Catalytic Mechanisms of Direct Pyrrole Synthesis via Dehydrogenative Coupling Mediated by PNP-Ir or PNN-Ru Pincer Complexes: Crucial Role of Proton-Transfer Shuttles in the PNP-Ir System

Abstract

Kempe et al. and Milstein et al. have recently advanced the dehydrogenative coupling methodology to synthesize pyrroles from secondary alcohols (e.g., 3) and β-amino alcohols (e.g., 4), using PNP-Ir (1) and PNN-Ru (2) pincer complexes, respectively. We herein present a DFT study to characterize the catalytic mechanism of these reactions. After precatalyst activation to give active 1A/2A, the transformation proceeds via four stages: 1A/2A-catalyzed alcohol (3) dehydrogenation to give ketone (11), base-facilitated C-N coupling of 11 and 4 to form an imine-alcohol intermediate (18), base-promoted cyclization of 18, and catalyst regeneration via H2 release from 1R/2R. For alcohol dehydrogenations, the bifunctional double hydrogen-transfer pathway is more favorable than that via β-hydride elimination. Generally, proton-transfer (H-transfer) shuttles facilitate various H-transfer processes in both systems. Notwithstanding, H-transfer shuttles play a much more crucial role in the PNP-Ir system than in the PNN-Ru system. Without H-transfer shuttles, the key barriers up to 45.9 kcal/mol in PNP-Ir system are too high to be accessible, while the corresponding barriers (<32.0 kcal/mol) in PNN-Ru system are not unreachable. Another significant difference between the two systems is that the addition of alcohol to 1A giving an alkoxo complex is endergonic by 8.1 kcal/mol, whereas the addition to 2A is exergonic by 8.9 kcal/mol. The thermodynamic difference could be the main reason for PNP-Ir system requiring lower catalyst loading than the PNN-Ru system. We discuss how the differences are resulted in terms of electronic and geometric structures of the catalysts and how to use the features in catalyst development.

Reduction of CO2 to Methanol Catalyzed by a Biomimetic Organo-Hydride Produced from Pyridine

“…68 It is important to recognize that commonly employed entropy evaluations within the rigid rotor, harmonic oscillator and ideal gas approximations normally overestimate the entropic cost for reactions occurring in solution phase, because ideal gas partition functions do not explicitly take into account hindered translation, rotation and vibration of the solute surrounded by solvent molecules. 25,[69][70][71][72][73][74] For example, Huang and coworkers observed that the calculated standard activation entropy values (-T∆S ‡ calc) consistently overestimate the experimental -T∆S ‡ exp values by ~4-5 kcal/mol at 298K. 71,72 Liang and coworkers also observed that -T∆S ‡ exp values are 50-60% of the computed -T∆S ‡ calc, and in some cases activation entropic costs -T∆S ‡ exp are overestimated by ~11 kcal/mol.…”

A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

“…The splitting of the H-H bond then occurs via a proton/hydride transfer process with the formation of the Metal−H hydride and a C-H or N-H bond. Recent studies on hydrogen activation by Wang and Huang et al [74,96] show completely different thermodynamic preferences between the Ru pincer complexes with -NPR 2 (Ru16) and -CHPR 2 (MRu5) arms (Figure 4(a) and 4(b)). The H 2 cleavage by Ru16 is thermodynamically less favorable than that by the MRu5 system.…”

“…When using one water and one alcohol molecule as the shuttle, the barriers can be further dropped to 24.6 (TS8_W) and 21.9 kcal/mol (TS8_OL), respectively. [74,96]. A c c e p t e d M a n u s c r i p t Figure 9.…”

“…A c c e p t e d M a n u s c r i p t Figure 9. The bifunctional double hydrogen transfer (BDHT) dehydrogenation pathway for PN 3 -Ir complex-catalyzed dehydrogenation of alcohol, along with the relative free energies [74,96].…”

“…M a n u s c r i p t Figure 10. A computed mechanism for the hydrogenation of ethyl acetate to ethanol catalyzed by Ru16 [74,96].…”