Computational study-led organocatalyst design: a novel, highly active urea-based catalyst for addition reactions to epoxides.
An in silico study examined the stabilities of hydrogen-bonded complexes between simple thiourea catalysts and three different electrophiles and identified a novel, highly active N-tosyl urea catalyst for the promotion of addition reactions to epoxide electrophiles. Synthesis and evaluation of 6 revealed it to be a powerful catalyst for the addition of 1,2-dimethylindole to styrene oxide under conditions in which simple N,N-bis-aryl ureas and thioureas (including 1) are inactive. Subsequent studies determined 6 to be compatible with a range of indole and epoxide substrates (including (E)-stilbene oxide) and found that relatively poor nucleophiles such as sterically and electronically deactivated anilines, thiophenol, and benzyl alcohol could be efficiently and regioselectively added to oxiranes under mild conditions.
Fleming
Eimear M
EM
Centre for Synthesis and Chemical Biology, School of Chemistry, University of Dublin, Trinity College, Dublin 2, Ireland.
Quigley
Cormac
C
Rozas
Isabel
I
Connon
Stephen J
SJ