The Mechanism of Iron(II)-Catalyzed Asymmetric Mukaiyama Aldol Reaction in Aqueous Media: Density Functional Theory and Artificial Force-Induced Reaction Study

Abstract

Density functional theory (DFT), combined with the artificial force-induced reaction (AFIR) method, is used to establish the mechanism of the aqueous Mukaiyama aldol reactions catalyzed by a chiral Fe(II) complex. On the bases of the calculations, we identified several thermodynamically stable six- or seven-coordinate complexes in the solution, where the high-spin quintet state is the ground state. Among them, the active intermediates for the selectivity-determining outer-sphere carbon-carbon bond formation are proposed. The multicomponent artificial force-induced reaction (MC-AFIR) method found key transition states for the carbon-carbon bond formation, and explained the enantioselectivity and diastereoselectivity. The overall mechanism consists of the coordination of the aldehyde, carbon-carbon bond formation, the rate-determining proton transfer from water to aldehyde, and dissociation of trimethylsilyl group. The calculated full catalytic cycle is consistent with the experiments. This study provides important mechanistic insights for the transition metal catalyzed Mukaiyama aldol reaction in aqueous media.

Artificial Force Induced Reaction (AFIR) Method for Exploring Quantum Chemical Potential Energy Surfaces

“…Applications have already been made to a variety of organo and organometallic catalyses 52–64. Catalysis of metal clusters has also been a target of previous applications 70,71.…”

“…This account will focus on the artificial force induced reaction46–49 (AFIR) method, developed by ourselves and implemented in the GRRM (global reaction route mapping) program 50,51. The AFIR has been applied most extensively to organo and organometallic catalysis, in combination with quantum chemical calculations 52–64. The other applications are: gas‐phase reactions;65–67 enzyme catalysis;68 domino reactions;69 and metal‐cluster catalysis 70,71.…”

Substitution Kinetics of [Fe(PDT/PPDT)n(phen)m]2+(n≠m;n,m= 1,2) with 2,2′-Bipyridine, 1,10-Phenanthroline, and 2,2′,6,2″-Terpyridine

“…The geometry optimizations, frequency calculations, and molecular orbital generations were carried out by means of DFT using the B3LYP functional method . The basis set 6–311+G* for nitrogen, 6–31G* for carbon and hydrogen , and Stuttgart‐Dresden (SDD) basis for iron was employed to get reliable results. The singlet state was used due to the low electronic spin of iron(II) complexes.…”

Artificial Force Induced Reaction Method for Systematic Determination of Complex Reaction Mechanisms

“…We have applied DFT and AFIR methods to rationalise the mechanism and selectivity of the aqueous Mukaiyama‐aldol reaction catalysed by a chiral iron(II) complex (Figure ) 26. According to our study, the first step of the mechanism is coordination of the aldehyde.…”