A direct approach to amines with remote stereocentres by enantioselective CuH-catalysed reductive relay hydroamination

Nature Chemistry
Shaolin ZhuStephen L Buchwald

Abstract

Amines with remote stereocentres (stereocentres that are three or more bonds away from the C-N bond) are important structural elements in many pharmaceutical agents and natural products. However, previously reported methods to prepare these compounds in an enantioselective manner are indirect and require multistep synthesis. Here, we report a copper-hydride-catalysed, enantioselective synthesis of γ- or δ-chiral amines from readily available allylic alcohols, esters and ethers using a reductive relay hydroamination strategy (a net reductive process in which an amino group is installed at a site remote from the original carbon-carbon double bond). The protocol was suitable for substrates containing a wide range of functional groups and provided remote chiral amine products with high levels of regio- and enantioselectivity. Sequential amination of substrates containing several carbon-carbon double bonds could be achieved, demonstrating the high chemoselectivity of this process.

References

Jun 10, 2005·Angewandte Chemie·Hideki Yorimitsu, Koichiro Oshima
Jul 12, 2008·Chemical Reviews·Carl Deutsch, Norbert Krause
Aug 30, 2008·Chemical Reviews·Thomas E MüllerMizuki Tada
Feb 5, 2011·Journal of the American Chemical Society·Jin Kyoon ParkD Tyler McQuade
Jun 28, 2011·Organic Letters·Zeyneb SahliChristian Bruneau
Mar 30, 2013·Science·Michael T PirnotDavid W C MacMillan
Oct 11, 2013·Journal of the American Chemical Society·Shaolin ZhuStephen L Buchwald
Apr 11, 2014·Nature·Tian-Sheng MeiMatthew S Sigman
Oct 24, 2014·Journal of the American Chemical Society·Shaolin Zhu, Stephen L Buchwald
Dec 6, 2014·Angewandte Chemie·Nootaree NiljianskulStephen L Buchwald
Dec 18, 2014·Nature Chemistry·Shi-Liang Shi, Stephen L Buchwald
Feb 28, 2015·Chemical Reviews·Liangbin HuangLukas J Gooßen
May 23, 2015·Science·Jinghan GuiPhil S Baran
Jul 7, 2015·Journal of the American Chemical Society·Dawen Niu, Stephen L Buchwald

❮ Previous
Next ❯

Citations

Apr 5, 2016·Journal of the American Chemical Society·Yi-Ming Wang, Stephen L Buchwald
May 7, 2016·Organic Letters·T N Thanh NguyenJohannes F Teichert
Jul 28, 2016·Chemical Reviews·Abraham J JordanJoseph P Sadighi
Aug 24, 2016·Journal of the American Chemical Society·Wusheng GuoArjan W Kleij
Oct 28, 2016·Journal of the American Chemical Society·Zi-Xuan WangBi-Jie Li
Jun 9, 2017·Journal of the American Chemical Society·Haoxuan WangStephen L Buchwald
Feb 13, 2018·Proceedings of the National Academy of Sciences of the United States of America·Zhe LiLi Deng
Nov 9, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sophie Bezzenine-LafolléeJérôme Hannedouche
Jan 20, 2019·Angewandte Chemie·Xi-Jie DaiStephen L Buchwald
Jun 8, 2019·Chemical Communications : Chem Comm·Zi-Chao WangShi-Liang Shi
May 18, 2017·Chemical Communications : Chem Comm·Tetsuaki FujiharaYasushi Tsuji
Nov 14, 2017·Chemical Communications : Chem Comm·Bin-Jie LiAndré M Beauchemin
Oct 12, 2017·Chemical Communications : Chem Comm·T N Thanh NguyenJohannes F Teichert
Apr 10, 2021·Journal of the American Chemical Society·Xiang LyuSukbok Chang
Jun 5, 2021·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Jinwon JeonSungwoo Hong
Oct 24, 2019·The Journal of Organic Chemistry·Fei-Fei ChenGao-Wei Zheng
Nov 19, 2020·Journal of the American Chemical Society·Jinwon JeonSungwoo Hong
May 14, 2020·Accounts of Chemical Research·Richard Y Liu, Stephen L Buchwald
Jul 7, 2020·Organic Letters·Achim LinkStephen L Buchwald
Nov 7, 2019·Organic Letters·Murugan SubaramanianEkambaram Balaraman
Oct 19, 2019·Organic Letters·Saki Ichikawa, Stephen L Buchwald
Jan 8, 2019·Journal of the American Chemical Society·Evan P VanableKami L Hull
Oct 30, 2018·Journal of the American Chemical Society·Sheng GuoStephen L Buchwald

❮ Previous
Next ❯

Methods Mentioned

BETA
hydroamination
X-ray

Software Mentioned

SEGPHOS
DTBM

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.