Title | Total Synthesis of K777: Successful Application of Transition-Metal-Catalyzed Alkyne Hydrothiolation toward the Modular Synthesis of a Potent Cysteine Protease Inhibitor |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Kiemele, ER, Wathier, M, Bichler, P, Love, JA |
Journal | Organic Letters |
Volume | 18 |
Pagination | 492-495 |
Abstract | We report the total synthesis of K777 and a series of analogues via alkyne hydrothiolation catalyzed by Wilkinson’s complex (ClRh(PPh3)3). The alkyne hydrothiolation reactions proceeded with excellent regio- and diastereoselectivity to generate the desired E-linear vinyl sulfides in high yield. The use of Ellman’s auxiliary generates the requisite propargyl amines in excellent enantiomeric excess (ee) and obviates the use of l-homophenylalanine, an expensive unnatural amino acid. The vinyl sulfone derivatives exhibit a large difference in rate toward Michael addition. Kinetic data are consistent with rate-limiting nucleophilic attack to generate the carbanion intermediate. |
URL | http://dx.doi.org/10.1021/acs.orglett.5b03535 |
DOI | 10.1021/acs.orglett.5b03535 |