Chiral amines as organocatalysts for asymmetric conjugate addition to nitroolefins and vinyl sulfones via enamine activation

Over the last decade the potential of organocatalysis has successfully been demonstrated. In particular, chiral amines such as pyrrolidine analogues have emerged as a broadly applicable class of organocatalyst for asymmetric conjugate addition via enamine activation. This Feature Article documents the development of these catalysts, emphasizing the design and mechanistic features that supply high selectivity in asymmetric Michael reactions

First organocatalyzed asymmetric Michael addition of aldehydes to vinyl sufones

The first asymmetric direct Michael addition of aldehydes to vinyl sulfones catalyzed by N-iPr-2,2'-bipyrrolidine is described. 1,4-Adducts are obtained in good yields and enantioselectivities. The determination of absolute configuration allowed us to postulate a Si,Si transition state model, as shown previously for nitroolefins

Organocatalyzed asymmetric reactions via microwave activation

Organocatalyzed asymmetric microwave-assisted reactions are described. Significant rate enhancements and a decrease of catalyst loading via microwave activation have been observed, while maintaining good to high yields and selectivities compared to literature results

First enantioselective organocatalytic conjugate addition of aldehydes to vinyl phosphonates

Chiral amines catalyze the enantioselective conjugate addition of aldehydes to vinyl phosphonates in high yields and with enantioselectivities up to 97% ee. This novel process provides synthetically useful chiral gamma-geminal phosphonate aldehydes which can be easily converted in a few steps into chiral beta-substituted vinyl phosphonates with conservation of the optical purity

The use of N-iPr-2,2'-bipyrrolidine derivatives as organocatalysts for asymmetric Michael additions

The recent rapid growth of organocatalysis has shown a new approach in organic chemistry and presents the obvious advantage in the avoidance of expensive and often toxic metals. Moreover, the organocatalysts are generally easier to make than standard catalytic reagents. Therefore, our laboratory has synthesized N-alkyl-2,2'bipyrrolidine derivatives as a new class of organocatalysts and applied them to the asymmetric Michael addition of ketones and aldehydes to nitroolefins via an enamine intermediate. We have furthermore developed the first asymmetric Michael addition of aldehydes to vinyl sulfones catalyzed with our diamines. The 1,4 adducts are obtained in good yields with enantioselectivities up to 80% ee. The determination of absolute configuration allowed us to postulate a Si,Si transition state model, as described previously for nitroolefins

Enantioselective organocatalytic conjugate addition of α-aminoketone to nitroolefins

The enantioselective organocatalytic conjugate addition of a-aminoketone to nitroolefins is reported

3,3'-Bimorpholine derivatives as a new class of organocatalysts for asymmetric michael addition

New N-alkyl-3,3'-bimorpholine derivatives (iPBM) were revealed to be efficient organocatalysts for the asymmetric direct Michael addition of aldehydes to nitroolefins and a vinyl sulfone. In these transformations using iPBM, 1,4-adducts were afforded in high yields, with good to high levels of diastereo- and enantioselectivity. The stereochemical outcome of the reaction could be explained by an acyclic synclinal model

Organocatalyst-mediated enantioselective intramolecular Michael addition of aldehydes to vinyl sulfones

Chiral amines with a hydrogen bond donor promote the intramolecular conjugate addition of aldehydes to vinyl sulfones. Chiral cyclic sulfone-aldehydes are obtained in good yields with an ee of up to 82%

Formation of Keteniminium Salts: Mechanistic Aspects and Substituent Effects

Keteniminium salts (KIs) are versatile intermediates in synthetic organic chemistry. Elucidation of the mechanistic aspects of KI formation reactions facilitates the design of KI intermediates that give access to complex compounds. In this study, in order to provide a comprehensive understanding of KI formation, various mechanisms were investigated using a density functional theory approach. Particularly, Ghosez’s KI formation mechanism, by activation of an amide with triflic anhydride, was extensively elaborated, since this procedure occurs under mild conditions and is, by far, the most frequently used method. Moreover, a broad range of substituents was examined to give insight on their potential contributions to the ease of formation of KIs. The effect of substituents on the reactivity of the corresponding starting amides was inspected by means of energetics, population analysis, frontier molecular orbitals (FMO) and reactivity descriptors. Computed data shows that electron donating groups lower the activation barrier by increasing the electron density of the amide carbonyl oxygen. Additionally, distortion/interaction model also confirmed the energetic outcomes. In addition, investigation of KI reactivity using FMO, and reactivity descriptors displayed that KI reactivity is inversely correlated with amide reactivity. Lastly, experimental outcomes are in line with computational predictions. We suggest that the reactivity of the amide has a crucial impact on the ease of KI formation and the reactivity of the corresponding KIs. This study gives pivotal insights into mechanistic aspects of KI formation and the role of the substituents