Studies related to the synthesis of dimethyl tetracyclo[5.2.1.0^2,6.0^3,8]decane-7,8-dicarboxylate

Abstract

A synthesis of dimethyl tetracyclo(5.2. I .02~h.0".x]decane-7,8-dicarboxylate, 3, whose key step implies the formation of the CI-C2 bond by regioselective intramolecular C-H insertion of a carbene generated from dimethyl (lR,2S,6R,7S)-lOoxotricyclo[5.2.1 .0'~6]decane-2,6-dicarboxylate, 1 via its tosylhydrazone, is described. Attempts to synthesize diester 3 or compounds containing its carbon skeleton, by forming the same C-C bond, starting from dimethyl (lR,2R,6S,7S)-4- (1) and its methyl (2) and 1,16-dimethyl derivatives (3), the first compounds containing such a type of carbocyclic skeleton. The synthesis of dodecahedrane, however, implies 23 consecutive steps from cyclopentadiene, the overall yield being in the range of 0.1%, which limits its supply. Consequently it is still a challenge to obtain it through a shorter and higher yielding sequence (4).As part of our contribution to polyquinane chemistry (5-7), we describe herein the studies that have led to the successful synthesis of dimethyl tetracyclo[5.2. 1.0"6.03.8]decane-7,8-dicarboxylate, 3, a possible intermediate for a convergent synthesis of dodecahedrane.The retrosynthetic analysis of diester 3 shows that cleavage of the strategic (8) C1-C2 bond gives the well-known tricyclo[5.2.1 .02.6]decane skeleton, in contrast with other cleavages, which give precursors that are not easily accessible. Since the C1 and C2 atoms and their neighbours in compound 3 have no functionality, intramolecular C-H insertion of a carbene was considered to be the reaction of choice to form the 'Author to whom correspondence may be addressed. C 1-C2 bond. As shown in Scheme 1, there exist two ways to carry out such a transformation, depending on the carbon atom at which the carbene is generated. In fact, Neff and Nordlander (9) had utilized the first way in order to synthesize tetracyclo-[5.2.1 .02,6.03*8]decane from tricyclo[5.2.1 .02,6]decan-1 0-one.Because the synthesis of dimethyl (1 R,2R,6S,7S)-4-oxotricyclo[5.2.1 .02s6]decane-2,6-dicarboxylate, 2, appeared to be easier (5) than that of dimethyl (1 R,2S,6R,7S)-1O-oxotricyclo-[5.2. l.02~6]decane-2,6-dicarboxylate, 1, and because we were looking for a new entry into this carbocyclic skeleton (9, lo), we undertook the preparation of ketodiester 2 through the sequence depicted in Scheme 2.The starting product for this synthesis was bicyclo[2.2.1]-hept-2-ene-2,3-dicarboxylic anhydride, 4 (1 1). Reaction of anhydride 4 with excess butadiene gave (1 R,2R,7S,8S)-tricyclo[6.2.1 .0'~7]undec-4-ene-2,7-dicarboxylic anhydride, 5, in 81% yield. This compound had been previously prepared by Alder and Backendorf (l2), but its configuration was not established. However, owing to the fact that reaction of bicyclo-[2.2.l]hepta-2,5-diene-2,3-dicarboxylic anhydride with butadiene (13) gives a 1 : 1 mixture of the endo and exo adducts, it seems reasonable that anhydride 4, with the C4-C5 bond Can. J. Chem. Downloaded from www.nrcresearchpress.com by 34.212.246.108 on 05/10/18For personal use only.