Transition Metal-Catalyzed Direct Stereoselective Oxygenations of C(sp3)–H Groups

Designing catalytic approaches to deliberate and selective C–H activation was listed by Bergman among the "Holy Grails" of synthetic chemistry in 1995, and continues to be a hot topic up to now, mostly in the context of late-stage functionalization of complex molecular structures ( Acc. Chem. Res. 1995, 28, 154−162, DOI: 10.1021/ar00051a009). This contribution surveys the asymmetric oxygenations of aliphatic C–H groups of organic molecules that have been reported to date, including enantio- and diastereoselective hydroxylations at prochiral C–H groups and oxidative desymmetrizations (through either ketonization or hydroxylation), via direct creation of new C–O bonds with the aid of synthetic transition metal based catalysts. Catalytic stereoselective C(sp3)–H oxygenations of complex structures of relevance for developing synthetic approaches for late-stage functionalization of bioactive molecules (such as, mostly, steroids and terpenoids) for drug discovery and development are considered. Synthetic aspects of the oxidative transformations as above are the major focus of the review. The mechanistic bases of the above processes are discussed briefly, in connection to the factors that govern the oxidation regio-, chemo-, and stereoselectivity.