Chiral (R)-1-phenylethylamine was successfully employed in a tandem aza-Henry addition-reduction reaction to give chiral β-nitro α-trifluoromethyl amines. A subsequent coupling reaction with N-Boc-protected amino acids leads to obtain optically pure CF3-modified dipeptides carrying two different N-protecting groups. These peptidomimetic units are characterized by the presence of the [CH(CF3)NH] group as mimetic of the natural [CONH] peptidic bond and can be used for the synthesis of more complex CF3-modified peptides after selective deprotection of one of the two amine functions. 2D NMR spectral analyses were employed to determine the absolute configurations of all newly synthesized chiral compounds.
Abstract:The reactivity of C-CH 3 substituted N-protected aldimines in aza-Henry addition reactions was compared with that of the analogous trifluoromethylated compounds. C-Alkyl aldimines easily reacted with nitro alkanes under solvent-free conditions and in the absence of catalyst, despite being worse electrophiles than C-CF 3 aldimines, they gave the aza-Henry addition only when ZrCl 4 was added. The presence of a bulky group on the imine carbon deeply influenced the reactivity.
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
L-α-amino esters were considered valuable chiral starting materials in the condensation reaction with trifluoroacetaldehyde (fluoral) ethyl hemiacetal to obtain new functionalized trifluoromethyl aldimines. Starting from these latter compounds, isovaleraldehyde was used in proline-catalyzed Mannich-type addition reactions to give trifluoromethyl syn- or anti-γ-amino alcohols bearing the L-α-amino ester function, simply by changing the reaction temperature.
A self-catalyzed aza-Henry addition of ethyl nitroacetate on N-alkyl trifluoromethyl aldimines was reported to synthesize β-amino α-nitro trifluoromethyl esters, precursors of α,β-diamino acid derivatives. In the presence of a resident chiral center on the imine nitrogen, the use of a suitable Lewis acid leads to a good stereofacial control, always resulting from a nucleophilic unlike attack. By starting from optically pure N-protected trifluoromethyl aldimines or directly from N-α-amino ester trifluoromethyl aldimines, small ψ[CH(CF3)NH]-peptidomimetic backbones can be achieved in which a new primary amine function represents a possible center for synthetic extension. Finally, a very interesting, and never observed before, palladium-catalyzed syn β-elimination occurred, leading to the selective nitro group reduction reaction on the syn-α-amino ester functionalized aza-Henry adducts and obtaining more stable optically pure trifluoromethyl conjugated imines.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.