[3,3]-Sigmatropic Rearrangement versus Carbene Formation in Gold-Catalyzed Transformations of Alkynyl Aryl Sulfoxides: Mechanistic Studies and Expanded Reaction Scope

Abstract

Gold-catalyzed intramolecular oxidation of terminal alkynes with an arenesulfinyl group as the tethered oxidant is a reaction in gold chemistry of high impact, as it introduced to the field the highly-valued concept of gold carbene generation via alkyne oxidation. The proposed intermediacy of α-oxo gold carbenes in these reactions, however, has never been substantiated. Detailed experimental studies suggest that the involvement of such reactive intermediates in the formation of dihydrobenzothiepinones is highly unlikely. Instead, a [3,3]-sigmatropic rearrangement of the initial cyclization intermediate offers a reaction path that can readily explain the high reaction efficiency and the lack of sulfonium formation. With internal alkyne substrates, however, the generation of a gold carbene species becomes competitive with the [3,3]-sigmatropic rearrangement. This reactive intermediate, nevertheless, does not proceed to afford the Friedel-Crafts type cyclization product. Extensive Density Functional Theory studies support the mechanistic conclusion that the cyclized product is formed via an intramolecular [3,3]-sigmatropic rearrangement instead of the previously proposed Friedel-Crafts type cyclization. With the new mechanistic insight, the product scope of this versatile formation of mid-sized sulfur-containing cycloalkenones has been expanded readily to various dihydrobenzothiocinones, a tetrahydrobenzocyclononenone, and even those without the entanglement of a fused benzene ring. Besides gold, Hg(OTf)2 can be an effective catalyst, thereby offering a cheap alternative for this intramolecular redox reaction.

A Desulfonylative Approach in Oxidative Gold Catalysis: Regiospecific Access to Donor‐Substituted Acyl Gold Carbenes

“…[2, 4],[5] While terminal alkynes are most frequently oxidized to terminal gold carbene intermediates, regioselective oxidations of internal alkynes can be challenging, and often only one regioisomer could be accessed selectively based on structural biases and upon optimizations of catalyst, oxidant and other reaction conditions. For example, in our previous work, [6] under optimal conditions, differences in steric bulk of the two alkyne ends were harnessed to achieve selective oxygen delivery to the less hindered C(sp) (e.g., 1 , Scheme 1B), and with electronically biased internal alkynes oxidation occurs selectively at the end most accommodating to positive charge development upon gold coordination, i.e., proximal to aryl, alkeny and N -amido (e.g., 2 – 3 , [7] Scheme 1B) [5l–o, 6] and distal to electron-withdrawing groups (e.g., 4 , Scheme 1B). [4f, 5e, 5f] There is, however, no viable approach to generating α-oxo gold carbenes selectively with regiochemistries opposite to the structurally preferred ones, let alone regiospecifically.…”

“…It is notable that 7a could not be generated cleanly via gold-catalyzed double oxidation [5k, 12] of the corresponding 1-methyl-4-(prop-1-yn-1-yl)benzene as facile 1,2-C-H insertions by the isomeric gold carbenes of type A would lead to the formation of enone side products. [6] [13] …”

A Desulfonylative Approach in Oxidative Gold Catalysis: Regiospecific Access to Donor‐Substituted Acyl Gold Carbenes

“…Much to our delight, the reaction yield was improved to ad ecent 72 %( entry 6). [6,13] We explored the scope of this desulfonylative double oxidation chemistry.Asshown in Table 2, the p-tolyl group of 5a could be replaced with either an electron-rich 4-methoxyphenyl (entry 1) or as lightly electron-deficient 4-bromophenyl (entry 2). Among them, 2-tert-butyl-4-chloropyridine N-oxide (6c), first reported by Gagosz, [5i] proved to be the most effective (entry 8), and 7a was isolated in 80 %yield.…”

Mechanistic study on the regioselectivity of Co-catalyzed hydroacylation of 1,3-dienes

“…Computational studies were performed with Gaussian 09 program [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Geometry optimization was conducted in gas phase with M06 method [24].…”