Room‐Temperature Gold‐Catalysed Arylation of Heteroarenes: Complementarity to Palladium Catalysis

Abstract

Tailoring of the pre-catalyst, the oxidant and the arylsilane enables the first room-temperature, gold-catalysed, innate C-H arylation of heteroarenes. Regioselectivity is consistently high and, in some cases, distinct from that reported with palladium catalysis. Tolerance to halides and boronic esters, in both the heteroarene and silane partners, provides orthogonality to Suzuki-Miyaura coupling.

Au-Catalyzed Biaryl Coupling To Generate 5- to 9-Membered Rings: Turnover-Limiting Reductive Elimination versus π-Complexation

“…In subsequent developments, Itami and Sagewa demonstrated that pyridylidene Au-complexation facilitates arylation of isoxazoles, indoles and benzothiophenes, 6 Jeon applied Aucatalyzed arylation to functionalize ortho-silyl aryl triflates generated via Rh/Ir-catalyzed traceless ortho-CH silation, 7 and we reported that silane and oxidant modification allows arylation of a range of heterocycles. 8 Major advances have also been made towards understanding the unique reactivity and selectivity of catalytic reactions proceeding via Au(I) and Au(III) intermediates. 6,9 Nonetheless, in comparison to many transition metal catalyzed processes, overall mechanistic understanding of homogeneous gold catalysis remains less well developed.…”

Formal Synthesis of (±)-Allocolchicine Via Gold-Catalysed Direct Arylation: Implication of Aryl Iodine(III) Oxidant in Catalyst Deactivation Pathways

“…As noted above neither 10 nor 18b undergo cyclisation (see Schemes 4,5). Moreover, inclusion of a catalytic amount of alcohol 18b in the reaction of 3 resulted in an even earlier onset of catalyst inhibition (Fig.…”

“…In conclusion, we have developed a synthetic route to a number of allocolchinoid analogues, including a formal synthesis of (±)-allocolchicine (±)-5 using a gold-catalysed direct arylation [1][2][3][4][5][6] in the key bond-forming step. The reaction is vulnerable to severe catalyst deactivation, with the likely cause identified as in situ inhibitor generation, involving a direct (uncatalysed) reaction of the substrate with the iodine(III) oxidant.…”

“…It is thus clear from this study that moving away from hypervalent iodine oxidants to other species will be essential in expanding the generality and utility of the Au-catalysed arylation reaction [1][2][3][4][5]. Despite this, the methodology in its current state provides a number of advantages over other processes, e.g.…”

“…We have also expanded the process to include (2). A mixture of iodobenzene diacetate and camphorsulfonic acid can be used where HCIB is formed in-situ Scheme 2 Cyclisation to generate an allocolchinoid skeleton (4) ∆ Scheme 3 Formal synthesis of allocolchicine, (±)-5. dcpp = 1,3-Bis(dicyclohexylphosphino)propane the intermolecular arylation of a broad range of heteroarenes at room temperature [5], and developed intramolecular arylations to generate 5-9 membered rings [6]. Of the more than 140 examples of the Au-arylation reaction studied to date [1][2][3][4][5][6], the majority proceed efficiently with low catalyst loadings (typically 1-2 mol% Au) under mild conditions, and quite frequently at ambient (20-25 °C) temperature.…”