Copper(I)-catalyzed diastereoselective formation of oxazolines and N-sulfonyl-2-imidazolines

A simple and short method for the reaction of methyl isocyanoacetate with aldehydes and N-sulfonylimines is presented. The reaction is catalyzed by copper(I) complexes and proceeds with excellent yields and high diastereoselectivities.     

Iron-catalyzed sulfonylimine synthesis under neutral conditions

A convenient FeCl₃-catalyzed synthesis of N-sulfonylimines via the condensation of aldehydes with N-sulfonylamides in mild and neutral conditions (in ethanol at room temperature) is reported. This procedure constitutes the first iron-catalyzed synthesis of N-sulfonylimines and is adapted to the condensation of both aromatic and aliphatic aldehydes.     

Imino ene-type reaction of enamines with N-sulfonylimines and application to diastereoselective synthesis of N-sulfonyl-1,3-diamines

Enamines react rapidly with N-sulfonylimines to afford imino ene-type adducts. The reaction proceeds even at −78 °C in the presence of acetic acid and shows high diastereoselectivity. Acid hydrolysis of imino ene-type products affords β-amino ketones, and reduction with NaBH₃CN furnishes N-sulfonyl-1,3-diamines with high diastereoselectivities. The stereochemistry of these transformations is considered based on transition state models.     

The features of the kinetics of radical reactions of quinone imines with 2-mercaptobenzothiazole

Kinetics of the reactions of N-phenyl-1,4-benzoquinone monoimine and N,N′-diphenyl-1,4-benzoquinone diimine with 2-mercaptobenzothiazole in chlorobenzene at T = 343 K has been studied by using kinetical spectrophotometry method (periodic spectral measurements and/or monitoring the wavelengths of the absorption band of quinone imines in the visible region). Two general features of the reactions, namely, radical mechanism and the existence of two steps were found. Kinetic features depend on the structure of a quinone imine. A reaction between N,N′-diphenyl-1,4-benzoquinone diimine and 2-mercaptobenzothiazole at first (initial) steps proceeds in an autoinhibition mode and has two independent channels, one of which being radical-chain. The addition of an initiator strongly accelerates the reaction only at the initial step, on completion of which the reaction rate decreases significantly and do not depend on the presence of the initiator. This testifies to the proceeding of the reaction by a non-chain mechanism subsequently to the initial step. The interaction involving N-phenyl-1,4-benzoquinone monoimine proceeds by a radical non-chain mechanism from the very beginning up to the end, and at the initial steps it proceeds in the autoaccelerating mode. The initiator has no influence on the reaction rate. For the process of the interaction of N,N′-diphenyl-1,4-benzoquinone monoimine and 2-mercaptobenzothiazole in the presence of 4-hydroxydiphenylamine, a radical mechanism was proposed, that serves to describe the kinetic features of the reaction and to obtain a quantitative estimation of some of its kinetic parameters.     

Organocatalytic asymmetric Mannich-type reaction of N-sulfonylimines with isocyanoacetate leading to optically active 2-imidazoline-4-carboxylates

The first asymmetric Mannich-type reaction of methyl isocyanoacetate with N-sulfonylimines catalyzed by cinchona alkaloid derivatives yielded 2-imidazolines with high diastereoselectivities and good enantioselectivities (up to >99:1 dr and 70% ee). This reaction provided a convenient route to access various substituted 2-imidazoline-4-carboxylates and related α,β-diamino acids in high enantiomeric purities.     

A highly diastereoselective synthesis of 3-carbethoxy-2,5-disubstituted-3-pyrrolines by phosphine catalysis

Tributylphosphine was used as catalyst to facilitate a [3+2] cycloaddition between γ-substituted allenoates and N-sulfonylimines. The resulting adducts, 3-carbethoxy-2,5-disubstituted-3-pyrrolines, were formed in excellent yields with high diastereoselectivity. The reaction went to completion in several hours at room temperature, and the starting materials were easily prepared with one step from commercially available compounds via known procedures.     

Binary 1,4-asymmetric induction toward imines from a single allyltin reagent with a chiral oxygen functional group

A single allyltin reagent possessing a chiral oxygen functional group afforded each diastereomeric product in the reaction with N-sulfonylimines promoted by appropriate Lewis acids in a binary stereoselective manner. InCl₃ selectively provided the syn-1,4-amino alcohol derivatives, while BF₃ and TiCl₄ gave the anti-products preferentially.     

Photosensitized [4+2]- and [2+2]-Cycloaddition Reactions of N-Sulfonylimines

The synthesis of polycyclic compounds is of high interest due to the prevalence of these motifs in drugs and natural products. Herein, we report on the stereoselective construction of 3D bicyclic scaffolds and azetidine derivatives by modulation of N-sulfonylimines to achieve either [4+2]- or [2+2]-cycloaddition reactions. The utility of the method was established by further modulation of the product. Mechanistic studies are also included, which support reaction via Dexter energy transfer.     

