Formal Asymmetric α‑Alkenylation of Aldehydes and the Synthetic Application toward Forming α-<i>exo</i>-Methylene-γ-butyrolactones and Skipped Dienes

A formal asymmetric α-alkenylation of aldehydes is reported based on the organocatalytic reaction of aldehydes with nitroacrylates. The reaction proceeds in a one-pot manner forming the products with up to 77% yield and up to >99% ee. This strategy is also successfully applied for the synthesis of α-<i>exo</i>-methylene-γ-butyrolactones and skipped diene scaffolds in a highly enantioselective manner

1,4-Naphthoquinones in H‑Bond-Directed Trienamine-Mediated Strategies

The synthesis of optically active, carboannulated dihydronaphthoquinone and naphthoquinone derivatives with up to four stereogenic centers is demonstrated by H-bond-directed, trienamine-mediated [4 + 2]-cycloadditions. The outcome of the reaction between 2,4-dienals and 1,4-naphthoquinones is controlled by the substituent in the 2-position of the 1,4-naphthoquinone. In the case of sterically demanding 2-substituted derivatives, dihydronaphthoquinones are obtained. However, when a hydrogen atom is present in the 2-position, a subsequent oxidation of the initially formed cycloadducts occurs yielding naphthoquinones

Asymmetric [3 + 2] Cycloaddition of Vinylcyclopropanes and α,β-Unsaturated Aldehydes by Synergistic Palladium and Organocatalysis

The stereoselective [3 + 2] cycloaddition between vinylcyclopropanes and α,β-unsaturated aldehydes promoted by combined palladium and organocatalysis is disclosed. The unique synergistic catalytic system allows for the stereoselective formation of highly substituted cyclopentanes with up to four stereocenters in high yields and selectivities. Vinylcyclopropanes with two different geminal substituents facilitate the formation of cyclopentanes containing a quaternary stereocenter. Furthermore, the developed reaction performs well on gram scale, and a number of transformations are demonstrated

Étienne-Hyacinthe de Ratte and Pierre Marie Auguste Broussonet, Montpellier, [France], to James Edward Smith, 12 Great Marlborough Street, London

De Ratte, secretary of the Académie des Sciences of Montpellier, informs Smith he has been elected a Correspondent Member. Broussonet has appended his own communication

Asymmetric [3 + 2] Cycloaddition of Vinylcyclopropanes and α,β-Unsaturated Aldehydes by Synergistic Palladium and Organocatalysis

The stereoselective [3 + 2] cycloaddition between vinylcyclopropanes and α,β-unsaturated aldehydes promoted by combined palladium and organocatalysis is disclosed. The unique synergistic catalytic system allows for the stereoselective formation of highly substituted cyclopentanes with up to four stereocenters in high yields and selectivities. Vinylcyclopropanes with two different geminal substituents facilitate the formation of cyclopentanes containing a quaternary stereocenter. Furthermore, the developed reaction performs well on gram scale, and a number of transformations are demonstrated

Catalytic Asymmetric Synthesis of 4‑Nitropyrazolidines: An Access to Optically Active 1,2,3-Triamines

The first catalytic enantio- and diastereoselective synthesis of 4-nitropyrazolidines is presented. Asymmetric hydrogen-bonding activation of nitro-olefins facilitated the 1,3-dipolar cycloaddition with hydrazones, affording optically active 4-nitropyrazolidines containing three continuous stereogenic centers as a single diastereomer in up to 99% ee. Furthermore, it is demonstrated that the optically active 4-nitropyrazolidines can be applied as precursors for the synthesis of highly interesting 1,2,3-triamines

Controlling Asymmetric Remote and Cascade 1,3-Dipolar Cycloaddition Reactions by Organocatalysis

