Stereodivergent Desymmetrization of Phenols En Route to Modular Access to Densely Functionalized Quinazoline and Oxazine Scaffolds

The de novo assembly of stereochemically
and skeletally diverse
scaffolds is a powerful tool for the discovery of novel chemotypes.
Hence, the development of modular, step- and atom-economic synthetic
methods to access stereochemically and skeletally diverse compound
collection is particularly important. Herein, we show a metal-free,
stereodivergent build/couple/pair strategy that allows access to a
unique collection of benzo[5,6][1,4]oxazino[4,3-a]quinazoline, quinolino[1,2-a]quinazoline and benzo[b]benzo [4,5]imidazo[1,2-d][1,4]oxazine
scaffolds with complete diastereocontrol and wide distribution of
molecular architectures. This metal-free process proceeds via desymmetrization of phenol derivatives. The cascade
unites Mannich with aza-Michael addition reactions, providing expeditious
entries to diverse classes of molecular shapes in a single operation.