A practical and green approach towards synthesis of new N-sulfonylimines under ultrasound irradiation

An efficient protocol was developed for the synthesis of N-sulfonylimines under environment friendly conditions. Ultrasonic energy was employed to obtain the desired products in excellent yields with high purity under solvent- and catalyst-free conditions. The synthesis of new N-sulfonylimines was accomplished from various N-sulfonamides and benzaldehyde.

The structures of the synthesized compounds are confirmed by elemental analysis as well as by ¹H, ¹³C NMR spectral data, IR and MS.     

C2-Symmetric bicyclo[3.3.1]nona-2,6-diene and bicyclo[3.3.2]deca-2,6-diene: new chiral diene ligands based on the 1,5-cyclooctadiene framework

As a new type of C₂-symmetric chiral diene ligands, which coordinate to a metal by their 1,5-cyclooctadiene framework, we prepared 2,6-disubstituted bicyclo[3.3.1]nona-2,6-diene (bnd*) and bicyclo[3.3.2]deca-2,6-diene (bdd*), and examined their catalytic activity and enantioselectivity for rhodium-catalyzed asymmetric 1,4-addition to α,β-unsaturated ketones and 1,2-addition to N-sulfonylimines. High enantioselectivity of the Ph-bnd* ligand was observed in the addition of phenylboroxine to N-tosylimine and N-4-nitrobenzenesulfonylimine of 4-chlorobenzaldehyde to give phenyl(4-chlorophenyl)methylamines in high enantiomeric excess (98–99% ee).     

Reactions of polyhalomethanes with olefins catalyzed by copper complexes with aromatic amino alcohols

Copper complexes with amino alcohols structurally similar to ephedrin (1-phenyl-3-(N-methylamino)propan-1-ol and 1-phenyl-2-(N-methylamino)ethanol) are catalytically very active in the free-radical addition of CCl₄ and CBr₄ to linear alk-1-enes. These amino alcohols themselves are initiators of radical addition reactions, and, in the reaction with CBr₄, they are more active than the metal complexes. In the presence of the amino alcohols, as distinct from classical radical initiators, the reaction is highly selective and affords an addition product. An analysis of kinetic equations and the data obtained for the reaction involving CHCl₃ suggest that the amino alcohols and the corresponding metal complexes are involved in different ways in the addition of CCl₄ and CBr₄ to linear alk-1-enes.     

C–H bond addition and copolymerization reactions of N-arylmaleimides: Fundamentals of coagent-assisted polymer cross-linking

Solid-state rheometry and model compound reactions are used to investigate free radical reactions of N-arylmaleimide coagents with saturated and unsaturated polymers. N,N′-m-phenylene dimaleimide (BMI) is shown to provide superior cross-link densities over diacrylate and diallyl coagents for all of the polymers studied, including linear low density polyethylene (LLDPE), poly(ethylene oxide) (PEO), cis-poly(butadiene) (PBD) and cis-poly(isoprene) (PIP). Studies of the N-phenylmaleimide (NPM) + cis-cyclooctane system show that C–H bond addition to yield N-aryl-2-alkylsuccimide grafts is the predominant reaction pathway, as opposed to maleimide homopolymerization. In contrast, peroxide-initiated reactions of cis-cyclooctene with small NPM concentrations generate highly alternating poly(cycloctene-alt-N-phenylmaleimide) in high yield, indicating that unsaturated mers in materials such as PBD engage maleimides in an efficient alternating copolymerization between electron-rich and electron-deficient monomer pairs. Factors that affect the reactivity of different polymers in these C–H bond additions and alternating copolymerizations are discussed.     

New chiral ferrocenyl amidophosphine ligand for remarkable improvement of enantioselectivities in copper-catalyzed addition of diethylzinc to N-sulfonylimines

(S)-N-Ferrocenoyl-2-[(diphenylphosphino)methyl]-pyrrolidine 3 was conveniently prepared from commercially available l-proline and ferrocenecarboxylic acid. In the presence of a catalytic amount of chiral ligand 3 (4 mol %) and Cu(OTf)₂ (3 mol %), the asymmetric addition of diethylzinc to N-sulfonylimines was achieved in 57-99% yield with up to 88% ee.     

Reactions of an aromatic σ,σ-biradical with amino acids and dipeptides in the gas phase

