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. 2007 Sep 17;63(38):9373-9381.
doi: 10.1016/j.tet.2007.06.117.

Effects of alpha-Alkoxy Substitution and Conformational Constraints on 6-exo Radical Cyclizations of Hydrazones via Reversible Thiyl and Stannyl Additions

Gregory K Friestad  1 , Alex K Mathies
Affiliations

Effects of alpha-Alkoxy Substitution and Conformational Constraints on 6-exo Radical Cyclizations of Hydrazones via Reversible Thiyl and Stannyl Additions

Gregory K Friestad et al. Tetrahedron. .

Abstract

Access to multifunctional hydrazones of relevance to dysiherbaine synthesis studies is described. Subsequent radical cyclizations of multifunctional hydrazones via a Si- and C-linked tethering strategy are shown to function effectively in 6-exo fashion. Conformational constraints are proposed to play a key role in suppressing unproductive premature reduction pathways. The stereochemical outcomes suggest that minimizing the dipole repulsion between neighboring C=N and C-O bonds favors a C(alpha)-C(=N) dihedral angle placing the C=N bond axial within a chairlike transition state, in contrast to the usual Beckwith-Houk model.

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Figures

Figure 1
Figure 1
Comparison of structural features in unsuccessful and successful 6-exo cyclizations.
Figure 2
Figure 2
Transition state models for 6-exo cyclizations of diastereomeric hydrazones.
Figure 3
Figure 3
Potential for use of Lewis acid chelation to override dipole repulsion.
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Scheme 9
See this image and copyright information in PMC

References

    1. Kolter T, Sandhoff K. Angew. Chem. Int Ed. 1999;38:1532–1568. - PubMed

    1. Reviews:Heightman TD, Vasella AT. Angew. Chem. Int. Ed. 1999;38:750–770.

    2. Bols M. Acc. Chem. Res. 1998;31:1–8.
    3. Chapleur Y, editor. Carbohydrate Mimics. Weinheim; Wiley-VCH: 1998.
    4. Nash RJ, Watson AA, Asano N. In: Alkaloids: Chemical and Biological Perspectives. Pelletier SW, editor. Pergamon; Tarrytown, New York: 1996. pp. 345–376.
    1. Arcamone F, Penco S. In: Anthracycline and Anthracenedione-Based Anticancer Agents. Lown JW, editor. Elsevier; New York: 1988.

    1. ReviewHauser FM, Ellenberger SR. Chem. Rev. 1986;86:35–67.

    1. Sakai R, Kamiya H, Murata M, Shimamoto K. J. Am. Chem. Soc. 1997;119:4112–4116.

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