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When run in the absence of ethylene the RORCM reaction of 23 gave a mixture of product 27 and unidentified oligomer (we have occasionally observed minor amounts (<5%) of oligomer from the RORCM reactions run in the presence of ethylene). We have not isolated any of the divinyl pyrrolidine intermediate expected from a stepwise reaction when the reaction was run in the presence of ethylene. Others have also reported the importance of ethylene to inhibit oligomer formation in related reactions. For example, see ref 81.
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While our plan had been to employ ester dienophiles as precursors to the desired substrates, the Diels-Alder cycloaddition reaction between N-Boc pyrrole and any number of ester dienenophiles (i.e., methyl acrylate, acrylaldehyde, ethyl propiolate, and methyl vinyl ketone) failed to give the corresponding 7-azanorbornenes in our hands. For a review on pyrrole Diels-Alder chemistry see: Chen, Z.; Trudell, M. L. Chem. Rev. 1996, 96, 1179.
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Perhydroindolines 25 and 27 also underwent efficient bromocyclization reactions.
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54
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0000016992
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Woodward's elegant synthesis of reserpine served as the inspiration for this approach to the C(8) stereocenter. See: Woodward, R. B.; Bader, F. E.; Bickel, H.; Frey, A. J.; Kierstead, R. W. Tetrahedron 1958, 2, 1.
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For a related iodolactonization on a pyrrolidine derivative see: Kinsman, R.; Lathbury, D.; Vernon, P.; Gallagher, T. J. Chem. Soc., Chem. Commun. 1987, 243.
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32644448893
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Interestingly, the C(1) acid from TBS ether 27 did not undergo the bromolactonization reaction.
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