Preparation of Dimethyl 7‐Oxobicyclo[2.2.1]heptane‐exo‐2, exo‐3— dicarboxylate. An Easy Route to Functionalized Norbornane Derivatives and Cage Compounds

Abstract

A four-step preparation of dimethyl ?-oxobicyclo[2.2.1~-atives which is used for an improved synthesis of the tricyclic heptane-exo-2,exo-3-dicarboxylate (4) in satisfactory yield diester ?, precursor of the cage compound 8. An alternative from the readily available 6,6-dimethylfulvene and maleic approach to diester 7 from dimethyl 74sopropylidenebi-anhydride is described. a compound of interest in connection with the synthesis of polyquinanes. This compound is easily prepared by intramolecular carbene insertion reaction of the 0x0 diester 7. The synthesis of 7 may be carried out by two different routes. However, 8 is not available in gram quantities as both routes suffer from serious drawbacks. In one case, a poorly stereoselective Diels-Alder reaction of the expensive 1 -cyclopentene-l,2-dicarboxylic anhydride*) with 6,6-dimethylfulvene is the key step. In the other route, the difficultly accessible and unstable 5,5-diethoxy~yclopentadiene~) is produced as an intermediate.In this paper we describe a highly improved synthesis of 0x0 diester 7 from 1 (Scheme l), readily accessible by hydrogenation of the Diels-Alder exo adduct of 6,6-dimethylfulvene with maleic anhydride4). The key intermediate in this 3).Ozonization of 2 is carried out by bubbling a stream of ozone-containing oxygen (approx. 3% ozone) through a CC4 solution of 2 at -25°C until the solution becomes blue-violet. The reaction mixture is then hydrogenated at atmospheric pressure by using 10% Pd on charcoal as catalyst until no more hydrogen is absorbed. Crystallization of the crude product from 2-propanol gives dimethyl 7-oxobicy-~10[2.2.l]heptane-exo-2,exo-3-dicarboxylate (4) in 68% yield.Two byproducts are formed in low yields in this reaction (less than 5% as determined by GLC). One of them is isolated from the mother liquors of 4 by column chromatography, crystallized from toluene, and characterized as methyl (1 RS,5SR,6RS,9SR,10SR)-5-hydroxy-4,4-dimethyl-2-0~0-3-oxatricyclo[4.4.0.05~9]decane-10-carboxylate5) (10) (Scheme 2). The other one is identified as the lactone 3. The proportion of compound 10 formed in this reaction seems to increase with rising polarity of the solvent and temperature of the reaction mixture. However, in each case 0x0 diester 4 is the major reaction product.The formation of 10 in the ozonization of 2 may be explained by initial epoxidation of the C = C bond to epoxide 9, followed by intramolecular nucleophilic opening (Scheme 2). To support this hypothesis, compound 2 is epoxidized with m-chloroperbenzoic acid in CH2C12 to a mixture of two