tert-Butyl as a Functional Group: Non-Directed Catalytic Hydroxylation of Sterically Congested Primary C-H Bonds.

The tert-butyl group is a common aliphatic motif extensively employed to implement steric congestion and conformational rigidity in organic and organometallic molecules. Because of the combination of a high bond dissociation energy (~100 kcal mol) and limited accessibility, in the absence of directing groups, neither radical nor organometallic approaches are effective for the chemical modification of tert-butyl C-H bonds. Herein we overcome these limits by employing a highly electrophilic manganese catalyst, [Mn(bpeb)(OTf)], that operates in the strong hydrogen bond donor solvent nonafluoro-tert-butyl alcohol (NFTBA) and catalytically activates hydrogen peroxide to generate a powerful manganese-oxo species that effectively oxidizes tert-butyl C-H bonds.

Highly Enantioselective Catalytic Lactonization at Nonactivated Primary and Secondary -C-H Bonds.

Chiral oxygenated aliphatic moieties are recurrent in biological and pharmaceutically relevant molecules and constitute one of the most versatile types of functionalities for further elaboration. Herein we report a protocol for straightforward and general access to chiral -lactones via enantioselective oxidation of strong nonactivated primary and secondary C()-H bonds in readily available carboxylic acids. The key enabling aspect is the use of robust sterically encumbered manganese catalysts that provide outstanding enantioselectivities (up to >99.

C-H Bonds as Functional Groups: Simultaneous Generation of Multiple Stereocenters by Enantioselective Hydroxylation at Unactivated Tertiary C-H Bonds.

Enantioselective C-H oxidation is a standing chemical challenge foreseen as a powerful tool to transform readily available organic molecules into precious oxygenated building blocks. Here, we describe a catalytic enantioselective hydroxylation of tertiary C-H bonds in cyclohexane scaffolds with HO, an evolved manganese catalyst that provides structural complementary to the substrate similarly to the lock-and-key recognition operating in enzymatic active sites. Theoretical calculations unveil that enantioselectivity is governed by the precise fitting of the substrate scaffold into the catalytic site, through a network of complementary weak non-covalent interactions.

Carboxylic Acid Directed γ-Lactonization of Unactivated Primary C-H Bonds Catalyzed by Mn Complexes: Application to Stereoselective Natural Product Diversification.

Reactions that enable selective functionalization of strong aliphatic C-H bonds open new synthetic paths to rapidly increase molecular complexity and expand chemical space. Particularly valuable are reactions where site-selectivity can be directed toward a specific C-H bond by catalyst control. Herein we describe the catalytic site- and stereoselective γ-lactonization of unactivated primary C-H bonds in carboxylic acid substrates.