Atom‐Efficient Gold(I)‐Chloride‐Catalyzed Synthesis of α‐Sulfenylated Carbonyl Compounds from Propargylic Alcohols and Aryl Thiols: Substrate Scope and Experimental and Theoretical Mechanistic Investigation

Abstract

Gold(I)-chloride-catalyzed synthesis of α-sulfenylated carbonyl compounds from propargylic alcohols and aryl thiols showed a wide substrate scope with respect to both propargylic alcohols and aryl thiols. Primary and secondary aromatic propargylic alcohols generated α-sulfenylated aldehydes and ketones in 60–97 % yield. Secondary aliphatic propargylic alcohols generated α-sulfenylated ketones in yields of 47–71 %. Different gold sources and ligand effects were studied, and it was shown that gold(I) chloride gave the highest product yields. Experimental and theoretical studies demonstrated that the reaction proceeds in two separate steps. A sulfenylated allylic alcohol, generated by initial regioselective attack of the aryl thiol on the triple bond of the propargylic alcohol, was isolated, evaluated, and found to be an intermediate in the reaction. Deuterium labeling experiments showed that the protons from the propargylic alcohol and aryl thiol were transferred to the 3-position, and that the hydride from the alcohol was transferred to the 2-position of the product. Density functional theory (DFT) calculations showed that the observed regioselectivity of the aryl thiol attack towards the 2-position of propargylic alcohol was determined by a low-energy, five-membered cyclic protodeauration transition state instead of the strained, four-membered cyclic transition state found for attack at the 3-position. Experimental data and DFT calculations supported that the second step of the reaction is initiated by protonation of the double bond of the sulfenylated allylic alcohol with a proton donor coordinated to gold(I) chloride. This in turn allows for a 1,2-hydride shift, generating the final product of the reaction.

Assessing Methodologies to Synthesize α‐Sulfenylated Carbonyl Compounds by Green Chemistry Metrics

“…Before it had been shown that other metal catalysts, such as rhenium(I), bismuth(III) or iron(III) promote direct substitution of the hydroxyl group to generate the corresponding propargylic thioether [49] . After optimization of the reaction conditions a range of α‐sulfenylated aldehydes and ketones could be obtained in 47–97 % yield (Scheme 17a) [48b] . Experimental and DFT (density functional theory) studies showed that the reaction proceeds in two steps.…”

“…Experimental and DFT (density functional theory) studies showed that the reaction proceeds in two steps. First, regioselective thiolation of the propargylic alcohol forms a sulfenylated allylic alcohol, which isomerizes to the desired α‐sulfenylated ketones [48b] . The methodology allowed the preparation of a wide range of ketones in a mild and efficient way.…”

Metal Catalysis in Thiolation and Selenation Reactions of Alkynes Leading to Chalcogen-Substituted Alkenes and Dienes

“…AuCl alone was found to catalyze both steps of the sequence as well; however, in this case, good selectivity was achieved only for interaction of aromatic thiols with internal alkynes . Thorough experimental and theoretical mechanistic investigations have been performed to shed light on Au‐catalyzed reaction sequence …”

“…[17] Thorough experimental and theoreticalm echanistic investigations have been performed to shed light on Au-catalyzed reactionsequence. [18] Ni complexes were found to be very promising in ZÀH( Z =S, Se) bond addition to alkynes to obtain Markovnikov-type products. In the first report on Ni catalysis, it was shown that Ni(PPh 2 Me) 4 allowed to perform additiono fP hSH to 1-octyne under very mild reactionc onditions leading to ah igh yield (92 %) and excellent selectivity (> 91 %) of the branched product in as hort time (3 hv ersus 16-20 hi nt he case of Pd).…”

Coinage-Metal-Catalyzed Reactions of Propargylic Alcohols

“…In an additional study, the substrate scope was widely investigated, and detailed experiments on the reaction mechanism were performed. 46 The transformation most likely proceeded by sequential gold-catalyzed regioselective hydrothiolation followed by isomerization via a 1,2-hydride migration to generate the desired products.…”