Lingmin Wu

Assembly of Fluorinated Quaternary Stereogenic Centers through Catalytic Enantioselective Detrifluoroacetylative Aldol Reactions

A Cu-catalyzed asymmetric detrifluoroacetylative aldol addition reaction of 2-fluoro-1,3-diketones/hydrates to aldehydes in the presence of base and chiral bidentate ligand was developed. The reaction was carried out under convenient conditions and tolerated a wide range of substrates, resulting in fluorinated quaternary stereogenic α-fluoro-β-hydroxy ketone products with good chemical yields, diastereo- and enantioselectivities. This catalytic asymmetric detrifluoroacetylative aldol addition reaction provides a new approach for the preparation of biologically relevant products containing C-F quaternary stereogenic centers.

LDA-promoted asymmetric synthesis of β-trifluoromethyl-β-amino indanone derivatives with virtually complete stereochemical outcome

We demonstrate that reactions between various 1-indanones and (SS)-N-tert-butanesulfinyl-(3,3,3)-trifluoroacetaldimine, conducted in the presence of catalytic amounts of LDA, occur with virtually complete stereochemical outcome, offering reliable and generalized access to biologically relevant β-trifluoromethyl-β-amino indanone derivatives. The products can be isolated in diastereomerically pure form simply by washing the crude reaction mixture with hexanes, underscoring practicality of the present method.

Asymmetric Friedel-Crafts reactions of N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines: general access to enantiomerically pure indoles containing a 1-amino-2,2,2-trifluoroethyl group.

We have demonstrated that 3,3,3-trifluoroacetaldimine (S)-1 easily reacts with indole derivatives under Friedel-Crafts reactions to provide reliable and generalized access to biologically interesting compounds containing the CF3CH(NH2)- pharmacophoric group. The reactions proceed with high rates and generally excellent yields (>90%) and stereochemical outcomes (99:1 dr).

Synthesis of Trifluoromethyl-Containing Vicinal Diamines by Asymmetric Decarboxylative Mannich Addition Reactions

Herein is reported a study of asymmetric decarboxylative Mannich addition reactions between (Ss)-N-t-butylsulfinyl-3,3,3-trifluoroacetaldimine and Schiff bases derived from various aldehydes and lithium 2,2-diphenylglycinate. These reactions proceed with excellent diastereoselectivities and good chemical yields, providing a practical method for preparation of trifluoromethyl-containing vicinal diamines. The procedures can be conducted under convenient conditions, rendering this approach of high synthetic value.

Asymmetric synthesis of amino-benzothiazol derivatives by additions of 2-lithiated benzothiazoles to (S)-N-t-butylsulfinyl-ketimines

The reactions between lithium-benzothiazoles and (S)-N-tert-butanesulfinylketimines have been found to be of general synthetic importance for asymmetric preparation of previously unknown type of amino-benzothiazol derivatives of high pharmaceutical potential. In most cases, the reactions proceed with excellent diastereoselectivities and good isolated yields of the target compounds rendering the developed procedure of high synthetic value and immediate practical use.

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

Summary A variety of chiral N-phosphinyl α-imino esters have been synthesized for the first time from ketoesters and phosphinylamide, which were then reduced by L-selectride to give the corresponding N-phosphinyl-protected α-amino esters. The reduction proceeded very well with excellent chemical yields (88–98%) as well as high diastereoselectivities (96:4 to 99:1). Some of these products could be obtained without column chromatography and recrystallization. The chiral phosphinyl auxiliary could be easily cleaved under acidic conditions.