Studies on hydrozirconation of 1-alkynyl sulfoxides or sulfones and the application for the synthesis of stereodefined vinyl sulfoxides or sulfones

The hydrozirconation reaction of 1-alkynyl sulfoxides or sulfones with Cp2Zr(H)Cl in THF at room temperature predominantly gave Z-beta-zirconated vinyl sulfoxides or sulfones with excellent regioselectivity. Compared with 1-alkynyl sulfoxides, the hydrozirconation reaction of 1-alkynyl sulfones exhibits great synthetic potential, leading to the efficient preparation of Z-beta-halovinyl sulfones, Z-beta-sulfonyl alpha,beta-unsaturated ketones, and Z-beta-alkynyl vinyl sulfones. Although the reaction mechanisms are still not clear, the neighboring group participation of the sulfinyl or sulfonyl group may be playing an important role in this unique hydrozirconation reaction.     

TMSCl-promoted selective oxidation of sulfides to sulfoxides with hydrogen peroxide

Selective oxidation of sulfides to sulfoxides is achieved using H₂O₂ and TMSCl as the promotor. Aromatic and aliphatic sulfides are oxidized to sulfoxides in excellent yields and in short reaction times. Different functional groups including ketone, alkene, ester, and alcohol are tolerated.     

A general and selective zinc-catalyzed oxidation of sulfides to sulfoxides

A general zinc-catalyzed oxidation of sulfides to sulfoxides has been developed. All the reactions proceeded at room temperature. Hydrogen peroxide was used as a green oxidant. Twenty-one examples of sulfoxides were prepared in moderate to excellent yields.     

Gas chromatographic determination of S-alk(en)ylcysteine sulfoxides

A new GC method for determination of S-alk(en)ylcysteine sulfoxides, important secondary metabolites occurring in many plant genera, has been developed. The method is based on isolation of the amino acid fraction by ion-exchange chromatography followed by derivatization with ethyl chloroformate at ambient temperature and reduction of derivatized S-alk(en)ylcysteine sulfoxides by sodium iodide. The main advantages of the new method are its high sensitivity, excellent resolution capability, accuracy and reliability, as well as the possibility to identify unknown compounds by means of GC-MS. The content of alliin and other S-alk(en)ylcysteine sulfoxides was determined in nine different samples of garlic (Allium sativum L.) originating from the Czech Republic, France, and China. The total content of S-alk(en)ylcysteine sulfoxide pool ranged between 0.53 and 1.3% fresh weight, with S-allylcysteine sulfoxide (alliin) being predominant. A novel S-alkylcysteine derivative, S-ethylcysteine sulfoxide (ethiin), not previously reported to occur in Allium species, was found in some of the samples examined.     

Oxidative kinetic resolution of heterocyclic sulfoxides with a porphyrin-inspired manganese complex by hydrogen peroxide

We have successfully reported here the low loading porphyrin-inspired high-valent manganese (IV)-oxo complex was applied in oxidative kinetic resolution (OKR) of racemic heterocyclic sulfoxides using the environmentally benign hydrogen peroxide for the first time. This approach allows for rapid OKR (0.5?h) of a variety of racemic sulfoxides (including pyridine, pyrimidine, pyrazine, thiazole, benzothiazole, thiophene) in excellent enantioselectivity (up to?>?99%?ee), simultaneously generating the corresponding sulfones in high yield (up to 80%). The catalytic system also showed an unexceptionable chemoselectivity for the sulfoxide substrates with hydroxyl groups in which only the sulfoxide group was oxidized. The practical utility of the method has been demonstrated in the OKR of gram-scale sulfoxides.     

Highly efficient and chemoselective reduction of sulfoxides using the system silane/oxo-rhenium complexes

This work reports a novel method for the reduction of sulfoxides with silanes catalyzed by high valent oxo-rhenium(V) and (VII) complexes. The catalytic system PhSiH₃/ReIO₂(PPh₃)₂ (1 mol %) proved to be highly efficient for the reduction of a wide range of sulfoxides in excellent yields under mild conditions. This novel methodology is also highly chemoselective, tolerating several functional groups such as –CHO, –CO₂R, –Cl, –NO₂, and double or triple bonds.     

Cross-metathesis reaction of vinyl sulfones and sulfoxides

Cross-metathesis reactions of α,β-unsaturated sulfones and sulfoxides in the presence of molybdenum and ruthenium pre-catalysts were tested. A selective metahesis reaction was achieved between functionalized terminal olefins and vinyl sulfones by using the ‘second generation’ ruthenium catalysts 1c-h while the highly active Schrock catalyst 1b was found to be functional group incompatible with vinyl sulfones. The cross-metathesis products were isolated in good yields with an excellent (E)-selectivity. Both the molybdenum and ruthenium-based complexes were, however, incompatible with α,β- and β,γ-unsaturated sulfoxides.     

