Chemoselective Synthesis of 1,1-Disubstituted Vinyl Triflates from Terminal Alkynes Using TfOH in the Presence of TMSN 3 Jumreang Tummatorn,* ,‡,§ Kunlayanee Punjajom, § Warabhorn Rodphon, § Sureeporn Ruengsangtongkul, ‡ Nattawadee Chaisan, § Kanyapat Lumyong, ‡ Charnsak Thongsornkleeb, †,§ Phongprapan Nimnual, § and Somsak Ruchirawat ‡,§ † Laboratory of Organic Synthesis, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand ‡ Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand § Program on Chemical Biology, Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology (EHT), Ministry of Education, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand * S Supporting Information ABSTRACT: 1,1-Disubstituted vinyl triflates are synthesized by direct hydrotriflation of terminal alkynes employing a combination of TfOH and TMSN 3 in DCM at room temperature. Interestingly, under these conditions, only terminal alkynes were selectively converted to the correspond- ing vinyl triflates, while internal alkynes were not reacted. A broad range of substrates were successfully converted to the corresponding 1,1-disubstituted vinyl triflates in good to excellent yields even those with internal alkyne moieties present in the molecules. V inyl triflate is an important functional group used in many synthetic transformations, especially for cross-coupling reactions including C-C, 1 C-O, 2 C-N, 3 and C-halogen 4 bond formations. The most general method for preparing vinyl triflate derivatives is the trifluoromethanesulfonylation or triflation of enolates using various triflating agents. 5 However, only a few reported methods employed alkynes as starting materials in spite of their ease of access (Scheme 1). In fact, the conditions using trifluoromethanesulfonic or triflic acid (TfOH) as the hydrotriflating agent has been reported. 6,7,4b However, most reactions needed to be carried out under low temperatures 8 to avoid solvolysis of the vinyl triflate product. 9 In addition, this method has no particular chemoselectivity toward the alkyne substrates; both internal and terminal alkynes could be converted to vinyl triflates nonselectively. A similar lack of selectivity was also observed when using rhodium, 10 ruthenium, 11 copper, 12 and zinc 13 complexes as the catalysts. Therefore, development of a new method for controlling chemoselectivity of hydrotriflation of alkynes is a challenging task. In this work, we discovered that combination of TMSN 3 and TfOH reagents could chemoselectively convert only the terminal alkynes to 1,1-disubstituted vinyl triflates at room temperature. This combination essentially lowered the reactivity of TfOH in hydrotriflation on internal alkynes, resulting in only trace amount of trisubstituted vinyl triflates while terminal alkynes readily reacted to give 1,1-disubstituted vinyl triflates in good conversion with no formation of the corresponding vinyl azides. This novel mode of reactivity observed in combination of TfOH and TMSN 3 was envisioned to be a potentially useful tool for chemical synthesis, especially when the reaction is performed on compounds containing both internal and terminal alkynes. To elaborate on these findings, reactions were performed with various internal alkynes as shown in Scheme 2. The Received: May 5, 2019 Scheme 1. Methods for the Synthesis of Vinyl Triflates Letter pubs.acs.org/OrgLett Cite This: Org. Lett. XXXX, XXX, XXX-XXX © XXXX American Chemical Society A DOI: 10.1021/acs.orglett.9b01576 Org. Lett. XXXX, XXX, XXX-XXX Downloaded by UNIV OF SOUTHERN INDIANA at 17:19:20:565 on June 11, 2019 from https://pubs.acs.org/doi/10.1021/acs.orglett.9b01576.