Chiral Carboxylic Acid Enabled Achiral Rhodium(III)‐Catalyzed Enantioselective C−H Functionalization

Abstract

Reported is an achiral CpxRhIII/chiral carboxylic acid catalyzed asymmetric C−H alkylation of diarylmethanamines with a diazomalonate, followed by cyclization and decarboxylation to afford 1,4‐dihydroisoquinolin‐3(2H)‐one. Secondary alkylamines as well as nonprotected primary alkylamines underwent the transformation with high enantioselectivities (up to 98.5:1.5 e.r.) by using a newly developed chiral carboxylic acid as the sole source of chirality to achieve enantioselective C−H cleavage by a concerted metalation‐deprotonation mechanism.

An Enantioselective CpxRh(III)‐Catalyzed C−H Functionalization/Ring‐Opening Route to Chiral Cyclopentenylamines

“…[5] Additionally,t he groups of You, [6] Antonchick and Waldmann, [7] and Perekalin [8] reported chiral Cp x ligands and subsequently applied them in asymmetric Rh III -catalyzed C À Hf unctionalizations.Acomplementary metallo-enzymatic approach based on supramolecular engineering was developed by the groups of Ward and Rovis. [10] Despite this recent progress,efficient and selective catalytic systems for new applications of Rh III -catalyzed enantioselective CÀHtransformations remain in high demand. [10] Despite this recent progress,efficient and selective catalytic systems for new applications of Rh III -catalyzed enantioselective CÀHtransformations remain in high demand.…”

“…[9] Matsunaga, Yoshino,and co-workers reported acombination of an achiral CpRh III complex and ac hiral acid co-catalyst for enantioselective C À Hf unctionalizations. [10] Despite this recent progress,efficient and selective catalytic systems for new applications of Rh III -catalyzed enantioselective CÀHtransformations remain in high demand.…”

Enantiodivergent Desymmetrization in the Rhodium(III)‐Catalyzed Annulation of Sulfoximines with Diazo Compounds

“…[7] In these asymmetric catalytic systems,t he stereodetermining process is the CÀHa ctivation (in desymmetrization), the migratory insertion process, [4a,b,8] or the reductive elimination. [11] On the other hand, Cramer and co-workers realized ad esymmetrizing amidation of phosphine oxides by making use of the cooperative effect of ac hiral catalyst and ac hiral acid (Scheme 1c). In principle,t he desymmetrizing CÀHa ctivation of an arene may be realized by using an achiral Rh III catalyst and achiral carboxylic acid where the chiral carboxylic acid renders the Rh III center chiral in aCMD mechanism.…”

“…Indeed, this scenario was elegantly realized by the group of Lin, Yishino,a nd Matsunaga (Scheme 1b). [11] On the other hand, Cramer and co-workers realized ad esymmetrizing amidation of phosphine oxides by making use of the cooperative effect of ac hiral catalyst and ac hiral acid (Scheme 1c). [12] In all of these systems,e ach reaction only led to as pecific configuration of the enantioenriched product when af ixed chiral catalyst/chiral additive was used, which will limit the synthetic applications.…”

“…Indeed, the e.r. generally decreased or was even inverted when as terically hindered benzoic acid was applied, as in the case of various 2,6-disubstituted benzoic acids (entries [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Although the electronic effect of the acid is also convoluted, there is no direct correlation of this effect with the enantioselectivity of the reaction.…”