Organocatalytic Access to Tetrasubstituted Chiral Carbons Integrating Functional Groups.
Keisuke AsanoSeijiro MatsubaraPublished in: Chemical record (New York, N.Y.) (2022)
Three-dimensional organic structures containing sp 3 carbons bearing four non-hydrogen substituents can provide drug-like molecules. Although such complex structures are challenging targets in synthetic organic chemistry, efficient synthetic approaches will open a new chemical space for pharmaceutical candidates. This review provides an account of our recent achievements in developing organocatalytic approaches to attractive molecular platforms based on optically active sp 3 carbons integrating four different functional groups. These methodologies include asymmetric cycloetherification and cyanation of multifunctional ketones, both of which take advantage of the mild characteristics of organocatalytic activation. Enzyme-like but non-enzymatic organocatalytic systems can be used to precisely manufacture molecules containing complex chiral structures without substrate specificity problems. In addition, these catalytic systems control not only stereoselectivity but also site-selectivity and do not induce side reactions even from substrates with rich functionality.