Gold-Catalyzed Oxidative Coupling Reactions with Aryltrimethylsilanes

Abstract

During continuing studies with a novel oxidative gold oxyarylation reaction, arylsilanes were found to be competent coupling partners, providing further evidence for an intramolecular electrophilic aromatic substitution mechanism. While providing complementary yields to the previously described boronic acid methods, the use of trimethylsilanes reduces the observation of homocoupling byproducts and allows for facile intramolecular coupling reactions.With the development of transition metal-catalyzed cross-coupling reactions, significant effort has been expended in the development of inexpensive and reliable organometallic reagents as coupling partners. 1 In this context, organosilanes present an attractive solution; however, there have been relatively few reports of transition metal-catalyzed reactions with the readily accessible aryltrimethylsilanes. Moreover, a stoichiometric additive such as fluoride or hydroxide is typically employed to activate the relatively unreactive silicon center for transmetallation. 2 Alternatively, a variety of reactive silicon reagents have been designed and utilized in transition metal catalyzed cross-coupling reactions on milder conditions. 3 During our recent examination of the Selectfluor mediated gold-catalyzed amino-and oxyarylation of terminal olefins with boronic acids, 4 mechanistic experimentation and computational analysis provided evidence against transmetallation to the gold center. Instead, studies suggested a bimolecular reductive elimination reminiscent of an electrophilic aromatic substitution. While unactivated trimethylarylsilanes do not typically directly engage in cross-couplings, 5 they can readily react as nucleophiles in aromatic substitution reactions. 6 We therefore hypothesized that arylsilanes might be utilized as the terminating nucleophile in oxidative gold-catalyzed coupling with alkenes.On the basis of this hypothesis, we were delighted to find that when olefin 1 was reacted with phenyltrimethylsilane under the previously described reaction conditions, the desired intermolecular oxyarylation product (2) was observed in 50% yield (Table 1, entry 1). No exogenous base or fluoride is required for silicon activation, and a wide variety of readily available silanes, silanols, and siloxanes are capable oxyarylation coupling partners. In attempting to identify the optimal silicon coupling regent, we found silanediols and -triols provided excellent yields (entries 5, 8), though rapid oligomerization lead to concerns regarding reproducibility. The more bench stable trisiloxane derivatives 7 unfortunately fdtoste@berkeley.edu.

AuI/AuIII Catalysis: An Alternative Approach for CC Oxidative Coupling

“…Independent reports by Toste and Russell demonstrated that aryltrimethylsilanes are similarly effective in the majority of cases using both intra-and intermolecular nucleophiles. [46] As for arylboronic acids, the presence of fluoride derived from the external oxidant, Selectfluor, is thought to aid the nucleophilicity of the aryl group through the formation of a strong Si À F bond. Arylsilanes are desirable sources of aryl moieties for oxidative coupling reactions, since they are readily prepared and purified and are comparatively stable with respect oxidation by the external oxidant.…”

Gold‐Catalysed Oxyarylation of Styrenes and Mono‐ and gem‐Disubstituted Olefins Facilitated by an Iodine(III) Oxidant

“…Intramolecular coupling of an olefin and a tethered arylsilane occurred in a 6-endo-trig fashion to give tetrahydronaphthalene 14 in a yield similar to that obtained with Selectfluor as the oxidant [10] (Scheme 2, top). By contrast, the two-component heteroarylation of olefins bearing tethered O-or N-nucleophiles did not proceed to afford the expected tetrahydrofurans or pyrrolidines: in the case of 4-penten-1-ol, a complex mixture of products was obtained, whilst N-(4-pentenyl)tosylamide furnished a 9:1 mixture of piperidine 15 and pyrrolidine 16 (Scheme 2, bottom).…”

“…[10] In addition, the combination of nucleophilic promoters (e.g., TBAF, TBAT = tetrabutylammonium triphenyldifluorosilicate) and alternative oxidants (e.g., PhIA C H T U N G T R E N N U N G (OAc) 2 ) afforded only traces of the desired oxyarylation products. [9] The evident inhibitory effect of basic additives on the transformation prompted us to assay the oxyarylation of 1-octene under Brønsted acidic conditions (Table 1).…”

“…[7] The concept has subsequently been extended to threecomponent oxyarylation (Scheme 1 b), [8] and the suitability of arylsilanes as the aryl source has been reported both by ourselves [9] and by Toste. [10] Importantly, replacement of the arylboronic acid by an arylsilane was found to reduce the formation of biaryl side products.…”

“…Scheme 1. a) Two- [6] and b) three-component [8][9][10] heteroarylation of monosubstituted olefins, employing Selectfluor as both terminal oxidant and fluoride source. c) Envisaged electrophilic fluorination of more-nucleophilic substrates.…”