Asymmetric Transformations of α-Hydroxy Enamides Catalyzed by Chiral Brønsted Acids

Abstract

2-Aminoallyl cations are reactive intermediates that undergo diverse reactions, such as cycloadditions, direct nucleophilic additions, Nazarov electrocyclizations, and rearrangements. We review recent development in asymmetric catalytic reactions (nucleophilic additions and Nazarov electrocyclizations) based on chiral counteranion-paired 2-aminoallyl cation intermediates generated through activation of α-hydroxy enamides in the presence of chiral Brønsted acid catalysts. With an understanding of their asymmetric catalysis modes and mechanisms, we expect more asymmetric catalytic reactions will be developed on the basis of this strategy in the near future.

Kinetic Resolution of Tertiary 2‐Alkoxycarboxamido‐Substituted Allylic Alcohols by Chiral Phosphoric Acid Catalyzed Intramolecular Transesterification

“…Recently, the combination of 2‐amidoallylic alcohol substrates (or “α‐hydroxy enamides”) with chiral Brønsted acid catalysis has become a useful strategy for the asymmetric synthesis of functionalized enamide derivatives . Our group and Kartika and co‐workers independently reported the asymmetric synthesis of β‐indolyl cyclopentenamides from α‐hydroxy cyclopentenamides by chiral phosphoric acid catalysis (Figure a).…”

Asymmetric Aza-Diels–Alder Reactions of in Situ Generated β,β-Disubstituted α,β-Unsaturated N–H Ketimines Catalyzed by Chiral Phosphoric Acids

“…Despite the fact that a series of different asymmetric catalytic methods have been developed for asymmetric synthesis of dihydropyridinones and tetrahydropyridines via enantioselective ADA reactions, the other coupling partner for cycloaddition in these reactions was limited to α,β-unsaturated imines possessing a mono-β-substitution, thus leading to the generation of azacyles with only a tertiary stereocenter at the C-4 position. , To the best of our knowledge, no example of β,β-disubstituted α,β-unsaturated imine precursors has been utilized in asymmetric ADA reactions, probably due to their relatively low reactivities and challenges in stereoselectivities control. With our continuous interest in developing novel asymmetric reactions of amido allylic alcohols, herein we report a novel asymmetric synthesis of dihydropyridinones with vicinal quaternary stereocenters via enantioselective aza-Diels–Alder reactions between 3-amido allylic alcohols and oxazolones enabled by chiral phosphoric acid (CPA) catalysis, in which an in situ generated β,β-disubstituted α,β-unsaturated N–H ketimine was proposed as the key intermediate (Figure b).…”

Kinetic Resolution of Tertiary 2‐Alkoxycarboxamido‐Substituted Allylic Alcohols by Chiral Phosphoric Acid Catalyzed Intramolecular Transesterification

“…[3j] Recently,t he combination of 2-amidoallylic alcohol substrates (or "a-hydroxy enamides") with chiral Brønsted acid catalysis has become au seful strategy for the asymmetric synthesis of functionalized enamide derivatives. [4] Our group [5] and Kartika [6] and co-workers independently reported the asymmetric synthesis of b-indolyl cyclopentenamides from a-hydroxy cyclopentenamides by chiral phosphoric acid catalysis (Figure 1a). On the other hand, Chan and coworkers reported adehydrative Nazarov-type electrocyclization of a-hydroxy enamides that provides access to chiral 1Hindene derivatives under chiral Brønsted acid catalysis [7] ( Figure 1b).…”