Chiral methylbenzylamines and arylbenzylamines are important structural motifs that are widely present in many bioactive compounds and drug molecules.In this study,we applied readily available ruthenium complexes,comp...Chiral methylbenzylamines and arylbenzylamines are important structural motifs that are widely present in many bioactive compounds and drug molecules.In this study,we applied readily available ruthenium complexes,comprised of a bisphosphine and two chiral amino acid anionic ligands,in asymmetric reductive amination of benzyl ketones with ammonium salts for the first time.Excellent enantioselectivities(up to 99%ee)have been achieved by merely fine-tuning the amino acid structure,thereby decreasing the need for more expensive bisphosphine ligands.We anticipate that this new method will find broad applications in organic synthesis,especially in the preparation of chiral pharmaceutical intermediates.展开更多
A highly efficient and enantioselective method for the asymmetric reductive amination ofβ-keto phosphine de-rivatives was disclosed,and the correspondingβ-amino phosphine oxides could be obtained in high yields(up t...A highly efficient and enantioselective method for the asymmetric reductive amination ofβ-keto phosphine de-rivatives was disclosed,and the correspondingβ-amino phosphine oxides could be obtained in high yields(up to 97%yield)and excellent enantioselectivities(up to 97%ee).Moreover,the reaction worked well on a gram scale,indicating that our protocol has potential applications in the synthesis of chiral ligands and organocatalysts.展开更多
Reductive amination by amine dehydrogenases is a green and sustainable process that produces only water as the by-product.In this study,a continuous flow process was designed utilizing a packed bed reactor filled with...Reductive amination by amine dehydrogenases is a green and sustainable process that produces only water as the by-product.In this study,a continuous flow process was designed utilizing a packed bed reactor filled with co-immobilized amine dehydrogenase wh84 and glucose dehydrogenase for the highly efficient biocatalytic synthesis of chiral amino alcohols.The immobilized amine dehydrogenase wh84 exhibited better thermo-,pH and solvent stability with high activity recovery.(S)-2-aminobutan-1-ol was produced in up to 99%conversion and 99%ee in the continuous flow processes,and the space-time yields were up to 124.5 g L-1 d-1.The continuous reactions were also extended to 48 h affording up to 91.8%average conversions.This study showcased the important potential to sustainable production of chiral amino alcohols in continuous flow processes.展开更多
基金supported by National Natural Science Foundation of China(Nos.22271307,22302048)the Shenzhen Science and Technology Innovation Program(Nos.JCYJ20240813161112017,JCYJ20220818100804010,GXWD20220811173736002,and KCXFZ20230731094904009)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2021B1515020062)the Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application.Q.Y.is indebted to Shenzhen University of Advanced TechnologyShenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,for providing a starting grant.
文摘Chiral methylbenzylamines and arylbenzylamines are important structural motifs that are widely present in many bioactive compounds and drug molecules.In this study,we applied readily available ruthenium complexes,comprised of a bisphosphine and two chiral amino acid anionic ligands,in asymmetric reductive amination of benzyl ketones with ammonium salts for the first time.Excellent enantioselectivities(up to 99%ee)have been achieved by merely fine-tuning the amino acid structure,thereby decreasing the need for more expensive bisphosphine ligands.We anticipate that this new method will find broad applications in organic synthesis,especially in the preparation of chiral pharmaceutical intermediates.
基金the National Natural Science Foundation of China(No.21901107)Shenzhen Bay Laboratory(No.SZBL2019062801006)+5 种基金Shenzhen Science and Technology Innovation Committee(No.KQTD20150717103157174)Key-Area Research and Development Program of Guangdong Province(No.2020B010188001)Stable Support Plan Program of Shenzhen Science and Technology Innovation Committee(No.20200925161222002)Innovative Team of Universities in Guangdong Province(No.2020KCXTD016).G.Q.Chen gratefully acknowledges the National Natural Science Foundation of China(Nos.21901107 and 22171129)the Guangdong Basic and Applied Basic Research Foundation(No.2022B1515020055)the Shenzhen Science and Technology Innovation Committee(No.JCYJ20210324104202007)for financial support.B.Ma is indebted to the financial support from the National Natural Science Foundation of China(No.22001113)B.Ma is the National Natural Science Foundation of China(No.22001113).
文摘A highly efficient and enantioselective method for the asymmetric reductive amination ofβ-keto phosphine de-rivatives was disclosed,and the correspondingβ-amino phosphine oxides could be obtained in high yields(up to 97%yield)and excellent enantioselectivities(up to 97%ee).Moreover,the reaction worked well on a gram scale,indicating that our protocol has potential applications in the synthesis of chiral ligands and organocatalysts.
基金supported by the National Key Research and Development Program of China(No.2021YFA0910400 and 2019YFA0905100)the National Natural Science Foundation of China(No.32171462)+1 种基金Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(No.TSBICIP-CXRC-040)the Natural Science Foundation of Tianjin(No.21JCJQJC00110).
文摘Reductive amination by amine dehydrogenases is a green and sustainable process that produces only water as the by-product.In this study,a continuous flow process was designed utilizing a packed bed reactor filled with co-immobilized amine dehydrogenase wh84 and glucose dehydrogenase for the highly efficient biocatalytic synthesis of chiral amino alcohols.The immobilized amine dehydrogenase wh84 exhibited better thermo-,pH and solvent stability with high activity recovery.(S)-2-aminobutan-1-ol was produced in up to 99%conversion and 99%ee in the continuous flow processes,and the space-time yields were up to 124.5 g L-1 d-1.The continuous reactions were also extended to 48 h affording up to 91.8%average conversions.This study showcased the important potential to sustainable production of chiral amino alcohols in continuous flow processes.
