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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Stereoselective construction of cyclic ethers using a tandem two-component etherification: elucidation of the role of
P Andrew Evans1, Jian Cui, Santosh J Gharpure
1Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA. paevans@indiana.edu
Abstract:
The stereodivergent construction of cyclic ethers remains an important area of synthetic interest, particularly given the ubiquity of C-glycoside derivatives in natural and unnatural pharmacologically important agents. This work describes a series of intramolecular etherification reactions of delta-trialkylsilyloxy aldehydes and ketones using catalytic bismuth tribromide and various trialkylsilyl nucleophiles for the construction of cis- and trans-2,6-di- and trisubstituted tetrahydropyrans. Furthermore, this study provides compelling evidence for the fact that the catalysis may be attributed to the hydrogen bromide and bismuth oxybromide derived from the hydrolysis of bismuth tribromide. The synthetic utility of this protocol is highlighted in the ability to construct adjacent tertiary ethers in a highly stereoselective manner and the development of a sequential two-component cross-coupling followed by reductive etherification process for the expeditious synthesis of nonadjacent tetrahydropyran rings.
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