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Reaction of 2-fluoro-1,3-diketone hydrates (I), (IV), and (VI) with aldehydes proceeds through a detrifluoroacetylative aldol addition mechanism to yield fluorinated aldol products in good stereoselectivities.

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.

Functionalization of the pyrrole ring using imine (II) as reagent takes place at position 3 of indoles (I) under Friedel—Crafts conditions, whereas position 2 of N-protected indoles (IV) is substituted in the presence of LDA.

A highly diastereoselective synthesis of a previously unknown type of aminobenzothiazol derivatives of high pharmaceutical potential is given.

The synthesis of a novel type of fluorinated sulfonamides with high pharmaceutical potential can be scaled up.

Enolates of indolin-2-ones react cleanly with the chiral imine (II) to afford adducts (III) and (V) in good diastereoselectivity.

CF3-containing chiral imines readily react with α,α-difluoroenolates affording a novel type of β-keto-amino compounds featuring the R-CO-CF2-CH(NH2)-CF3 moiety. The reactions feature exceptional generality allowing preparation of various aromatic, hetero-aromatic and aliphatic derivatives in high yields and diastereoselectivity. The products are configurationally stable and can be transformed to more functionalized complex compounds.

Here we describe the first attempts to scale up five addition reactions between (SS)-N-tert-butanesulfinyl-(3,3,3)-trifluoroacetaldimine 6 with C-nucleophiles derived from ketones (two examples), glycine Schiff base and heterocycles (two examples). In all cases studied, the observed stereochemical outcome of the scaled up (5.0–25.0 mmol) reactions was lower as compared with the original 0.5 mmol scale. However, the observed worsening of yields and diastereoselectivity was not identical and depended on the reaction conditions and reaction mechanisms. In general, scaling up of the reactions conducted at ambient temperatures presented no problems while the low-temperature (−78 °C) processes would require special equipment to provide strict maintenance of the reaction temperature to obtain the desirable outcome. Importantly, using procedures described here, series of biologically relevant compounds containing 2,2,2-trifluoro-1-(amino)ethyl [CF3 CH(NH2)-] pharmacophore unit can be prepared in enantiomerically pure form on up to 5 g scale, allowing their systematic biological studies.

The main feature of the synthesis of unexpected bis(benzothiazolyl)ethanes is the unusual role of CF3-imine, which serves as a precursor to the bridging ethylene moiety.

Compound (IIIa) can be further transformed to the corresponding β-amino alcohol by stereoselective reduction of its ketone moiety.

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.

In the title reaction, the N-tert-butylsulfinyl group serves not only as an efficient chiral auxiliary, but also as an amine protecting group.