La Cruz Thomas E, Rychnovsky Scott D
Department of Chemistry, 516 Rowland Hall, University of California-Irvine, Irvine, CA 92697-2025, USA.
J Org Chem. 2006 Feb 3;71(3):1068-73. doi: 10.1021/jo052166u.
The cyclization of alkyllithium reagents onto methoxy alkenes has been investigated. The alkyllithium reagent was generated by reductive lithiation of an alkyl nitrile. In an unbiased substrate, a methoxy leaving group attached to a stereogenic secondary carbon atom led to the cyclization product with high optical purity. The configuration of the product demonstrated that the cyclization had proceeded with high syn-S(N)' selectivity. Previously we have shown that 2-lithiotetrahydropyran reagents cyclize to form spirocycles with the alkene cis to the pyran oxygen. Substrates were prepared to evaluate the importance of the configuration of the secondary allyl methyl ether against the alpha-alkoxy alkyllithium configuration. In the matched case (cyano acetal 38), a very selective cyclization ensued. In the mismatched case (cyano acetal 39), the spiro ether selectivity dominated. The syn-S(N)' selectivity overcame the normal E selectivity in the cyclization and accounted for the major product, Z-alkene 45. Thus the stereochemical preference in these alkyllithium cyclizations is dominated by the spiroether effect, followed by the syn-S(N)' selectivity and finally the preference for E-alkene formation.
已对烷基锂试剂与甲氧基烯烃的环化反应进行了研究。烷基锂试剂通过烷基腈的还原锂化反应生成。在无偏向的底物中，连接在立体异构仲碳原子上的甲氧基离去基团导致生成具有高光学纯度的环化产物。产物的构型表明环化反应以高顺式-S(N)'选择性进行。此前我们已表明，2-锂代四氢吡喃试剂会环化形成与吡喃氧处于顺式的烯烃的螺环。制备底物以评估仲烯丙基甲基醚的构型相对于α-烷氧基锂构型的重要性。在匹配的情况（氰基缩醛38）下，会发生非常选择性的环化反应。在不匹配的情况（氰基缩醛39）下，螺醚选择性占主导。顺式-S(N)'选择性在环化反应中克服了正常的E选择性，并构成了主要产物Z-烯烃45。因此，这些烷基锂环化反应中的立体化学偏好主要由螺醚效应主导，其次是顺式-S(N)'选择性，最后是对E-烯烃形成的偏好。
