Topics in Current Chemistry (2020) 378:1
1 3
7 Enamine Catalysis in the Presence of Lewis Acids
in Multicomponent Reactions: Hetero‑Diels–Alder
and Multicomponent Reactions
Multicomponent reactions (MCRs) have been amongst the targets of organocatalysis
for several reasons. The possibility to combine different activation modes, in particular iminium and enamine catalysis, can be advantageously used to drive consecutive reactions towards the obtainment of cyclic products. In addition to diversity
and complexity, the main advantage of multicomponent organocatalytic reactions
relies in the possibility to control the formation of multiple stereocenters with high
enantiomeric and diastereoisomeric excesses. To add interest to the multicomponent
reactions, the organocatalytic simple reaction conditions with simple starting materials in a single reaction step have been applied to the synthesis of various enantiopure
natural products and interesting intermediate for chiral drugs, dropping the number
of required steps. Therefore, organocatalysis was employed to access optically pure
compounds for pharmaceutical and agricultural applications. Organocatalysis was
employed in asymmetric multicomponent reactions [113]. Although metal contamination can be a problem, particularly in drug synthesis, the combination of Lewis
acid catalysis with organocatalysis can unveil new possibilities. As an example of
multicomponent reaction that takes advantage of both organocatalytic and Lewis
acid activation modes, Wang described a direct enamine catalysis for the preparation
of hetero Diels–Alder adducts (Scheme 19) [114].
Asymmetric inverse-electron-demand hetero-Diels–Alder (IED-HAD) reactions
of electron-rich alkenes with electron-deficient enones can give practical access
to dihydro- and tetrahydropyran derivatives, useful scaffolds commonly found in
many natural products. The reported IED-HAD between cyclic ketones and β,γunsaturated-α-ketoesters takes advantage of the enamine catalysis in the presence
Scheme 18 The enantioselective preparation of enantioselective of α-methyl-substituted cyclopentanes
mediated by organocatalysis and copper complexes
Reprinted from the journal
52
1 3
7 Enamine Catalysis in the Presence of Lewis Acids
in Multicomponent Reactions: Hetero‑Diels–Alder
and Multicomponent Reactions
Multicomponent reactions (MCRs) have been amongst the targets of organocatalysis
for several reasons. The possibility to combine different activation modes, in particular iminium and enamine catalysis, can be advantageously used to drive consecutive reactions towards the obtainment of cyclic products. In addition to diversity
and complexity, the main advantage of multicomponent organocatalytic reactions
relies in the possibility to control the formation of multiple stereocenters with high
enantiomeric and diastereoisomeric excesses. To add interest to the multicomponent
reactions, the organocatalytic simple reaction conditions with simple starting materials in a single reaction step have been applied to the synthesis of various enantiopure
natural products and interesting intermediate for chiral drugs, dropping the number
of required steps. Therefore, organocatalysis was employed to access optically pure
compounds for pharmaceutical and agricultural applications. Organocatalysis was
employed in asymmetric multicomponent reactions [113]. Although metal contamination can be a problem, particularly in drug synthesis, the combination of Lewis
acid catalysis with organocatalysis can unveil new possibilities. As an example of
multicomponent reaction that takes advantage of both organocatalytic and Lewis
acid activation modes, Wang described a direct enamine catalysis for the preparation
of hetero Diels–Alder adducts (Scheme 19) [114].
Asymmetric inverse-electron-demand hetero-Diels–Alder (IED-HAD) reactions
of electron-rich alkenes with electron-deficient enones can give practical access
to dihydro- and tetrahydropyran derivatives, useful scaffolds commonly found in
many natural products. The reported IED-HAD between cyclic ketones and β,γunsaturated-α-ketoesters takes advantage of the enamine catalysis in the presence
Scheme 18 The enantioselective preparation of enantioselective of α-methyl-substituted cyclopentanes
mediated by organocatalysis and copper complexes
Reprinted from the journal
52