Abstract:A novel catalytic enantioselective methodology based on synergistic catalysis for the synthesis of chiral 2-acyl pyridines and pyrazines is reported. The strategy involves the metal-Lewis acid activation of acetyl aza-arenes and the secondary-amine activation of enals. The proposed mechanism is supported by DFT calculations.
“…A double synergistic Michael addition followed by an intramolecular aldol reaction and dehydration affords the final products in high yields, high diastereo‐ and enantioselectivities (97–99 % ee ) (Scheme 27). [56] …”
Section: Combining Aminocatalysis and Transition Metal Catalysismentioning
confidence: 99%
“…The mechanism was supported by DFT calculations which suggested that zinc coordination also favors the interaction of HOMO of the enolate with the LUMO of the iminium ion and hence plays a key role in enolate addition to the iminium ion (Scheme 28). [56] …”
Section: Combining Aminocatalysis and Transition Metal Catalysismentioning
The combination of organocatalysis with transition metal catalysis is an emerging research area for the scientific community. Various unprecedented transformations that are otherwise inaccessible by individual catalytic systems can be achieved with good efficiency and stereocontrolled manner by this dual-catalytic strategy. This Review presents a detailed discussion on the recent advances in dual catalytic systems combining organocatalysis and transition metal catalysis, covering the literature of the last five years. A wide variety of combinations of transition metals with organocatalysts including aminocatalysts, such as secondary amines and more recent primary amines, Brønsted acid catalysts, especially phosphoric acids based on the chiral BINOL scaffold and N-heterocyclic carbene catalysts, are discussed. Considering the great contribution of this domain to organic synthesis, the present and future potential of this new and exciting research field is highlighted.
“…A double synergistic Michael addition followed by an intramolecular aldol reaction and dehydration affords the final products in high yields, high diastereo‐ and enantioselectivities (97–99 % ee ) (Scheme 27). [56] …”
Section: Combining Aminocatalysis and Transition Metal Catalysismentioning
confidence: 99%
“…The mechanism was supported by DFT calculations which suggested that zinc coordination also favors the interaction of HOMO of the enolate with the LUMO of the iminium ion and hence plays a key role in enolate addition to the iminium ion (Scheme 28). [56] …”
Section: Combining Aminocatalysis and Transition Metal Catalysismentioning
The combination of organocatalysis with transition metal catalysis is an emerging research area for the scientific community. Various unprecedented transformations that are otherwise inaccessible by individual catalytic systems can be achieved with good efficiency and stereocontrolled manner by this dual-catalytic strategy. This Review presents a detailed discussion on the recent advances in dual catalytic systems combining organocatalysis and transition metal catalysis, covering the literature of the last five years. A wide variety of combinations of transition metals with organocatalysts including aminocatalysts, such as secondary amines and more recent primary amines, Brønsted acid catalysts, especially phosphoric acids based on the chiral BINOL scaffold and N-heterocyclic carbene catalysts, are discussed. Considering the great contribution of this domain to organic synthesis, the present and future potential of this new and exciting research field is highlighted.
“…Furthermore, the group of Rios also successfully disclosed various strategies for the preparation of carbocycles type molecules. For instance, through the enantioselective ring expansion of vinyl cyclopropanes, providing highly substituted [86], formal ring contraction for the generation of spiropyrazolones 106 [87], the asymmetric synthesis of cyclopentanes with four stereogenic centers 108 [88], the enantioselective acetyl aza-arene addition to α,β-unsaturated aldehydes affording chiral 2-acyl pyridines and pyrazines 110 [89], or, very recently disclosed, the highly enantioselective cascade reaction for the synthesis of dihydroacridines 112 (Scheme 23) [90]. Topics in Current Chemistry (2019) 377:38…”
The concept of merging enamine activation catalysis with transition metal catalysis is an important strategy, which allows for selective chemical transformations not accessible without this combination. The amine catalyst activates the carbonyl compounds through the formation of a reactive nucleophilic enamine intermediate and, in parallel, the transition metal activates a wide range of functionalities such as allylic substrates through the formation of reactive electrophilic π-allyl-metal complex. Since the first report of this strategy in 2006, considerable effort has been devoted to the successful advancement of this technology. In this chapter, these findings are highlighted and discussed.
“…Furthermore, the group of Rios also successfully disclosed various strategies for the preparation of carbocycles type molecules. For instance, through the enantioselective ring expansion of vinyl cyclopropanes, providing highly substituted spirocyclopentanes 104 [86], formal ring contraction for the generation of spiropyrazolones 106 [87], the asymmetric synthesis of cyclopentanes with four stereogenic centers 108 [88], the enantioselective acetyl aza-arene addition to α,β-unsaturated aldehydes affording chiral 2-acyl pyridines and pyrazines 110 [89], or, very recently disclosed, the highly enantioselective cascade reaction for the synthesis of dihydroacridines 112 (Scheme 23) [90]. Scheme 23Various chemical strategies for the preparation of various carbocyclic compounds…”
Section: Transition Metal- and Amine-catalyzed Carbocyclization Reactmentioning
The concept of merging enamine activation catalysis with transition metal catalysis is an important strategy, which allows for selective chemical transformations not accessible without this combination. The amine catalyst activates the carbonyl compounds through the formation of a reactive nucleophilic enamine intermediate and, in parallel, the transition metal activates a wide range of functionalities such as allylic substrates through the formation of reactive electrophilic π-allyl-metal complex. Since the first report of this strategy in 2006, considerable effort has been devoted to the successful advancement of this technology. In this chapter, these findings are highlighted and discussed.
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.
