Daisuke Asada

Isolation of α,α-difluoroketene silyl acetal and its application to asymmetric aldol reactions

Abstract Salt-free α,α-difluoroketene silyl acetal 1 was prepared in pure form. Aldol reactions of 1 with aldehydes catalyzed by catalytic amounts of chiral Lewis acids 2 and 3 proceeded with excellent enantiomeric excess to give optically active α,α-difluoro-β-hydroxy esters 4–11 (up to 98% ee).

Asymmetric aldol addition of aldehydes to a difluoroketene silyl acetal catalyzed by chiral Lewis acids

Abstract Aldol reaction of aldehydes with difluoroketene ethyl trimethylsilyl acetal (1) in the presence of a substoichiometric amount of chiral Lewis acid 2 or 3 provides the corresponding α,α-difluoro β-hydroxy esters 4–12 with high enantioselectivities (up to 98% ee). Reaction temperature has a great influence on the enantiofacial selection of aldehydes; the reactions of benzyloxyacetaldehyde catalyzed by Lewis acid 2 at −78 and −30°C gave the (+)- and (−)-α,α-difluoro β-hydroxy esters 7 in optical yields of 98% and 85%, respectively.

Enantioselective synthesis of 2,2-difluoro-3-hydroxycarboxylates by rhodium-catalyzed hydrogenation

Abstract The highly enantioselective synthesis of 2,2-difluoro-3-hydroxycarboxylates has been achieved by hydrogenating 2,2-difluoro-3-oxocarboxylates in the presence of chiral rhodium-(amidephosphine-phosphinite) complexes. Ethyl 4,4,4-trifluoroacetoacetate can be successfully transformed into the enantiomerically enriched 4,4,4-trifluoro-3-hydroxybutanoate in the same manner.

Enantioselective synthesis of 1,1,1-trifluoroalkan-2-ols by ruthenium-catalyzed hydrogenation

Abstract The highly enantioselective synthesis of 1,1,1-trifluoroalkan-2-ols has been achieved by hydrogenating 1,1,1-trifluoroalkan-2-one enol acetates in the presence of chiral ruthenium catalysts. An enol acetate, 2-acetoxy-3,3,3-trifluoro-1-(phenylthio)propene, can be successfully transformed into enantiomerically pure trifluorolactic acid.

Preparation of optically active α,α-difluoro-β-hydroxyketones

Abstract The stereoselective synthesis of α,α-difluoro-β-hydroxyketones of high enantiomeric purity is described starting from optically active α,α-difluoro-β-hydroxy esters. The esters were converted to the corresponding N -methoxy- N -methyl amides, which were treated with Grignard and organolithium reagents to provide the α,α-difluoro-β-hydroxyketones with up to 100% ee.

Diastereoselective perfluoroalkylation of chiral imide enolates with perfluoroalkyl iodides mediated by triethylborane

Abstract The perfluoroalkylation of lithium enolates of chiral N -acyloxazolidinones with perfluoroalkyl iodides mediated by triethylborane proceeds with good diastereomeric excess (55%–93% de).

Diastereoselective introduction of an EtO2CCF2- group into chiral imide enolates mediated by triethylborane

Abstract The introduction of an EtO 2 CCF 2 - group into lithium enolates of chiral N-acyloxazolidinones with ethyl difluoroiodoacetate mediated by triethylborane proceeds with good diastereomeric excess (86->98% de).

DIASTEREOSELECTIVE BROMODIFLUOROMETHYLATION AND DIFLUOROMETHYLATION OF CHIRAL IMIDE ENOLATES VIA INSERTION OF DIFLUOROCARBENE

Abstract Lithium enolates of chiral N -acyloxazolidinones reacted with dibromodifluoromethane and bromodifluoromethane to give α-bromodifluoromethyl and α-difluoromethyl carboximides, respectively, with good diastereomeric excess. These reactions proceed not via a radical mechanism but via an ionic chain mechanism involving insertion of difluorocarbene.

Diastereoselective bromodifluoromethylation of chiral imide enolates via insertion of difluorocarbene

Abstract The bromodifluoromethylation of lithium enolates of chiral N-acyloxazolidinones via the insertion of difluorocarbene proceeds with good diastereomeric excess (68–92% de).