Solvent-controlled stereoselective formation of a cyclic ether in the Lewis acid-mediated allylation of an α-chloroacetoxy acyclic ether. Very high stereoselectivity in CH3CN vs low stereoselectivity in CH 2Cl2

Ilya D. Gridnev, Shigetoshi Kikuchi, Abeda S. Touchy, Isao Kadota, Yoshinori Yamamoto

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(Chemical Equation Presented) The MgBr2·OEt 2-mediated intramolecular allylation of a 4:1 diastereoisomeric mixture of the α-chloroacetoxyl ether 1a bearing the A-G/JK ring system of brevetoxin B in CH2Cl2 gave a 1:1 diastereoisomeric mixture of the trans- and cis-cyclization products 4a and 5a having the A-G/I-K ring system, while that in CH3CN afforded the trans-isomer 4a nearly as the single product. To help clarify a reason for this marked solvent effect in the cyclization of the brevetoxin B precursor, DFT computations for the starting materials, intermediates, transition states, and products were carried out. The cyclization would proceed through a carbocation intermediate 3a having sp2 flat structure (SNI type mechanism) in CH2Cl 2, in which the activation energies leading to both diastereoisomers are approximately identical, while in CH3CN alkylnitrilium salts 6a would be formed through the coordination of CH3CN to the carbocation leading to an sp3-type intermediate in which sever steric hindrance takes place in the transition state leading to the undesired diastereoisomer. The scope of this novel solvent-controlled stereoselectivity was tested for simple compounds. In small model compounds the marked solvent dependence was absent, but the model bearing two consecutive cyclic ether rings 1b exhibited a remarkable solvent effect similar to that observed in the brevetoxin B system.

Original languageEnglish
Pages (from-to)8371-8375
Number of pages5
JournalJournal of Organic Chemistry
Issue number22
Publication statusPublished - Oct 26 2007


ASJC Scopus subject areas

  • Organic Chemistry

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