N-arylated Sulfoximines Research Articles

Cu(II)-Catalyzed, Site Selective Sulfoximination to Indole and Indolines via Dual C-H/N-H Activation.

A copper-catalyzed protocol furnishing N-arylated sulfoximines has been developed via dual N-H/C-H activation. Arylalkyl- and less reactive diarylsulfoximines were efficiently coupled with privileged scaffolds like indolines, indoles, and N-Ar-7-azaindoles. Sulfoximines based on medicinally relevant scaffolds (phenothiazine, dibenzothiophene, thioxanthenone) were also well tolerated. Detailed mechanistic studies indicate that the deprotometalation and protodemetalation step is the reversible step.

Autocatalytic photoredox Chan-Lam coupling of free diaryl sulfoximines with arylboronic acids

N-Arylation of NH-sulfoximines represents an appealing approach to access N-aryl sulfoximines, but has not been successfully applied to NH-diaryl sulfoximines. Herein, a copper-catalyzed photoredox dehydrogenative Chan-Lam coupling of free diaryl sulfoximines and arylboronic acids is described. This neutral and ligand-free coupling is initiated by ambient light-induced copper-catalyzed single-electron reduction of NH-sulfoximines. This electron transfer route circumvents the sacrificial oxidant employed in traditional Chan-Lam coupling reactions, increasing the environmental friendliness of this process. Instead, dihydrogen gas forms as a byproduct of this reaction. Mechanistic investigations also reveal a unique autocatalysis process. The C–N coupling products, N-arylated sulfoximines, serve as ligands along with NH-sulfoximine to bind to the copper species, generating the photocatalyst. DFT calculations reveal that both the NH-sulfoximine substrate and the N-aryl product can ligate the copper accounting for the observed autocatalysis. Two energetically viable stepwise pathways were located wherein the copper facilitates hydrogen atom abstraction from the NH-sulfoximine and the ethanol solvent to produce dihydrogen. The protocol described herein represents an appealing alternative strategy to the classic oxidative Chan-Lam reaction, allowing greater substrate generality as well as the elimination of byproduct formation from oxidants.

Copper-Catalyzed 8-Aminoquinoline-Directed Oxidative C-H/N-H Coupling for N-Arylation of Sulfoximines.

A copper-catalyzed cross-dehydrogenative C-H/N-H coupling has been devised to access a series of N-arylated sulfoximines in high yield from 8-aminoquinoline-derived benzamides and sulfoximines. The reaction is scalable, and mechanistic studies favor the involvement of an organometallic pathway, where C-H bond cleavage is presumed to be the kinetically relevant step. The utility of sulfoximine-coupled benzamides was displayed through the nickel-catalyzed acceptorless dehydrogenative olefination of benzyl alcohols.

N-Arylation of NH-Sulfoximines via Dual Nickel Photocatalysis.

The pharmaceutically underexplored sulfoximine moiety has emerged as a potentially active pharmaceutical ingredient. We developed a scalable synthetic route to N-arylated sulfoximines from the respective “free” NH-sulfoximines and bromoarenes. Our strategy is based on a dual nickel photocatalytic approach, is applicable for a broad scope of substrates, and exhibits a highly functional group tolerance. In addition, we could demonstrate that other sulfoximidoyl derivatives like sulfonimidamides and sulfinamides proceed smoothly under the developed reaction conditions.

Reactions of Arynes with Sulfoximines: Formal Sulfinylamination vs. N-Arylation

Reactions of arynes with sulfoximines are reported. The fate of these reactions depends on the substituents of the sulfoximines. S,S-Diarylsulfoximines reacted with arynes to selectively afford o-sulfinylanilines, whereas a simple N-arylation reaction was observed when S-alkyl-S-aryl- or S,S-dialkylsulfoximine was used to selectively afford the corresponding N-arylated sulfoximines.

ChemInform Abstract: N‐Arylations of Sulfoximines with 2‐Arylpyridines by Copper‐Mediated Dual N—H/C—H Activation.

