Isothiourea-Catalyzed Enantioselective Addition of 4-Nitrophenyl Esters to Iminium Ions
Publication Date
2018
Journal Title
ACS Catalysis
Abstract
© 2017 American Chemical Society. Isothioureas catalyze the enantioselective addition of 4-nitrophenyl esters to tetrahydroisoquinoline-derived iminium ions. 4-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the 4-nitrophenyl ester, is used to facilitate catalyst turnover in this reaction process. Optimization showed that 4-nitrophenyl esters give the best reactivity in this protocol over a range of alternative aryl esters, with the observed enantioselectivity markedly dependent on the nature of the iminium counterion. Highest yields and enantioselectivity were obtained using iminium bromide ions generated in situ via photoredox catalysis using BrCCl3and Ru(bpy)3Cl2(0.5 mol %) and commercially available tetramisole (5 mol %) as the Lewis base catalyst. The scope and limitations of this procedure was developed, giving the desired β-amino amide products in up to 96% yield, 79:21 diastereomeric ratio (dr), and ermajor (2R,1′S)99.5:0.5.
Volume Number
8
Issue Number
2
Pages
1153 - 1160
Document Type
Article
Status
Faculty
Facility
School of Medicine
Primary Department
Urology
DOI
10.1021/acscatal.7b02697