Stereoselectivity of intramolecular SN' cyclizations of alkyllithium reagents on methoxy alkenes.
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.
La Cruz
Thomas E
TE
Department of Chemistry, 516 Rowland Hall, University of California-Irvine, Irvine, CA 92697-2025, USA.
Rychnovsky
Scott D
SD
D000080:Acetals / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry*; D000478:Alkylation; D003500:Cyclization; D004987:Ethers / Q000737:chemistry; D007454:Iodides / Q000737:chemistry; D008094:Lithium / Q000737:chemistry*; D008745:Methylation; D015394:Molecular Structure; D013237:Stereoisomerism
D000080:Acetals; D000475:Alkenes; D004987:Ethers; D007454:Iodides; D008094:Lithium