1-chlorovinyl P-tolyl Sulfoxides Research Articles

Use of 1-chlorovinyl p-tolyl sulfoxides as alkynylmagnesium chloride sources

A method for generating alkynylmagnesium chlorides from 1-chlorovinyl p-tolyl sulfoxides and an isopropylmagnesium chloride–lithium chloride complex (turbo Grignard reagent) has been developed. The method consists of a sulfoxide/magnesium exchange reaction of 1-chlorovinyl p-tolyl sulfoxides and a turbo Grignard reagent, a Fritsch–Buttenberg–Wiechell rearrangement of the resulting magnesium alkylidene carbenoids, and a deprotonation of terminal alkynes with a turbo Grignard reagent. The resulting alkynylmagnesium chlorides are reacted with a variety of electrophiles to generate internal alkynes.

Fritsch-Buttenberg-Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes.

A series of 1-heteroatom-substituted vinyl p-tolyl sulfoxides were prepared and treated with organometallic reagents to evaluate which combination of sulfoxides and organometallic reagents yielded alkynes the most efficiently. The use of 1-chlorovinyl p-tolyl sulfoxide and isopropylmagnesium chloride was optimal for this purpose. A variety of 1-chlorovinyl p-tolyl sulfoxides were prepared from carbonyl compounds and chloromethyl p-tolyl sulfoxide and were converted into alkynes via the sulfoxide/magnesium exchange reaction and subsequent Fritsch–Buttenberg–Wiechell (FBW) rearrangement of the resulting magnesium alkylidene carbenoids. The mechanism of the FBW rearrangement of magnesium alkylidene carbenoids was studied by using 13C-labeled sulfoxides and by using DFT calculations.

Consecutive reaction of 1-chlorovinyl p-tolyl sulfoxides with [chloro(p-tolylsulfinyl)methyl]lithium leading to the formation of multi-functionalized methylenecyclopropanes

The reaction of 1-chlorovinyl p-tolyl sulfoxides with excess [chloro(p-tolylsulfinyl)methyl]lithium gave methylenecyclopropanes consisting of a chloro(p-tolylsulfinyl)methylene moiety and a (p-tolylsulfinyl)cyclopropylidene moiety. Treating the methylenecyclopropanes with butyllithium resulted in the formation of conjugated enynes.

Efficient Synthesis of Cyclopropanecarboxylic Acid Esters Starting from the Conjugate Addition of Lithium Ester Enolates to 1-Chlorovinyl p-Tolyl ­Sulfoxides

An efficient synthesis of tert-butyl cyclopropanecarboxylates was achieved in three steps using 1-chlorovinyl p-tolyl sulfoxides as key materials. The conjugate addition of lithium ester enolates to the sulfoxides gave tert-butyl 4-chloro-4-(p-tolylsulfinyl)butanoates in high yield. The p-tolylsulfinyl group in the resultant adducts was then removed by the sulfoxide–magnesium exchange reaction with i-PrMgCl at –60 °C. Cyclization of the desulfinylated products, tert-butyl 4-chlorobutanoates, took place in the presence of NaHMDS in a THF–DMPU mixture to afford tert-butyl cyclopropanecarboxylates in good yield. The asymmetric synthesis of both enantiomers of tert-butyl cyclopropanecarboxylate was successfully achieved using optically active (E)- and (Z)-sulfoxides with high enantiomeric excesses.

Coupling Reaction of Magnesium Alkylidene Carbenoids with α-Sulfonyl­allyllithiums: An Efficient Route to Multi-Substituted Vinylallenes

A variety of vinylallenes were successfully synthesized from 1-chlorovinyl p-tolyl sulfoxides and allyl or vinyl sulfones. Allyl and vinyl sulfones served as α-sulfonylallyllithium sources were prepared from carbonyl compounds in three or four steps in good overall yields. The coupling reaction of α-sulfonylallyllithiums with magnesium alkylidene carbenoids, which were generated from 1-chlorovinyl p-tolyl sulfoxides and isopropylmagnesium chloride, afforded multi-substituted vinylallenes in up to 88% yield.

ChemInform Abstract: New Synthesis of Multi‐Substituted α‐Chlorocyclobutanones from 1‐Chloro‐3‐cyanoalkyl p‐Tolyl Sulfoxides by 4‐exo‐dig Nucleophilic Ring Closure of Magnesium Carbenoids to Nitrile Group as the Key Reaction.

1-Chloro-3-cyanoalkyl p-tolyl sulfoxides were easily prepared from 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from carbonyl compounds and chloromethyl p-tolyl sulfoxide, with lithium α-cyano carbanion of acetonitrile derivatives in good yields. Treatment of these sulfoxides with i-PrMgCl resulted in the formation of multi-substituted α-chlorocyclobutanones in good to high yields via the 4-Exo-Dig nucleophilic ring closure of the generated magnesium carbenoid intermediates to the nitrile group. This procedure provides a new and good way for the synthesis of multi-substituted α-chlorocyclobutanones from carbonyl compounds and substituted acetonitriles with formation of three carbon–carbon bonds in relatively short steps.

