Recent Advances in Asymmetric Transformations of Unactivated Alkanes and Cycloalkanes through Direct C-H Functionalization

Comprehensive Summary The direct conversion of unactivated alkanes and cycloalkanes into structurally diverse molecules through aliphatic C-H functionalization is a useful process, which has attracted intense interest from academia and industry. Methods to control chemo- and site-selectivity, combined with asymmetric catalysis, provide appealing access to high value-added enantiomer-enriched compounds but are far less developed. This review focuses on recent progress in (i) asymmetric reactions of alkanes or cycloalkanes with prochiral substrates which generate a stereocenter adjacent to the cleaved C(sp(3))-H bond, and (ii) C(sp(3))-H enantiodiscriminatory reactions creating a new stereogenic center on the carbon of a cleaved C(sp(3))-H bond. Elegant strategies are discussed, including (a) metal carbene-induced C-H insertions by chiral rhodium catalysts, (b) metal-oxo-mediated C-H oxidation by biomimetic manganese catalysts, (c) enzyme catalysis by cytochromes P450 variants, and (d) dual catalysis by a photocatalyst and a chiral Lewis acid (CLA) or a chiral phosphoric acid (CPA). These catalytic systems can not only precisely recognize primary, secondary and tertiary C-H bonds at specific positions in alkanes and cycloalkanes, but also support a high level of stereoselectivity in the reactions. It is expected that the advances will stimulate further progress in asymmetric catalysis, synthetic methodology, pharmaceutical development and industrial processes.