Iridium(I)-Catalyzed Isoindolinone-Directed Branched-Selective Aromatic C–H Alkylation with Simple Alkenes

Abstract

We report an iridium(I)-catalyzed branched-selective C–H alkylation of N-arylisoindolinones with simple alkenes as the alkylating agents. The amide carbonyl group of the isoindolinone motif acts as the directing group to assist the ortho C–H activation of the N-aryl ring. With this atom-economic and highly branched-selective protocol, an array of biologically relevant N-arylisoindolinones were obtained in good yields. Asymmetric control was achieved with up to 87:13 er when a BiPhePhos-like chiral ligand was employed.

Precise control of the site selectivity in ruthenium-catalyzed C–H bond amidations using cyclic amides as powerful directing groups

“…In this case, no C–H bond functionalization was detected, indirectly demonstrating the importance of the carbonyl group in assisting the catalysis likely via coordination to ruthenium. 14,15 In addition, deuteration experiments were performed under the catalytic conditions but in the absence of the amidating partner 2 with a mixture of solvents TFE : D 2 O (Scheme 6, bottom). Under these conditions, 17% deuteration incorporation was observed in the ortho -C–H bonds of the phenyl ring attached to the nitrogen atom with no deuteration observed elsewhere in the molecule (Scheme 6, bottom).…”

“…Control experiments, preliminary mechanistic studies and thorough DFT calculations unambiguously support that cyclic amides enable the formation of catalytically productive six-membered ruthenacycles as unique intermediates 14 as it was evoked but never demonstrated in C–O and C–C bond forming reactions. 15 It is noteworthy that cyclic amides, such as isoindolinones employed in this study, are prevalent motifs encountered in several daily-life chemicals (Scheme 2C, framed); 16 therefore the presented methodology paves the way towards the use of ruthenium catalysts in C–H bond late-stage functionalization strategies. 17 An in-depth comparative study with other types of common directing groups is presented, indicating the suitability of weak amide directing groups over more coordinating ones, such as pyridines, for ruthenium-catalyzed C–H bond amidations.…”

Transition-metal-catalyzed C–H bond alkylation using olefins: recent advances and mechanistic aspects

“…Very recently, Yang and Xing disclosed a methodology to demonstrate branched-selective C–H alkylation of N -arylisoindolinones with simple alkenes under Ir( i ) catalysis (Scheme 34B). 98 Here, the isoindolinone moiety acted as a directing group and enabled the site-selective ortho -C–H activation of the N -aryl ring. Mechanistically, the transformation followed the type II catalytic pathway ( cf.…”

An Aza-Enolate Strategy Enables Iridium-Catalyzed Enantioselective Hydroalkenylations of Minimally Polarized Alkenes en Route to Complex N-Aryl β2-Amino Acids

“…8b The branched selectivity arises upon conversion of Int-II to Int-III and may reflect either a preference for the bulky Ir-center to move to the less hindered end of the alkene, or electronic effects. 24 An outer sphere carbometalation pathway, involving attack of Int-I onto an Ir-π-complex, is disfavored because we observe first order kinetics with respect to the catalyst (see the Supporting Information). An alternative pathway involving N-directed C− H activation from Int-I cannot be discounted, although we disfavor this because of the high strain of the azairidacyclobutene that would arise 25 and because the conversion of Int-II to Int-III is consistent with the Ir-enolate-based reactivity we have previously observed.…”