Pyridinium-Derived Mesoionic N-Heterocyclic Olefins (py-mNHOs).

Mesoionic polarization allows access to electron-rich olefins that have found application as organocatalysts, ligands, or nucleophiles. Herein, we report the synthesis and characterization of a series of 3-methylpyridinium-derived mesoionic olefins (py-mNHOs). We used a DFT-supported design concept, which showed that the introduction of aryl groups in the 1-, 2-, 4-, and 6-positions of the heterocyclic core allowed the kinetic stabilization of the novel mesoionic compounds.

Nucleophilicity of 4-(Alkylthio)-3-imidazoline Derived Enamines.

Imidazolidine-4-thiones (ITOs) are cyclic, secondary amines that were considered as potential prebiotic organocatalysts for light-driven α-alkylations of aldehydes by bromoacetonitrile (BAN). Recent studies showed that the initially supplied ITOs represent the pre-catalyst because they undergo S-alkylation with BAN to give 4-(alkylthio)-3-imidazolines (TIMs). Given that the same reagent mix that undergoes light-driven α-alkylations is also effective in the dark, we synthesized ten ITO- or TIM-derived enamines of aldehydes and characterized their nucleophilic reactivities by kinetic studies in acetonitrile.

Pushing the Upper Limit of Nucleophilicity Scales by Mesoionic N-Heterocyclic Olefins.

A series of mesoionic, 1,2,3-triazole-derived N-heterocyclic olefins (mNHOs), which have an extraordinarily electron-rich exocyclic CC-double bond, was synthesized and spectroscopically characterized, in selected cases by X-ray crystallography. The kinetics of their reactions with arylidene malonates, ArCH=C(CO Et) , which gave zwitterionic adducts, were investigated photometrically in THF at 20 °C. The resulting second-order rate constants k (20 °C) correlate linearly with the reported electrophilicity parameters E of the arylidene malonates (reference electrophiles), thus providing the nucleophile-specific N and s parameters of the mNHOs according to the correlation lg k (20 °C)=s (N+E).

Reactivity of electrophilic cyclopropanes.

Cyclopropanes that carry an electron-accepting group react as electrophiles in polar, ring-opening reactions. Analogous reactions at cyclopropanes with additional C2 substituents allow one to access difunctionalized products. Consequently, functionalized cyclopropanes are frequently used building blocks in organic synthesis.

Access to β-Alkylated γ-Functionalized Ketones via Conjugate Additions to Arylideneisoxazol-5-ones and Mo(CO)-Mediated Reductive Cascade Reactions.

1,4-Conjugate addition of ((chloromethyl)sulfonyl)benzenes to arylideneisoxazol-5-ones, followed by one-pot, N-selective trapping in the presence of electrophiles, was investigated. This strategy led to the synthesis of new, stable N-protected isoxazol-5-ones in good yields and high diastereolectivity. The study of the reactivity of obtained products in the presence of the Mo(CO)/HO system allowed the development of a cascade reaction leading to novel methyl ketones in high yields and unchanged dr bearing an uncommon chloromethinearylsulfonyl end group.

Enantioselective Catalytic Synthesis of α-Halogenated α-Aryl-β-amino Acid Derivatives.

The enantioselective synthesis of a broad variety of novel differently functionalized α-halogenated α-aryl-β-amino acid derivatives by means of an ammonium-salt-catalyzed asymmetric α-halogenation of isoxazolidin-5-ones was accomplished. Key to success to obtain high levels of enantioselectivities was the use of Maruoka's spirocyclic binaphthyl-based ammonium salts, and detailed accompanying mechanistic studies using density functional theory methods revealed the key features for the catalyst-substrate interactions.

Enantioselective Bifunctional Ammonium Salt-Catalyzed Syntheses of 3-CFS-, 3-RS-, and 3-F-Substituted Isoindolinones.

We herein report the ammonium salt-catalyzed synthesis of chiral 3,3-disubstituted isoindolinones bearing a heteroatom functionality in the 3-position. A broad variety of differently substituted CFS- and RS-derivatives were obtained with often high enantioselectivities when using Maruoka's bifunctional chiral ammonium salt catalyst. In addition, a first proof-of-concept for the racemic synthesis of the analogous F-containing products was obtained as well, giving access to one of the rare examples of a fairly stable α-F-α-amino acid derivative.

CF-Containing -Quinone Methides for Organic Synthesis.

A new family of CF-containing -quinone methides (CF-QMs) was systematically investigated for its suitability in organic synthesis. Addition of different nucleophiles gives access to target molecules with a benzylic CF-containing stereogenic center straightforwardly. The electrophilicity parameter of the prototypical CF-QM 2,6-di--butyl-4-(2,2,2-trifluoroethylidene)cyclohexa-2,5-dien-1-one was determined to be -11.

Electrophilic Reactivities of Vinyl -Quinone Methides.

The electrophilic reactivity of a series of 8-arylated vinyl -quinone methides (VQMs) was determined by analyzing the kinetics of their reactions with carbanions in DMSO at 20 °C according to the linear free energy relationship log = s( + ). The electrophilicity parameters for VQMs were used to successfully predict Michael-additions with structurally diverse C-, N-, S-, and H-nucleophiles.

Enantioselective catalytic synthesis of α-aryl-α-SCF-β-amino acids.

We herein report a novel entry towards chiral α-SCF3-β2,2-amino acids by carrying out the ammonium salt-catalyzed α-trifluoromethylthiolation of isoxazolidin-5-ones. This approach allowed for high enantioselectivities and high yields and the obtained heterocycles proved to be versatile platforms to access other targets of potential interest.

Quaternary β-amino acid derivatives by asymmetric addition of isoxazolidin-5-ones to para-quinone methides.

The highly enantioselective (>99.5% ee) synthesis of a new class of densely functionalized β-amino acid derivatives by reacting isoxazolidin-5-ones with para-quinone methides in the presence of chiral ammonium salt phase-transfer catalysts was developed. The reaction proceeds with exceptionally low catalyst loadings down to 20 ppm on gram scale and the utilization of the primary addition products towards further manipulations was demonstrated for selected examples.

Asymmetric phase-transfer catalysed β-addition of isoxazolidin-5-ones to MBH carbonates.

A novel high yielding, and diastereoselective protocol for the synthesis of α-allylated highly functionalised β-amino acid derivatives by adding isoxazolidin-5-ones to MBH carbonates under asymmetric phase-transfer catalysis has been developed.

Syntheses of Highly Functionalized Spirocyclohexenes by Formal [4+2] Annulation of Arylidene Azlactones with Allenoates.

A straightforward phosphine-catalyzed formal [4+2] annulation between α-branched allenoates and arylidene azlactones has been developed to access highly functionalized spirocyclohexenes. This cyclization favors the γ-addition of the phosphine-activated allenoates over a β'-addition pathway. Detailed computational studies support the proposed mechanism and provide a reasonable explanation for the observed regioselectivity and the noted effect of the catalyst.