Yang Xiaoyu, research group, Shanghai University of science and technology: high efficient kinetic resolution of 2- aminoallyl tertiary alcohol catalyzed by chiral phosphoric acid

The optically active alcohol is an important intermediate for the synthesis of chiral drugs and natural products with physiological activity The kinetic resolution of alcohols (including enzyme catalysis and non enzyme catalysis) is one of the most effective and reliable methods for the synthesis of chiral alcohols However, both enzyme catalyzed and non enzyme catalyzed acyl transfer reactions are more suitable for the secondary alcohol substrate, while the efficient kinetic resolution of tertiary alcohol (at the same time, the chiral raw materials and products are obtained by high enantioselectivity) is rare Recently, Yang Xiaoyu's research group of Shanghai University of science and technology reported that the high-efficiency kinetic resolution of 2-aminoallyl-tert-alcohol was realized by using chiral phosphoric acid catalyst, and relevant results were published online on angelw Chem Int ed., 2019, DOI: 10.1002/anie.201905034 Brief introduction of Assistant Professor Yang Xiaoyu, assistant professor and doctoral supervisor of School of material science and technology, Shanghai University of science and technology In 2007, he received his bachelor's degree from school of chemistry and chemical engineering, Nanjing University; in 2012, he received his doctor's degree in organic chemistry from Shanghai Institute of Organic Chemistry (Tutor: researcher Yu Biao); in 2013-2016, he received his bachelor's degree from University of California, Berkeley and Lawrence- Berkeley National Laboratory is engaged in postdoctoral research in asymmetric catalysis methodology and chemical biology, with Dean toste as the co tutor Since June 2016, Yang Xiaoyu has joined the school of material science and technology of Shanghai University of science and technology as an assistant professor, researcher and project leader Professor Yang Xiaoyu has won the honor of the 13th batch of national youth thousand talents program, Shanghai Pujiang talent plan, etc at present, the research direction of the research group includes asymmetric catalysis, sugar chemistry, etc (homepage of the research group: http://spst.shanghai.edu.cn/2018/0301/c2349a17316/page.htm) Cutting edge research achievements: the research group of Professor Yang Xiaoyu of Shanghai University of science and technology devoted to the realization of novel asymmetric reaction of 2-aminoallyl-tert-alcohol substrate using chiral br / nsted Acid Catalyst recently In 2018, the research group realized the regioselective asymmetric addition of indole to 2-aminocyclopenteenol (angelw Chem Int ed 2018, 57, 13489) In this reaction, the 2-aminoallylic positive ion paired with chiral anion is the key intermediate of the reaction Fig 1 the regioselective asymmetric addition of indole to 2-aminocyclopenteenol (angel Chem Int ed.) recently, Yang Xiaoyu's research team reported that the efficient kinetic resolution of 2-aminoallyl-tert-alcohol was realized by using chiral phosphoric acid catalyst (Fig 2) It was found that when the allyl tertiary alcohol was substituted by n-formic acid ester, the 2-aminoallyl cation intermediate was not produced in the reaction catalyzed by chiral phosphoric acid, but the cyclic oxazolidone derivative 2a was formed by intramolecular transesterification In this reaction, the chiral phosphoric acid catalyst (tcyp) can achieve excellent kinetic resolution of the substrate At the same time, the raw materials of chiral allyl tertiary alcohol and oxazolidone products can be obtained with high enantioselectivity Fig 2 high efficiency kinetic resolution of 2-aminoallyl tertiary alcohol (angel Chem Int ed.) the reaction has excellent substrate applicability (Fig 3) Allyl 3-position aryl or alkyl substitution and 1,1 '- various aryl / alkyl substitution can be well applied The s factor of kinetic resolution can reach up to 164.6 This reaction can even realize the high enantioselective recognition of methyl with other and primary alkyl groups (1P, n-amyl), and the high enantioselective synthesis of this kind of challenging substrate In Figure 3, the author also proved the practicability of the reaction through the gram scale experiment; under the gram scale, the reaction only needs 1 mol% catalyst to realize the high enantioselectivity kinetic resolution of the substrate, and the s factor has no significant decrease compared with the use of 10 mol% Finally, the potential application of the reaction in organic synthesis was demonstrated by converting the chiral products into Evans type chiral oxazolone cofactors and chiral β - amino tertiary alcohols Fig 4 gram scale experiment and product derivatization (angel Chem Int ed.) summary, Yang Xiaoyu's research team reported a highly efficient method for the kinetic resolution of 2-aminoallyl-tert-alcohol by molecular lactone exchange reaction catalyzed by chiral phosphoric acid This method has a wide range of substrate applicability, whether aryl / alkyl or alkyl / alkyl substituted allylic alcohols can achieve excellent kinetic resolution results, and the highest selectivity factor can reach 164 Gram scale experiments and the convenient conversion of chiral products into useful chiral synthetic fragments prove the potential of this reaction in the synthesis of chiral drug molecules and natural products Rajkumar, a postdoctoral student of Yang Xiaoyu's research group, and he Shunlong, a postgraduate student, are the co authors of this paper The work was supported by the "Youth Program" of the thousand talents program, the National Natural Science Foundation of China, the Shanghai Pujiang talent program and the Shanghai University of science and technology Related achievements are published in angel Chem Int ed (angel Chem Int ed., 2019, DOI: 10.1002/anie.201905034) A review of previous reports by the authors: the asymmetric synthesis of Cyclopentanone containing β - indole by Yang Xiaoyu's group of Shanghai University of science and Technology Professor Yang Xiaoyu's group of Shanghai University of science and technology Today, science and technology elements are increasingly valued in economic life, China has ushered in the "node of science and technology explosion" Behind the progress of science and technology is the work of countless scientists In the field of chemistry, in the context of the pursuit of innovation driven, international cooperation has been strengthened, the influence of Returned Scholars in the field of R & D has become increasingly prominent, and many excellent research groups have emerged in China For this reason, CBG information adopts the 1 + X reporting mechanism CBG information, chembeangoapp, chembeango official microblog, CBG wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the domestic representative research group, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.