Rhodium(III)‐Catalyzed Enantio‐ and Diastereoselective C−H Cyclopropylation of N‐Phenoxylsulfonamides: Combined Experimental and Computational Studies

Abstract

Cyclopropane rings are a prominent structural motif in biologically active molecules. Enantio‐ and diastereoselective construction of cyclopropanes through C−H activation of arenes and coupling with readily available cyclopropenes is highly appealing but remains a challenge. A dual directing‐group‐assisted C−H activation strategy was used to realize mild and redox‐neutral RhIII‐catalyzed C−H activation and cyclopropylation of N‐phenoxylsulfonamides in a highly enantioselective, diastereoselective, and regioselective fashion with cyclopropenyl secondary alcohols as a cyclopropylating reagent. Synthetic applications are demonstrated to highlight the potential of the developed method. Integrated experimental and computational mechanistic studies revealed that the reaction proceeds via a RhV nitrenoid intermediate, and Noyori‐type outer sphere concerted proton‐hydride transfer from the secondary alcohol to the Rh=N bond produces the observed trans selectivity.

Rhodium(III)‐Catalyzed Atroposelective Synthesis of Biaryls by C−H Activation and Intermolecular Coupling with Sterically Hindered Alkynes

“…Stoichiometric CÀHa ctivation of 1a with Rh-1 in the presence of AgOAc,followed by addition of PPh 3 ,a llowed isolation of the rhodacycle 11 in high yield (Scheme 7a). [17,18] Thecomplex 11 was characterized by NMR spectroscopy and X-ray crystallography (CCDC 1978298 contains the supplementary crystallographic data for this paper.T hese data can be obtained free of charge from The Cambridge Crystallographic Data Centre). In the crystal structure,the less hindered benzene ring of the benzamide is disposed toward the chiral ligand for minimized steric interactions,w hich sets up ac hiral environment for the incoming alkyne.…”

Cobalt‐Catalyzed Diastereo‐ and Enantioselective Hydroarylation of Cyclopropenes with Arylboronic Acids

“…In the context of catalytic enantioselective functionalization of cyclopropenes, Rh‐catalyzed hydrostannation, [8] hydroboration, [9] hydrothiolation, [10] hydroformylation, [11] hydroacylation [12] and hydroarylation, [13] Cu‐catalyzed hydroboration, [14] hydronitronylation, [15] carbocupration, [16] carbozincation, [17] carbomagnesiantion [18] and hyroallylation, [19] Fe‐ [20] and Pd‐catalyzed carbozincation, [21] hydroalkynylation, [22] hydrophosphination [23] and lanthanide‐catalyzed hydroamination, [24] hydroalkynylation, [25] and addition of 2‐methyl azaarenes, [26] Co‐catalyzed hydroalkenylation [27] and hydrosilylation, [28] Ni‐catalyzed hydroalkylation, [29] hydroaryloxy‐ and hydroalkoxycarbonylation [30] and NHC‐catalyzed hydroacylation [31] have been reported for enantioselective synthesis of a variety of functionalized cyclopropanes. Although enantioselective hydroboration of cyclopropenes followed by Pd‐catalyzed cross‐coupling with aryl halides represents an indirect approach to incorporate an aryl unit on the three‐membered rings, [8,14,26] a more general and step‐economic solution to this problem is the utility of more robust aryl boronic acids with higher functional group tolerance and diversity as nucleophiles for catalytic enantioselective hydroarylation of cyclopropenes.…”

Enantioselective and Diastereoselective C–H Alkylation of Benzamides: Synergized Axial and Central Chirality via a Single Stereodetermining Step

“…In this context, asymmetric catalytic C−H bond activation of arenes has flourished, because of the ready availability of arenes without necessity of preactivation. 1 Several classes of metal complexes such as Pd(II), 2 Rh(III), 3 and Ir(I) 4 have been applied as powerful chiral catalysts to effect asymmetric C−H bond activation. 5 In these systems, unsaturated reagents such as olefins, alkynes, enynes, allenes, diazo reagents, and imides have been often employed as the coupling reagents for construction of chiral centers, with C−H activation, 6 migratory insertion, 7 or reductive elimination 8 being enantio-determining.…”