Highly stereoselective synthesis of functionalized beta,beta-di- and trisubstituted vinylic sulfoxides by Cu-catalyzed conjugate addition of organozinc reagents

beta,beta-Disubstituted chiral vinylic sulfoxides bearing functionalities have been synthesized via Cu-catalyzed conjugate addition of organozinc reagents to chiral 1-alkynyl sulfoxides. Due to the availability of functionalized organozinc reagents and high syn-selectivity of the reaction, both geometric beta,beta-disubstituted vinylic sulfoxides were selectively synthesized. Furthermore, 1-alkynyl sulfoxides were derivatized into trisubstituted vinylic sulfoxides by trapping the resulting alpha-sulfinyl vinylic carbanion with electrophiles. Highly diastereoselective THF and THP ring formations were accomplished by means of this methodology followed by an intramolecular Michael addition.     

THE REACTION OF ANHYDROUS HCI/CHLOROFORM WITH DIARYL SULFOXIDES

Abstract

The reaction of variously substituted diaryl sulfoxides with anhydrous HCl in chloroform was examined. The products ranged from the corresponding sulfides to mono- and dichlorinated sulfides and sulfoxides. The same reaction in the presence of phenol afforded primarily the corresponding sulfides accompanied by o- and p-chlorophenol. The latter reaction is an efficient means for deoxygenating diaryl sulfoxides. The mechanism of the reaction and the nature of the chlorinating species are discussed.     

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.     

Diaryl Sulfoxides from Aryl Benzyl Sulfoxides: A Single Palladium‐Catalyzed Triple Relay Process

A novel approach to produce diaryl sulfoxides from aryl benzyl sulfoxides is reported. Optimization of the reaction conditions was performed using high‐throughput experimentation techniques. The [Pd(dba)₂]/NiXantPhos catalyst system successfully promotes a triple relay process involving sulfoxide α‐arylation, C? S bond cleavage, and C? S bond formation. The byproduct benzophenone is formed by an additional palladium‐catalyzed process. It is noteworthy that palladium‐catalyzed benzylative C? S bond cleavage of sulfoxides is unprecedented. A wide range of aryl benzyl sulfoxides, as well as alkyl benzyl sulfoxides with various (hetero)aryl bromides were employed in the triple relay process in good to excellent yields (85–99 %). Moreover, aryl methyl sulfoxides, dibenzyl sulfoxides, and dimethylsulfoxide could be utilized to generate diaryl sulfoxides involving multiple catalytic cycles by a single catalyst.     

Molecular transformations of unsaturated thiacrown ethers

Unsaturated thiacrown ethers with 15, 18, and 21 members were oxidized to sulfoxides by the reaction with m-CPBA. The reaction with t-BuOCl at -20 degrees C also afforded sulfoxides, whereas the reaction at room temperature yielded cis-trans isomerized compounds. The cis-trans isomerized compound was also obtained by the photochemical reaction or by the reaction with NCS and NCP. Meanwhile, the reaction with NBS and NBP provided an acetal via 1,2-bridged bromonium intermediate.     

cis-Carbocuperation of acetylenic sulfoxides and corresponding applications in the regio- and stereoselective synthesis of polysubstituted vinyl sulfoxides

cis-Carbocuperation reaction of monoorganocopper reagent with acetylenic sulfoxides, followed by electrophilic reaction with a variety of electrophiles, provided a regio- and stereoselective method to prepare the versatile polysubstituted vinyl sulfoxides. Sonogashira cross-coupling reaction of the obtained α-iodovinyl sulfoxides with terminal acetylenes was also investigated to afford the versatile conjugate sulfinyl enynes.     

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.     

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.     

Geometrically selective synthesis of functionalized beta,beta-disubstituted vinylic sulfoxides by Cu-catalyzed conjugate addition of organozinc reagents to 1-alkynyl sulfoxides

[reaction: see text] A new synthetic method of chiral beta,beta-disubstituted vinylic sulfoxides bearing various functionalities has been developed by employing Cu-catalyzed conjugate addition of an organozinc reagent to chiral 1-alkynyl sulfoxide. Since the reaction proceeds with very high syn-selectivity, both geometric beta,beta-disubstituted vinylic sulfoxides were stereoselectively synthesized by changing the combination of 1-alkynyl sulfoxide and the organozinc reagent.     

General route to racemic and enantiomeric carbo- and heterocyclic vinyl sulfoxides via tandem Michael addition/Horner olefination of alpha-phosphorylvinyl sulfoxides

A new one-pot synthesis of heterocyclic and carbocyclic vinyl sulfoxides has been developed which involves reaction of alpha-phosphorylvinyl sulfoxides with carbonyl compounds bearing oxygen, nitrogen, and carbon nucleophilic centers. Use of optically active alpha-phosphorylvinyl p-tolyl sulfoxides in this tandem Michael addition/Horner olefination reaction leads to the corresponding optically active cyclic sulfoxides. In this way, a variety of optically active chromene, pyrrolizine, chinoline, and cyclopentene sulfoxides have been efficiently prepared.     

Alternative approach to the synthesis of optically active β-keto sulfoxides by furylhydroperoxides enantioselective oxidations

Enantiomerically enriched β-keto sulfoxides are obtainable by an alternative method to the classical reaction of the enantiomerically pure α-sulfinyl anion with esters or by Andersen's synthesis, through Sharpless modified kinetic resolution of racemic β-keto sulfoxides. High e.e.s are achieved by combining asymmetric oxidation and kinetic resolution using furylhydroperoxides as oxidants.     