Gas-phase reactivity of a positively charged aromatic σ,σ-biradical (N-methyl-6,8-didehydroquinolinium) was examined toward six aliphatic amino acids and 15 dipeptides by using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR) and laser-induced acoustic desorption (LIAD). While previous studies have revealed that H-atom and NH₂ abstractions dominate the reactions of related monoradicals with aliphatic amino acids and small peptides, several additional, unprecedented reaction pathways were observed for the reactions of the biradical. For amino acids, these are 2H-atom abstraction, H₂O abstraction, addition — CO₂, addition — HCOOH, and formation of a stable adduct. The biradical reacts with aliphatic dipeptides similarly as with aliphatic amino acids, but undergoes also one additional reaction pathway, addition/C-terminal amino acid elimination (addition — CO — NHCHR_C). These reactions are initiated by H-atom abstraction by the biradical from the amino acid or peptide, or nucleophilic addition of an NH₂ or a HO group of the amino acid or peptide at the radical site at C-6 in the biradical. Reactions of the unquenched C-8 radical site then yield the products not observed for related monoradicals. The biradical reacts with aromatic dipeptides with an aromatic ring in N-terminus (i.e., Tyr-Leu, Phe-Val, and Phe-Pro) similarly as with aliphatic dipeptides. However, for those aromatic dipeptides that contain an aromatic ring in the C-terminus (i.e., Leu-Tyr and Ala-Phe), one additional pathway, addition/N-terminal amino acid elimination (addition — CO — NHCHR_N), was observed. This reaction is likely initiated by radical addition of the biradical at the aromatic ring in the C-terminus. Related monoradicals add to aromatic amino acids and small peptides, which is followed by Cα-Cβ bond cleavage, resulting in side-chain abstraction by the radical. For biradicals, with one unquenched radical site after the initial addition, the reaction ultimately results in the loss of the N-terminal amino acid. Similar to monoradicals, the C-S bond in amino acids and dipeptides was found to be especially susceptible to biradical attack.     

Radical oxyamination of vinyl azides with N-hydroxyphthalimide under the action of [bis(trifluoroacetoxy)iodo]benzene

O,O′-Bis(phthalimido)-modified 2-(hydroxyimino)ethanols containing N–O–N fragment were synthesized in high yields via the reaction of vinyl azides with N-hydroxyphthalimide under the action of hypervalent iodine-based oxidant. The reaction proceeds under mild conditions and is compatible with a wide range of vinyl azides. Presumably, the process starts with the oxidative formation of phthalimide-N-oxyl radical, followed by its addition to vinyl azide with the subsequent trapping of the generated iminyl radical with the second phthalimide-N-oxyl radical.     

Reactions of fluoroalkanesulfonyl azides with cyclic vinyl ethers

The addition reactions of fluoroalkanesulfonyl azides to dihydropyran or dihydrofuran were studied. These reactions do not give the corresponding N-fluoroalkanesulfonyl azilidines but N-fluoroalkanesulfonyl-tetrahydropyranon-2-imines or N-fluoroalkanesulfonyl-tetrahydro-furano-2-imines. The reaction mechanism is discussed.     

Synthesis of oxindoles via Cu-mediated reactions between N-phenylacrylamides and ethyl 2-bromo-2-methylpropionate

A novel way of synthesizing alkylated oxindoles via Cu-mediated atom transfer radical addition reaction between N-phenylacrylamides and ethyl 2-bromo-2-methylpropionate has been described. It was found that the use of N,N,N′,N′-1,1,2,2,-tetramethylethylenediamine as ligand was important for achieving good yields. Additionally, the use of DMSO as solvent and running the reaction at 130?°C were also crucial. In some cases, the product can be further brominated when the reaction temperature was raised to 150?°C.     

Atmospheric oxidative catalyst-free cross-dehydrogenative coupling of aldehydes with N-hydroxyimides

Cross-dehydrogenative coupling (CDC) reactions of aldehydes with N-hydroxyimidates such as N-hydroxysuccinimide (NHSI), N-hydroxyphthalimide (NHPI) under catalyst-free conditions is described. Moreover, the desired products can be obtained simply by recrystallization from ethanol. This method is also applicable to the synthesis of amides in excellent yields. A radical mechanism of the type shown in Scheme 4 is proposed based upon the inhibition of the reaction in the presence of TEMPO.     

Development of radical addition-cyclization-elimination reaction of oxime ether and its application to formal synthesis of (±)-martinelline

Radical addition-cyclization-elimination (RACE) reaction of oxime ether carrying unsaturated ester provides a novel method for the construction of pyrroloquinoline. Treatment of oxime ethers with Bu₃SnH and AIBN gave N-norpyrroloquinoline as a major product, which was also obtained by the radical reaction of the corresponding hydrazone and imine. The radical reaction of aldehyde and ketone carrying unsaturated ester proceeded stereoselectively to give cis-furoquinolines and cis-hydroxyesters. The RACE reactions by using each of Bu₃SnNMe₂, Bu₃SnD, and/or D₂O were also examined in order to propose a reaction pathway to N-norpyrroloquinoline. Furthermore, the synthetic utility of RACE reaction is demonstrated by preparation of a key intermediate for the synthesis of (±)-martinelline.     

Enantioselective Radical‐Polar Crossover Reactions of Indanonecarboxamides with Alkenes

Highly efficient asymmetric intermolecular radical‐polar crossover reactions were realized by combining a chiral N,N′‐dioxide/Ni^II complex catalyst with Ag₂O under mild reaction conditions. Various terminal alkenes and indanonecarboxamides/esters underwent radical addition/cyclization reactions to afford spiro‐iminolactones and spirolactones with good to excellent yields (up to 99 %) and enantioselectivities (up to 97 % ee). Furthermore, a range of different radical‐mediated oxidation/elimination or epoxide ring‐opening products were obtained under mild reaction conditions. The Lewis acid catalysts exhibited excellent performance and precluded the strong background reaction.