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

Abstract

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A Review on Oxidative Gold‐Catalyzed C‐H Arylation of Arenes – Challenges and Opportunities

“…Lloyd-Jones and co-workers further implemented the C-H arylation in the total synthesis of a number of (±)-allocolchicine analogs. [44] While this was a groundbreaking advance for the field of gold-catalyzed oxidative C-H functionalization, this method was not without limitations, as electron-rich arylsilanes gave poor yields, often due to increased homocoupling of the arylsilane. Additionally, arylsilanes containing ortho-substitution or heteroarenes also were inefficient in the first-generation approach.…”

Homogeneous Gold-Catalyzed Aryl–Aryl Coupling Reactions

“…The intramolecular aryl-aryl coupling reaction was subsequently applied for the formal synthesis of (±)-allocolchicine (Scheme 9). 20 During the optimization and investigation of the key cyclization step, it was discovered that a gold catalyst inhibitor is formed by an uncatalyzed reaction between the hypervalent iodine oxidant and the nucleophilic trimethoxyaryl moiety. Although the product was still obtained in 56% yield, the authors argued that the development of novel oxidants could help expand the generality and utility of gold-catalyzed oxidative coupling reactions.…”

Au-Catalyzed Oxidative Arylation: Chelation-Induced Turnover of ortho-Substituted Arylsilanes

“…For the vast majority of cases, the turnover-rate limiting event is intermolecular C-H arylation (k5,6), proceeding with a first-order kinetic dependence on 2 and a negative entropy of activation. 5 Whilst the substrate scope for the coupling has proven to be reasonably broad, [4][5][6][7][8] ortho-substituted arylsilanes (o-1) undergo slow intermolecular coupling, requiring prolonged reaction times or elevated temperatures, Scheme 1. 4,5,8b Indeed, a number of examples of hindered ortho-substituted arylsilanes fail to couple at all.…”