New synthesis of multi-substituted α-chlorocyclobutanones from 1-chloro-3-cyanoalkyl p-tolyl sulfoxides by 4-Exo-Dig nucleophilic ring closure of magnesium carbenoids to nitrile group as the key reaction

1-Chloro-3-cyanoalkyl p-tolyl sulfoxides were easily prepared from 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from carbonyl compounds and chloromethyl p-tolyl sulfoxide, with lithium α-cyano carbanion of acetonitrile derivatives in good yields. Treatment of these sulfoxides with i-PrMgCl resulted in the formation of multi-substituted α-chlorocyclobutanones in good to high yields via the 4-Exo-Dig nucleophilic ring closure of the generated magnesium carbenoid intermediates to the nitrile group. This procedure provides a new and good way for the synthesis of multi-substituted α-chlorocyclobutanones from carbonyl compounds and substituted acetonitriles with formation of three carbon–carbon bonds in relatively short steps.

New synthesis of multisubstituted cyanocyclopropanes by the intramolecular SN2 alkylation and 1,3-CC insertion reaction of magnesium carbenoids as the key reactions

Addition reaction of 1-chlorovinyl p-tolyl sulfoxides derived from ketones and aldehydes with lithium α-cyano carbanions gave nitrile adducts in high to quantitative yields. Treatment of the nitrile adducts derived from acetonitrile with excess i-PrMgCl in THF resulted in the formation of cyanocyclopropanes via the intramolecular SN2 alkylation of the generated magnesium carbenoids. The intermediate of this reaction was proved to be a cyclopropylmagnesium chloride and was reactive with electrophiles to give multisubstituted cyanocyclopropanes. On the other hand, the reaction of the nitrile adducts derived from arylacetonitriles with i-PrMgCl resulted in the formation of 2-arylcyanocyclopropanes by the 1,3-carbon–carbon (1,3-CC) insertion reaction of the generated magnesium carbenoid intermediates. This reaction was found to proceed in a highly stereospecific manner. The key reactions, intramolecular SN2 alkylation and 1,3-CC insertion reaction of the magnesium carbenoids, are the first examples for the reaction of the magnesium carbenoids bearing a nitrile functional group.

ChemInform Abstract: Synthesis, Including Asymmetric Synthesis, of 1‐Substituted Cyclopentenes from Cyclobutanones with One‐Carbon Ring‐Expansion by 1,2‐Carbon—Carbon Insertion of Magnesium Carbenoids.

ChemInformVolume 42, Issue 23 Isocyclic Compounds ChemInform Abstract: Synthesis, Including Asymmetric Synthesis, of 1-Substituted Cyclopentenes from Cyclobutanones with One-Carbon Ring-Expansion by 1,2-Carbon—Carbon Insertion of Magnesium Carbenoids. Tsuyoshi Satoh, Tsuyoshi Satoh Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorYu Awata, Yu Awata Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorYuichi Kato, Yuichi Kato Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorShingo Ogata, Shingo Ogata Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorMasashi Ishigaki, Masashi Ishigaki Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorShimpei Sugiyama, Shimpei Sugiyama Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorHideki Saitoh, Hideki Saitoh Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this author Tsuyoshi Satoh, Tsuyoshi Satoh Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorYu Awata, Yu Awata Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorYuichi Kato, Yuichi Kato Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorShingo Ogata, Shingo Ogata Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorMasashi Ishigaki, Masashi Ishigaki Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorShimpei Sugiyama, Shimpei Sugiyama Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this authorHideki Saitoh, Hideki Saitoh Grad. Sch. Chem. Sci. Technol., Sci. Univ. Tokyo, Shinjuku, Tokyo 162, JapanSearch for more papers by this author First published: 12 May 2011 https://doi.org/10.1002/chin.201123052Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume42, Issue23June 7, 2011 RelatedInformation

Multisubstituted α,β-Unsaturated γ-Lactones from 1-Chlorovinyl p-Tolyl Sulfoxides and tert-Butyl Carboxylates Using Pummerer-Type Cyclization as the Key Reaction

The addition reaction of 1-chlorovinyl p-tolyl sulfoxides, derived from aldehydes and chloromethyl p-tolyl sulfoxide, with the lithium enolate of tert-butyl carboxylates gave adducts in quantitative yields. Treatment of the adducts with trifluoroacetic anhydride in the presence of sodium iodide resulted in the formation of γ-lactones bearing a p-tolylsulfanyl group at the γ-position through Pummerer-type cyclization. Oxidation of the sulfanyl group to the sulfinyl group followed by thermal syn-elimination gave α,β-unsaturated γ-lactones (γ-butenolides) in moderate to good yields. Trapping the intermediates of the addition reaction with iodoalkanes gave alkylated adducts, from which α,γ- and β,γ-disubstituted γ-butenolides were obtained. These procedures provide a good way to synthesize multisubstituted γ-butenolides from aldehydes.

