Chiral NCN Pincer Iridium(III) Complexes with Bis(imidazolinyl)phenyl Ligands: Synthesis and Application in Enantioselective C–H Functionalization of Indoles with α-Aryl-α-diazoacetates

Abstract

A series of chiral NCN pincer iridium(III) complexes 2a−h with bis(imidazolinyl)phenyl ligands were synthesized via the central aryl C2−H bond activation of the 1,3-bis(2′-imidazolinyl)benzene ligands. The incorporation of a 5tert-butyl group into the central aryl ring of the ligands was found to markedly improve the efficiency of the desired C2-metalation, leading to an obvious enhancement in the yields of the Ir(III) complexes. Consequently, complexes with a tert-butyl group on the central aryl ring were obtained in 34−47% yields, whereas those without the group were produced in only 13−16% yields. All of the new complexes have been characterized by elemental analysis and 1 H and 13 C{ 1 H} NMR spectroscopy. In addition, the molecular structures of complexes 2c, 2d, and 2g′ have been determined by X-ray single-crystal diffraction. 2c and 2d are, indeed, the anticipated six-coordinate pincer Ir(III) complexes. In contrast, 2g′ is a coordinatively unsaturated five-coordinate pincer Ir(III) complex. The Ir(III) complexes were used as the catalysts for the asymmetric C−H insertion reaction of α-aryl-α-diazoacetates with N-protected indoles. With a catalyst loading of 3 mol % and in the presence of 6 mol % of NaBAr F , a variety of optically active indole derivatives bearing chiral functional groups at the C3 position were obtained in good yields with moderate to good enantioselectivities (up to 86% ee).

Recent advances in transition-metal-catalyzed carbene insertion to C–H bonds

“…A chiral pincer iridium( iii )–NCN complex 567 bearing a 1,3-bis (2′-imidazolinyl)phenyl ligand was found to be an effective catalyst for the C(3)–H functionalization of the N -protected indoles (eqn (164)). 470 In the presence of 3 mol% 567 catalyst with the assistance of NaBAr′ 4 , N -protected indoles reacted with aryldiazoacetates 14 to result in the carbene insertion products 558 functionalized at 3-position of the indolyl moiety in low to excellent yields (21–99%) with moderate to good levels of asymmetric induction (37–86% ee). These results have demonstrated the catalyst diversity for enantioselective indolyl C–H functionalization of indoles by carbene insertion, and more work can be done to develop efficient catalyst systems for this purpose.…”

Chiral Imidazoline Ligands and Their Applications in Metal‐Catalyzed Asymmetric Synthesis†

“…N ‐Protected indoles were applicable, delivering the alkylation product with moderate to good yield and up to 86% ee . [ 113 ]…”

Chiral Tridentate-Based Ligands

“…146,147 148 Phebim ligands were used in the platinum-catalyzed alkylation of indoles with nitroalkenes (yield = 61-99%, ee = 34-83% for the ligand with R 1 = iPr, R 2 = R 3 = R 4 = R 6 = H, R 5 = Cy), 149,150 in the palladium-catalyzed aza-Morita-Baylis-Hillman reaction of acrylonitrile with imines (yield = 75-98%, ee = 76-98% for the ligand with R 1 = R 3 = 1-naphtyl, R 2 = R 4 = R 6 = H, R 5 = Ac), 151 in the rhodium-catalyzed allylation of aldehydes with allyltributyltin (yield = 78-99%, ee = 37-97% for the ligand with R 1 = Bn, R 2 = R 3 = R 4 = R 6 = H, R 5 = p-tolyl), 152 in the rhodium-catalyzed carbonyl-ene of ethyl trifluoropyruvates with 2-arylpropene (yield = 60-89%, ee = 65-94% for the ligand with R 1 = tBu, R 2 = R 3 = R 4 = R 6 = H, R 5 = p-tolyl), 152 in the rhodium-catalyzed alkynylation of ethyl trifluoropyruvates (with aromatic terminal alkynes: yield = 80-99%, ee = 94-99% for the ligand with R 1 = R 3 = Ph, R 2 = R 4 = H, R 5 = p-tolyl, R 6 = NO2; with aliphatic terminal alkynes: yield = 68-86%, ee = 52-99% for the ligand with R 1 = R 3 = Ph, R 2 = R 4 = H, R 5 = ptolyl, R 6 = NO2), 153 in the palladium-catalyzed hydrophosphination of enones with diphenylphosphine (yield = 20-90%, ee = 79-94% for the ligand with R 1 = R 3 = Ph, R 2 = R 4 = R 6 = H, R 5 = p-tolyl) 154 and in the iridium-catalyzed C-H functionalization of indoles with aryl--diazoacetates (yield = 21-99%, ee = 6-86% for the ligand with R 1 = R 3 = Ph, R 2 = R 4 = H, R 5 = p-tolyl, R 6 = tBu). 155…”