Design of catalysts for site-selective and enantioselective functionalization of non-activated primary C–H bonds

Abstract

C-H functionalization represents a promising approach for the synthesis of complex molecules. Instead of relying on modifying the functional groups present in a molecule, the synthetic sequence is achieved by carrying out selective reactions on the C-H bonds, which traditionally would have been considered to be the unreactive components of a molecule. A major challenge is to design catalysts to control both the site- and stereoselectivity of the C-H functionalization. We have been developing dirhodium catalysts with different selectivity profiles in C-H functionalization reactions with donor/acceptor carbenes as reactive intermediates. Here we describe a new dirhodium catalyst capable of the functionalization of non-activated primary C-H bonds with high levels of site selectivity and enantioselectivity.

Copper‐Catalyzed C(sp3)−H Amidation: Sterically Driven Primary and Secondary C−H Site‐Selectivity

“…In 2008, Che and co‐workers showed that a sterically encumbered Rh‐porphyrin catalyst demonstrates high primary selectivity in carbenoid transfer reactions (Figure a) . Most recently, the Davies group reported a new dirhodium catalyst that is highly effective for the functionalization of primary C−H bonds with high levels of site‐ and enantioselectivity via [Rh]=CR 2 intermediates . By altering the sterics of the carboxylate ligands, site‐selectivity can be tuned to prefer either tertiary, secondary or primary C−H bonds…”

Optimized Immobilization Strategy for Dirhodium(II) Carboxylate Catalysts for C−H Functionalization and Their Implementation in a Packed Bed Flow Reactor

“…After immobilization on the silica surface,t he active site of the catalyst 3a would open toward the silica support (entry b, Figure 2), where the surface species might interact with the active site or hinder the substrate accessibility.T hus,w e decided to move forward with the linker located on ring B,as its equatorial position is conserved in other catalyst geometries in the tetracarboxylate family,m aking it the optimal anchor site for all known TPCP-based dirhodium catalysts. [13,14]…”

C–H Functionalization Approach for the Synthesis of Chiral C2 Symmetric 1,5-Cyclooctadienes Ligands

“…The Chiral COD ligands 1 and 2 have shown considerable promise but their synthesis requires a multistep synthesis and a resolution. 4b This has led to the synthesis of other skipped cyclic dienes as chiral ligands, [4][5][6] including a number of C2 symmetric ligands 3-6. However, all require a multistep synthesis and most involve a racemic synthesis followed by resolution [4][5][6].…”

“…4b This has led to the synthesis of other skipped cyclic dienes as chiral ligands, [4][5][6] including a number of C2 symmetric ligands 3-6. However, all require a multistep synthesis and most involve a racemic synthesis followed by resolution [4][5][6]. In this paper we describe an enantioselective C-H functionalization method for the direct synthesis of C2 symmetric COD derivatives 7, with four stereogenic centers.…”