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Tsuyoshi Satoh - One of the best experts on this subject based on the ideXlab platform.
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synthesis of 2 azabicyclo 2 1 0 pentanes by the intramolecular nucleophilic substitution of cyclopropylmagnesium carbenoids with magnesium anilide
Tetrahedron, 2017Co-Authors: Tsutomu Kimura, Toshiki Nishimura, Natsumi Wada, Tsuyoshi SatohAbstract:Abstract A variety of 2-azabicyclo[2.1.0]pentanes were synthesized by the intramolecular nucleophilic substitution of cyclopropylmagnesium carbenoids with magnesium anilide. The 1-chlorocyclopropyl p -tolyl Sulfoxides possessing an N -aryl-substituted aminomethyl group were prepared from dichloromethyl p -tolyl sulfoxide, α,β-unsaturated carboxylic acid esters, and anilines in four steps. The deprotonation of the amine with t -BuMgCl followed by sulfoxide/magnesium exchange of the Sulfoxides with i -PrMgCl led to the generation of the cyclopropylmagnesium carbenoids possessing a magnesium anilide moiety. Subsequent intramolecular nucleophilic substitution of the cyclopropylmagnesium carbenoids occurred in a 4-exo-tet manner to give the 2-azabicyclo[2.1.0]pentanes. The optically active 2-azabicyclo[2.1.0]pentane was synthesized using a p -tolylsulfinyl group as a chiral auxiliary.
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synthesis of 3 azabicyclo 3 1 0 hexanes by insertion of cyclopropylmagnesium carbenoids into an intramolecular c h bond adjacent to a nitrogen atom
Tetrahedron, 2015Co-Authors: Tsutomu Kimura, Natsumi Wada, Takahiro Tsuru, Taro Sampei, Tsuyoshi SatohAbstract:Abstract A variety of 3-azabicylo[3.1.0]hexanes were synthesized via 1,5-C–H insertion of cyclopropylmagnesium carbenoids as a key step. 1-Chlorocyclopropyl p -tolyl Sulfoxides with an N , N -disubstituted aminomethyl group on the cyclopropane ring were prepared from dichloromethyl p -tolyl sulfoxide, α,β-unsaturated carboxylic acid esters, primary amines, and alkyl halides. Treatment of the Sulfoxides with i -PrMgCl generated cyclopropylmagnesium carbenoids, which were inserted into an intramolecular C–H bond adjacent to a nitrogen atom to give 3-azabicyclo[3.1.0]hexanes in yields of up to 94%. The reactivity of the C–H bond toward the insertion increased in the order of NC H 3 , NC H 2 CH 3 , N CH 2 Ph, and NC H (CH 3 ) 2 . Optically active 3-azabicyclo[3.1.0]hexane was successfully synthesized using an S -chiral p -tolylsulfinyl group as a chiral auxiliary.
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degree of vinylidene character of α heteroatom substituted vinylmagnesium chlorides a dft study to discern the role of the halogen atom in magnesium alkylidene carbenoid chemistry
Tetrahedron, 2013Co-Authors: Tsutomu Kimura, Tsuyoshi SatohAbstract:Abstract DFT calculations were performed on a series of α-heteroatom-substituted vinylmagnesium chlorides, CH 2 CXMgCl·2(OMe 2 ) (X=NMe 2 , OMe, F, SMe, Cl, SeMe, and Br), at the B3LYP/6-311++G(d,p) level to elucidate the degree of vinylidene character of such species. α-Halo-substituted vinylmagnesium chlorides were found to have considerable vinylidene character. A donor–acceptor interaction between the C–Mg bonding orbital and the C–X antibonding orbital was responsible for the vinylidene character of α-heteroatom-substituted vinylmagnesium chlorides. A sulfoxide/magnesium exchange reaction of 1-halovinyl phenyl Sulfoxides with i -PrMgCl was more exothermic than the exchange reaction of phenyl vinyl sulfoxide with i -PrMgCl by 12.8–13.9 kcal/mol.
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efficient synthesis of cyclopropanecarboxylic acid esters starting from the conjugate addition of lithium ester enolates to 1 chlorovinyl p tolyl Sulfoxides
Synlett, 2013Co-Authors: Tsutomu Kimura, Hitoshi Momochi, Nobuhito Nakaya, Yoshiaki Hattori, Tsuyoshi SatohAbstract: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.
