Collect. Czech. Chem. Commun. 2002, 67, 55-74

Synthesis of Methoxynor Polyisoprenoid Alcohols by Alkylation of (3-Methoxyallyl)lithium Reagents

Qingwu Jin and Robert M. Coates*

Department of Chemistry, Roger Adams Laboratory, Box 40-5, University of Illinois, 600 South Mathews Avenue, Urbana, IL 61801, U.S.A.


A series of six methyl enol ether analogs 8-13 of geraniol, (E,E)-farnesol, and (E,E,E)-geranylgeraniol was synthesized from a group of three allylic methyl ethers and three allylic chlorides. Lithiation of the 1-methyl-, or 1-alkenylvinyl ethers with sec-butyllithium at -78 °C followed by alkylations of the resulting (Z)-(3-methoxyallyl)lithium reagents afforded the six possible Z-configured(trans) methoxynor polyprenyl benzyl ethers bearing the methoxy substituent at the internal and terminal double bonds with high Z/E ratios (5 : 1-31 : 1) and 47-80% yields. Reductive cleavage of the benzyl groups with lithium in liquid ammonia gave the corresponding methoxynor polyprenols. 11-Methoxy-18-nor and 7-methoxy-19-nor geranylgeraniols (13 and 12) were converted to the corresponding diphosphates, 7 and 32, by the Poulter displacement method. The stability of the enol ether in 7 in aqueous solution at pH 8 was verified by NMR analyses. The diphosphates of the methoxynor polyprenols may prove useful as substrate analogs for terpene synthases to capture transient intermediates in cyclization reactions catalyzed by these enzymes.

Keywords: Lithiations; Allyllithium reagents; Alkylations; Enol ethers; Terpenoids; Isoprenoids; Polyenes.

References: 63 live references.