NUCLEOPHILIC ELIMINATIVE RING FISSION OF BRIDGEHEAD SUBSTITUTED 1,3-BISHOMOCUBYL ACETATES

Article abstract of DOI:10.1016/S0040-4020(01)96416-6

The base induced cage fission of three different types of functionalized bridgehead substituted 1,3-bishomocubyl acetates, viz A, B and C is described.The synthesis of two 6-functionalized 1,3-bishomocubyl 4-acetates (type A), viz 4-acetoxypentacyclo<5.3.0.0^2,5.0^3,9.0^4,8>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-acetoxypentacyclo<5.3.0^2,5.0^3,9.0^4,8>decan-6-one 15, its ethylene acetal 16 and the parent acetate 20has 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 constrast, 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 totetracyclo<5.3.0^2,5.0^4,8>decenone 37.In constrast the syn-epimer 36a, under similar conditions, only affords the bridgehead alcohol 38.