Nucleophilic eliminative ring fission of bridgehead substituted 1,3-bishomocubyl acetates

The base induced cage fission of three different types of functionalized bridgehead substituted 1,3-bishomocubyl acetates, vizA,B and C is described. The synthesis of two 6-functionalized 1,3-bishomocubyl 4-acetates (type A), viz4-acetoxypentacyclo5.3.0.0^2,5.0^3,9.0^4,8]decan-6-one 5 and its ethylene acetal 6 has been accomplished starting from the readily available Diels-Alder adduct 4. The synthesis of three 1,3-bishomocubyl 8-acetates (type B), viz 8-acetoxypentacyclo5.3.0^2,5.0^3,9.0^4,8]decan-6-one 15, its ethylene acetal 16 and the parent acetate 20 has been carried out starting from the cyclopentadiene-benzoquinone adduct 7. Base induced homoketonization of 6, 16 and 20 leads regio- and stereospecifically to the thermodynamically favored half cage ketones 22,28 and 31, respectively. In contrast, the cage opening of the β-ketoacetates 5 and 15 is essentially directed by the β-ketone function. In the case of 5, regiospecific cleavage of the central C₄-C₅ bond is observed producing in a stereospecific manner diketone 25 in quantitative yield. Under similar conditions, acetate 15 gives a complex mixture of cage opened products arising from further fragmentation of the initially formed diketone 34. Deuterium labeling experiments reveal an anti-Bredt behavior of half cage ketones 28 and 31. The synthesis of a bridgehead acetate of type C has been accomplished by stereoselective reduction of ketone acetate 5 with LiAlH(t-OBu)₃ followed by mesylation. A mixture of epimers 36a and 36b (ratio 1:4) is obtained from which the predominant anti-epimer 36b could be isolated. An X-ray analysis established its structure. Base induced cage fission of 36b leads regiospecifically to tetracyclo5.3.0.0^2,5.04,8]decenone 37. In contrast the syn-epimer 36a, under similar conditions, only affords the bridgehead alcohol 38.