Cp*Rh(III)-Catalyzed Regioselective C(sp³)–H Methylation of 8-Methylquinolines with Organoborons

Abstract

Rh­(III)-catalyzed highly regioselective methylation of the unactivated C­(sp3)–H bond of 8-methylquinolines with bench stable organoboron reagents is described. A variety of substituted 8-methylquinolines provided the highly regioselective monomethylated products with potassium methyltrifluoroborates/methylboronic acid through primary C­(sp3)–H bond activation. Complete chemoselectivity and regioselectivity were observed in all cases as methylation at the C2 position or dimethylation of the C­(sp3)–H bond of 8-methylquinoline was not detected. The mechanistic study uncovered the fact that the reaction may proceed through the five-membered rhodacycle intermediate.

Cp*RhIII‐Catalyzed Sterically Controlled C(sp3)−H Selective Mono‐ and Diarylation of 8‐Methylquinolines with Organoborons**

“…During the com-pilation of the current work, Ghosh and Samantar eported the Rh-catalyzed C(sp 3 )ÀHa ctivation of 8-methylquinolinesf ollowed by functionalization with diazo compounds butt his methodi sonly applicable for the introduction of naphthol/ phenol moieties. [17] In continuation of our interest in C(sp 3 )ÀHb ond activation/ functionalization of 8-methylquinolines [18] herein, we unveiled the first Rh III -catalyzed highly selectivem onoarylationo f8methylquinolines with bench-stable arylboronic acids. The chemo selectivity is sterically controlled in case of C7-substituted 8-methylquinolines, whereas in the case of 8-methylquinolines without C7 substituent mono-o rs ymmetrical diarylation is achieved by controlling the amounto fa rylboronic acids.…”

Installing the “magic methyl” – C–H methylation in synthesis

“…However, in 2020, Sharma described the directed C(sp 3 )-H methylation of 8-methylquinoline structures using a Cp*Rh III catalyst system. 173 This method also allowed for the use of MeBF 3 K as a nucleophilic methyl source. While the yields of this methylation protocol remained modest, the demonstrated quinoline scope was notably broad (Scheme 66).…”

Rhodium‐Catalyzed Selective C−H Bond Functionalization of Quinolines

“…Along with this, phenyltrifluoroborates also utilized in this reaction but failed to provide an arylated product (Scheme 38). [68] In 2020, Sharma and coworkers have done the sp 3 arylation by exploring aryl boronic acid which readily undergoes a homocoupling reaction to give biphenyl adducts (Scheme 39a, 39b, 39c). This arylating reagent investigated for mono-arylation with a wide array of 8-methylquinolines.…”

“…The corresponding rhodacycle was synthesized with 8‐methylquinoline and proved as an intermediate in the reaction mechanism. Along with this, phenyltrifluoroborates also utilized in this reaction but failed to provide an arylated product (Scheme ) …”