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Even though epoxides 5 were previously reported (ref 4a), to the best of our knowledge this is the first account where spectroscopic analysis for these species is provided (see Supporting Information).
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We revisited the synthesis of epoxides 5 at this point with the purpose to obtain epimeric mixtures enriched in the major isomer, that in turn would maximize the yield of 19(S)-27 and thus the yield of macrocycle (+)-30. However, treatment of aldehyde (+)-11 with (R)-(dimethylamino)methylphenyloxosulfoxonium fluoroborate generated 5 as a diastereomeric mixture (3.7:1) in favor of the desired epimer, which we considered only a modest improvement relative to Matteson methylenation. See: (a) Johnson, C. R.; Haake, M.; Schroeck, C. W. J. Am. Chem. Soc. 1970, 92, 6594-6598.
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1H NMR of the reaction mixture revealed a doublet of low intensity at 5.05 ppm (J = 10.1 Hz), characteristic of the vinyl proton expected in 35; correct mass for the RCM product was observed by LRMS.
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A NOESY cross-peak was also observed between the methyl of the 4-OTBS group and the C(5)-H benzylic proton in (+)-36, supporting a C(4)-OTBS-C(5)-H synclinal orientation.
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74
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33646129856
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COSY and NOESY NMR experiments were employed to assign the regio- and stereochemistry of the C(14,15) e-olefin 37.
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1H NMR signals distinct from those of (-)-42, indicating that the two samples were isomers.
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85
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