Asymmetric Hydrogenation of Cationic Intermediates for the Synthesis of Chiral N,O-Acetals

Sun，Yongjie1; Zhao，Qingyang2; Wang，Heng1; Yang，Tilong3; Wen，Jialin1,4; Zhang，Xumu1

2020-09-04

10.1002/chem.202002930

CHEMISTRY-A EUROPEAN JOURNAL   影响因子和分区

0947-6539

1521-3765

For over half a century, transition-metal-catalyzed homogeneous hydrogenation has been mainly focused on neutral and readily prepared unsaturated substrates. Although the addition of molecular hydrogen to C=C, C=N, and C=O bonds represents a well-studied paradigm, the asymmetric hydrogenation of cationic species remains an underdeveloped area. In this study, we were seeking a breakthrough in asymmetric hydrogenation, with cationic intermediates as targets, and thereby anticipating applying this powerful tool to the construction of challenging chiral molecules. Under acidic conditions, both N- or O-acetylsalicylamides underwent cyclization to generate cationic intermediates, which were subsequently reduced by an iridium or rhodium hydride complex. The resulting N,O-acetals were synthesized with remarkably high enantioselectivity. This catalytic strategy exhibited high efficiency (turnover number of up to 4400) and high chemoselectivity. Mechanistic studies supported the hypothesis that a cationic intermediate was formed in situ and hydrogenated afterwards. A catalytic cycle has been proposed with hydride transfer from the iridium complex to the cationic sp carbon atom being the rate-determining step. A steric map of the catalyst has been created to illustrate the chiral environment, and a quantitative structure–selectivity relationship analysis showed how enantiomeric induction was achieved in this chemical transformation.

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For over half a century, transition-metal-catalyzed homogeneous hydrogenation has been mainly focused on neutral and readily prepared unsaturated substrates. Although the addition of molecular hydrogen to C=C, C=N, and C=O bonds represents a well-studied paradigm, the asymmetric hydrogenation of cationic species remains an underdeveloped area. In this study, we were seeking a breakthrough in asymmetric hydrogenation, with cationic intermediates as targets, and thereby anticipating applying this powerful tool to the construction of challenging chiral molecules. Under acidic conditions, both N- or O-acetylsalicylamides underwent cyclization to generate cationic intermediates, which were subsequently reduced by an iridium or rhodium hydride complex. The resulting N,O-acetals were synthesized with remarkably high enantioselectivity. This catalytic strategy exhibited high efficiency (turnover number of up to 4400) and high chemoselectivity. Mechanistic studies supported the hypothesis that a cationic intermediate was formed in situ and hydrogenated afterwards. A catalytic cycle has been proposed with hydride transfer from the iridium complex to the cationic sp carbon atom being the rate-determining step. A steric map of the catalyst has been created to illustrate the chiral environment, and a quantitative structure–selectivity relationship analysis showed how enantiomeric induction was achieved in this chemical transformation.

Acetals Asymmetric Catalysis Cations Chirality Hydrogenation Reaction Mechanisms

SCI ; EI

英语

第一 ; 通讯

National Natural Science Foundation of China[21801118][21602172]

Chemistry

Chemistry, Multidisciplinary

WOS:000556294000001

WILEY-V C H VERLAG GMBH

20203209021324

Rhodium compounds ; Stereochemistry ; Catalysis ; Iridium compounds ; Transition metals ; Chemical analysis ; Reaction intermediates ; Catalyst selectivity ; Hydrides ; Hydrogen bonds

Metallurgy and Metallography:531 ; Chemistry:801 ; Physical Chemistry:801.4 ; Chemical Reactions:802.2 ; Chemical Agents and Basic Industrial Chemicals:803 ; Chemical Products Generally:804 ; Inorganic Compounds:804.2

CHEMISTRY

2-s2.0-85089067010

Scopus

1.Shenzhen Grubbs Institute and Department of Chemistry,Southern University of Science and Technology,Shenzhen,1088 Xueyuan Road,518055,China
2.School of Pharmaceutical Sciences (Shenzhen),Sun Yat-sen University,Shenzhen,518107,China
3.Department of chemistry,The Hong Kong University of Science and Technology,Kowloon,Clear Water Bay,Hong Kong
4.Academy for Advanced Interdisciplinary Studies,Southern University of Science and Technology,Shenzhen,1088 Xueyuan Road,518055,China

Sun，Yongjie,Zhao，Qingyang,Wang，Heng,et al. Asymmetric Hydrogenation of Cationic Intermediates for the Synthesis of Chiral N,O-Acetals[J]. CHEMISTRY-A EUROPEAN JOURNAL,2020,26(50):11470-11477.

Sun，Yongjie,Zhao，Qingyang,Wang，Heng,Yang，Tilong,Wen，Jialin,&Zhang，Xumu.(2020).Asymmetric Hydrogenation of Cationic Intermediates for the Synthesis of Chiral N,O-Acetals.CHEMISTRY-A EUROPEAN JOURNAL,26(50),11470-11477.

Sun，Yongjie,et al."Asymmetric Hydrogenation of Cationic Intermediates for the Synthesis of Chiral N,O-Acetals".CHEMISTRY-A EUROPEAN JOURNAL 26.50(2020):11470-11477.