Gold Catalysis: Deuterated Substrates as the Key for an Experimental Insight into the Mechanism and Selectivity of the Phenol Synthesis

Abstract

The second phase of the gold-catalyzed phenol synthesis, the ring opening of the intermediate arene oxide, follows general acid catalysis. The product selectivity is determined by the substrate only and can be explained by the stability of the intermediate arenium ions. Thus, even remote substitutents can be used to control the chemoselectivity of the overall reaction by electronic influences and their influence is stronger than the steric influence of neighboring substituents. This is supported by quantum chemical calculations of the intermediates. The lack of exchange of deuterium labels excludes even equilibria with acetylide or vinylidene intermediates and the observed deuterium distribution in the final products is in accord with the NIH-shift reaction. In addition, these findings now explain previously obtained results.

Gold Catalysis: Domino Reaction of En‐Diynes to Highly Substituted Phenols

“…The conversion of 15 o revealed a selectivity pattern that was comparable to earlier studies that concern furans with two additional substituents as nucleophiles in the furan-yne cyclization (Scheme 5). [4] As in the case of 15 n, the formation of six-ring annulated systems delivered considerably higher yields than five-membered derivatives. Here an overall yield of 89 % was obtained, which splits up into three different products.…”

Olefin‐Metathesis‐Based Synthesis of Furans by an RCM/Deprotonation/Phosphorylation Sequence and Their Diels–Alder Reactions

“…[34][35][36] The gold-catalysed [37] rearrangement of furans with a pendant alkyne side-chain also gives phenols, but proceeds via an arene oxide rather than a Diels-Alder adduct. [38,39] A few examples of the Diels-Alder reactions of furans with electron-donating substituents at the 2-position and subsequent rearrangement to phenols have been reported. For example, as shown in Scheme 4, 2-methoxyfuran (9) was found to undergo a cycloaddition reaction with hexafluorobutyne (10) to give 11, which rearranges thermally, even in the absence of acid, to phenol 12.…”

DFT insights into the cycloisomerization of ω-alkynylfuran catalyzed by planar gold clusters: mechanism and selectivity, as compared to Au(i)-catalysis

“…15 Remarkable works have also been performed regarding the elucidation of this mechanism including the successful isolation of several key intermediates, that is, the arene oxide and oxepine. 7,16 The breakage and formation of four bonds during this reaction is clearly not an elementary reaction. Because the rate-limiting step possesses lowest reaction rate in the overall reactions (reaction kinetic theory), the reaction intermediate of this step should be opulent and be detectable by the NMR, IR etc.…”

“…2 The Hashmi group showed that the reaction does not proceed via an alkynyl or a vinylidene complex because a primary kinetic isotope effect was not observed with a substrate deuterated at the alkyne. 16 The Echavarren group found that the intramolecular reaction of furans with alkynes catalyzed by PtCl 2 is mechanistically related to that of enyne in polar solvents. 13,14 The PtCl 2 -catalyzed reaction is initiated by the nucleophilic attack of the furan on a (h 2 -alkyne)-Pt(II) complex to form a cyclopropyl platinum carbene via density functional theory calculations.…”

“…13,14 The PtCl 2 -catalyzed reaction is initiated by the nucleophilic attack of the furan on a (h 2 -alkyne)-Pt(II) complex to form a cyclopropyl platinum carbene via density functional theory calculations. According to 18 O labeling experiments, 1 substrate deuteration studies, 16 and in situ NMR spectroscopy, 7,17 Hashmi et al proposed a mechanism for the Au(III)-catalyzed phenol synthesis reaction shown in Scheme 3. The reaction kinetic studies provided strong evidence that the actual Au(I) catalyst was likely the Ph 3 PAu + complex, which was under equilibrium with precatalyst [Ph 3 P-Au-triazole] + as shown by the Shi group.…”