Asymmetric methods for the synthesis of flavanones, chromanones, and azaflavanones

Flavanones, chromanones, and related structures are privileged natural products that display a wide variety of biological activities. Although flavanoids are abundant in nature, there are a limited number of available general and efficient synthetic methods for accessing molecules of this class in a stereoselective manner. Their structurally simple architectures belie the difficulties involved in installation and maintenance of the stereogenic configuration at the C2 position, which can be sensitive and can undergo epimerization under mildly acidic, basic, and thermal reaction conditions. This review presents the methods currently used to access these related structures. The synthetic methods include manipulation of the flavone/flavanone core, carbon-carbon bond formation, and carbon-heteroatom bond formation. Flavanoids are plant-derived natural products. Although they are ubiquitous in nature, general asymmetric methods for their generation are rarer, due to the lability of the stereochemistry at C2. We discuss methods for the generation of enantio-enriched flavanones, chromanones, andazaflavanones, including chemical and enzymatic resolution, asymmetric reduction, and conjugate addition reactions.