Sulfinyl Carbanion Research Articles

Stereocontrolled Addition of Scrambling ortho-Sulfinyl Carbanions: Easy Access to Homopropargylamines and α-Allenylamines.

An unprecedented behavior of ortho-sulfinylpropargyl carbanions in the presence of optically active sulfinylimines affords two different families of compounds: this peculiar chemodivergency is importantly affected by the nature of the employed base, and assisted by the configuration of the electrophile, displaying no alteration in the stereocontrol of both reactions. α-Allenylamines are formed exclusively, using R-sulfinyl aldimines as electrophiles, while homopropargylamines result when S-sulfinyl aldimines are employed.

Asymmetric Synthesis of Secondary and Tertiary Propargylic Alcohols by Umpolung of Acetylenic Sulfones and ortho-Sulfinyl Carbanions.

The generation of diastereomerically enriched secondary benzyl propargyl alcohols by the asymmetric addition of ortho-sulfinylbenzyl carbanions to sulfonylacetylene derivatives via formation of a Csp-Csp3 bond is described. This reaction proceeds through an unusual α-attack (anti-Michael addition) of the ortho-sulfinylbenzyl carbanions, followed by elimination of the arylsulfonyl moiety. The scope of this alkynylation reaction is also discussed. Moreover, the development of a new approach for the synthesis of optically active tertiary benzylpropargyl alcohols is described, discussing the possible stereocourse of the reaction so as the influence of the ether 18-crown-6 and steric importance of acetylenic substituent.

ChemInform Abstract: A General Synthesis of 5-Alkylidene-4-hydroxy-2-cyclopentenones.

Abstract A new general method for the preparation of 5-alkyidene-4-hydroxy-2-cyclopentenones, involving the intramolecular acylation of α- sulfinyl carbanion followed by flash vacuum pyrolysis, is described.

ChemInform Abstract: Role of Heterocycles on the Stereoselective Reactions of α- Sulfinyl Carbanions Using Optically Active 2-Pyridylmethyl p-Tolyl and 2-(N-Methylimidazolyl)methyl p-Tolyl Sulfoxides with Aldehydes.

Optically active 2-pyridylmethyl p-tolyl (1) and 2-(N-methylimidazolyl)methyl p-tolyl sulfoxides (2) were synthesized and the reactions of their chiral α-sulfinyl carbanions with aldehydes afforded stereoselectively the condensation products. The absolute configurations of the products were determined by X-ray crystallographic analysis and chemical reactions. The mechanism for the reactions is described

ChemInform Abstract: Direct Transformations of Ketones to γ-Unsaturated Thiols via [2,3]-Sigmatropic Rearrangement of Allyl Sulfinyl Carbanions: A Combined Experimental and Computational Study.

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Reactivity of lithium 2,3-dihydro-1-benzothiophene-1-oxide toward aldehydes and imines and DFT calculations

The sulfinyl carbanion derived from 2,3-dihydro-1-benzothiophene-1-oxide and its lithium salt has been investigated by DFT calculations. The lithium carbanion was treated with aldehydes and imines to give chiral hydroxy and amino derivatives, with high stereoselectivity at the carbon α to the sulfoxide group (trans diastereoisomers), but with low diastereoselectivity at the hydroxyl or amine group. DFT calculations were used to rationalize the different stereochemical behavior of cyclic and acyclic lithiated sulfoxides in the reaction with aldehydes and azomethines.

Aromatic azo-polyamide electrolyte with liquid crystal structure and photoelectrical properties

A dissoluble aromatic azo-polyamide electrolyte containing azobenzene derivatives in the main-chain is successfully prepared by ionizing amide nitrogens of poly( p-phenylene, 4,4′-azobenzene phthalamide) (Azo-PA) with the sodium methyl sulfinyl carbanion. The conductometric titration measurement shows that 95–98 mol.% of amide nitrogens were converted into anions. Orthogonal polarizing optical microscope images and UV–vis spectra reveal that this Azo-PA anion solution has formed a kind of lytropic liquid crystal structure in anhydrous dimethyl sulfoxide (DMSO) and represents great photoresponsive properties. The Azo-PA formed typical spherocrystal structure after precipitating from the solution when came across water. The photoelectrical properties are investigated by a precise digital conductance instrument and a ZF-7A UV-light examining lamp which can produce 365 nm UV-light. The results indicate that the conductivity value increases by a factor of 0.300–0.320 ms/cm upon UV irradiation and comes back to the initial value under visible light.

