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Enantioselective Synthesis of Acyclic Stereotriads Featuring Fluorinated Tetrasubstituted Stereocenters
Author(s) -
Shao Na,
Liu Xueyang,
Monnier Valérie,
Charles Laurence,
Rodriguez Jean,
Bressy Cyril,
Quintard Adrien
Publication year - 2022
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202103874
Subject(s) - stereocenter , enantioselective synthesis , kinetic resolution , aldol reaction , diastereomer , chemistry , combinatorial chemistry , organocatalysis , stereochemistry , organic chemistry , catalysis
Abstract Elaboration of enantioenriched complex acyclic stereotriads represents a challenge for modern synthesis even more when fluorinated tetrasubstituted stereocenters are targeted. We have been able to develop a simple strategy in a sequence of two unprecedented steps combining a diastereoselective aldol‐Tishchenko reaction and an enantioselective organocatalyzed kinetic resolution. The aldol‐Tishchenko reaction directly generates a large panel of acyclic 1,3‐diols possessing a fluorinated tetrasubstituted stereocenter by condensation of fluorinated ketones with aldehydes under very mild basic conditions. The anti 1,3‐diols featuring three contiguous stereogenic centers are generated with excellent diastereocontrol (typically >99 : 1 dr ). Depending upon the precursors both diastereomers of stereotriads are accessible through this flexible reaction. Furthermore, from the obtained racemic scaffolds, development of an organocatalyzed kinetic resolution enabled to generate the desired enantioenriched stereotriads with excellent selectivity (typically er >95 : 5).