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

Abstract

Multisubstituted alkenes are accessible by a gold-catalyzed acyloxyalkynylation of ynamides with ethynylbenziodoxolones (EBXs) with perfect atom-economy. The EBX reagents transfer both the carboxylate as well as the alkynyl entity. Overall, this cascade comprises the in situ generation of an alkynyl gold(III) species, a stereoselective C(sp)−C(sp 2 ) bond formation, and a C−O coupling at the alkynyl position of the ynamides. This reaction proceeds under mild conditions and accepts a wide range of substrates. A number of tetrasubstituted amide enol 2-iodobenzoates bearing different functional groups were obtained in good to excellent yields. DFT calculations explain the observed regioselectivity. The synthetic potential of the reaction was further demonstrated by a number of selected follow-up transformations.

Recent progress in alkynylation with hypervalent iodine reagents

“…More recently, the same strategy was applied by the Hashmi group for the 1,2-oxyalkynylation of propargylamines leading to highly functionalized alkenes. 156 In 2020, our group reported a photoredox-catalyzed oxyalkynylation of enols and enamides (Scheme 46). 148 It should be noted that better yields were obtained with an organic dye than via direct photoexcitation of EBX reagents (vide supra).…”

“…More recently, the same strategy was applied by the Hashmi group for the 1,2-oxyalkynylation of propargylamines leading to highly functionalized alkenes. 156 …”

Reductive Elimination Reactions in Gold(III) Complexes Leading to C(sp3)–X (X = C, N, P, O, Halogen) Bond Formation: Inner-Sphere vs SN2 Pathways

“…The advances in the field of Au­(I)/Au­(III) catalysis during the last decade − have boosted research on fundamental aspects of gold redox reactions. − Thus, the oxidative addition of substrates containing C–halogen, C–N 2 + , or strained C–C bonds to Au­(I) complexes, regarded as the most challenging step of these catalytic cycles, has received considerable attention. − By contrast, reductive eliminations in Au­(III) complexes have been less studied, despite the fact that the degree of selectivity in this step dramatically affects the outcome of the catalytic processes . Pioneering studies carried out during the 1970s − revealed that reductive elimination in square planar Au­(III) complexes can occur (a) through tricoordinate intermediates formed after ligand dissociation or (b) directly from the tetracoordinate complexes (Scheme A). , Alternatively, a concerted mechanism where C–C and B–F bonds form simultaneously has been proposed for the reaction of Au­(III) alkyl fluorido complexes with arylboronic acids (Scheme B) .…”

“…The advances in the field of Au(I)/Au(III) catalysis during the last decade 1 − 15 have boosted research on fundamental aspects of gold redox reactions. 16 − 23 Thus, the oxidative addition of substrates containing C–halogen, C–N 2 + , or strained C–C bonds to Au(I) complexes, regarded as the most challenging step of these catalytic cycles, has received considerable attention.…”

Hypervalent iodine(iii) promoted C–H/C–H amination/annulation tandem reactions: synthesis of benzimidazoles from simple anilines and aldehydes

“…Direct C–H functionalization using hypervalent iodine( iii ) reagents (HIR) 11 has emerged as a valuable method to construct complex molecules, where new carbon–carbon 12 and carbon–heteroatom 13,14 bonds are formed, because it is an effective, safe, and environmentally benign reaction with readily available starting materials, while the generation of nitrogen-centered radical intermediates using HIR, followed by inter or intramolecular reactions, is an efficient method for the construction of C–N bonds. 15 Tandem cyclization reactions have become powerful protocols for the construction of nitrogen heterocyclic products due to their step-economy and high efficiency.…”