Stereochemistry of the Conversion of γ-Substituted (<i>E</i>)-Vinylsulfones to the Corresponding Allylsulfones. Determination of the Relative Degree of “Syn-Effect”

Inomata, Katsuhiko; Hirata, Takaki; Suhara, Hiroshi; Kinoshita, Hideki; Kotake, Hiroshi; Senda, Hitoshi

doi:10.1246/cl.1988.2009

Cited by 27 publications

(8 citation statements)

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“…It was found that the choice of base, temperature and reaction duration were all significant factors affecting the isomerization. Previously reported methods of isomerization used KOtBu 52 , DBU 53 or n-BuLi/t-BuOOH 40 . The use of 1 eq.…”

Section: Formation Of the Allyl Sulfonementioning

confidence: 99%

“…Addition of n-BuLi in absence of t-BuOOH exclusively results in complete elimination of the sulfonyl group, with no allyl sulfone intermediate observed. Chelation of Li +55 as well as the "syn-effect," forming a homoaromatic system between Li + and the delocalized anionic intermediate 53,56 , may be factors that explain the requirement of n-BuLi instead of DBU or KOtBu, assisting in the stabilization of the delocalized intermediate.…”

Section: Formation Of the Allyl Sulfonementioning

confidence: 99%

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Optimization of peptidyl allyl sulfones as clan CA cysteine protease inhibitors

Fennell

Warren

Chung

et al. 2012

Journal of Enzyme Inhibition and Medicinal Chemistry

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Section: Formation Of the Allyl Sulfonementioning

confidence: 99%

Section: Formation Of the Allyl Sulfonementioning

confidence: 99%

Optimization of peptidyl allyl sulfones as clan CA cysteine protease inhibitors

Fennell

Warren

Chung

et al. 2012

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Especially, the crystal structure of 2-ethyl-1-tosyl-1-butene (36), which afforded exclusively (Z)-2-ethyl-1-tosyl-2-butene (37) by treatment with DBU (Scheme 11), 17,24a revealed that "syn-effect" works in 36 itself as shown in Figure 17. 17,24,25 That is, H1, C1, C2, C3 and C4 exist on the same plane, and C3-H2 and C3-H3 bonds are aligned with p*-orbital on C2 to allow the s p* interaction. 24,25 Such a structure makes the g-protons H2 and H3 of the methylene trans to the sulfonyl group more reactive, i.e., more acidic, than H7 and H8 of the methylene cis to the sulfonyl group toward a base, and also allows the stabilization of the resulting anionic intermediate 38 by 6p-electron homoaromaticity proposed as an explanation for the "syn-effect".…”

Section: "Syn--effect" Observed In Other Reactionsmentioning

confidence: 99%

“…In order to reveal which explanation is most reasonable in the case of the isomerization of vinylic sulfones to allylic sulfones, we tried to determine the relative degree of the "syn-effect" for the various g-substituents by a series of experiments for g-monosubstituted 24b, 25 and g,gdisubstituted 25 vinylic sulfones including the time-course of the reactions. g-Monosubstituted (E)-1-tosyl-1-propenes (E)-30 were treated with DBU in acetonitrile at room temperature (25 ) to isomerize to the corresponding allylic sulfones 31 in a similar manner to that described above. The results are summarized in Table 3.…”

Section: Relativementioning

confidence: 99%

“…24b, 25 The structures of (E)-and (Z)-isomers of the resulting allylic sulfones were determined by the measurement of NOE or based on the empirical rule 25 that the protons of alkyl group syn to the tosylmethyl group in an allylic sulfone appear at higher field in NMR spectrum than those anti to the tosylmethyl group. 26 The isomerization of vinylic sulfone 32a was performed to determine the difference of "syn-effect" between methyl and ethyl groups.…”

Section: Relativementioning

confidence: 99%

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"Syn-Effect" in the Base-Induced Isomerization of Vinylic Sulfones to Allylic Sulfones and the Related Various Reactions

