Mechanistic Investigation of Chiral Phosphoric Acid Catalyzed Asymmetric Baeyer–Villiger Reaction of 3‐Substituted Cyclobutanones with H₂O₂ as the Oxidant

Abstract

The mechanism of the chiral phosphoric acid catalyzed Baeyer-Villiger (B-V) reaction of cyclobutanones with hydrogen peroxide was investigated by using a combination of experimental and theoretical methods. Of the two pathways that have been proposed for the present reaction, the pathway involving a peroxyphosphate intermediate is not viable. The reaction progress kinetic analysis indicates that the reaction is partially inhibited by the gamma-lactone product. Initial rate measurements suggest that the reaction follows Michaelis-Menten-type kinetics consistent with a bifunctional mechanism in which the catalyst is actively involved in both carbonyl addition and the subsequent rearrangement steps through hydrogen-bonding interactions with the reactants or the intermediate. High-level quantum chemical calculations strongly support a two-step concerted mechanism in which the phosphoric acid activates the reactants or the intermediate in a synergistic manner through partial proton transfer. The catalyst simultaneously acts as a general acid, by increasing the electrophilicity of the carbonyl carbon, increases the nucleophilicity of hydrogen peroxide as a Lewis base in the addition step, and facilitates the dissociation of the OH group from the Criegee intermediate in the rearrangement step. The overall reaction is highly exothermic, and the rearrangement of the Criegee intermediate is the rate-determining step. The observed reactivity of this catalytic B-V reaction also results, in part, from the ring strain in cyclobutanones. The sense of chiral induction is rationalized by the analysis of the relative energies of the competing diastereomeric transition states, in which the steric repulsion between the 3-substituent of the cyclobutanone and the 3- and 3'-substituents of the catalyst, as well as the entropy and solvent effects, are found to be critically important.

Baeyer–Villiger oxidation under Payne epoxidation conditions

“…[10][11][12][13][14][15][16][17] Other metals used for the activation of hydrogen peroxide in the BV oxidation include Se, 18 Re, 19 Li and Ca borates, 20 Pt, [21][22][23] Pd, 24 Si polyoxometalates, 25 and Zr. 26 Metal-free methods also exist and make use of enzymes, 27 ionic liquids, 28 carboxylic acids, 29 phosphoric acids, 30,31 and bisflavins 32 to activate the peroxide. Of these methods, a few have been shown to be effective for enantioselective BV oxidations, which include metals such as Pt, Pd or Zr with chiral ligands, 21,24,26 pro-chiral carboxylic acids, 29 phosphoric acids, 30,31 and bisflavins.…”

“…26 Metal-free methods also exist and make use of enzymes, 27 ionic liquids, 28 carboxylic acids, 29 phosphoric acids, 30,31 and bisflavins 32 to activate the peroxide. Of these methods, a few have been shown to be effective for enantioselective BV oxidations, which include metals such as Pt, Pd or Zr with chiral ligands, 21,24,26 pro-chiral carboxylic acids, 29 phosphoric acids, 30,31 and bisflavins. 32 While there are a variety of methods of activating hydrogen peroxide, it is still desirable to develop methods to broaden the transformation, specifically by defining new pathways to potential asymmetric oxidations.…”

Axially Chiral Imidodiphosphoric Acid Catalyst for Asymmetric Sulfoxidation Reaction: Insights on Asymmetric Induction

“…In general, these axially chiral Brønsted acids have been demonstrated to be capable of imparting exceptionally high enantioselectivities in asymmetric aldol, Mannich, Friedel–Crafts, Diels–Alder, imine hydrogenation, and Tsuji–Trost allylation reactions 9. The larger substituents at the 3,3′‐positions of the binol framework, such as that in 2,4,6‐triisopropylphenyl, are known to be vital for obtaining a high degree of stereoselectivity 9j–n. However, the efficiency of catalysts I and II in sulfoxidation was reported to be unexpectedly low 10.…”

Advances in Chemocatalytic Asymmetric Baeyer–Villiger Oxidations

“…Later in 2010, a mechanistic investigation of this chiral phosphoric acid‐catalyzed asymmetric B‐V reaction using NMR analysis, kinetic studies and DFT calculations was conducted by Li and Ding. Based on these studies, a plausible mechanism was proposed (Scheme ) . The H 8 ‐BINOL‐derived phosphoric acid served as a bifunctional catalyst throughout the catalytic cycle to form hydrogen‐bonding networks.…”