Enantioselective Synthesis of Acyclic Stereotriads Featuring Fluorinated Tetrasubstituted Stereocenters

Na Shao (1) , Xueyang Liu (1) , Valérie Monnier (2) , Laurence Charles (3) , Jean Rodriguez (1) , Cyril Bressy (1) , Adrien Quintard (1)

1 ISM2 - Institut des Sciences Moléculaires de Marseille
2 FSCM - Fédération des Sciences Chimiques de Marseille
3 ICR - Institut de Chimie Radicalaire

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).

Mots clés: fluorine; kinetic resolution; organocatalysis; polyketide; Enantioselectivity

Domaines: Chimie organique

Na Shao, Xueyang Liu, Valérie Monnier, Laurence Charles, Jean Rodriguez, et al.. Enantioselective Synthesis of Acyclic Stereotriads Featuring Fluorinated Tetrasubstituted Stereocenters. Chemistry - A European Journal, 2022, 28 (5), pp.e202103874. ⟨10.1002/chem.202103874⟩. ⟨hal-03615869⟩