Sulfonamide Nucleophiles Research Articles

Exploring Interrupted Nazarov Cyclizations Using Tethered Sulfonamide Nucleophiles: Insights into Capture Pathways

AbstractThis manuscript describes a study of diverse reaction outcomes that stem from the ionization of aza‐alkynyl‐Prins adducts. Experimental results have demonstrated unexpected behavior in the nitrogen‐containing systems compared to the analogous oxygen derivatives derived from oxa‐Prins/halo‐Nazarov sequences. In‐depth experimental studies and computational analysis revealed an intricate mechanism involving competing halo‐Nazarov and imino‐Nazarov pathways. These findings further elucidate the reaction chemistry of 3‐halo‐pentadienyl cation intermediates, and expand their utility in synthetic transformations.

Mechanism of Iron-Catalyzed Oxidative α-Amination of Ketones with Sulfonamides.

We report the mechanism of the iron-catalyzed oxidative α-amination of ketones with sulfonamides. Using linear free energy relationships, competition experiments, and identification of reaction intermediates, we have found that the mechanism of this reaction proceeds through rate-limiting electron transfer to 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) from an iron enolate in the process of forming an α-DDQ adduct. The adduct then serves as the electrophile for substitution with sulfonamide nucleophiles, accelerated by iron and additional DDQ. This mechanistic study rules out formation of an α-carbocation intermediate and purely radical mechanistic hypotheses.

Copper(II)-Catalyzed Three-Component Arylation/Hydroamination Cascade from Allyl Alcohol: Access to 1-Aryl-2-sulfonylamino-propanes.

A new straightforward approach to 1-aryl-2-aminopropanes using easily accessible substrates has been developed. Simple allyl alcohol is shown to be an ideal synthetic equivalent of the C3 propane-1,2-diylium bis-cation synthon in three-component cascade reactions with arenes and sulfonamide nucleophiles to regioselectively afford 1-aryl-2-aminopropanes. The reaction is catalyzed by Cu(OTf)2 and is expected to involve a Friedel-Crafts-type allylation of the arene, followed by hydroamination.

Alkene Oxyamination Using Malonoyl Peroxides: Preparation of Pyrrolidines and Isoxazolidines.

Treatment of homoallylic N-tosyl amines or allylic N-tosyl hydroxylamines with 1.5 equiv of a malonoyl peroxide provides a stereoselective method to access functionalized pyrrolidines and isoxazolidines. This metal free alkene oxyamination proceeds in 50-85% yield and up to 13:1 trans-selectivity. In addition, the relative stereochemistry of the oxygen and nitrogen substituents can be inverted through an oxidation/reduction sequence or inverting the stereochemistry of the starting alkene. Mechanistic investigations show a higher reactivity for hydroxyl nucleophiles over sulfonamide nucleophiles revealing a preference for dioxygenation over oxyamination.

Ligand Bite Angle‐Dependent Palladium‐Catalyzed Cyclization of Propargylic Carbonates to 2‐Alkynyl Azacycles or Cyclic Dienamides

The regioselectivity of the palladium-catalyzed cyclization of propargylic carbonates with sulfonamide nucleophiles is critically dependent on the bite angle of the bidentate phosphine ligand. Ligands with small bite angles favor attack on the central carbon atom of an allenylpalladium intermediate to afford cyclic dienamide products, whereas the use of those with large bite angles leads to alkynyl azacycles, with high stereoselectivity. A computational analysis of the reaction pathway is also presented.

Ligand Bite Angle‐Dependent Palladium‐Catalyzed Cyclization of Propargylic Carbonates to 2‐Alkynyl Azacycles or Cyclic Dienamides

AbstractThe regioselectivity of the palladium‐catalyzed cyclization of propargylic carbonates with sulfonamide nucleophiles is critically dependent on the bite angle of the bidentate phosphine ligand. Ligands with small bite angles favor attack on the central carbon atom of an allenylpalladium intermediate to afford cyclic dienamide products, whereas the use of those with large bite angles leads to alkynyl azacycles, with high stereoselectivity. A computational analysis of the reaction pathway is also presented.

Investigating the Reactivity of Radical Cations: Experimental and Computational Insights into the Reactions of Radical Cations with Alcohol and p-Toluene Sulfonamide Nucleophiles

The reactivity of electrochemically generated radical cations toward alcohol and p-toluene sulfonamide nucleophiles was directly investigated through competition experiments. Alcohol-trapping of the radical cation is the kinetically favored pathway and is reversible. Trapping with the sulfonamide leads to the thermodynamic product. Both reaction pathways were investigated computationally with density functional theory (UB3LYP/6-31G(d)) calculations.

Mg(ClO4)2-catalyzed intramolecular allylic amination: application to the total synthesis of demethoxyfumitremorgin C

A Mg(ClO4)2-catalyzed intramolecular amination of allylic alcohols with carbamate or sulfonamide nucleophiles to form substituted piperidine and pyrrolidine derivatives has been developed. This method has been successfully applied to the total synthesis of demethoxyfumitremorgin C.

Copper triflate/ t-BuOOAc-catalyzed amidation of allylic and benzylic acetates with sulfonamides

A copper triflate/ t-BuOOAc-catalyzed amidation of allylic and benzylic acetates has been developed which is suitable for the coupling of a wide variety of functionalized sulfonamide nucleophiles with acetate electrophiles. The methodology allows for the amidation of benzylic substrates which are not further activated by an additional adjacent alkene or alkyne, enabling simple allylic acetates and primary benzylic acetates to be used as reaction partners.

Formation of Enamides via Palladium(II)‐Catalyzed Vinyl Transfer from Vinyl Ethers to Nitrogen Nucleophiles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Formation of enamides via palladium(II)-catalyzed vinyl transfer from vinyl ethers to nitrogen nucleophiles.

Palladium(II) complexes catalyze the formation of enamides via the formal cross-coupling reaction between nitrogen nucleophiles and vinyl ethers. These vinyl transfer reactions proceed in good yields with amide, carbamate, and sulfonamide nucleophiles, and the optimal catalyst is (DPP)Pd(OCOCF(3))(2) (DPP = 4,7-diphenyl-1,10-phenanthroline). [reaction: see text]