[(NHC)Au^I]‐Catalyzed Formation of Conjugated Enones and Enals: An Experimental and Computational Study

Abstract

The [(NHC)AuI]-catalyzed (NHC=N-heterocyclic carbene) formation of alpha,beta-unsaturated carbonyl compounds (enones and enals) from propargylic acetates is described. The reactions occur at 60 degrees C in 8 h in the presence of an equimolar mixture of [(NHC)AuCl] and AgSbF6 and produce conjugated enones and enals in high yields. Optimization studies revealed that the reaction is sensitive to the solvent, the NHC, and, to a lesser extent, to the silver salt employed, leading to the use of [(ItBu)AuCl]/AgSbF6 in THF as an efficient catalytic system. This transformation proved to have a broad scope, enabling the stereoselective formation of (E)-enones and -enals with great structural diversity. The effect of substitution at the propargylic and acetylenic positions has been investigated, as well as the effect of aryl substitution on the formation of cinnamyl ketones. The presence or absence of water in the reaction mixture was found to be crucial. From the same phenylpropargyl acetates, anhydrous conditions led to the formation of indene compounds via a tandem [3,3] sigmatropic rearrangement/intramolecular hydroarylation process, whereas simply adding water to the reaction mixture produced enone derivatives cleanly. Several mechanistic hypotheses, including the hydrolysis of an allenol ester intermediate and SN2' addition of water, were examined to gain an insight into this transformation. Mechanistic investigations and computational studies support [(NHC)AuOH], produced in situ from [(NHC)AuSbF6] and H2O, instead of cationic [(NHC)AuSbF6] as the catalytically active species. Based on DFT calculations performed at the B3LYP level of theory, a full catalytic cycle featuring an unprecedented transfer of the OH moiety bound to the gold center to the C[triple chemical bond]C bond leading to the formation of a gold-allenolate is proposed.

Gold‐ vs. Platinum‐Catalyzed Polycyclizations by O‐Acyl Migration. Solvent‐Free Reactions

“…Minor amounts (< 10 %) of a,bunsaturated aldehyde possibly originating from adventitious hydrolysis of allenyl esters 3b were also observed. [9] Contrary to our initial fear, switching to a central 7-membered ring did not cause any difficulty since a quantitative yield of 2c was obtained with PtCl 2 . Gold catalysis was not as efficient, and allenyl ester 3c was formed in around 30 % yield (entry 3).…”

Gold‐Catalyzed Homogeneous Oxidative Cross‐Coupling Reactions

“…Although the initial yield was low, we were intrigued by the reaction and proposed a working mechanism. As shown in Scheme 1, gold-catalyzed tandem reactions of propargylic acetate 1, as established by previous studies by us and others, [10,11] should lead to the formation of intermediate A upon hydrolysis, which is then oxidized by Selectfluor to a give a Au(III) species (i.e., B). The transmetalation from A to B could lead to the diorganogold(III) intermediate C, which could then undergo reductive elimination to give dimer 2 and regenerate the gold(I) catalyst.…”

“…To our surprise, when propargylic acetate 1 was treated with [Ph 3 PAu]NTf 2 (5 mol %) and Selectfluor (1 equiv) in acetone in a sealed vial at 80 8C, enone dimer 2 was formed in 19 % yield along with 11 % of enone 3 [10] and some unreacted starting material [Eq. (1)].…”

Triazole‐Gold‐Promoted, Effective Synthesis of Enones from Propargylic Esters and Alcohols: A Catalyst Offering Chemoselectivity, Acidity and Ligand Economy

“…The authors have performed comprehensive mechanistic investigations. [8] Through both experimental and computational studies, the S N 2' water addition to the goldactivated alkyne was suggested as the mechanism by avoiding the formation of allene [Scheme 3(A)]. This mechanism was further supported by two other experimental observations: (i) no enone formation was observed with t-Bu-substituted alkyne 1b [Scheme 3 + and [PPh 3 -Au] + ) gave only the thermodynamically stable Z-isomers, the application of TA-Au led to the selective formation the kinetically favored Eisomers.…”

“…[7] One application of this process was the synthesis of enones from sequential hydration of the allene-acetate 2a intermediates (Scheme 2, path B). [8] Although this direct transformation provided one attractive strategy in preparing enones under mild conditions, it suffered from limited substrate scope due to the side reactions caused by the gold-promoted allene activation. One side reaction was the intramolecular Friedel-Crafts cyclization of 2a, giving the indene 3a.…”