Synthesis of 4‐Aminotropones from [(Sulfinyl or Sulfonyl)methyl]‐Substituted p‐Quinamines

An efficient synthesis of 4-aminotropones has been achieved in excellent yields by simple treatment of 4-amino-4-[(p-tolylsulfinyl)methyl]-2,5-cyclohexadienones (p-quinamines) with NaH. The method allowed regiocontrolled access to 3-methyl, 5-methyl- and 3,5-dimethyl-substituted derivatives starting from p-quinamines with adequate substituents at the cyclohexadienone moiety and/or at the carbon linked to the sulfur function. The p-quinamines in turn were easily accessible from N-Boc p-anisidines (Boc=tert-butoxycarbonyl) by electrochemical oxidation in MeOH to quinone imine monoketals, followed by addition of a alpha-lithium sulfinyl carbanion to the imino group, and ketal hydrolysis. Oxidation of the sulfoxide gave the sulfonyl-substituted p-quinamines that, upon basic treatment, behave similarly. The p-quinamine 55 and bis-p-quinamine 56, resulting in the addition of the anion derived from dimethyl sulfone to the p-quinonimine ketal 14, also gave the 4-aminotropone. The mechanism involves the initial formation of a alpha-sulfonyl carbanion, which intramolecularly attacks the cyclohexadienone giving a norcaradiene-like enolate intermediate, the evolution of which through a ring-expansion process, pushes off a methyl sulfinate anion or SO2. This efficient process fulfils the criteria of atom economy. The introduction of a proline substituent in the nitrogen of the starting p-quinamine allowed the synthesis of an enantiopure 4-aminotropone, the asymmetric Diels-Alder reactions of which with maleimide occurred in a highly endo and pi-facial diastereoselective manner.

Deletion of Cg-emb in Corynebacterianeae Leads to a Novel Truncated Cell Wall Arabinogalactan, whereas Inactivation of Cg-ubiA Results in an Arabinan-deficient Mutant with a Cell Wall Galactan Core

The cell wall of Mycobacterium tuberculosis has a complex ultrastructure that consists of mycolic acids connected to peptidoglycan via arabinogalactan (AG) and abbreviated as the mAGP complex. The mAGP complex is crucial for the survival and pathogenicity of M. tuberculosis and is the target of several anti-tubercular agents. Apart from sharing a similar mAGP and the availability of the complete genome sequence, Corynebacterium glutamicum has proven useful in the study of orthologous M. tuberculosis genes essential for viability. Here we examined the effects of particular genes involved in AG polymerization by gene deletion in C. glutamicum. The anti-tuberculosis drug ethambutol is thought to target a set of arabinofuranosyltransferases (Emb) that are involved in arabinan polymerization. Deletion of emb in C. glutamicum results in a slow growing mutant with profound morphological changes. Chemical analysis revealed a dramatic reduction of arabinose resulting in a novel truncated AG structure possessing only terminal arabinofuranoside (t-Araf) residues with a corresponding loss of cell wall bound mycolic acids. Treatment of wild-type C. glutamicum with ethambutol and subsequent cell wall analyses resulted in an identical phenotype comparable to the C. glutamicum emb deletion mutant. Additionally, disruption of ubiA in C. glutamicum, the first enzyme involved in the biosynthesis of the sugar donor decaprenol phosphoarabinose (DPA), resulted in a complete loss of cell wall arabinan. Herein, we establish for the first time, (i) that in contrast to M. tuberculosis embA and embB mutants, deletion of C. glutamicum emb leads to a highly truncated AG possessing t-Araf residues, (ii) the exact site of attachment of arabinan chains in AG, and (iii) DPA is the only Araf sugar donor in AG biosynthesis suggesting the presence of a novel enzyme responsible for "priming" the galactan domain for further elaboration by Emb, resulting in the final maturation of the native AG polysaccharide.

A New Synthesis of Allyl Sulfoxides via Nucleophilic Addition of Sulfinyl Carbanions to Group 6 Fischer Carbene Complexes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A New Synthesis of Allyl Sulfoxides via Nucleophilic Addition of Sulfinyl Carbanions to Group 6 Fischer Carbene Complexes

[reaction: see text] A novel synthesis of allyl sulfoxides has been developed. Primary alpha-lithiosulfinyl carbanions react with group 6 Fischer carbene complexes to give allyl sulfoxides as products. The Fischer carbene complex experiments involve a 1,2-addition of two molecules of sulfinyl carbanion to give an intermediate that, after a beta-elimination, furnishes the mentioned product.