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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
Tetrahedron Letters, 2012Co-Authors: Hideki Saitoh, Tsutomu Kimura, Taro Sampei, Yuichi Kato, Naoyuki Ishida, Tsuyoshi SatohAbstract: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.
Bruce W Turnbull - One of the best experts on this subject based on the ideXlab platform.
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mechanistic investigations into the application of Sulfoxides in carbohydrate synthesis
Chemistry: A European Journal, 2016Co-Authors: M A Fascione, Robin Brabham, Bruce W TurnbullAbstract:The utility of Sulfoxides in a diverse range of transformations in the field of carbohydrate chemistry has seen rapid growth since the first introduction of a sulfoxide as a glycosyl donor in 1989. Sulfoxides have since developed into more than just anomeric leaving groups, and today have multiple roles in glycosylation reactions. These include as activators for thioglycosides, hemiacetals, and glycals, and as precursors to glycosyl triflates, which are essential for stereoselective β-mannoside synthesis, and bicyclic sulfonium ions that facilitate the stereoselective synthesis of α-glycosides. In this review we highlight the mechanistic investigations undertaken in this area, often outlining strategies employed to differentiate between multiple proposed reaction pathways, and how the conclusions of these investigations have and continue to inform upon the development of more efficient transformations in sulfoxide-based carbohydrate synthesis.
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mechanistic studies on a sulfoxide transfer reaction mediated by diphenyl sulfoxide triflic anhydride
Chemistry: A European Journal, 2012Co-Authors: Martin A. Fascione, Sophie J. Adshead, Pintu K. Mandal, Colin A. Kilner, Andrew G. Leach, Bruce W TurnbullAbstract: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.
Hilkka I Kenttamaa - One of the best experts on this subject based on the ideXlab platform.
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identification of n oxide and sulfoxide functionalities in protonated drug metabolites by using ion molecule reactions followed by collisionally activated dissociation in a linear quadrupole ion trap mass spectrometer
Journal of Organic Chemistry, 2016Co-Authors: Huaming Sheng, Ravikiran Yerabolu, Raghavendhar R Kotha, Joann P Max, Minli Zhang, Weijuan Tang, James S Riedeman, John J Nash, Hilkka I KenttamaaAbstract:The in vivo oxidation of sulfur and nitrogen atoms in many drugs into sulfoxide and N-oxide functionalities is a common biotransformation process. Unfortunately, the unambiguous identification of these metabolites can be challenging. In the present study, ion-molecule reactions of tris(dimethylamino)borane followed by collisionally activated dissociation (CAD) in an ion trap mass spectrometer are demonstrated to allow the identification of N-oxide and sulfoxide functionalities in protonated polyfunctional drug metabolites. Only ions with N-oxide or sulfoxide functionality formed diagnostic adducts that had lost dimethyl amine (DMA). This was demonstrated even for an analyte that contains a substantially more basic functionality than the functional group of interest. CAD of the diagnostic product ions (M) resulted mainly in type A (M - DMA) and B fragment ions (M - HO-B(N(CH3)2)2) for N-oxides, but Sulfoxides also formed diagnostic C ions (M - O═BN(CH3)2), thus allowing differentiation of the functionalities. Some protonated analytes yielded abundant TDMAB adducts that had lost two DMA molecules instead of just one. This provides information on the environment of the N-oxide and sulfoxide functionalities. Quantum chemical calculations were performed to explore the mechanisms of the above-mentioned reactions. The method can be implemented on HPLC for real drug analysis.
Martin A. Fascione - One of the best experts on this subject based on the ideXlab platform.
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mechanistic studies on a sulfoxide transfer reaction mediated by diphenyl sulfoxide triflic anhydride
Chemistry: A European Journal, 2012Co-Authors: Martin A. Fascione, Sophie J. Adshead, Pintu K. Mandal, Colin A. Kilner, Andrew G. Leach, Bruce W TurnbullAbstract: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.
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Mechanistic Studies on a Sulfoxide Transfer Reaction Mediated by Diphenyl Sulfoxide/Triflic Anhydride
Chemistry - A European Journal, 2012Co-Authors: Martin A. Fascione, Sophie J. Adshead, Pintu K. Mandal, Colin A. Kilner, Andrew G. Leach, W. Bruce TurnbullAbstract: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.
Tsutomu Kimura - One of the best experts on this subject based on the ideXlab platform.
