A direct approach to amines with remote stereocenters by enantioselective CuH-catalysed reductive relay hydroamination
Amines with remote stereocenters (stereocenters 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 re...
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2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724644/ |
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pubmed-47246442016-07-04 A direct approach to amines with remote stereocenters by enantioselective CuH-catalysed reductive relay hydroamination Zhu, Shaolin Niljianskul, Nootaree Buchwald, Stephen L. Article Amines with remote stereocenters (stereocenters 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 C–C 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. 2016-01-04 2016-02 /pmc/articles/PMC4724644/ /pubmed/26791897 http://dx.doi.org/10.1038/nchem.2418 Text en Reprints and permissions information is available online at www.nature.com/reprints (http://www.nature.com/reprints) . Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
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NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Zhu, Shaolin Niljianskul, Nootaree Buchwald, Stephen L. |
| spellingShingle |
Zhu, Shaolin Niljianskul, Nootaree Buchwald, Stephen L. A direct approach to amines with remote stereocenters by enantioselective CuH-catalysed reductive relay hydroamination |
| author_facet |
Zhu, Shaolin Niljianskul, Nootaree Buchwald, Stephen L. |
| author_sort |
Zhu, Shaolin |
| title |
A direct approach to amines with remote stereocenters by enantioselective CuH-catalysed reductive relay hydroamination |
| title_short |
A direct approach to amines with remote stereocenters by enantioselective CuH-catalysed reductive relay hydroamination |
| title_full |
A direct approach to amines with remote stereocenters by enantioselective CuH-catalysed reductive relay hydroamination |
| title_fullStr |
A direct approach to amines with remote stereocenters by enantioselective CuH-catalysed reductive relay hydroamination |
| title_full_unstemmed |
A direct approach to amines with remote stereocenters by enantioselective CuH-catalysed reductive relay hydroamination |
| title_sort |
direct approach to amines with remote stereocenters by enantioselective cuh-catalysed reductive relay hydroamination |
| description |
Amines with remote stereocenters (stereocenters 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 C–C 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. |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724644/ |
| _version_ |
1613527611066023936 |