Direct transformations of ketones to gamma-unsaturated thiols via

The reaction of a series of ketones with dimsylsodium in dimethyl sulfoxide resulting in the formation of gamma-unsaturated thiols was studied experimentally. [2,3]-Sigmatropic rearrangements of beta-unsaturated sulfinyl carbanions are involved at the key step of those transformations. DFT computations at the B3LYP/6-31+G level indicated that such rearrangements, as well as some typical [2, 3]-sigmatropic rearrangements, e.g., thermal rearrangements of allyl sulfoxides and Wittig rearrangements of sulfur ylides and lithiated allyloxy methyl anions, are concerted and moderately synchronous processes. Negative (diatropic) nucleus-independent chemical shifts (NICS) and high diamagnetic susceptibility exaltations indicate that the transition structures of these [2,3]-sigmatropic migrations are aromatic.

Detection of DNA and globin adducts of polynuclear aromatic hydrocarbon diol epoxides by gas chromatography-mass spectrometry and -3H-CH3I postlabeling of released tetraols.

Gas chromatography-negative ion chemical ionization mass spectrometry--selected ion monitoring (GC-NICI-MS-SIM) was employed to detect tetramethyl ether derivatives of tetraols formed upon hydrolysis of DNA and globin adducts derived from diol epoxides of benzo[a]-pyrene (BP) and other polynuclear aromatic hydrocarbons (PAH). The tetramethyl ether derivatives could also be detected by [3H]CH3I postlabeling. The methodology involves the following steps: (1) isolation of DNA or globin; (2) mild acid hydrolysis under vacuum; (3) isolation of the resulting tetraols and derivatization to the corresponding tetramethyl ethers using methyl sulfinyl carbanion and unlabeled or 3H-labeled CH3I; (4) analysis by GC-NICI-MS-SIM or HPLC with radioflow detection. The optimum conditions for hydrolysis of adducts and derivatization of the resulting tetraols as well as the feasibility of this approach for detecting PAH adducts in mice and humans were explored. Using the set of four BP-tetraols that can be formed upon hydrolysis of adducts formed from r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) or r-7,t-8-dihydroxy-c-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (syn-BPDE) as models, the stability of the tetraols under the hydrolysis conditions was investigated. Adducts derived from anti-BPDE yield predominantly the stable r-7,t-8,9-c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (trans-anti-BP-tetraol), while adducts derived from syn-BPDE released cis-syn-BP-tetraol as a major hydrolysis product. Hydrolysis under vacuum significantly increased the recovery of tetraols. Conditions for derivatization of the BP-tetraols as well as tetraols derived from several other PAH anti-diol epoxides were investigated. Tetramethyl ethers proved to be superior derivatives that were stable, easy to prepare in high yields, and detectable with high sensitivity by GC-NICI-MS-SIM (1-50 fmol per injection). Alternatively, these derivatives could be detected by HPLC with radioflow detection if [3H]CH3I were employed for derivatization. The methodology was tested by comparing levels of DNA and globin adducts in mice treated with either unlabeled or 3H-labeled BP. Good agreement was obtained among the GC-NICI-MS-SIM, [3H]CH3I postlabeling, and conventional radiometric methods. Moreover, analysis of human hemoglobin by GC-NICI-MS-SIM resulted in detection of adducts derived from anti-BPDE and r-1,t-2-dihydroxy-t-3,4-epoxy-1,2,3,4-tetrahydrochrysene. The results of this study demonstrate that GC-NICI-MS-SIM of tetramethyl ethers of tetraols formed by hydrolysis of PAH diol epoxide DNA and globin adducts is a promising approach for detection and quantitation of adducts derived from a broad range of PAH.

Recent Developments in Organic Synthesis with 1-Haloalkyl Aryl Sulfoxides

This account deals with recent developments in organic synthesis with 1-haloalkyl aryl sulfoxides, especially with 1-chloroalkyl aryl sulfoxides. 1-Chloroalkyl aryl sulfoxides are quite easily prepared from alkyl aryl sulfides. Sulfinyl carbanions and sulfinylated carbon radicals can easily be generated from 1-chloroalkyl aryl sulfoxides. The sulfinyl carbanions were added to carbonyl compounds to give the adducts, from which various kinds of new carbonyl compounds with carbon homologation were synthesized. Optically active 1-chloroalkyl p-tolyl sulfoxides were obtained from optically active (-)-chloromethyl p-tolyl sulfoxide. Asymmetric syntheses of epoxides, α-amino aldehydes, aziridines, α-hydroxy acids and their derivatives, and propargylic alcohols were realized starting from the optically active (-)-1-chloroalkyl p-tolyl sulfoxides. 1.Introduction 2.Synthesis of 1-Haloalkyl Aryl Sulfoxides 3.Organic Synthesis with 1-Haloalkyl Aryl Sulfoxides 4.Organic Synthesis with Sulfinyloxiranes 4.1.Reaction of Sulfinyloxiranes under Heating or with Lewis Acids 4.2.Reaction of Sulfinyloxiranes with Benzeneselenolate and Thiolates 4.3. Reaction of Sulfinyloxiranes with Amines, Cesium Acetate, and Metal Halides 4.4. Reaction of Sulfinyloxiranes with Alkylmetals 5.Asymmetric Synthesis with Optically Active (-)-1-Chloroalkyl p-Tolyl Sulfoxides 5.1. Preparation of Optically Active Sulfinyloxiranes and a Synthesis of Optically Active Epoxides, α-Amino Aldehydes, and Aziridines 5.2. Asymmetric Synthesis of Both Enantiomers of α-Hydroxy Acids, Esters, Amides, and Propargylic Alcohols 6. Conclusion