Iron‐Catalyzed Imidative Kinetic Resolution of Racemic Sulfoxides

Kinetic resolution of racemic sulfoxides requires either custom substrates or shows moderate enantioselectivity, leading to achiral coproducts (such as sulfones) as an intrinsic part of the process. A new strategy is demonstrated that allows the resolution of racemic sulfoxides through catalytic asymmetric nitrene‐transfer reactions. This approach gives rise to both optically active sulfoxides and highly enantioenriched sulfoximines. By using a chiral iron catalyst and a readily available iodinane reagent, high selectivity factors have been achieved under very practical reaction conditions. With respect to the substrate scope, it is noteworthy that this unprecedented imidative kinetic resolution of racemic sulfoxides provides access to both aryl–alkyl and dialkyl sulfoximines in highly enantioenriched forms.     

Mechanistic studies on a sulfoxide transfer reaction mediated by diphenyl sulfoxide/triflic anhydride

Sulfoxides are frequently used in organic synthesis as chiral auxiliaries and reagents to mediate a wide variety of chemical transformations. For example, diphenyl sulfoxide and triflic anhydride can be used to activate a wide range of glycosyl donors including hemiacetals, glycals and thioglycosides. In this way, an alcohol, enol or sulfide is converted into a good leaving group for subsequent reaction with an acceptor alcohol. However, reaction of diphenyl sulfoxide and triflic anhydride with oxathiane-based thioglycosides, and other oxathianes, leads to a different process in which the thioglycoside is oxidised to a sulfoxide. This unexpected oxidation reaction is very stereoselective and proceeds under anhydrous conditions in which the diphenyl sulfoxide acts both as oxidant and as the source of the oxygen atom. Isotopic labelling experiments support a reaction mechanism that involves the formation of oxodisulfonium (S-O-S) dication intermediates. These intermediates undergo oxygen-exchange reactions with other sulfoxides and also allow interconversion of axial and equatorial sulfoxides in oxathiane rings. The reversibility of the oxygen-exchange reaction suggests that the stereochemical outcome of the oxidation reaction may be under thermodynamic control, which potentially presents a novel strategy for the stereoselective synthesis of sulfoxides.     

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.     

Non-stereospecific ring expansions of 5-membered heterocyclic sulfoxides

Non-stereospecific ring expansion reactions of 5-membered heterocyclic sulfoxides, 1,3-benzoxathiole sulfoxides, 1,3-benzodithiole sulfoxides, and 1,3-dithiolane sulfoxides having a heteroatom at β-position to the sulfinyl group with acetic anhydride or p-toluenesulfonic acid are described together with thier reaction mechanism involving a sulfonium ion intermediate.     

A Novel Efficient Method for Synthesis of β-Organoseleno Substituted Allyl Sulfoxides

In the last few decades,there has been remarkable interest in the synthesis of vinylic chalcogenides and their synthetic application1.Hydrochalcogenation reaction of electron-deficent C-C triple bond,i.e.1-alkynylphosphonates2,1-alkynylphosphine oxides3,propargylaldehydle4,etc.have become a very powerful tool for the highly stereoselective synthesis of functionalized vinylic chalcogenides.We have reported the anti-hydrotelluration of acetylenic sulfones and acetylenic phosphonates5a,hydrotellu…     

Hydrogenation of Sulfoxides to Sulfides under Mild Conditions Using Ruthenium Nanoparticle Catalysts

The first demonstration of the hydrogenation of sulfoxides under atmospheric H₂ pressure is reported. The highly efficient reaction is facilitated by a heterogeneous Ru nanoparticle catalyst. The mild reaction conditions enable the selective hydrogenation of a wide range of functionalized sulfoxides to the corresponding sulfides. The high redox ability of RuO_x nanoparticles plays a key role in the hydrogenation.     

Cyclopropylation of arylamines at the 2-position with cyclopropylmagnesium carbenoids

Direct cyclopropylation of arylamines at the 2-position with 1-chlorocyclopropyl phenyl sulfoxides was achieved. The reaction of N-lithio arylamines with cyclopropylmagnesium carbenoids, which are generated from 1-chlorocyclopropyl phenyl sulfoxides with i-PrMgCl via the sulfoxide-magnesium exchange reaction, is the key of this procedure. This method offers an unprecedented way for the synthesis of arylamines having a cyclopropane ring at the 2-position directly from arylamines.     

Generation of Glycosyl Radicals from Glycosyl Sulfoxides and Its Use in the Synthesis of C‐linked Glycoconjugates

We here report glycosyl sulfoxides appended with an aryl iodide moiety as readily available, air and moisture stable precursors to glycosyl radicals. These glycosyl sulfoxides could be converted to glycosyl radicals by way of a rapid and efficient intramolecular radical substitution event. The use of this type of precursors enabled the synthesis of various complex C‐linked glycoconjugates under mild conditions. This reaction could be performed in aqueous media and is amenable to the synthesis of glycopeptidomimetics and carbohydrate‐DNA conjugates.     

Pd-catalyzed sulfinylzincation of activated alkynes with 1-alkynyl sulfoxides as a sulfinyl source

Unprecedented Pd-catalyzed sulfinylzincation with 1-alkynyl sulfoxide as a sulfinyl source was developed. Bis-sulfinyl alkenes were formed in good yields on treatment of 1-alkynyl sulfoxides with Et(2)Zn in the presence of a Pd-catalyst, wherein zinc sulfenate (or sulfinylzinc) species would be generated in situ to undergo highly syn-selective conjugate addition to the 1-alkynyl sulfoxides. By using 3,3-dimethyl-1-butynyl sulfoxides, formation of the bis-sulfinyl alkenes was completely suppressed and the sulfinylzincation of activated alkynes was accomplished. The reaction tolerates various functionalities, and was promoted considerably by the neighboring group participation of the heteroatom at the delta-position in the alkynoates. Stereodivergent synthesis of two diastereomeric vinylic sulfoxides and reaction of the resulting vinylzinc species with electrophiles were also described.