Bridging of macrodithionolactones to bicyclic systems. Synthesis and modeling of oxapolycyclic frameworks

K. C. Nicolaou, C. K. Hwang, B. E. Marron, S. A. DeFrees, E. A. Couladouros, Y. Abe, P. J. Carroll, J. P. Snyder

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

A new reaction involving bridging of macrodithionolactones to bicyclic systems is described. A series of macrodiolides was prepared and converted to the requisite macrodithionolactones. The latter substrates were induced to undergo bridging across the macrocyclic ring by exposure to sodium naphthalenide, leading to stable bicyclic systems upon addition of methyl iodide. The mixed thioketals so obtained were converted to a number of saturated or unsaturated bicyclic or polycyclic systems by removal of the sulfurs. The stereochemistry of bridging follows the relative energy of the cis and trans products rather than the conformational preferences of the macrocycles. This is confirmed by MM2 calculations and X-ray crystal structure determinations. The unusual stereochemical course of some of the reported reactions, elucidated by X-ray, has been given a mechanistic basis by conformation searching coupled by energy evaluation by MM2 and PRDDO. Several new sets of MM2 parameters were evolved during this work.

Original languageEnglish
Pages (from-to)3040-3054
Number of pages15
JournalJournal of the American Chemical Society
Volume112
Issue number8
Publication statusPublished - 1990 Apr 11
Externally publishedYes

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X-Rays
X rays
Stereochemistry
Sulfur
Conformations
Crystal structure
Sodium
Substrates
methyl iodide

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Nicolaou, K. C., Hwang, C. K., Marron, B. E., DeFrees, S. A., Couladouros, E. A., Abe, Y., ... Snyder, J. P. (1990). Bridging of macrodithionolactones to bicyclic systems. Synthesis and modeling of oxapolycyclic frameworks. Journal of the American Chemical Society, 112(8), 3040-3054.

Bridging of macrodithionolactones to bicyclic systems. Synthesis and modeling of oxapolycyclic frameworks. / Nicolaou, K. C.; Hwang, C. K.; Marron, B. E.; DeFrees, S. A.; Couladouros, E. A.; Abe, Y.; Carroll, P. J.; Snyder, J. P.

In: Journal of the American Chemical Society, Vol. 112, No. 8, 11.04.1990, p. 3040-3054.

Research output: Contribution to journalArticle

Nicolaou, KC, Hwang, CK, Marron, BE, DeFrees, SA, Couladouros, EA, Abe, Y, Carroll, PJ & Snyder, JP 1990, 'Bridging of macrodithionolactones to bicyclic systems. Synthesis and modeling of oxapolycyclic frameworks', Journal of the American Chemical Society, vol. 112, no. 8, pp. 3040-3054.
Nicolaou KC, Hwang CK, Marron BE, DeFrees SA, Couladouros EA, Abe Y et al. Bridging of macrodithionolactones to bicyclic systems. Synthesis and modeling of oxapolycyclic frameworks. Journal of the American Chemical Society. 1990 Apr 11;112(8):3040-3054.
Nicolaou, K. C. ; Hwang, C. K. ; Marron, B. E. ; DeFrees, S. A. ; Couladouros, E. A. ; Abe, Y. ; Carroll, P. J. ; Snyder, J. P. / Bridging of macrodithionolactones to bicyclic systems. Synthesis and modeling of oxapolycyclic frameworks. In: Journal of the American Chemical Society. 1990 ; Vol. 112, No. 8. pp. 3040-3054.
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