Theoretical Investigation of Enolborane Addition to α-Heteroatom-Substituted Aldehydes. Relevance of the Cornforth and Polar Felkin-Anh Models for Asymmetric Induction.

The addition of enolborane nucleophiles to chiral α-heteroatom-substituted aldehydes (CHCH-(X)CHO, X = F, Cl, OMe, SMe, NMe, and PMe) was investigated using density functional theory by means of B3LYP/6-31G(d) calculations, with particular emphasis on determining the relevance of the polar Felkin-An...

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Publicado en:Journal of the American Chemical Society Vol. 128; no. 9; pp. 2920 - 2931
Autores principales: Cee, Victor J., Cramer, Christopher J., Evans, David A.
Formato: Artículo
Publicado: American Chemical Society 3/8/2006
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Acceso en línea:Ver este registro en EBSCOhost
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        10.1021/ja0555670
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        atl: Theoretical Investigation of Enolborane Addition to α-Heteroatom-Substituted Aldehydes. Relevance of the Cornforth and Polar Felkin-Anh Models for Asymmetric Induction.
      aug:
        au:
          Cee, Victor J.
          Cramer, Christopher J.
          Evans, David A.
        affil:
          Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138
          Department of Chemistry and Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota 55455
      su:
        Density functionals
        Aldehydes
        Asymmetric synthesis
        Chirality
        Functional analysis
        Organic compounds
      sug:
        subj:
          Density functionals
          Aldehydes
          Asymmetric synthesis
          Chirality
          Functional analysis
          Organic compounds
      ab: The addition of enolborane nucleophiles to chiral α-heteroatom-substituted aldehydes (CHCH-(X)CHO, X = F, Cl, OMe, SMe, NMe, and PMe) was investigated using density functional theory by means of B3LYP/6-31G(d) calculations, with particular emphasis on determining the relevance of the polar Felkin-Anh and Cornforth models for asymmetric induction in these reactions. The relative energy of the polar Felkin-Anh and Cornforth transition-state structures is found to depend on the nature of the α-heteroatom substituent, with electronegative substituents (F, OMe, CI) favoring Cornforth structures, while less electronegative substituents (PMe, SMe, NMe) favor polar Felkin-Anh structures. These transition-state preferences are correlated with the relative energy of the corresponding rotamer of the uncomplexed reactant aldehyde, indicating that the transition states are particularly sensitive to the conformation of the aldehyde. The proposed Nu ↵ σ* interaction that forms the basis of the polar Felkin-Anh model appears to be insignificant in reactions with enolborane nucleophiles. The calculated transition-state structures for the addition of E- and Z-enolborane nucleophiles to 2-methoxypropanal predict a diastereofacial selectivity that is in good agreement with the experimentally determined values.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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