Inomata

2009

J. Synth. Org. Chem. Jpn.

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: "Syn-effect" has been recognized as a major cause of stabilizing the syn-conformation at the transition state of a number of reactions against the steric hindrance. This account deals with the origin of the "syn-effect" on the basis of the stereochemical outcome in the isomerization of vinylic sulfones leading to the formation of allylic sulfones and in the related various reactions. We proposed that a s p* interaction between the s-orbital(s) of the allylic C-H s-bond(s) (or of the C-H s-bond(s) at the a-position for carbonyl compounds) and the antibonding orbital (p*) of the C=C double bond (or of the C=O double bond for carbonyl compounds) is the most important and essential factor for the "syn-effect", though the contribution of a 6p-electron homoaromaticity and/or of a hydrogen bonding cannot be entirely ruled out. Scheme 2fied (Scheme 3). 13Therefore, we started to prepare stereochemically well-defined vinylic sulfones and study the detailed stereochemistry of the isomerization. Consequently, we have found that (E)-vinylic sulfones preferentially provided sterically unfavorable (Z)-allylic sulfones, whose stereochemical course was explainable by so-called "syn-effect". Herein we will briefly introduce the stereochemical outcome in the isomerization of vinylic sulfones to allylic sulfones and in the related various reactions, and discuss the origin of this effect in detail. Regio--and Stereoselective Preparation of Vinylic SulfonesOur initial study focused on the stereoselective synthesis of (E)-and (Z)-vinylic sulfones 14, since the iodotosylation of 1-alkenes followed by triethylamine-induced dehydroiodination of the resulting 2-iodo-1-tosylalkanes 13 mostly provided a mixture of (E)-and (Z)-isomers of vinylic sulfones 14 as summarized in Scheme 4 and their separation into pure isomers turned out to be difficult. [14][15][16] Gratifyingly, 2-pyrrolidinyl-1-tosylalkanes 15 derived from 13 and an excess amount of pyrrolidine underwent a selective Cope elimination upon treatment of the crude products 15 with mCPBA in dichloromethane in the presence of Na 2 CO 3 to provide stereochemically pure (E)-vinylic sulfones (E)-14 in high yields (Scheme 5). 17 This procedure was much easier than an alternative method via a-phenylselenation of 1-tosylalkanes 16 and was applicable on a large scale.A possible key factor for success in the exclusive formation of (E)-14 may be the formation of 16 in favor of 17 in the transition state where the N-oxy-1-pyrrolidinyl group and the hydrogen should adopt eclipsed conformation, in order to avoid a severe steric congestion developed by an alkyl substituent R and the tosyl group (Ts) in 17 (Figure 2).The intermediary b-pyrrolidinylsulfones 15 were also used to prepare a-alkylated vinylic sulfones through a-alkylation followed by oxidative elimination of the pyrrolidinyl group. 15On the other hand, (Z)-14 were selectively synthesized in high yields by the Pd-catalyzed hydrogenation of (E)-2-iodo-1-tosyl-1-alkenes 18, which were prepared by the regio-and stereoselectiv...

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A Unified Strategy Toward 5‐, 6‐, and 7‐Membered Nitrogen Heterocycles Through Free Radical then Metal‐Mediated Functionalization of Ene‐carbamates

et al. 2017

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Free-radical carbo-alkenylation of N-aryl, N-benzyl, and N-phenethyl-ene-carbamates with a disulfone provides vinylsulfones which may then be functionalized and engaged in Heck-type coupling to furnish highly substituted 5-, 6-and 7-membered nitrogen heterocycles. Grignardmediated cyclization starting from the same substrates further allowed a nucleophilic cascade process, affording a straightforward access to hydrocarbazoles, which may be regarded as potent intermediates for the synthesis of alkaloids of the aspidosperma family.

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Stereochemistry of the Conversion of γ-Substituted (E)-Vinylsulfones to the Corresponding Allylsulfones. Determination of the Relative Degree of “Syn-Effect”

Cited by 27 publications

References 5 publications

Optimization of peptidyl allyl sulfones as clan CA cysteine protease inhibitors

Optimization of peptidyl allyl sulfones as clan CA cysteine protease inhibitors

"Syn-Effect" in the Base-Induced Isomerization of Vinylic Sulfones to Allylic Sulfones and the Related Various Reactions

A Unified Strategy Toward 5‐, 6‐, and 7‐Membered Nitrogen Heterocycles Through Free Radical then Metal‐Mediated Functionalization of Ene‐carbamates

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