目前,α-羟基羰基化合物存在于多种天然产物和药物分子中,并都具有生物活性。羰基化合物的直接α-官能化是构建C-C键和C-X键最有效、最直接的方法之一;合成α-羟基羰基化合物可通过羰基化合物的α-羟基化来实现。分子氧丰富、廉价、易得、对环境友好,可以作为羰基化合物α-羟基的理想氧源。因此,以氧气为氧源的羰基化合物的直接α-羟基受到了广泛的关注。本文从金属有机催化和有机小分子催化两个角度出发,主要阐述了近年来羰基化合物的不对称有氧α-羟基化反应的研究进展。Currently, α-hydroxycarbonyl compounds exist in a variety of natural products and drug molecules, and all of them are biologically active. Direct α-functionalization of carbonyl compounds is one of the most effective and direct methods to construct C-C and C-X bonds;the synthesis of α-hydroxycarbonyl compounds can be achieved by α-hydroxylation of carbonyl compounds. Molecular oxygen is abundant, cheap, easy to obtain, and environmentally friendly, and can be used as an ideal oxygen source for the α-hydroxylation of carbonyl compounds. Therefore, the direct α-hydroxylation of carbonyl compounds using oxygen as an oxygen source has received extensive attention. This paper focuses on the research progress of asymmetric aerobic α-hydroxylation reactions of carbonyl compounds in recent years from the perspectives of both metal-organic catalysis and organic small molecule catalysis.
P450 enzymes-catalyzed aromatic hydroxylation plays an important role in detoxification,biosynthesis,and potential carcinogenic effect of aromatic compounds.Though it has been explored for decades,the actual process of aromatic hydroxylation and mechanism of regioselectivity catalyzed by cytochrome P450 monooxygenases remained ambiguous.Here,we have resolved these issues.With a stable chiral organofluorine probe,and especially with X-ray data of two isolated arene oxides derivatives,we demonstrate that an arene oxide pathway is definitely involved in P450-catalyzed aromatic hydroxylation.By the capture,isolation,identification and reactivity exploration of the arene 1,2-oxide and arene 2,3-oxide intermediates,together with advanced QM calculations,the mechanism of how two intermediates go to the same product has been elucidated.In addition to the model substrate,we also confirmed that an arene oxide intermediate is involved in the P450-catalyzed hydroxylation pathway of a natural product derivative methyl cinnamate,which indicates that this intermediate appears to be universal in P450-catalyzed aromatic hydroxylation.Our work not only provides the most direct evidence for the arene oxide pathway and new insights into the regioselectivity involved in P450-catalyzed aromatic hydroxylation,but also supplies a new synthetic approach to achieve the dearomatization of aromatic compounds.