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synthesis of 2 azabicyclo 2 1 0 pentanes by the intramolecular nucleophilic substitution of cyclopropylmagnesium carbenoids with magnesium anilide
Tetrahedron, 2017Co-Authors: Tsutomu Kimura, Toshiki Nishimura, Natsumi Wada, Tsuyoshi SatohAbstract:Abstract A variety of 2-azabicyclo[2.1.0]pentanes were synthesized by the intramolecular nucleophilic substitution of cyclopropylmagnesium carbenoids with magnesium anilide. The 1-chlorocyclopropyl p -tolyl Sulfoxides possessing an N -aryl-substituted aminomethyl group were prepared from dichloromethyl p -tolyl sulfoxide, α,β-unsaturated carboxylic acid esters, and anilines in four steps. The deprotonation of the amine with t -BuMgCl followed by sulfoxide/magnesium exchange of the Sulfoxides with i -PrMgCl led to the generation of the cyclopropylmagnesium carbenoids possessing a magnesium anilide moiety. Subsequent intramolecular nucleophilic substitution of the cyclopropylmagnesium carbenoids occurred in a 4-exo-tet manner to give the 2-azabicyclo[2.1.0]pentanes. The optically active 2-azabicyclo[2.1.0]pentane was synthesized using a p -tolylsulfinyl group as a chiral auxiliary.
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synthesis of 3 azabicyclo 3 1 0 hexanes by insertion of cyclopropylmagnesium carbenoids into an intramolecular c h bond adjacent to a nitrogen atom
Tetrahedron, 2015Co-Authors: Tsutomu Kimura, Natsumi Wada, Takahiro Tsuru, Taro Sampei, Tsuyoshi SatohAbstract:Abstract A variety of 3-azabicylo[3.1.0]hexanes were synthesized via 1,5-C–H insertion of cyclopropylmagnesium carbenoids as a key step. 1-Chlorocyclopropyl p -tolyl Sulfoxides with an N , N -disubstituted aminomethyl group on the cyclopropane ring were prepared from dichloromethyl p -tolyl sulfoxide, α,β-unsaturated carboxylic acid esters, primary amines, and alkyl halides. Treatment of the Sulfoxides with i -PrMgCl generated cyclopropylmagnesium carbenoids, which were inserted into an intramolecular C–H bond adjacent to a nitrogen atom to give 3-azabicyclo[3.1.0]hexanes in yields of up to 94%. The reactivity of the C–H bond toward the insertion increased in the order of NC H 3 , NC H 2 CH 3 , N CH 2 Ph, and NC H (CH 3 ) 2 . Optically active 3-azabicyclo[3.1.0]hexane was successfully synthesized using an S -chiral p -tolylsulfinyl group as a chiral auxiliary.
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degree of vinylidene character of α heteroatom substituted vinylmagnesium chlorides a dft study to discern the role of the halogen atom in magnesium alkylidene carbenoid chemistry
Tetrahedron, 2013Co-Authors: Tsutomu Kimura, Tsuyoshi SatohAbstract:Abstract DFT calculations were performed on a series of α-heteroatom-substituted vinylmagnesium chlorides, CH 2 CXMgCl·2(OMe 2 ) (X=NMe 2 , OMe, F, SMe, Cl, SeMe, and Br), at the B3LYP/6-311++G(d,p) level to elucidate the degree of vinylidene character of such species. α-Halo-substituted vinylmagnesium chlorides were found to have considerable vinylidene character. A donor–acceptor interaction between the C–Mg bonding orbital and the C–X antibonding orbital was responsible for the vinylidene character of α-heteroatom-substituted vinylmagnesium chlorides. A sulfoxide/magnesium exchange reaction of 1-halovinyl phenyl Sulfoxides with i -PrMgCl was more exothermic than the exchange reaction of phenyl vinyl sulfoxide with i -PrMgCl by 12.8–13.9 kcal/mol.
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efficient synthesis of cyclopropanecarboxylic acid esters starting from the conjugate addition of lithium ester enolates to 1 chlorovinyl p tolyl Sulfoxides
Synlett, 2013Co-Authors: Tsutomu Kimura, Hitoshi Momochi, Nobuhito Nakaya, Yoshiaki Hattori, Tsuyoshi SatohAbstract: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.
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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
Tetrahedron Letters, 2012Co-Authors: Hideki Saitoh, Tsutomu Kimura, Taro Sampei, Yuichi Kato, Naoyuki Ishida, Tsuyoshi SatohAbstract: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.
