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Stereocontrolled Total Synthesis of (−)‐Stemaphylline

Homologation of readily available α‐boryl pyrrolidines with metal carbenoids is especially challenging even when good leaving groups (Cl(−)) are employed. By performing a solvent switch from Et(2)O to CHCl(3), efficient 1,2‐metalate rearrangement of the intermediate boronate occurs with both halide...

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Autores principales: Varela, Ana, Garve, Lennart K. B., Leonori, Daniele, Aggarwal, Varinder K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484348/
https://www.ncbi.nlm.nih.gov/pubmed/28097799
http://dx.doi.org/10.1002/anie.201611273
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author Varela, Ana
Garve, Lennart K. B.
Leonori, Daniele
Aggarwal, Varinder K.
author_facet Varela, Ana
Garve, Lennart K. B.
Leonori, Daniele
Aggarwal, Varinder K.
author_sort Varela, Ana
collection PubMed
description Homologation of readily available α‐boryl pyrrolidines with metal carbenoids is especially challenging even when good leaving groups (Cl(−)) are employed. By performing a solvent switch from Et(2)O to CHCl(3), efficient 1,2‐metalate rearrangement of the intermediate boronate occurs with both halide and ester leaving groups. The methodology was used in the total synthesis of the Stemona alkaloid (−)‐stemaphylline in just 11 steps (longest linear sequence), with high stereocontrol (>20:1 d.r.) and 11 % overall yield. The synthesis also features a late‐stage lithiation–borylation reaction with a tertiary amine containing carbenoid.
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spelling pubmed-54843482017-07-24 Stereocontrolled Total Synthesis of (−)‐Stemaphylline Varela, Ana Garve, Lennart K. B. Leonori, Daniele Aggarwal, Varinder K. Angew Chem Int Ed Engl Communications Homologation of readily available α‐boryl pyrrolidines with metal carbenoids is especially challenging even when good leaving groups (Cl(−)) are employed. By performing a solvent switch from Et(2)O to CHCl(3), efficient 1,2‐metalate rearrangement of the intermediate boronate occurs with both halide and ester leaving groups. The methodology was used in the total synthesis of the Stemona alkaloid (−)‐stemaphylline in just 11 steps (longest linear sequence), with high stereocontrol (>20:1 d.r.) and 11 % overall yield. The synthesis also features a late‐stage lithiation–borylation reaction with a tertiary amine containing carbenoid. John Wiley and Sons Inc. 2017-01-18 2017-02-13 /pmc/articles/PMC5484348/ /pubmed/28097799 http://dx.doi.org/10.1002/anie.201611273 Text en © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Communications
Varela, Ana
Garve, Lennart K. B.
Leonori, Daniele
Aggarwal, Varinder K.
Stereocontrolled Total Synthesis of (−)‐Stemaphylline
title Stereocontrolled Total Synthesis of (−)‐Stemaphylline
title_full Stereocontrolled Total Synthesis of (−)‐Stemaphylline
title_fullStr Stereocontrolled Total Synthesis of (−)‐Stemaphylline
title_full_unstemmed Stereocontrolled Total Synthesis of (−)‐Stemaphylline
title_short Stereocontrolled Total Synthesis of (−)‐Stemaphylline
title_sort stereocontrolled total synthesis of (−)‐stemaphylline
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484348/
https://www.ncbi.nlm.nih.gov/pubmed/28097799
http://dx.doi.org/10.1002/anie.201611273
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