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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Diastereoselective synthesis of cyclopropyl sulfoxides via hydrosulfenation
Liyan Yuwen1, Jiazhong Tang1, Yayu Qi1
1Key Laboratory of Precision and Intelligent Chemistry, Department of Chemistry, University of Science and Technology of China Hefei 230026 China qingweiz@ustc.edu.cn.
Abstract:
Cyclopropyl sulfoxides, merging two privileged motifs in medicinal chemistry, remain synthetically challenging despite their pharmaceutical potential. Herein, we report a mild, metal-free hydrosulfenation strategy that enables their direct synthesis, achieving exceptional diastereoselectivity (dr up to > 20 : 1) in systems with up to eight possible diastereomers. Chiral sulfoxides with 4 to 7 stereogenic centers were also synthesized in high dr. The methodology provides direct access to medicinally relevant architectures, including cyclopropyl sulfones, sulfoximines, and drug-conjugated hybrids. Mechanistic studies reveal stereochemical control via collective spatial factors including endo/exo, facial and side selectivities during the cycloaddition step.
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