Highly stereoselective synthesis of cyclopentanes bearing four stereocentres by a rhodium carbene-initiated domino sequence
Stereoselective synthesis of a cyclopentane nucleus by convergent annulation constitutes a significant challenge for synthetic chemists. Although a number of biologically relevant cyclopentane natural products are known, more often than not, the cyclopentane core is assembled in a stepwise manner be...
Saved in:
Published in: | Nature communications 2014-08, Vol.5 (1), p.4455-4455, Article 4455 |
---|---|
Main Authors: | , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Stereoselective synthesis of a cyclopentane nucleus by convergent annulation constitutes a significant challenge for synthetic chemists. Although a number of biologically relevant cyclopentane natural products are known, more often than not, the cyclopentane core is assembled in a stepwise manner because of the lack of efficient annulation strategies. Here we report the rhodium-catalysed reactions of vinyldiazoacetates with (
E
)-1,3-disubstituted 2-butenols generate cyclopentanes, containing four new stereogenic centres with very high levels of stereoselectivity (99% ee, >97: 3 dr). The reaction proceeds by a carbene-initiated domino sequence consisting of five distinct steps: rhodium-bound oxonium ylide formation, [2,3]-sigmatropic rearrangement, oxy-Cope rearrangement, enol—keto tautomerization and finally an intramolecular carbonyl ene reaction. A systematic study is presented detailing how to control chirality transfer in each of the four stereo-defining steps of the cascade, consummating in the development of a highly stereoselective process.
Rhodium catalysts can be used for the generation of cyclopentanes with four stereogenic centres. Here, the authors study the origin of stereoselectivity across multiple steps, ultimately leading to a process displaying extremely high enantio- and diastereoselectivity. |
---|---|
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/ncomms5455 |