Nucleophilic epoxidation of alpha'-hydroxy vinyl sulfoxides

The nucleophilic epoxidation of a variety of alpha'-(1-hydroxyalkyl) vinyl sulfones and sulfoxides has been studied. The sulfones give rise to anti oxiranes with modest (E) or excellent (Z) selectivities and in good yields. The (E)-sulfoxides display low reactivity within a reinforcing/nonreinforcing scenario. The use of t-BuOOLi in Et(2)O allows for a highly syn-selective epoxidation-oxidation. The (Z)-sulfoxides display a remarkably high reactivity under these conditions. The reinforcing (S,S(S)) diastereomers (3e-g) yield hydroxy sulfinyl oxiranes with high yields and selectivities. In contrast, the (R,S(S)) diastereomers (4e-g) show diminished reactivities and a very substrate-dependent stereochemical outcome. The structure of these oxiranes has been secured by chemical correlations and an X-ray crystal structure.     

Synthesis of functionalized allylic sulfoxides and their use in the construction of 2,3,4-trisubstituted furans via a [3 + 2] annulation

A route to 2,3,4-trisubstituted furan derivatives based on a [3 + 2] annulation of functionalized allylic sulfoxides and aldehydes is described. In this strategy, the precursors of allylic sulfoxides 4, allylic sulfides 3, were synthesized via a thiomethylation reaction of an alpha-EWG ketene-S,S-acetal 1 (EWG: electron-withdrawing group), formaldehyde, and a thiol 2 in high to excellent yields. Allylic sulfoxides 4 were prepared by a highly regioselective oxidation of 3, using m-chloroperoxybenzoic acid as oxidant. Thus, starting from these readily available sulfoxides 4, 2-alkylthio-3,4-disubstituted furans 6 were efficiently constructed via the [3 + 2] annulation reaction of 4 with aldehydes 5 under mild conditions. Further replacement of the 2-alkylthio group of 6 with amines led to the formation of 2-amino-3,4-disubstituted furan derivatives 7.     

Sulfoxide-controlled S(N)2' displacements between cyanocuprates and epoxy vinyl sulfoxides

Two short and convergent routes have been devised for the preparation of enantiomerically pure acyclic epoxy vinyl sulfoxides. These substrates undergo highly regio- and stereoselective S(N)2' displacements with lithium cyanocuprates to give alpha'-alkylated, gamma-oxygenated Z alpha,beta-unsaturated sulfoxides in moderate to good yields and with good to excellent diastereoselectivities. The absolute configuration of the newly formed carbon-carbon bond is primarily controlled by the chiral sulfur atom, which in a nonreinforcing situation can override the intrinsic anti tendency of the vinyl oxirane moiety and forces the cuprate to undergo syn addition. The hydroxy vinyl sulfoxide functionality of the resulting adducts should allow for subsequent asymmetric transformations thus enhancing the synthetic usefulness of this methodology.     

Nucleophilic ortho allylation of aryl and heteroaryl sulfoxides

Aryl and heteroaryl sulfoxides undergo ortho allylation upon treatment with Tf(2)O and allylsilanes. The method complements the use of sulfoxides to direct ortho-metalation and reaction with electrophiles as it allows allylic carbon nucleophiles to be added ortho to the directing group in a metal-free process. The versatile sulfide adducts can be selectively manipulated using various methods including Kumada-Corriu cross-coupling of the organosulfanyl group.     

Hydrotelluration and carbotelluration of acetylenic sulfoxides: regio- and stereoselective preparation of α- and β-organotellurovinyl sulfoxides

(Z)-β-Organotellurovinyl sulfoxides were synthesized via a highly regio- and stereoselective anti-hydrotelluration of acetylenic sulfoxides. α-Organotellurovinyl sulfoxides were obtained from a three component syn-carbotelluration reaction of acetylenic sulfoxides, that is, syn-addition of monoorganocopper reagents to acetylenic sulfoxides followed by the electrophilic reaction of the vinyl copper intermediates with benzenetellurenyl iodide at low temperature. Synthetic applications of the organotellurovinyl sulfoxides have been investigated.     

The syntheses of sulfides by deoxygenation of sulfoxides using Woollins’ reagent

Woollins’ reagent (WR) acts as a deoxygenation reagent for a wide range of sulfoxides affording the corresponding sulfides in good to excellent yields (up to 99% isolated yield) under mild conditions.     

Two-dimensional NMR studies of 2-substituted thioxanthene sulfoxides

2-Fluoro-, 2-chloro-, 2-bromo-, 2-methyl-, and 2-methoxythioxanthene have been prepared by borane reduction of the corresponding thioxanthone. The corresponding sulfoxides were prepared by m-chloroperoxybenzoic acid oxidation of these sulfides. Proton and carbon chemical shifts have been assigned to these thioxanthene sulfoxides with the aid of LROCSCM and SROCSCM experiments. Carbon chemical shifts in the unsubstituted rings occur at approximately 125 ppm (C5); 128 ppm (C6); 130 ppm (C7); 128 ppm (C8); and 36 ppm (C9). The methylene protons appears as AB doublets at approximately 4.2 and 3.8 ppm. All sulfoxides have the same, pseudo-equatorial geometry.     

