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Volumn 75, Issue 10, 2010, Pages 3251-3259

Diastereoselective synthesis of tetrahydrofurans from Aryl 3-chloropropylsulfoxides and aldehydes

Author keywords

[No Author keywords available]

Indexed keywords

ALDOL ADDITION; AROMATIC RINGS; CARBONYL GROUPS; CYCLIC TRANSITIONS; DIASTEREO-SELECTIVITY; DIASTEREOSELECTIVE SYNTHESIS; ELECTRON-DONATING GROUP; ELECTRON-WITHDRAWING SUBSTITUENTS; INTRAMOLECULAR SUBSTITUTIONS; SULFUR ATOMS; TETRA-HYDROFURAN; TETRAHYDROFURANS;

EID: 77952531667     PISSN: 00223263     EISSN: 15206904     Source Type: Journal    
DOI: 10.1021/jo1002196     Document Type: Article
Times cited : (4)

References (49)
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    • For a preliminary communication of the synthesis of tetrahydrofurans from 4-chlorobutyronitrile and aldehydes under basic phase transfer catalysis conditions, see
    • For a preliminary communication of the synthesis of tetrahydrofurans from 4-chlorobutyronitrile and aldehydes under basic phase transfer catalysis conditions, see: Ma̧kosza, M.; Przyborowski, J.; Klajn, R.; Kwast, A. Synlett 2000, 1773
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    • note
    • The configurations at C-2 and C-3 of newly formed tetrahydrofurans depend on the selectivity of the aldol addition and cyclization process. However, in the end proportion of trans and cis isomers (relative C-2 to C-3 configuration) approaches the thermodynamic limit after the base-induced C-3 epimerization.
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    • note
    • Alternatively, aldol-type adducts may isomerize by epimerization. For some hint that it actually involves a dissociation-addition sequence see note 17 in ref 15.
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    • note
    • By definition, a chiral auxiliary is a unit that is temporarily incorporated into the molecule, so that the synthesis can be carried out in an asymmetric manner. A chiral auxiliary is capable of being recycled, and therefore we refer to sulfoxides as formal chiral auxiliaries. (21) Our attempts to synthesize the pure enantiomer of 1 by oxidation of 3-chloropropyl phenyl sulfide (Brunel, J.-M.; Diter, P.; Duetsch, M.; Kagan, H. B. J. Org. Chem. 1995, 60, 8086) failed (ee <15%).
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    • As lifetimes of typical γ-halocarbanions are on the order of only seconds or shorter at -78 °C, to avoid cyclization to cyclopropanes, base is added to a mixture of an aldehyde and γ-halocarbanion precursor (so-called Barbier conditions). Under these conditions many strong bases such as n -BuLi or LDA add preferentially to the carbonyl group (see, for example;) of nonenolizable aldehyde rather than deprotonate γ-halocarbanion precursor, and thus t -BuOK remains a reagent of choice for this one-pot process.
    • As lifetimes of typical γ-halocarbanions are on the order of only seconds or shorter at -78 °C, to avoid cyclization to cyclopropanes, base is added to a mixture of an aldehyde and γ-halocarbanion precursor (so-called Barbier conditions). Under these conditions many strong bases such as n -BuLi or LDA add preferentially to the carbonyl group (see, for example Commins, D. L.; Brown, J. D. J. Org. Chem. 1984, 49, 1078) of nonenolizable aldehyde rather than deprotonate γ-halocarbanion precursor, and thus t -BuOK remains a reagent of choice for this one-pot process. See refs 7, 8
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    • Commins, D.L.1    Brown, J.D.2    Judka, M.3    Wojtasiewicz, A.4    Danikiewicz, W.5    Ma̧kosza, M.6
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    • note
    • Pentachlorophenyl 3-chloropropyl sulfoxide was synthesized but decomposed when subjected to reaction with benzaldehyde in the presence of t -BuOK at low temperature (see Supporting Information for details).
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    • We assume that the selectivity derives from decreased reactivity of more stabilized carbanions and less electrophilic aldehydes in agreement with common reactivity-selectivity principle. For some criticizm on reactivity-selectivity principle see
    • We assume that the selectivity derives from decreased reactivity of more stabilized carbanions and less electrophilic aldehydes in agreement with common reactivity-selectivity principle. For some criticizm on reactivity-selectivity principle see: Mayr, H.; Ofial, A. R. Angew. Chem., Int. Ed. 2006, 45, 1844
    • (2006) Angew. Chem., Int. Ed. , vol.45 , pp. 1844
    • Mayr, H.1    Ofial, A.R.2
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    • note
    • 4Cl to release the substrate (when their cyclization is a rate-determining step). The possibility is less plausible because under the similar conditions (1) adducts with less electrophilic aldehydes cyclize to tetrahydrofurans in high yield, (2) average rates of cyclization of adducts of sulfones, esters, and nitriles under similar conditions range from seconds to minutes (see Supporting Information for details), and (3) cyclization of the sulfoxide 2 in the absence of an aldehyde is a slow process in contrast to the behavior of more acidic precursors such as sulfones, nitriles, and esters.
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    • We wish to acknowledge the use of a free version of Ortep-3 for Windows program
    • We wish to acknowledge the use of a free version of Ortep-3 for Windows program: Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565
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    • note
    • The same observation was made when 2 was reacted with benzaldehyde in DMF to give tetrahydrofurans (6, 45%; 6a: 6b = 1:1.4) and cyclopropane (15, 51%).
  • 46
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    • note
    • The modern explanation of the gem -dimethyl effect for increased rates of cyclizations of medium size rings is based on the "reactive rotamer" idea, associated with changes in conformer populations as clarified in the text. (33) The alternative concept of a valence distortion posed by substituents, the so-called Thorpe-Ingold effect, would be too small to rationalize the observed differences.


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