Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters

Yongjie Shi; Xuefeng Tan; Shuang Gao; Yao Zhang; Jingxin Wang; Xumu Zhang; Qin Yin

doi:10.1021/acs.orglett.0c00669

Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters

Yongjie Shi
, Xuefeng Tan
, Shuang Gao
, Yao Zhang
, Jingxin Wang
, Xumu Zhang
, Qin Yin^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

53 Citations (Scopus)

Abstract

Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology. Copyright © 2020 American Chemical Society.

Original language	English
Pages (from-to)	2707-2713
Journal	Organic Letters
Volume	22
Issue number	7
Online published	19 Mar 2020
DOIs	https://doi.org/10.1021/acs.orglett.0c00669
Publication status	Published - 3 Apr 2020
Externally published	Yes

Funding

Dedicated to Prof Henry N. C. Wong (The Chinese University of Hong Kong) on the occasion of his 70th birthday. We are grateful to the National Natural Science Foundation of China (no. 21801119), Shenzhen Nobel Prize Scientists Laboratory Project (C17783101), and Shenzhen Science and Technology Innovation Committee (no. KQTD20150717103157174).

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title = "Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters",

abstract = "Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97\% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology. Copyright {\textcopyright} 2020 American Chemical Society.",

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T1 - Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters

AU - Shi, Yongjie

AU - Tan, Xuefeng

AU - Gao, Shuang

AU - Zhang, Yao

AU - Wang, Jingxin

AU - Zhang, Xumu

AU - Yin, Qin

PY - 2020/4/3

Y1 - 2020/4/3

N2 - Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology. Copyright © 2020 American Chemical Society.

AB - Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology. Copyright © 2020 American Chemical Society.

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U2 - 10.1021/acs.orglett.0c00669

DO - 10.1021/acs.orglett.0c00669

M3 - RGC 21 - Publication in refereed journal

C2 - 32191039

SN - 1523-7060

VL - 22

SP - 2707

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JO - Organic Letters

JF - Organic Letters

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ER -

Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters

Abstract

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