An Entry to Functionalized 2,8-Ethanonoradamantane Derivatives

Abstract

The synthesis of a functionalized derivative containing the 2,8-ethanonoradamantane carbocyclic skeleton, whose key-step consists of an intramolecular Diels-Alder reaction, is described. Chemoselective reduction of an intermediate enone required protection of the maleimide function through their Diels-Alder adducts with furan.

Improved synthesis of 5-(t-butyldimethylsilyloxymethyl)-2-methyl-5,6-dihydrocyclopenta[c]pyrrole-1,3(2H,4H)-dione from N-methylmaleimide

“…We have developed a synthetic sequence to prepare silyl ether 5 from N-methylmaleimide (10) which implies six steps with an overall yield of 21%, five times higher than that previously described, 1 starting from N-methylsuccinimide, that requires five steps with a global yield of 4.3%. The key points of the new procedure consists of: (1) protection of the C=C bond of the maleimide 9 as a Diels-Alder adduct with 9-benzyloxymetoxyanthracene, (ii) a thermal retroDiels-Alder reaction of the mixture of silyl ethers 22 and 24 to regenerate the C=C bond of the maleimide, and (iii) although the hydroboration/oxidation of 27 gives a stereoisomeric mixture of alcohols, it is not necessary to separate this mixture, since both stereoisomers gave the same product at the end of the synthetic sequence.…”

“…1 However, the preparation of the key intermediate, alcohol 6 or derivatives, such as silyl ether 5 or mesylate 7, implies several low yielding steps, resulting in difficult access to 8 in the required quantities for further transformations (Scheme 1). To solve this problem we planned an alternative approach to 5 or 6 which overcomes the low yielding conversion of the succinimide 4 to the maleimide 5, by phenylselenylation followed by oxidative elimination.…”

Alternative Access to Functionalized 2,8-Ethanonoradamantane Derivatives

“…Some time ago, the synthesis of the functionalized polycycle 13 as a new scaffold for the preparation of compounds with potential biological activity was described [ 1 ]. Later on, improvements of the synthesis of 13 were performed [ 2 , 3 ], the highly-optimized synthetic route to this compound is shown in Scheme 1 .…”