The regio- and stereoselective control of cycloaddition reactions to polyconjugated systems has been demonstrated by applying asymmetric organocatalysis. Reaction of 2,4-dienals with nitrones allows for a highly regio- and stereoselective 1,3-dipolar cycloaddition in the presence of an aminocatalyst. The first cycloaddition on the remote olefin can be followed either by a cascade reaction or by other selective reactions of the remaining olefin. The chiral products are obtained in good to high yields and excellent diastereo- and enantioselectivities. The remote selective concept has been extended to 2,4,6-trienals by means of a novel enantioselective triple cascade 1,3-dipolar cycloaddition reaction. The formation of chiral poly 1,3-amino alcohols is also demonstrated

Beyond Classical Reactivity Patterns: Shifting from 1,4- to 1,6-Additions in Regio- and Enantioselective Organocatalyzed Vinylogous Reactions of Olefinic Lactones with Enals and 2,4-Dienals

Organocatalysis is shown to expand the classical reactivity pattern for conjugate addition reactions. It is demonstrated that the site selectivity can be extended from 1,4- to 1,6-additions for the enantioselective vinylogous additions of methyl-substituted vinylogous lactones to enals and 2,4-dienals. This novel reactivity is demonstrated for methyl-substituted olefinic azlactones and butyrolactones. Their synthetic potential is first highlighted by the development of the organocatalytic regioselective vinylogous 1,4-addition to enals which proceeds with a very high level of double-bond geometry control and excellent enantioselectivity. The concept is developed further for the unprecedented intermolecular enantioselective organocatalyzed vinylogous 1,6-addition to linear 2,4-dienals, by which the site selectivity of the process is extended from the β-position to the remote δ-position of the 2,4-dienal. The organocatalyst controls the newly generated stereocenter six bonds away from the stereocenter of the catalyst with a high level of enantiocontrol, and the products are obtained with full control of double-bonds configuration. The scope of these new reaction concepts is demonstrated for a series of aliphatic and aryl-substituted enals and 2,4-dienals undergoing enantioselective vinylogous reactions with methyl-substituted olefinic azlactones and butyrolactones. Furthermore, mechanistic considerations are presented which can account for the change from 1,4- to 1,6-selectivity. Finally, a number of different transformations of the optically active 1,4- and 1,6-addition products are demonstrated

Beyond Classical Reactivity Patterns: Shifting from 1,4- to 1,6-Additions in Regio- and Enantioselective Organocatalyzed Vinylogous Reactions of Olefinic Lactones with Enals and 2,4-Dienals

Organocatalysis is shown to expand the classical reactivity pattern for conjugate addition reactions. It is demonstrated that the site selectivity can be extended from 1,4- to 1,6-additions for the enantioselective vinylogous additions of methyl-substituted vinylogous lactones to enals and 2,4-dienals. This novel reactivity is demonstrated for methyl-substituted olefinic azlactones and butyrolactones. Their synthetic potential is first highlighted by the development of the organocatalytic regioselective vinylogous 1,4-addition to enals which proceeds with a very high level of double-bond geometry control and excellent enantioselectivity. The concept is developed further for the unprecedented intermolecular enantioselective organocatalyzed vinylogous 1,6-addition to linear 2,4-dienals, by which the site selectivity of the process is extended from the β-position to the remote δ-position of the 2,4-dienal. The organocatalyst controls the newly generated stereocenter six bonds away from the stereocenter of the catalyst with a high level of enantiocontrol, and the products are obtained with full control of double-bonds configuration. The scope of these new reaction concepts is demonstrated for a series of aliphatic and aryl-substituted enals and 2,4-dienals undergoing enantioselective vinylogous reactions with methyl-substituted olefinic azlactones and butyrolactones. Furthermore, mechanistic considerations are presented which can account for the change from 1,4- to 1,6-selectivity. Finally, a number of different transformations of the optically active 1,4- and 1,6-addition products are demonstrated

A New Organocatalytic Concept for Asymmetric α‑Alkylation of Aldehydes

The organocatalytic asymmetric α-alkylation of aldehydes by 1,6-conjugated addition of enamines to <i>p</i>-quinone methides is described. Employing a newly developed class of chiral secondary amine catalysts, α-diarylmethine-substituted aldehydes with two contiguous stereocenters have been synthesized in a simple manner with good diastereo­control and excellent enantio­selectivity