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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Parallel synthesis of a desketoraloxifene analogue library via iodocyclization/palladium-catalyzed coupling
Chul-Hee Cho1, Dai-Il Jung, Benjamin Neuenswander
1Department of Chemistry, Iowa State University, Ames, 50011, United States.
Abstract:
For a future structure-activity relationship (SAR) study, a library of desketoraloxifene analogues has been prepared by parallel synthesis using iodocyclization and subsequent palladium-catalyzed coupling reactions. Points of desketoraloxifene diversification involve the two phenolic hydroxyl groups and the aliphatic amine side chain. This approach affords oxygen-bearing 3-iodobenzo[b]thiophenes 4 in excellent yields, which are easily further elaborated using a two-step approach involving Suzuki-Miyaura and Mitsunobu coupling reactions to give multimethoxy-substituted desketoraloxifene analogues 6. Various hydroxyl-substituted desketoraloxifene analogues 7 were subsequently generated by demethylation with BBr(3).
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