Gong Liuzhu, Professor of University of science and technology of China, and Han Zhiyong, associate research team: asymmetric hydroxylation of o-aminophenol derivatives to conjugated dienes catalyzed by chiral palladium

Chiral 3,4-dihydro-2h-1,4-benzoxazine skeletons are widely found in natural products, drugs and bioactive molecules, so the construction of such skeletons has attracted the attention of synthetic chemists However, it is very rare to synthesize chiral 3,4-dihydro-2h-1,4-benzoxazine skeleton from simple and easily available materials According to the characteristics of 3,4-dihydro-2h-1,4-benzoxazine skeleton, Gong Liuzhu, Professor of China University of science and technology, and Han Zhiyong, associate research team, conceived a direct way to construct such skeleton, that is, asymmetric hydroxylation of 2-aminophenol to olefins, which is difficult to achieve through the existing asymmetric hydroxylation reaction In this paper, we propose that the hydroxylation of N-sulfonyl protected o-aminophenol with high regioselectivity and enantioselectivity to conjugated olefins can be realized by using palladium as catalyst Palladium catalyzed hydroxylation of n-sulfonylprotected o-aminophenol (source: angel Chem Int ed., DOI: 10.1002/anie.201712350) In the reaction process envisaged by the author, it is possible to start the reaction by N-Pd or o-PD to obtain intermediate I or II, followed by intramolecular asymmetric allylation to obtain the target skeleton Two independent steps in this process need to be catalyzed by palladium, so the catalyst has many functions It not only needs to realize the first aza Wacker reaction with high efficiency and high regioselectivity, but also can control the second asymmetric allylation reaction with high enantioselectivity The template substrates are o-aminophenol protected by n-p-toluenesulfonyl and isoprene widely used in industry Through the selection of ligands, oxidants, palladium sources and additives, the optimum reaction conditions were determined at 70 ℃, using palladium diacetone as palladium source, tetraphenyl substituted pyridine dioxazoline as ligand, thymoquinone as oxidant and 3 Å molecular sieve as additives In the process of substrate expansion, chiral 3,4-dihydro-2h-1,4-benzoxazine derivatives were obtained with good to excellent yield, high regioselectivity and high enantioselectivity Using this method, the author has completed a simple synthesis of a prostaglandin D2 antibody antagonist Under the optimal reaction conditions, the chiral 3,4- two hydrogen -2 H -1,4- benzoxazine derivatives (source: Angew Chem Int Ed., DOI: 10.1002/anie.201712350) were obtained with good yield, high regioselectivity and high enantioselectivity, 4-benzoxazine skeleton provides a new way for the construction of this kind of skeleton This achievement was published on angelw.chem.int.ed., the first author was Shen Hongcheng, a doctoral candidate, and the corresponding author was Professor Gong Liuzhu and Han Zhiyong, a special associate researcher The research work is supported by the National Natural Science Foundation, Anhui Natural Science Foundation and Chinese Academy of Sciences Before that, the author also reported the series reaction of SP 2 Hydrocarbon activation / asymmetric allylation catalyzed by multifunctional chiral palladium catalyst, which can efficiently convert arylurea and 1,3-diene into chiral indolines with optical activity (angelw Chem Int ed., 2017, 56, 6641) Arylurea and 1,3-diene are efficiently converted into optically active chiral indolines (source: angelw Chem Int ed, Doi: 10.1002/anie.201702745) paper link: http://onlinelibrary.willey.com/doi/10.1002/anie.201712350/full Gong Liuzhu research group homepage: http://staff.ustc.edu.cn / ~ gongglz / index_.htmgong Liuzhu introduction: http://scms.ustc.edu.cn/2010/0925/c13449a28526/page.htmgong Liuzhu Professor