New Methodology Toward the Formation of Highly Substituted Tetrahydropyranones
Authors:Chloe Yu Yi Huang, Gidget C. Tay
Mentor:Scott Rychnovsky, Professor of Chemistry , University of California, Irvine
THPs and tetrahydropyranones (THPOs) are common core structures found in numerous medicinal compounds and natural products, such as cyanolide A. Furthermore, highly substituted chiral THPs are in various small molecules that can lead to bioactive pharmaceutical intermediates. The significance of this class of molecules motivated our research group to develop a new and efficient methodology to build THPs. The key step in our route to make highly substituted tetrahydropyranones diastereoselectively is a cyclization between a 1,3–hydroxy silyl enol ether and an aldehyde. This modular synthesis can form up to three stereocenters and one quaternary center on the THPOs. Formation of two of the stereocenters occurs during cyclization, which is promoted by TMSOTf or BF3•OEt. The variation of the substituent comes from readily accessible precursors. This reaction tolerates many functional groups and it affords yields ranging from 52% to 97%.