Propargyl Alcohols as One-Carbon Synthons: Redox-Neutral Rhodium(III)-Catalyzed C–H Bond Activation for the Synthesis of Isoindolinones Bearing a Quaternary Carbon

Abstract

Herein, rhodium(III)-catalyzed C-H activation/subsequent [4 + 1] cyclization reactions between benzamides and propargyl alcohols are reported in which propargyl alcohols serve as unusual one-carbon units. This title transformation led to a series of isoindolinones bearing a quaternary carbon with moderate to good yields without the requirement for external metal oxidants. Due to the mild and simple reaction conditions, this reaction is compatible with various functional groups.

Transition‐Metal‐Catalyzed C−H Functionalization for Construction of Quaternary Carbon Centers

“…Propargyl alcohols as ao ne-carbon unit to participate in a redox-neutral [4+ +1] annulation with benzamides under either rhodiumo rr uthenium catalysis was disclosed recently by Liu, Zhou, and co-workers( Scheme 79). [125] This transformation gave as eries isoindolinones 258 with an N-substituted quaternary center in good yields.…”

Rh(III)-Catalyzed C–H Bond Activation for the Construction of Heterocycles with sp3-Carbon Centers

“…In recent years, our group has been devoted to developing some highly efficient synthetic strategies to extend our heterocyclic compounds library for the screening of biologically active lead compounds [75−85]. In 2017, we built a novel isoindolone scaffold bearing a quaternary carbon via Rh(III)-catalyzed C−H bond cleavage and subsequent [4 + 1] cyclization tandem reactions between In recent years, our group has been devoted to developing some highly efficient synthetic strategies to extend our heterocyclic compounds library for the screening of biologically active lead compounds [75][76][77][78][79][80][81][82][83][84][85]. In 2017, we built a novel isoindolone scaffold bearing a quaternary carbon via Rh(III)-catalyzed C−H bond cleavage and subsequent [4 + 1] cyclization tandem reactions between benzamides and propargyl alcohols (Scheme 13) [76].…”

“…In recent years, our group has been devoted to developing some highly efficient synthetic strategies to extend our heterocyclic compounds library for the screening of biologically active lead compounds [75−85]. In 2017, we built a novel isoindolone scaffold bearing a quaternary carbon via Rh(III)-catalyzed C−H bond cleavage and subsequent [4 + 1] cyclization tandem reactions between benzamides and propargyl alcohols (Scheme 13) [76]. The biggest merit of this transformation is that a novel synthetic utility of propargyl alcohols as a one-carbon synthon has been found, which can give an unusual [4 + 1] transformation.…”

Synthesis and Organocatalytic Asymmetric Nitro-aldol Initiated Cascade Reactions of 2-Acylbenzonitriles Leading to 3,3-Disubstituted Isoindolinones

“…In this way, a number of interesting 3,3-disubstituted isoindolinones were obtained as racemates via a carbonyl addition step followed by a Dimroth type rearrangement of the immediate intermediate (Scheme 2) [8]. It is worthy to note that the number of methodologies for the asymmetric synthesis of 3,3-disubstituted isoindolinones is limited [31][32][33] and the reported strategies are mainly based on racemate resolution [31][32][33] or on the use of chiral auxiliaries [31][32][33], while asymmetric catalytic procedures are relatively rare [34][35][36][37][38][39]. Therefore, we were interested to investigate the reactivity of 2-acylbenzonitriles with common nucleophiles employing chiral organocatalytic systems in order to achieve a direct construction of chiral 3,3-disubstituted isoindolinones.…”

“…The best results in terms of enantioselectivity were obtained in the presence of the bifunctional ammonium salt C1 derived from trans-1,2-cyclohexyldiamine recently developed by our group [41,42], which gave a quantitative yield and moderate enantioselectivity (41% ee). On the other hand, (di)azepino based PTC E1 (Maruoka's catalyst) [43] and E2 (Lygo's catalyst) [43] were not effective (Entries 5, 6), which highlights the importance to use bifunctional ammonium salts with an effective hydrogen donor It is worthy to note that the number of methodologies for the asymmetric synthesis of 3,3-disubstituted isoindolinones is limited [31][32][33] and the reported strategies are mainly based on racemate resolution [31][32][33] or on the use of chiral auxiliaries [31][32][33], while asymmetric catalytic procedures are relatively rare [34][35][36][37][38][39]. Therefore, we were interested to investigate the reactivity of 2-acylbenzonitriles with common nucleophiles employing chiral organocatalytic systems in order to achieve a direct construction of chiral 3,3-disubstituted isoindolinones.…”