Two Metals Are Better Than One in the Gold Catalyzed Oxidative Heteroarylation of Alkenes

Abstract

We present a detailed study of the mechanism for oxidative heteroarylation, based on DFT calculations and experimental observations. We propose binuclear Au(II)-Au(II) complexes to be key intermediates in the mechanism for gold catalyzed oxidative heteroarylation. The reaction is thought to proceed via a gold redox cycle involving initial oxidation of Au(I) to binuclear Au(II)-Au(II) complexes by Selectfluor, followed by heteroauration and reductive elimination. While it is tempting to invoke a transmetalation/reductive elimination mechanism similar to that proposed for other transition metal complexes, experimental and DFT studies suggest that the key C-C bond forming reaction occurs via a bimolecular reductive elimination process (devoid of transmetalation). In addition, the stereochemistry of the elimination step was determined experimentally to proceed with complete retention. Ligand and halide effects played an important role in the development and optimization of the catalyst; our data provides an explanation for the ligand effects observed experimentally, useful for future catalyst development. Cyclic voltammetry data is presented that supports redox synergy of the Au···Au aurophilic interaction. The monometallic reductive elimination from mononuclear Au(III) complexes is also studied from which we can predict a ~15 kcal/mol advantage for bimetallic reductive elimination.

Methyl Complexes of the Transition Metals

“…155 The agostic nature of the interaction of the bridging methyl was determined partly based on analysis of its JCH coupling constant, which, at ca. 125 Hz, according to the authors, was deemed significantly lower, than that found for other methyl fragments (135)(136)(137)(138)(139)(140). This was attributed to thermal averaging of the normal C-H coupling of ca.…”

“…In a recent report, Toste described the isolation of several alkylgold(III) difluoride species like 3.32 that mimic the speculative intermediates previously proposed in Au(I)/Au(III) C-C coupling reactions, showing that indeed they are competent for this kind of transformation. 135 Scheme 38. Recent TM-CH3 complexes relevant to catalytic C-C crosscoupling reactions (refs.…”

Unique distal size selectivity with a digold catalyst during alkyne homocoupling

“…5 and Supplementary Discussion) 22,23 . X-ray Diffraction together with cyclic voltammetry studies showed that while 5a presents aurophilic bonding between two gold atoms 14 , 5c has no aurophilic bonds at all 14 and 5b has an intermediate behaviour, depending on the counteranion 24,25 . The results indicate that aurophilic bonding has a positive influence on the reaction rate but none on the distal size selectivity.…”

“…Despite the increasing number of new transformations reported, particularly with alkynes 11,12 , fundamental studies covering the elemental steps of the goldcatalysed redox cycle remain scarce 13,14 .…”

Gold‐Catalysed Oxyarylation of Styrenes and Mono‐ and gem‐Disubstituted Olefins Facilitated by an Iodine(III) Oxidant

“…[4] In this regard, the Selectfluor [5] -mediated two-component heteroarylation of olefins with arylboronic acids [6] (Scheme 1 a) constitutes a particularly significant development, as it served to illustrate the feasibility of oxidative CA C H T U N G T R E N N U N G (sp 3 )-CA C H T U N G T R E N N U N G (sp 2 ) bond formation in an intermolecular (i.e., cross-coupling) fashion. [7] The concept has subsequently been extended to threecomponent oxyarylation (Scheme 1 b), [8] and the suitability of arylsilanes as the aryl source has been reported both by ourselves [9] and by Toste. [10] Importantly, replacement of the arylboronic acid by an arylsilane was found to reduce the formation of biaryl side products.…”