Trifluoromethyl syn- or anti-γ-amino alcohols by one-pot solvent-free Mannich-type reactions under temperature control

Abstract

Starting from trifluoroacetaldehyde ethyl hemiacetal, chiral amines and suitable aldehydes, diastereomerically pure fluorinated synor anti-g-amino alcohols can be obtained by a friendly one-pot solventfree L-proline catalysed Mannich-type reaction only by changing the temperature.Scheme 2 L-Proline methyl ester catalysed Mannich-type reaction.This journal is

New Synthesis of Trifluoromethyl Aldimines Containing L‐α‐Amino Ester Moieties and Their Use in Mannich‐Type Reactions

“…In order to obtain the facial stereoselectivity of attack, the reaction temperature was changed . While at 40°C only complex crude mixtures were obtained, working at 0°C and −20°C different reaction outcomes were observed.…”

“…In order to obtain the facial stereoselectivity of attack, the reaction temperature was changed. 32 While at 40°C only complex crude mixtures were obtained, working at 0°C and À20°C different reaction outcomes were observed. In fact, under the first of these conditions (0°C, 2 d), in addition to the two signals already detected in the 19 F NMR spectra and corresponding to the syn diastereomers, 33 a new single signal related to a possible anti isomer was observed.…”

“…On the basis of our previous results on similar reactions, a hypothesis may be advanced to explain the formation at low temperature of the only one chiral pure anti diastereomer. 32 Working at À20°C, we can assume that a possible transition state (TS) I (Figure 4), controlled only by steric effects, could be strongly favored, because of the presence of a resident chiral center on the starting aldimines.…”

Trifluoromethyl aldimines: an overview in the last ten years

“…More recently, Fioravanti and co-workers. 39 have highlighted the role of solvent and temperature on the proline-catalyzed Mannich-type additions to trifluoromethyl aldimines, obtaining relevant stereochemical results only by changing the reaction temperature, when the additions were performed under solvent-free conditions. Aldimines 3a and 11 were reacted with different linear or branched aldehydes without solvent, at different temperatures, and in the presence of L-proline (10 mol %).…”

In Pursuit of β‐Amino‐α‐nitro‐β‐(trifluoromethyl) Ketones: Nitro‐Mannich versus Mannich‐Type Reactions

“…Starting from our previous results on stereoselective additions of enolisable nitro alkanes, aldehydes and especially α‐nitro esters to trifluoromethyl aldimines, our next challenge was the study of nitro‐Mannich and Mannich‐type additions of suitable α‐nitro ketones to C ‐CF 3 ‐substituted aldimines to obtain interesting multi‐functionalised β‐amino‐α‐nitro‐β‐(trifluoromethyl) ketones …”