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note
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Similar to Hanna's approach (ref 3q) to construct seven- and six-membered rings simultaneously through ring-closing metathesis, our initial strategy was to generate the seven- and six-membered ring of guanacastepene A at the same time as shown below: (equation presented) Starting from the (E)-vinyl iodide known in the literature, the skeletal framework of guanacastepene A was assembled rapidly in four steps. However, the intramolecular Diels-Alder reaction (IMDA) to generate the [5-7-6] core structure of guanacastepene A did not take place even with various modifications on either the diene or the dienophile moiety. Nonetheless, the design of our current synthetic plan benefited greatly from our initial approach because the same reaction tools such as organocuprate coupling, Diels-Alder reaction, and tandem conjugate addition/aldol reaction are maintained.
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For literature examples of forming a seven-membered ring or an azulene ring through intramolecular Mukaiyama aldol reaction, see: (b) Alexakis, A.; Chapdelaine, M. J.; Posner, G. H.; Runquist, A. W. Tetrahedron Lett. 1978, 19, 4205.
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0141602009
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note
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4 in the Mukaiyama aldol reaction.
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