RETRACTED: Asymmetric remote C–H borylation of aliphatic amides and esters with a modular iridium catalyst

Abstract

Site selectivity and stereocontrol remain major challenges in C–H bond functionalization chemistry, especially in linear aliphatic saturated hydrocarbon scaffolds. We report the highly enantioselective and site-selective catalytic borylation of remote C(sp3)–H bonds γ to the carbonyl group in aliphatic secondary and tertiary amides and esters. A chiral C–H activation catalyst was modularly assembled from an iridium center, a chiral monophosphite ligand, an achiral urea-pyridine receptor ligand, and pinacolatoboryl groups. Quantum chemical calculations support an enzyme-like structural cavity formed by the catalyst components, which bind the substrate through multiple noncovalent interactions. Versatile synthetic utility of the enantioenriched γ-borylcarboxylic acid derivatives was demonstrated.

Rhodium-catalysed selective C–C bond activation and borylation of cyclopropanes

“… 6 The coordination of directing groups with the TM catalysts can deliver hydroboration products with controllable distal 7 and/or proximal 8 selectivity. Recently, directed borylation of aliphatic C–H bonds with proximal 9 and distal 10 selectivity has also gained momentum. The functionalization of the C–C bond is one of the most attractive strategies in organic chemistry.…”

Site-selective functionalization of remote aliphatic C–H bonds via C–H metallation

“…An eminent proof-of-concept approach that took advantage of multiple non-covalent interactions harnessed remote methylene C(sp 3 )–H borylation even in an enantioselective fashion. 26 To date, catalytic asymmetric remote C(sp 3 )–H functionalization via forming classical metallacycles without compromise in the substrate structure is not seen, and one of the formidable challenges would be conformational flexibility of larger-sized metallacycles. The utilization of enzyme-like interactions could be regarded as a vital progress for such asymmetric catalysis as well as a paradigm without installation and removal of directing groups, despite the fact that non-covalent interaction involved iridium catalysis is largely limited to C–H borylation reactions thus far.…”

“…Quite recently, an iridium-catalyzed regio- and enantioselective borylation for the γ-methylene C(sp 3 )–H bond of aliphatic amides and esters without a specialized directing moiety was reported by the Sawamura group ( Scheme 14a ). 26 The key to success of this approach is to constitute an enzyme like chiral cavity by modular assembly of an iridium center, a bulky chiral phosphite ligand, a urea-pyridine based H-bond receptor ligand ( RL ) and pinacolatoboryl groups. Different from the above mentioned reactions that typically form small-sized metallacycles, such as 5-, 6- or 7-membered ones, the remote site-selectivity was achieved without the formation of a conventional metallacycle, or with the formation of a macrocyclic metal intermediate if one regards the H-bond as a part of the cycle.…”

Iridium‐Catalyzed Enantioselective Unbiased Methylene C(sp3)–H Borylation of Acyclic Amides

“…Nonetheless, these weakly coordinating substrates are more readily available and transformable, thereby improving the utility of the methods and providing a promise of greatly accelerating the discovery of a diverse range of C−H borylation reactions [18] . In 2020, the group of Sawamura reported an elegant enantioselective γ‐C(sp 3 )‐H borylation of amides using a hydrogen bond strategy [17g] . However, the reaction of other positions remains elusive.…”