Synthesis, pharmacological effects, and conformation of 4,4-disubstituted 1,4-dihydropyridines

4,4-Disubstituted 1,4-dihydropyridines are synthesized by intramolecular addition of sulfinyl carbanions to pyridines. These disubstituted derivatives show a loss of Ca antagonistic potency of up to three powers of 10 both in vitro on aortic rings and in vivo on anaesthetized dogs as compared to examples that are monosubstituted at the 4-position of the DHP ring. As the X-ray structure shows, the 4-aryl substituent is present not in the accustomed axial conformation, but in an equatorial one. This dramatic change in conformation could be the reason for the major loss of activity and would indicate the need for axial conformation of the aryl residue in pharmacologically active 1,4-dihydropyridines. The change in conformation was also confirmed by quantum chemical calculations (AM1).

A general synthesis of 5-Alkylidene-4-hydroxy-2-cyclopentenones

A new general method for the preparation of 5-alkyidene-4-hydroxy-2-cyclopentenones, involving the intramolecular acylation of α- sulfinyl carbanion followed by flash vacuum pyrolysis, is described.

Sulfoxides

The most common route to sulfoxides is the oxidation of the corresponding sulfide. This oxidation can be achieved by virtually every class of oxidants. The difficulty is to avoid overoxidation to the sulfone—a step that often occurs with almost the same facility as the first oxidation. A number of other reagents that have been used for the oxidation of sulfides to sulfoxides include iodosobenzene, chromic acid, nitric acid, ozone, and dinitrogen tetraoxide. The last is used in a catalytic cycle for the air oxidation of dimethyl sulfide in industrial processes for di-methyl sulfoxide. Nonoxidative methods for the preparation of sulfoxides include the elaboration of sulfinyl carbanions by addition of electrophiles and the reaction of sulfinyl chlorides with reactive carbon nucleophiles, for example, silylenol ethers. The most important nonoxidative process is the Andersen synthesis of optically pure sulfoxides by the reaction of Grignard reagents with optically pure menthyl sulfinates.

Intramolecular acylation of [formula omitted]-sulfinyl carbanion: A new general route to 5-substituted Δ 2 cyclopentenones

A general method for the preparation of 5-substituted Δ 2-cyclopentenones via the intramolecular acylation of αot -sulfinyl carbanions has been demonstrated.

High-performance liquid chromatographic mass spectrometric examination ofC-methylation artifacts from the permethylation reaction of peptides

Combined high performance liquid chromatography mass spectrometry using a moving belt interface was used to investigate C-methylation artifacts arising from the permethylation reaction of peptides with methyl sulfinyl carbanion and methyl iodide. C-Methylation was not limited to glycine but, depending on the reaction conditions, other amino acids were also susceptible to it. In the absence of a glycine residue, preference for C-methylation of the C-terminus amino acid was observed. The use of on-line high performance liquid chromatography mass spectrometry allowed the separation of N, O, C-methylated from the N, O, S-permethylated derivatives, thus facilitating interpretation of the mass spectra.

Reactions of sulfinyl carbanions with organometallic compounds: Preparation of (η 5-C 5H 5) 2T [formula omitted]6H 4

Sulfinyl carbanions, [RS(O)CHR′] −Li + (R = Ph, Me; R′ = H, Ph) have been observed to have often low reactivity towards neutral transition metal organometallic systems. When reactions do occur they usually involve salt eliminations and formation of complex mixtures containing inter alia organic sulfides, disulfides, freed ligands or their oxides and reduced forms of the organometallic reactants. From the sulfinyl ylide [PhS(O)CH 2]Li, exo-[η 5-C 6H 6CH 2S(O)Ph]Mn(CO) 3 and the new metallocyclic compound (η 5-C 5H 5) 2TiCH 2SC 6H 4 have been prepared, some properties of the latter examined and its sulfonium derivative [(η 5-C 5H 5) 2 TiCH 2S(Me)C 6 H 4]BF 4 isolated.