Tetrasubstituted 1,3-Enynes by Gold-Catalyzed Direct C(sp²)–H Alkynylation of Acceptor-Substituted Enamines

Abstract

A gold-catalyzed synthesis of tetrasubstituted 1,3-enynes from hypervalent iodine­(III) reagents and activated alkenes is reported. This reaction involves an in situ formed alkynyl Au­(III) species and a subsequent direct C­(sp2)–H functionalization of alkenes, offering 26 enynes in 62–92% yield with excellent functional group tolerance.

Recent Advances in Alkenyl sp2 C–H and C–F Bond Functionalizations: Scope, Mechanism, and Applications

“…In a recent report, Hashmi, Tian, and their co-workers reported the use of enamines as substrates to couple with hypervalent iodine(III) reagents under gold catalysis, in which a series of tetrasubstituted conjugated 1,3-enynes were obtained in a regioselective manner (Scheme 380). 608 Mechanistically, the Au(I) species I was initially produced under the typical conditions, which then undergoes oxidative addition with hypervalent iodine reagent to afford the alkynyl Au(III) intermediate II. Subsequent alkenyl C−H functionalization of enamines with alkynyl Au(III) species III followed by a facile reductive elimination process would release the corresponding 1,3-enynes and simultaneously regenerate the Au(I) catalyst.…”

Dual Gold/Silver Catalysis: Indolizines from 2-Substituted Pyridine Derivatives via a Tandem C(sp3)–H Alkynylation/Iminoauration

“…On the basis of previous reports, − a plausible mechanism is described in Scheme . First, Au­(I) species A undergoes an oxidative addition with the hypervalent iodine reagent 2 to form the alkynyl Au­(III) complex B (see Scheme S4b in the Supporting Information).…”

“…Gold­(I)/gold­(III) catalytic cycles in bimetallic processes are rarely involved . Recently, our group reported dual gold/silver-catalyzed C­(sp 2 )–H alkynylations of cyclopropenes (Scheme a) and phenols (Scheme b), gold-catalyzed alkynylation reactions of N -propargyl­carboxamides, acceptor-substituted enamines, and acceptor-substituted carbonyl compounds . The key intermediate, an alkynyl gold­(III) species, was generated by oxidative addition of a hypervalent iodine reagent to a gold­(I) species.…”

Synthesis of Amide Enol 2-Iodobenzoates by the Regio- and Stereoselective Gold-Catalyzed Acyloxyalkynylation of Ynamides with Hypervalent Iodine Reagents

“…Recently, gold-catalyzed conversions of alkynyl iodine­(III) reagents have obtained increasing attention, often in work involving the gold­(I)/gold­(III) catalytic cycles . Our group also achieved gold-catalyzed C–H alkynylation reactions with substrates like cyclopropenes, phenols, N -propargylcarboxamides, acceptor-substituted enamines, acceptor-substituted carbonyl compounds, and 2-substituted pyridines, all triggered by the alkyne moiety of hypervalent iodine­(III) reagents. Nevertheless, the EBX reagents suffer from the drawback that the conversions frequently are restricted to specific alkynyl groups, and 2-iodobenzoic acid or hexafluoro-2-(2-iodophenyl)­propan-2-ol are obtained as stoichiometric byproducts, overall leading to low atom economy.…”

“…A plausible mechanism is based on DFT calculations and on previous reports − (Scheme ). Initially, in the presence of L1 the Au­(I) species A is formed.…”