Epoxides have long enjoyed popularity as synthetic intermediates because of their facile preparation, often with substantial stereochemical control, and their high chemical reactivity, a feature attributable to the ring strain of these small-ring heterocycles. The preponderance of synthetic applications involves nucleophilic opening of the epoxide ring, and an enormous range of nucleophilic species has been utilized for this purpose. The conversion of epoxides to isomeric compounds under the influence of acidic reagents has also been used preparatively for some time. However, it is only relatively recently that such isomerizations have been effected by strong, non-nucleophilic base such as lithium dialkylamides (LiNR2). This chapter is concerned with the synthetic potential of these base-promoted reactions of epoxides.



Although several types of isomeric products are observed on treatment of epoxides with strong bases, the most interesting conversion from a synthetic point of view is the formation of allylic alcohols. This subject constitutes the major emphasis of this discussion.



A second, much less common transformation is typified by the conversion of cis-cyclooctene oxide to endo-2-bicyclo[3.3.0]octanol, along with some of the expected allylic alcohol. This early observation attracted considerable attention because of the unanticipated generation of a new carbon skeleton in the isomerization process and is largely responsible for the subsequent flurry of activity in the area of base isomerizations of epoxides.



A third type of conversion also occasionally observed leads to the production of an isomeric carbonyl compound.



The final isomerization pathway included in this survey involves the transformation of epoxides possessing allylic, propargylic, or benzylic methylene groups with a 1,3 relationship to an epoxide carbon into cyclopropylcarbinols by lithium amides in the presence of hexamethylphosphoramide (HMPA).



This review attempts to provide the necessary information for predicting the type of isomerization to be expected for a given epoxide under a specified set of conditions and, where possible, for manipulating these conditions to achieve the desired conversions. The survey is limited to the isomerizations of simple epoxides by powerful, relatively non-nucleophilic bases. Thus the significant literature concerning epoxides with proximate carbonyl functions and other anion-stabilizing substituents is not considered since the chemistry of such molecules is typical of the stabilized anions (intramolecular alkylations, Favorskii rearrangements, etc.) with the epoxide unit serving the trivial function of a good leaving group. In addition to lithium amides and organolithium reagents, the recently developed dialkylaluminum amides are systematically covered. Studies utilizing non-nucleophilic alkoxides (e.g., potassium tert-butoxide), particularly in polar aprotic solvents, are also included. However, the vast literature concerning the interaction of epoxides with metal alkoxides in alcohol solvents is not reviewed since these conditions are generally conducive to nucleophilic addition and are only rarely effective in promoting the epoxide isomerizations of concern in this chapter.


Keywords:

base-promoted isomerizations;
epoxides;
allylic alcohol;
cyclic alcohol;
ketones;
cyclopropyl carbinols;
saturated epoxides;
unsaturated epoxides;
functional epoxides;
lithium amide reactions;
organolithium reactions;
aluminum amide reactions;
side reactions;
oxiranes;
scope;
limitations;
experimental procedures

Base-Promoted Isomerizations of Epoxides

Reduction of abieta-5,8,11,13-tetraen-3-one with lithium aluminium hydride afforded the corresponding alcohol, which was submitted to catalytic hydrogenation to yield abieta-8,11,13-trien-3β-ol (7) together with its 5βH-isomer. Acetylation of 7, followed by the Friedel-Crafts acylation, afforded 3β-acetoxy-12-acetylabieta-8,11,13-triene. This compound was converted into 3β,12-diacetoxyabieta-8,11,13-triene (11) by the Baeyer-Villiger oxidation. Treatment of 11 with lithium aluminium hydride yielded hinokiol, which was oxidized to hinokione. Subsequently, hinokiol was methylated and the resulting 12-methyl ether was dehydrated to afford 12-methoxyabieta-2,8,11,13-tetraene. The tetraene was then submitted to hydroboration-oxidation to give 12-methoxyabieta-8,11,13-trien-2α-ol (15) which, on demethylation with ethanethiol and anhydrous aluminium chloride, afforded salviol. Oxidation of 15 with pyridinium chlorochromate, followed by demethylation, gave 2-oxoferruginol.

Synthesis of (+)-hinokiol, (+)-hinokione, (+)-salviol, and (+)-2-oxoferruginol.

Derivatives of nordehydroabietane from pine bark

New labdane diterpenes from Araucaria cooki

Conversion of resin acids into steroidal compounds. a review

A convenient route from abieta-8,11,13-trien-18-oic acid (10) to abieta5,8,11,13-tetraen-3-one (27) has been developed involving selective epoxidation of the alkene mixture (2) obtained by oxidative decarboxylation of the acid with lead tetraacetate. Treatment of the 3a,4a-epoxide (9) with lithium diethylamide gives a quantitative yield of the allylic alcohol (19). Brief treatment of this allylic alcohol with N-lithioethylenediamine gives the α, β-unsaturated alcohol (25), which on oxidation affords the enone (24). Methylation of the latter compound with methyl iodide and potassium t-butoxide in t-butanol yields abieta-5,8,11,13-tetraen-3-one (27) in 43% overall yield from the alkene mixture (2). Other reactions of the 3α, 4α-epoxide (9) are reported and discussed.

RC Cambie

Papers

Chemistry of the Podocarpaceae. XXIV. Ring-A modifications of Abieta- 8,11,13-trien-18-oic acid