Remarkably mild and simple preparation of sulfenate anions from beta-sulfinylesters: a new route to enantioenriched sulfoxides

[reaction: see text] A general, efficient, and experimentally simple method for the generation of sulfenate salts has been developed using beta-sulfinylesters as substrates. The process is based on a retro-Michael reaction, initiated by deprotonation at low temperature. Upon treatment with alkyl halides, the liberated sulfenates are subsequently converted into sulfoxides in good to excellent yield. Extension of the methodology to an unprecedented access to nonracemic sulfoxides by introduction of an enantiopure ligand, (-)-sparteine, is also described.     

Reduction of sulfoxides with boranes catalyzed by MoO2Cl2

The first example of an organic reduction with boranes catalyzed by a high valent oxo-complex is reported. The systems catecholborane/MoO₂Cl₂(H₂O)₂ (5 mol %) and BH₃·THF/MoO₂Cl₂ (5 mol %) proved to be very efficient for the reduction of sulfoxides to the corresponding sulfides in excellent yields.     

Development of new synthetic methods with aryl 1-chlorovinyl sulfoxides

Aryl 1-chlorovinyl sulfoxides were easily synthesized from ketones and aldehydes with aryl chloromethyl sulfoxide in three-steps with high overall yields. Low-temperature treatment of the aryl 1-chlorovinyl sulfoxides with alkyllithium or a Grignard reagent gave alkylidene carbenoids via a sulfoxide-metal exchange reaction. From the alkylidene carbenoids, acetylenic compounds, tetra-substituted olefins, and allenes were synthesized. Enolization of alpha-chloro alpha-sulfinyl ketones, which were synthesized from methyl esters and chloromethyl phenyl sulfoxide, is another method for the generation of aryl 1-chloroalkyl sulfoxides. Treatment of 1-chlorovinyl phenyl sulfoxides so generated with t-BuLi followed by some nucleophiles having an acidic hydrogen gave one-carbon elongated carboxylic acids and their derivatives. Conjugate addition of some carbanions with 1-chlorovinyl p-tolyl sulfoxides was found to have taken place. For example, reaction of 1-chlorovinyl p-tolyl sulfoxides with cyanomethyllithium gave high yields of cyclic enaminonitriles. Acidic treatment of the enaminonitriles afforded good yields of 4,4-disubstituted 2-cyclopentenones. By using unsymmetrical ketones and optically pure chloromethyl p-tolyl sulfoxide, this procedure suggests a good method for an asymmetric synthesis of optically pure 4,4-disubstituted 2-cyclopentenones. This method achieved an asymmetric total synthesis of (+)-alpha-cuparenone starting from methyl 4-methylphenyl ketone and (R)-(-)-chloromethyl p-tolyl sulfoxide. A novel synthesis of 2,4,4-trisubstituted 2-cyclopentenones is also successful using cyanomethyllithium and its homologues. Conjugate addition of the lithium enolate of tert-butyl acetate and its homologues gave high yields of the adduct, 3,3-disubstituted esters. Synthesis of various kinds of carboxylic acids and their derivatives and lactones was realized from the adducts.     

The conformation of alkyl sulfoxides

Parameters for sulfoxides used in force field MM1 were modified to be incorporated into force field MM2. The conformations of ten alkyl sulfoxides were then calculated using MM2 with these new parameters. The alkyl groups used were methyl, ethyl, isopropyl, and t-butyl. It was found that of the many possible conformations for these compounds, only one or two stable conformers exist, and that the number of these conformers agrees with the number of reported S? O stretching frequencies in almost every case. No apparent correlation between the vibration frequency and the molecular structure was found.     

Silver-catalyzed imination of sulfoxides and sulfides

[reaction: see text] Silver salts in the presence of a chelating ligand efficiently catalyze the stereospecific imination of sulfoxides and sulfides with sulfonylamides and PhI(OAc)(2) to afford sulfoximines and sulfilimines, respectively, in good yields.     

Fe2O3-catalyzed Pummerer rearrangement of acyl chlorides and sulfoxides: Facile synthesis of alkylthiomethyl ester

A simple, effective approach for the Pummerer rearrangement of acyl chlorides with sulfoxides by using a low-cost and more abundant Fe catalyst has been described. The alkylthiomethyl ester products were prepared in good to excellent yields for a range of different substrates including asymmetrical sulfoxides and acyl chlorides with a variety of functional groups under mild reaction conditions. The reaction features short reaction time, simple manipulation, cheap reagents and a broad substrate scope. Single crystal X-ray analysis of a representative methylthiomethyl (MTM) group containing product was also reported.