Coupling of Sulfoxonium Ylides with Arynes: A Direct Synthesis of Prochiral Aryl Ketosulfoxonium Ylides and Its Application in the Preparation of α‑Aryl Ketones Alexa ́ nder Garay Talero, Bruna Simõ es Martins, and Antonio C. B. Burtoloso* ,a Instituto de Química de Sã o Carlos, Universidade de Sã o Paulo, CEP 13560-970 Sã o Carlos, SP, Brazil * S Supporting Information ABSTRACT: A general, mild, and versatile synthesis of the challenging α-aryl-β-ketosulfoxonium ylides has been developed for the first time, substituting traditional methods starting from diazo compounds. The arylation of easily accessible β- ketosulfoxonium ylides using aryne chemistry allowed the preparation of a large scope of the pro-chiral ylides in very good yields (40 examples; up to 85%). As applications, these ylides were smoothly converted into α-aryl ketones after desulfurization in good yields (up to 98%) as well as in other important derivatives. S ulfonium and sulfoxonium ylides 1,2 have played significant roles in organic synthesis as important building blocks in total synthesis, 3-9 chemical materials, 10-12 and pharmaceut- icals, 13-15 among others. 16,17 These ylides have also proven to be alternative metallocarbene surrogates to diazo com- pounds, 18 having many reactions in common such as insertion, 19-21 cyclopropanation, 21 epoxidation, 22 aziridina- tion, 23 dimerizations, 24 and Wolff 24,25 and Stevens rearrange- ments. 26,27 Furthermore, when compared with diazo com- pounds, these ylides are generally crystalline solids, more stable, have already been used in industrial scales, 15 and are easier/safer to prepare (since they do not involve the use of potentially explosive compounds such as azides, diazomethane, and its derivatives). 28 Over many years, sulfoxonium ylides have received less attention compared to sulfonium ylides. However, in the past few years, this class of compounds has resurfaced as a powerful and versatile synthetic tool in the arsenal of organic chemists. Two examples are the seminal work of Baldwin 20 in metal- catalyzed N-H insertion reactions and from Mangion 19,29 at Merck, where β-ketosulfoxonium ylides were applied as diazo carbonyl surrogates. Since these contributions, this type of ylide has been employed in several important and new transformations that explore its ambiphilic behavior. For- mation of C-C, C-N, C-O, and C-halogen bonds, synthesis of naphthols, 30 indoles, 13 and pyrroles, 13 cross-coupling reactions, 31,32 and synthesis of difunctionalized haloketones, 33 among others, 34-43 are some of the very recent examples (Figure 1). Importantly, many of these reactions are fruitless when the equivalent sulfonium ylide or diazo carbonyl are employed in place of sulfoxonium ylides, showing that these three classes of compounds (though similar) can also have distinct behavior. Regardless of the appearance of these new methodologies, the limitation of the substitution pattern in the ylide center (only Received: October 1, 2018 Figure 1. Sulfur ylides as diazo compound surrogates in different reactions with limited substitution patterns. Letter pubs.acs.org/OrgLett Cite This: Org. Lett. XXXX, XXX, XXX-XXX © XXXX American Chemical Society A DOI: 10.1021/acs.orglett.8b03126 Org. Lett. XXXX, XXX, XXX-XXX Downloaded via UNIV OF WINNIPEG on October 26, 2018 at 12:58:52 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.