Enantioselective synthesis of 2-methyl indolines by palladium catalysed asymmetric C(sp3)–H activation/cyclisation

Abstract

The first example of the enantioselective methyl C-H activation by an intramolecular ArPdX species and subsequent cyclisation was developed. Palladium catalysts using commercially available chiral diphosphines yield good ee's (up to 93% ee) in the synthesis of 2-methyl indolines from 2-halo N-isopropyl anilides. This approach was also employed for the synthesis of enantioenriched cyclohexyl fused indolines with moderate enantioselectivities.

Palladium–N‐Heterocyclic Carbene (NHC)‐Catalyzed Asymmetric Synthesis of Indolines through Regiodivergent C(sp3)H Activation: Scope and DFT Study

“…The groups of Kagan [9] and Cramer [10] chose the chiral phosphine ligands Duphos and Sagephos, respectively; the latter outperformed the former. Related research, aimed at substituted chiral indanes, was published by Baudoin et al [11] Experimental studies showed that a palladium-coordinated carboxylate ligand was important for the reaction and computational analysis pointed to an inner-sphere, carboxylate-assisted CMD pathway analogous to that formulated previously for C Ar ÀH functionalization.…”

Complementary Strategies for Directed C(sp3)−H Functionalization: A Comparison of Transition‐Metal‐Catalyzed Activation, Hydrogen Atom Transfer, and Carbene/Nitrene Transfer

“…[183] Thus, tricyclic 459 can be obtained from vinyl triflate 457.F or the activation of primary CÀHb onds,K agan and co-workers showed that the use of chiral phosphine Me-DUPHOS (LG12)a llows for the desymmetrization of vinyl bromide 460 to access indoline 461 (Scheme 86). [184] Fort he synthesis of enantiomerically enriched dihydroindene 463 from vinyl bromide 462,C lot, Baudoin, and co-workers utilized axially chiral phosphine LG13 (Scheme 87). [185] TheY uresearch group demonstrated an enantioselective palladium-catalyzed carbonyl-directed C(sp 3 )ÀHa ctivation.…”

Palladium(0)-catalyzed asymmetric C(sp3)–H arylation using a chiral binol-derived phosphate and an achiral ligand

“…5a,c,6,7a In contrast, a single example of fused indoline-cyclobutane has been reported in its racemic form by Fagnou and co-workers. 23 Using our optimized conditions, compounds 2aa and 2ab were obtained with high enantioselectivity (e.r.…”