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15 halogenated 2,2′-bifuranyl natural products had been reported. A 2,2′-bifuranyl structure for elatenyne was considered less likely than the corresponding pyrano[3,2-b]pyran: J. G. Hall, Ph. D. Thesis, La Trobe University (Australia), 1984 For a summary of the advantages of two-directional synthesis see:
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Z. Rappoportand Y. Apeloig, John Wiley & Sons Ltd., New York, p. 1688 In model studies related to this project we have demonstrated that the intramolecular hydrosilation of glucose and galactose-derived exo-cyclic enol ethers gives rise to the corresponding 1,3-diols For the trans-selective hydroboration/oxidation of 6-membered exo-cyclic enol ethers see:
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4-methanol to which 10 mol% acetyl chloride had been added. Beginning either with a mixture of the 2,2′-bifuranyls 15 or a 1: 1 mixture of 15: 9 gave the equilibrium ratios after 10 hours at room temperature which did not change after one week. In a separate experiment, a mixture of the pyrano[3,2-b]pyrans 9 also readily equilibrated to the same mixture of 15: 9 on stirring in acidic methanol. The pyrano[3,2-b]pyrans 9 exist as a 1: 1.3 mixture of diastereomers at equilibrium which is in keeping with the magnitude of the anomeric effect for 2-methoxytetrahydropyran in methanol see:
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Prior to this work, Nelson reported the equilibration of a 2,2′-bifuranyl dimethyl acetal to the corresponding trans-fused pyrano[3,2-b]pyran in a beautiful synthesis of a ladder toxin intermediate see:
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13C NMR which indicated that the anomeric iodides were in intermediate exchange on the NMR timescale; cooling the sample did not result in significant sharpening of the resonances
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We orginally attempted to methylenate the bis-δ-lactone 8 with dimethyl titanocene to give the corresponding bis-exo-cyclic enol ether which would under go allylic oxidation to give 6 directly. However, exposure of 8 to dimethyltitanocene delivered solely the bis-endo-cyclic enol ether 42 in variable yield; the use of the Tebbe reagent resulted in decomposition. Attempted allylic oxidation of the enol ether 42 with either stoichiometric or catalytic selenium dioxide was also unsuccessful
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We attempted to convert the asymmetric diol 53b into the symmetric diol 53a by an oxidation, epimerisation, reduction sequence. Treatment of the mixture of diols 53 with Jones' reagent gave the corresponding separable diketones. Disappointingly, attempted epimerisation of the resulting diketones under basic conditions resulted in decomposition (see ESI)
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13C NMR chemical shifts for the natural and synthetic material see the ESI Compounds 71 and 72 were formed as mixtures (and yields are for the mixture) along with their corresponding diastereomers arising from silylation of the diol 53b. The minor diastereomer was removed after chlorination to give 73 The reported conditions were particularly effective:
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