Dienamine Catalysis:  Organocatalytic Asymmetric γ-Amination of α,β-Unsaturated Aldehydes

Abstract

A new concept in organocatalysis is presented, the direct asymmetric gamma-functionalization of alpha,beta-unsaturated aldehydes. We disclose that secondary amines can invert the usual reactivity of alpha,beta-unsaturated aldehydes, enabling a direct gamma-amination of the carbonyl compound using azodicarboxylates as the electrophilic nitrogen-source. The scope of the reaction is demonstrated for the enantioselective gamma-amination of different alpha,beta-unsaturated aldehydes, giving the products in moderate to good yields and with high enantioselectivities up to 93% ee. Experimental investigations and DFT calculations indicate that the reaction might proceed as a hetero-Diels-Alder cycloaddition reaction. Such a mechanism can explain the "unexpected" stereochemical outcome of the reaction.

Alternative tandem cyclisation pathways in the reaction between imines and enones

“…The same generic outcome was found when using the respective Jørgensen and Hayashi catalysts, 22 which, in addition to the observed conjugate addition of amines to methyl vinyl ketone 22, 25 explains the lack of e.e. and poor catalytic performance (see above).…”

Singlet oxygen addition to cyclo-1,3-hexadienes from natural sources and from organocatalytic enal dimerization

“…26,27 When these conditions were applied to α,ß-unsaturated aldehydes, complex mixtures of peroxides were observed that could not be separated. We expected the formation of dieneamines, as described in the work by Jørgensen et al 28,29 Obviously, we were not able to trap these dienes with singlet oxygen. Thus, the reaction conditions were modified and the photooxygenation was designed as a delayed step.…”

Solvent-Free Selective Condensations Based on the Formation of the Olefinic (C=C) Bond Catalyzed by Organocatalyst

“…The result suggested that cyclic amines with moderate alkalinity and two active centers exhibited high activity. Plausible pathways are shown in Scheme 2 and we consider that the ratio of the aldol condensation was promoted by the hydrogen bonding between the amino group or the hydroxy group of 3-pyrrolidinamine or 3-pyrrolidinol and the aldehyde [24,25]. …”