A Proton‐Responsive Pyridyl(benzamide)‐Functionalized NHC Ligand on Ir Complex for Alkylation of Ketones and Secondary Alcohols

Abstract

A Cp*Ir(III) complex (1) of a newly designed ligand L 1 featuring a proton-responsive pyridyl(benzamide) appended on N-heterocyclic carbene (NHC) has been synthesized. The molecular structure of 1 reveals a dearomatized form of the ligand. The protonation of 1 with HBF 4 in tetrahydrofuran gives the corresponding aromatized complex [Cp*Ir(L 1 H)Cl]BF 4 (2). Both compounds are characterized spectroscopically and by X-ray crystallography. The protonation of 1 with acid is examined by 1 H NMR and UV-vis spectra. The proton-responsive character of 1 is exploited for catalyzing α-alkylation of ketones and β-alkylation of secondary alcohols using primary alcohols as alkylating agents through hydrogen-borrowing methodology. Compound 1 is an effec-tive catalyst for these reactions and exhibits a superior activity in comparison to a structurally similar iridium complex [Cp*Ir(L 2 )Cl]PF 6 (3) lacking a proton-responsive pendant amide moiety. The catalytic alkylation is characterized by a wide substrate scope, low catalyst and base loadings, and a short reaction time. The catalytic efficacy of 1 is also demonstrated for the syntheses of quinoline and lactone derivatives via acceptorless dehydrogenation, and selective alkylation of two steroids, pregnenolone and testosterone. Detailed mechanistic investigations and DFT calculations substantiate the role of the proton-responsive ligand in the hydrogen-borrowing process.À OH/=O, À CH 2 /=CH and À NH/ = N motifs on pyridine, [25][26][27] bipyridine, [28][29][30][31][32] bipyrimidine [33] and azole-pyridine/ pyrimidine [34][35][36][37] are particularly effective. Some of the representative examples that have been employed for catalyzing (de) hydrogenation and alkylation reactions are given in Scheme 1. Yamaguchi and co-workers reported a Cp*Ir(III) compound with

A Protic Mn(I) Complex Based on a Naphthyridine-N-oxide Scaffold: Protonation/Deprotonation Studies and Catalytic Applications for Alkylation of Ketones

“…The generation of C from A can follow either a concerted proton and hydride transfer at the ligand and the metal center, respectively, 108,109 or via the formation of a manganese alkoxide species, followed by a β-hydride elimination (see the Supporting Information). 109,110 A high retention of deuterium in the alkylated product supports the concerted pathway for the formation of C, 24 though an alternate stepwise pathway may not be excluded. The aldehyde undergoes base catalyzed aldol condensation to form an α,β-unsaturated ketone.…”

“…This blue shift on protonation is consistent with literature examples. 24,57,85 After several additions, the appearance of an isosbestic point suggests a solution phase equilibrium between the deprotonated (lactam) and the protonated (lactim) forms. α-Alkylation of Ketones with Primary Alcohols.…”

Ru-Catalyzed Asymmetric Addition of Arylboronic Acids to Aliphatic Aldehydes via P-Chiral Monophosphorous Ligands

“…3-phenyl-1-(p-tolyl)propan-1-ol (3aa) [85] [a] [a] 20 D = +10.5 (c 0.32, CH 2 Cl 2 ). Yield: 97% (130.2 mg) as a yellow oil; 1 H NMR (400 MHz, CDCl 3 ) δ 7.54-6.94 (m, 9H), 4.63 (dd, J = 7.9, 5.4, 1H), 2.99-2.54 (m, 2H), 2.25-1.98 (m, 2H), 1.95 (s, 1H) and 1.31 (s, 9H).…”

“…1,3-diphenylpropan-1-ol (3ap) [85] [a] [a] 20 D = +15.0 (c 0.28, CH 2 Cl 2 ). Yield: 23% (29.5 mg) as a colorless oil; 1 H NMR (400 MHz, CDCl 3 ) δ 7.48-6.97 (m, 6H), 6.82 (d, 2H), 4.63 (t, J = 6.7, 1H), 3.78 (s, 3H), 2.74-2.54 (m, 2H), 2.34 (s, 3H), 2.18-1.95 (m, 2H) and 1.80 (s, 1H).…”

Selective Synthesis of Ketones and Chiral Allylic Alcohols from the Addition of Arylboronic Acids to α,β-Unsaturated Aldehydes Mediated by a Transition Metal/Monophosphorus Ligand System

“…To date, alkylation of ketones with alcohols and dehydrogenative cross-coupling of alcohols have been used with good results to construct aryl alkyl ketones (Scheme a). For example, metals such as Pd, Ru, Ir, Rh, Fe, Mg, Co, and Ni have been used in the catalytic α-alkylation of ketones. Similarly, Ir, Cu, Ni, Co, and Mn complexes were employed in the dehydrogenative cross-coupling of alcohols to afford aryl alky ketones.…”