Synthesis of conjugated enynes from ketones and aldehydes by 1,2-CC insertion and 1,2-CH insertion of carbenoids as the key reactions

The addition reactions of 1-chlorovinyl p-tolyl sulfoxides, which were derived from ketones and chloromethyl p-tolyl sulfoxide, with lithium acetylides gave adducts in moderate to good yields. Treatment of the adducts with Grignard reagents resulted in the formation of conjugated enynes in good to high yields via the 1,2-carbon–carbon insertion (1,2-CC insertion) reaction of the generated magnesium carbenoid intermediates. On the other hand, the addition reactions of 1-chlorovinyl p-tolyl sulfoxides derived from aldehydes with lithium acetylides directly gave conjugated enynes bearing a p-tolyl sulfinyl group at the 1-position through the 1,2-carbon–hydrogen insertion (1,2-CH insertion) reaction of the generated lithium carbenoid intermediates. These procedures provide a good way for the synthesis of multi-substituted conjugated enynes from ketones and aldehydes.

Synthesis, including asymmetric synthesis, of 1-substituted cyclopentenes from cyclobutanones with one-carbon ring-expansion by 1,2-carbon-carbon insertion of magnesium carbenoids

Treatment of 1-chlorovinyl p-tolyl sulfoxides, which were derived from cyclobutanones and chloromethyl p-tolyl sulfoxide, with lithium enolate of tert-butyl carboxylates, amides, lithium α-sulfonyl carbanions, and lithium α-carbanion of acetonitrile gave adducts in high to quantitative yields. The adducts were treated with Grignard regents, such as i-PrMgCl and EtMgCl in toluene to afford 1-substituted cyclopentenes in good to high yields with one-carbon ring-expansion via 1,2-carbon–carbon (1,2-CC) insertion reaction of the generated magnesium carbenoid intermediates. The magnesium carbenoid 1,2-CC insertion was found to be highly stereospecific. When optically pure chloromethyl p-tolyl sulfoxide was used in this procedure, optically active 1-substituted cyclopentenes were obtained in high optical purity.

ChemInform Abstract: A Method for the Synthesis of Cyclopropanes by Regiospecific and Regioselective Magnesium Carbenoid 1,3‐CH Insertion as the Key Reactions.

Addition reaction of two geometrical isomers of 1-chlorovinyl p-tolyl sulfoxides, derived from unsymmetrical ketones and chloromethyl p-tolyl sulfoxide, with lithium enolate of tert-butyl acetate gave single diastereomers of the adduct, respectively. Treatment of each diastereomer with i-PrMgCl resulted in the formation of magnesium carbenoid. Highly regiospecific 1,3-CH insertion reaction was found to take place from each magnesium carbenoid to afford cyclopropanes. On the other hand, when the unsymmetrical ketones bearing an oxygen- or a nitrogen-functional group on the α-carbon were used in this procedure, the regioselective 1,3-CH insertion reaction proceeded mainly. Stereochemistry of the adducts, reaction mechanism, and essence of the specificity and the selectivity are discussed.

A method for the synthesis of cyclopropanes by regiospecific and regioselective magnesium carbenoid 1,3-CH insertion as the key reactions

Addition reaction of two geometrical isomers of 1-chlorovinyl p-tolyl sulfoxides, derived from unsymmetrical ketones and chloromethyl p-tolyl sulfoxide, with lithium enolate of tert-butyl acetate gave single diastereomers of the adduct, respectively. Treatment of each diastereomer with i-PrMgCl resulted in the formation of magnesium carbenoid. Highly regiospecific 1,3-CH insertion reaction was found to take place from each magnesium carbenoid to afford cyclopropanes. On the other hand, when the unsymmetrical ketones bearing an oxygen- or a nitrogen-functional group on the α-carbon were used in this procedure, the regioselective 1,3-CH insertion reaction proceeded mainly. Stereochemistry of the adducts, reaction mechanism, and essence of the specificity and the selectivity are discussed.

A new synthesis of cyanocyclopropanes by the intramolecular alkylation of magnesium carbenoids as the key reaction

Addition reaction of 1-chlorovinyl p-tolyl sulfoxides, derived from ketones and chloromethyl p-tolyl sulfoxide, with cyanomethyllithium gave adducts in quantitative yields. Treatment of the adducts with i-PrMgCl in THF resulted in the formation of cyanocyclopropanes via the intramolecular alkylation of the generated magnesium carbenoids. The intermediate of this reaction was proved to be a cyclopropylmagnesium chloride, and it was found to be reactive with electrophiles to give multi-substituted cyanocyclopropanes. The key reaction, intramolecular alkylation of magnesium carbenoid, is the first example for the reaction of the magnesium carbenoids with nitrile-stabilized carbanions.

