Synthesis of highly enantioenriched 3,4-dihydroquinolin-2-ones by 6-exo-trig radical cyclizations of axially chiral alpha-halo-ortho-alkenyl anilides.
Radical cyclizations (Bu(3)SnH, Et(3)B/air, rt) of racemic alpha-halo-ortho-alkenyl anilides provide 3,4-dihydroquinolin-2-ones in high yield. Cyclizations of enantioenriched precursors occur in similarly high yields and with transfer of axial chirality to the new stereocenter of the products with exceptionally high fidelity (often >95%). Single and tandem cyclizations of alpha-halo-ortho-alkenyl anilides bearing an additional substituent on the alpha-carbon occur with high chirality transfer and high diastereoselectivity. Straightforward models are proposed to interpret both the chirality transfer and diastereoselectivity aspects. These first examples of an approach for axial chiral transfer from a reactive species in the amide to an acceptor suggest broad potential for extension both within and beyond radical reactions.
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
David B
DB
Guthrie
Steven J
SJ
Geib
Dennis P
DP
Curran
D000475:Alkenes / Q000737:chemistry*; D000813:Anilides / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D015363:Quinolones / Q000138:chemical synthesis*; D013237:Stereoisomerism
C546846:3,4-dihydroquinolin-2-one; D000475:Alkenes; D000813:Anilides; D005609:Free Radicals; D015363:Quinolones