Solvent-Controlled Stereoselective Formation of a Cyclic Ether in the Lewis Acid-Mediated Allylation of an α-Chloroacetoxy Acyclic Ether. Very High Stereoselectivity in CH_3CN vs Low Stereoselectivity in CH_2C1_2

摘要

The MgBr_2·OEt_2-mediated intramolecular allylation of a 4:1 diastereoisomeric mixture of the α-chlo-roacetoxyl ether la bearing the A-G/JK ring system of brevetoxin B in CH_2Cl_2 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 CH_3CN 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 sp~2 flat structure (S_N1 type mechanism) in CH_2Cl_2, in which the activation energies leading to both diastereoisomers are approximately identical, while in CH_3CN alkylnitrilium salts 6a would be formed through the coordination of CH_3CN to the carbocation leading to an sp~3-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.