Asymmetric synthesis of bicyclo[ n.1.0]alkanes by the enantioselective 1,3-CH insertion reaction of chiral magnesium carbenoids

Treatment of enantiomerically pure 1-chlorovinyl p-tolyl sulfoxides, derived from cyclic ketones and ( R)-chloromethyl p-tolyl sulfoxide, with the lithium enolate of tert-butyl carboxylates gave adducts in quantitative yields as single diastereomers. The adducts were treated with i-PrMgCl in toluene to afford optically active bicyclo[ n.1.0]alkanes bearing a tert-butyl carboxylate moiety in up to 99% enantiomeric excess through the enantioselective 1,3-CH insertion reaction of the generated chiral magnesium carbenoids. This is the first example of the enantioselective 1,3-CH insertion reaction of magnesium carbenoid.

Synthesis of conjugated enynes by assembly of three components, ketones, chloromethyl p-tolyl sulfoxide, and acetylenes, with the magnesium carbenoid 1,2-CC insertion as the key reaction

The reaction of 1-chlorovinyl p-tolyl sulfoxides, which were derived from ketones and chloromethyl p-tolyl sulfoxide, with lithium acetylides gave adducts in moderate to good yields. Treatment of the adducts with Grignard reagents resulted in the formation of magnesium carbenoids by the sulfoxide-magnesium exchange reaction. 1,2-Carbon–carbon insertion (1,2-CC insertion) reaction of the generated magnesium carbenoids took place to afford conjugated enynes in good to high yields. This procedure provides a good method for the synthesis of multi-substituted conjugated enynes.

A new synthesis of β,γ-unsaturated esters and allenic esters with construction of a carbon–carbon bond between α- and β-positions by the reaction of magnesium alkylidene carbenoids with lithium ester enolates

Treatment of lithium ester enolates with magnesium alkylidene carbenoids, generated from 1-chlorovinyl p-tolyl sulfoxides with isopropylmagnesium chloride via the sulfoxide–magnesium exchange reaction, gave β,γ-unsaturated esters in moderate to good yields. When this reaction was conducted with the lithium ester enolates of α-chlorocarboxylic acid esters, allenic esters were obtained. This procedure provides an unprecedented way for the synthesis of β,γ-unsaturated esters and allenic esters from ketones with the construction of a carbon–carbon bond between α- and β-positions.

A new synthesis, including asymmetric synthesis, of alkylidenecyclopropanes by 1,2-CC insertion of cyclobutylmagnesium carbenoides as the key reaction

Treatment of 1-chlorovinyl p-tolyl sulfoxides, derived from ketones and chloromethyl p-tolyl sulfoxide, with lithium enolate of carboxylic acid tert-butyl esters gave adducts in high yields. The adducts were converted to 1-chlorocyclobutyl p-tolyl sulfoxides in four steps in high overall yields. Treatment of the 1-chlorocyclobutyl p-tolyl sulfoxides with cyclopentylmagnesium chloride in THF at −40 °C resulted in the formation of cyclobutylmagnesium carbenoids. The magnesium carbenoid 1,2-CC insertion reaction took place smoothly from the cyclobutylmagnesium carbenoids to afford alkylidenecyclopropanes in good to high yields. An asymmetric synthesis of optically active alkylidenecyclopropane was successfully achieved starting from optically active 1-chlorovinyl p-tolyl sulfoxide.

Alkenylation of thiophenes and furans at the 2-position and a synthesis of allenes conjugated with α,β-unsaturated ester with magnesium alkylidene carbenoids

The reaction of 1-chlorovinyl p-tolyl sulfoxides, derived from ketones and chloromethyl p-tolyl sulfoxide, with i-PrMgCl at −78 °C gave magnesium alkylidene carbenoids. Treatment of the magnesium carbenoids with 2-lithiothiophenes and 2-lithiofurans resulted in the formation of 2-alkenylated thiophenes and furans, respectively, in good to high yields. The intermediates of these reactions were found to be alkenylmagnesium, which could be trapped with several electrophiles to afford thiophenes and furans bearing a fully substituted alkene at the 2-position. Treatment of the magnesium alkylidene carbenoids with 2-lithio-5-methoxyfuran afforded allenes conjugated with α,β-unsaturated methyl ester in moderate yields. These procedures offer a new and versatile one-pot synthesis of 2-alkenylthiophenes, 2-alkenylfurans, and allenes conjugated with α,β-unsaturated methyl ester from 1-chlorovinyl p-tolyl sulfoxides.