A high-yielding method providing rapid access to new N-arylated sulfoximines has been developed. A stoichiometric amount of copper facilitates the C-H activation of 2-arylpyridines which then undergo oxidative C-N cross-couplings with various sulfoximine derivatives.

N-Arylations of Sulfoximines with 2-Arylpyridines by Copper-Mediated Dual N–H/C–H Activation

A high-yielding method providing rapid access to new N-arylated sulfoximines has been developed. A stoichiometric amount of copper facilitates the C-H activation of 2-arylpyridines which then undergo oxidative C-N cross-couplings with various sulfoximine derivatives.

Efficient Copper‐Catalyzed N‐Arylation of Sulfoximines with Aryl Iodides and Aryl Bromides.

Two simple and inexpensive systems for copper-catalyed N-arylations of sulfoximines with aryl bromides and aryl iodides have been developed. Using 10 mol % of a copper(I) salt in combination with 20 mol % of a 1,2-diamine and Cs2CO3 provides N-arylated sulfoximines in high yields. Various functional groups and heteroatoms are tolarated. The method is complementary to the known protocols for N-arylations of sulfoximines, which require stoichiometric quantities of copper salts or cost-intensive palladium/BINAP catalysts.

Cu(OAc)2‐Catalyzed N‐Arylations of Sulfoximines with Aryl Boronic Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Efficient Copper-Catalyzed N-Arylation of Sulfoximines with Aryl Iodides and Aryl Bromides

Two simple and inexpensive systems for copper-catalyzed N-arylations of sulfoximines with aryl bromides and aryl iodides have been developed. Using 10 mol % of a copper(I) salt in combination with 20 mol % of a 1,2-diamine and Cs2CO3 provides N-arylated sulfoximines in high yields. Various functional groups and heteroatoms are tolerated. The method is complementary to the known protocols for N-arylations of sulfoximines, which require stoichiometric quantities of copper salts or cost-intensive palladium/BINAP catalysts.

Cu(OAc)2-Catalyzed N-Arylations of Sulfoximines with Aryl Boronic Acids

[reaction: see text] A simple and mild copper salt-catalyzed N-arylation of sulfoximines in high yields is reported. Cu(OAc)(2) activates aryl boronic acids for the reaction with NH-sulfoximines without additional base or heating. Furthermore, this new method allows the preparation of N-arylated sulfoximines, which have previously been more difficult to access.

Copper‐Mediated Cross‐Coupling Reactions of N‐Unsubstituted Sulfoximines and Aryl Halides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Copper-mediated cross-coupling reactions of N-unsubstituted sulfoximines and aryl halides.

[reaction: see text] Copper-mediated cross-coupling reactions of sulfoximines with aryl iodides and aryl bromides provide N-arylated sulfoximines in high yields. The method is complementary to the known palladium-catalyzed N-arylation and allows the preparation of N-arylated sulfoximines, which have previously been inaccessible.

Palladium-catalyzed N-arylation of sulfoximines with aryl bromides and aryl iodides

Various N-arylated sulfoximines have been synthesized in high yield by a direct approach which is based on a palladium-catalyzed cross-coupling strategy. Aryl bromides of variable substitution pattern were found to be the most effective coupling partners, whereas aryl iodides showed a nonpredictable behavior requiring lithium or silver salts as additives to ensure product formation in acceptable yields. Coupling of (S)-2-(2'-bromophenyl)-4-tert-butyloxazoline with enantiomerically pure (-)-(RS)-S-methyl-S-phenylsulfoximine afforded the corresponding product in good yield as a single diastereomer, showing that the palladium-catalyzed arylation proceeds in a stereospecific manner. The reaction with dibromobenzenes yielded the monosulfonimidoyl arenes in all cases, suggesting that the introduction of the sulfonimidoyl moiety deactivates the arene, thus preventing a second coupling step.

Palladium-catalyzed carbonnitrogen bond formation: A novel, catalytic approach towards N-arylated sulfoximines

The coupling of sulfoximines 1 with various aryl bromides of different substitution pattern in the presence of a catalytic amount of Pd(OAc) 2 and a chelating bisphosphine affords N-arylated products 3 with yields of up to 96%.