Enantioselective Synthesis of Highly Functionalized Phosphonate-Substituted Pyrans or Dihydropyrans Through Asymmetric [4+2] Cycloaddition of β,γ-Unsaturated α-Ketophosphonates with Allenic Esters

摘要

The phosphonate group, commonly used as a phosphate mimic in biological systems,is generally regarded as a bioisostere of a carboxylic acid group in drug design. In contrast to carboxylic acid, the phosphonic acid has higher acidity and stronger electrostatic interaction with the guani-dine group. Some drugs, such as tamiphosphor, guanidino-tamiphosphor, phosphono-zanamivir and phosphono-glycosyl acetates, which bear a phosphonic acid group instead of a carboxylic acid group, possess more inhibitory activity against the neuraminidases of the influenza viruses ; also, phosphorus-chromones are important intermediates for producing platelet-aggregation inhibitors (Figure 1). Recently, allenoates have been found to be an attractive substrate class for Lewis base catalyzed reactions and have attracted synthetic interest. A large number of phosphine-catalyzed cycloaddition reactions of allenoates have been reported after the pioneering work by Lu and co-workers in 1995.