sp3‐hybridized carbon electrophiles, respectively. The method encompasses a large substrate scope, as various alkynyl, aryl, alkenyl, acyl, and alkyl halides are suitable coupling partners. Compared with conventional carbometalation reactions of alkynes, the current method avoids pre‐made organometallic reagents and has a distinct stereoselectivity.

Cobalt-Catalyzed Carbozincation of Ynamides

“…Following our recent study on cobalt catalyzed carbozincation reactions, and in our long-term quest for the metal mediated functionalization of enamides, we disclose here a broadly applicable and original ynamide carbozincation. It is worth mentioning that carbometalation of alkynes, and, in particular, carbozincation, is one of the most important reactions due to the high functional group compatibility of organozinc reagents. Of particular interest is the cobalt-catalyzed carbometalation of alkynes, in view of the low cost and the low toxicity of cobalt.…”

Palladium‐Catalyzed Formal Hydroalkylation of Aryl‐Substituted Alkynes with Hydrazones

“…[3,4] Despite requiring a stoichiometric amount of reductant or organometallic reagent, transition-metal-catalyzed "formal" hydroalkylation reaction between alkynes and alkyl halides, pseudohalides, or boranes is considered an appealing strategy in this field and has attracted great interest (Scheme 1 a). [5][6][7][8] Without using halides and other functional groups, C(sp 3 )ÀH bond alkenylation represents a promising method for conversion of alkynes to alkenes, and some elegant examples have been disclosed involving the direct C À H activation [9] and radical processes (Scheme 1 b). [10] Very recently, MacMillan and Rueping independently developed Ir and Ni dual-catalytic photoredox decarboxylative hydroalkylation reactions with carboxylic acids as the alkyl donors (Scheme 1 c).…”

Z-Selective Synthesis of Vinyl Boronates through Fe-Catalyzed Alkyl Radical Addition

“…Our approach is based on Fe-catalyzed stereoselective addition of an alkyl radical, generated from an alkyl halide under reductive conditions, to ethynylboronic acid pinacol ester ( 1 , Figure b). The approach is built upon our previous work, − which showed that an alkyl radical was generated through the reaction of an alkyl halide with an Fe­(I) species, produced by reduction of an Fe­(II) catalyst with Zn (Figure c,d). The alkyl radical could be trapped by a terminal aryl alkyne to form a vinyl radical stabilized by an aryl group.…”