Highly Efficient Syntheses of C−N Axially Chiral 1‐(ortho‐hydroxyaryl)uracil using a Chiral Auxiliary and a Chiral Base

Abstract

AbstractWe achieved a highly diastereoselective synthesis of 1‐aryl‐6‐aminouracils, which are C−N atropisomeric compounds, through the combined use of a chiral auxiliary and a chiral base under mild conditions. We found that the (R)‐5‐allyl‐2‐oxabicyclo[3.3.0]oct‐1‐yl group is a good chiral auxiliary that, when combined with quinidine, efficiently affords 1‐aryl‐6‐aminouracils with high diastereoselectivity (up to 98 % ee after isolation). The chiral alcohol moiety in quinidine appears to be crucial for achieving stereoselectivity during cyclization. Furthermore, the chiral auxiliary was easily removed from the product under acidic conditions to provide the atropisomer with high enantiomeric excess (up to 96 % ee). The developed method is an efficient diastereoselective‐cyclization method for the generation of C−N axial chirality.