Synthesis and conformational properties of several maximally substituted hexa(spirotetrahydrofuranyl)cyclohexanes. Assessment of the pronounced bias of the All-Trans D3d-symmetric isomer for total equatorial oxygen occupancy

L. A. Paquette, J. Tae, B. M. Branan, D. G. Bolin, S. W.E. Eisenberg

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The poly(spirotetrahydrofuranyl)cyclohexanes 1-4 were prepared in a series of steps that began with oxidative demercuration of pentaspirocyclic chloromercurials. Once the resulting alcohols were transformed into their ketones, it proved possible to cap this center with the Normant reagent and introduce the final heterocyclic ring. The cyclohexanones and the title compounds showed a strong tendency to project their C-O bonds equatorially to the maximum extent possible. The reluctance of these systems to participate in chair-to-chair conformational equilibration was made apparent during measurements to assess their coordination capability toward alkali metal ions. Although 3 was superior to its isomers, this polyether was overshadowed by 15 to an extent in excess of two powers of 10 in their relative capability to coordinate lithium cations. The synthesis, conformation, and low-level dynamic character of 5 are also detailed. To set the stereochemistry of the sixth spirotetrahydrofuranyl ring properly in this case, it was necessary to implement a novel strategy involving late-stage introduction of the oxygen atom. This protocol required intermediate formation of homoallylic alcohol 39, the epoxidation of which proceeded principally in the desired direction. X-ray crystallographic analysis of 5 established that the chair conformation which is adopted has all six C-O bonds projected equatorially. The total inability of 5 to bind to Li+, Na+, and K+ denotes the existence of a substantial barrier to ring inversion. DNMR studies undertaken to assess the magnitude of this barrier demonstrated no change in high-field 1H and 13C line shapes up to 573K in 1,3-([D3]methoxy)benzene. Consequently, 5 may qualify as the cyclohexane having the highest chair-chair conformational inversion barrier to the present time.

Original languageEnglish
Pages (from-to)9172-9179
Number of pages8
JournalJournal of Organic Chemistry
Issue number26
Publication statusPublished - 2000 Dec 29


All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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