title: Stereoselective addition of 2-phenyloxazol-4-yl trifluoromethanesulfonate to N-sulfinyl imines: application to the synthesis of the HCV protease inhibitor boceprevir.
abstract: The stereoselective addition of 2-phenyloxazol-4-yl trifluoromethanesulfonate to N-sulfinylimines is described. Vinyl anions derived from enol triflate 2 undergo 1,2-addition with a variety of aldimines to afford the corresponding secondary sulfonamides as single diastereomers. The absolute stereochemistry was confirmed by X-ray crystallography which provides support that the reaction proceeds through an open, nonchelate transition state. This methodology has been applied to the synthesis of the ketoamide fragment of the protease inhibitor boceprevir.
authors.affiliation: Department of Process Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. william.morris2@merck.com
authors.forename: William J
authors.initials: WJ
authors.lastname: Morris
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Muppalla
authors.forename: Cameron
authors.initials: C
authors.lastname: Cowden
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ball
mesh_terms: D018360:Crystallography, X-Ray; D016174:Hepacivirus / Q000737:chemistry* / Q000187:drug effects*; D007097:Imines / Q000737:chemistry*; D008698:Mesylates / Q000737:chemistry*; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry*; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: C583347:2-phenyloxazol-4-yl trifluoromethanesulfonate; D007097:Imines; D008698:Mesylates; D010080:Oxazoles; D011480:Protease Inhibitors; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline