State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, P.R. China.
Chemistry. 2010 Mar 8;16(10):3021-35. doi: 10.1002/chem.200902698.
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.
手性磷酸催化环丁酮与过氧化氢的 Baeyer-Villiger（B-V）反应的机理通过实验和理论相结合的方法进行了研究。在所提出的两种反应途径中，涉及过氧磷酸盐中间体的途径是不可行的。反应进度动力学分析表明，反应被γ-内酯产物部分抑制。初始速率测量表明，反应遵循米氏-门捷列夫型动力学，与双功能机制一致，其中催化剂通过与反应物或中间体的氢键相互作用，积极参与羰基加成和随后的重排步骤。高水平的量子化学计算强烈支持两步协同机制，其中磷酸通过部分质子转移以协同方式激活反应物或中间体。催化剂同时作为一种广义酸，通过增加羰基碳的亲电性，增加过氧化氢作为路易斯碱在加成步骤中的亲核性，并促进 Criegee 中间体在重排步骤中 OH 基团的解离。整个反应是高度放热的，Criegee 中间体的重排是速率决定步骤。这种催化 B-V 反应的观察到的反应性部分也来自于环丁酮的环张力。通过对竞争非对映过渡态的相对能量的分析，合理地解释了手性诱导的意义，其中环丁酮的 3-取代基与催化剂的 3-和 3'-取代基之间的空间排斥以及熵和溶剂效应被发现是至关重要的。
