Palladium-Catalyzed Enantioselective C–H Activation of Aliphatic Amines Using Chiral Anionic BINOL-Phosphoric Acid Ligands

Abstract

The design of an enantioselective Pd(II)-catalyzed C-H amination reaction is described. The use of a chiral BINOL phosphoric acid ligand enables the conversion of readily available amines into synthetically valuable aziridines in high enantiomeric ratios. The aziridines can be derivatized to afford a range of chiral amine building blocks incorporating motifs readily encountered in pharmaceutically relevant molecules.

Pentamethylcyclopentadienyl rhodium(III)–chiral disulfonate hybrid catalysis for enantioselective C–H bond functionalization

“…[31][32][33][34][35][36] This strategy is quite attractive because an organocatalyst component can realize enantioselective transformation without using chiral ligands. The application of an organo/metal hybrid system in transition metal-catalyzed C-H bond activation has mainly focused on enantioselective C-H bond cleavage 13,14,19,37 in which an organocatalyst component, often regarded as an anionic ligand, functions as a base for concerted metalation deprotonation (CMD). 38,39 In this context, Chang and co-workers reported enantioselective amidation of phosphine oxides using a chiral carboxylic acid and a Cp*Ir(III) catalyst, but the observed enantioselectivities were less than 66:34 er.…”

Synthesis of Axially Chiral Biaryl‐2‐amines by PdII‐Catalyzed Free‐Amine‐Directed Atroposelective C−H Olefination

“…Although aniline-type amines have been used as efficient DGs in transition-metal-catalyzed CÀH functionalization of biaryl compounds, [12] the development of their asymmetric versions is more challenging and remains limited. [13] Recently, Inspired by the elegant work of Yu and co-workers on a chiral transient-directing-group strategy, [14] our group achieved several examples of Pd II -catalyzed atroposelective CÀH functionalization of biaryl aldehydes with commercially available tert-leucine (Tle) as a catalytic transient chiral auxiliary (TCA). [10] Attempts to adopt this strategy to biaryl-2-amines by searching for suitable chiral aldehydes as TCAs failed.…”

“…Then, a set of chiral SPA ligands with different steric and electronic properties were explored, giving only inferior results (entries 2-7). Other kinds of CPAs, namely BINOL-derived phosphoric acids (entries [8][9][10][11][12][13] and H8-BINOL-derived phosphoric acids (entry 14), were also investigated and L1 was found to be the optimal one. We believe that the SPAs provide a more rigid and narrower chiral pocket compared with their BINOL-derived counterparts, thereby leading to better non-covalent interactions with the substrates.…”

Enantioselective C(sp3)–H Amidation of Thioamides Catalyzed by a CobaltIII/Chiral Carboxylic Acid Hybrid System

“…[16] Group 9C p*M III , [17] Pd, [18] and other catalysts [19] have been used for directed intermolecular b-C(sp 3 ) À Hamination/ amidation reactions under the assistance of carbonyl-based directing groups,thereby providing astraightforward route to b-amino carbonyl compounds.A symmetric variants of these reactions provide attractive methods for synthesizing related chiral building blocks,but they have scarcely been studied. [20] Herein, we report an achiral Cp x Co III /chiral carboxylic acid hybrid system that catalyzes the C(sp 3 ) À Ha midation of thioamides (Scheme 1d). Good enantioselectivity was achieved when using ar eadily available ligand and carboxylic acid under mild conditions through an enantioselective carboxylate-assisted concerted metalation-deprotonation (CMD).…”