Attempted synthesis of 2-oxo-N -phenyltetracyclo[

The diastereoselective preparation of 4  -(diazomethylcarbonyl)- N -phenyltricyclo[5.2.1.0 2,6 ]- decane-2  ,6  -dicarboximide and attempts to transform this compound into a derivative containing the tetracyclo[7.2.1.0 2,6 .0 5,11 ]dodecane skeleton are described.


Introduction
We have been working for many years on the preparation and reactivity of different cage compounds. 1We have recently prepared different amine derivatives containing several of these skeletons to study their biological activity with quite interesting results. 2 With the aim of preparing novel cage compounds as scaffolds for the preparation of new derivatives with potential biological activity, we planned the preparation of compound 6 containing the tetracyclo[7.2.1.0 2,6.0 5,11]dodecane skeleton (Scheme 1).Only one paper describing two compounds containing this carbocyclic skeleton prepared from a longifolene derivative have so far been described. 3However, the methods used for the preparation of these compounds can not be generally applied to obtain compounds with this carbocyclic skeleton.Recently, we described an easy access to compound 1 (Scheme 1) by double alkylation of the dianion derived from endo-N-phenylnorbornane-2,3-dicarboximide with 3-chloro-2-chloromethyl-1-propene. 4 We envisaged that compound 6 might be prepared from alkene 1 as shown in Scheme 1, the keystep consisting of an intramolecular insertion of an -ketocarbene, generated from diazoketone 5, into an unactivated C-H bond with formation of a seven-membered ring.These types of transformations are well known and have been widely applied to the elaboration of three to sixmembered rings, formation of five-membered rings being usually preferred. 5The formation of seven-membered rings by intramolecular -ketocarbene insertions into S-H, O-H or N-H bonds is well known.5b Several examples of carbene insertions into an unactivated C-H bond leading to seven-membered heterocycles (oxepanes, 6 or 1,2-oxazepines 6a ) or even larger heterocycles 7 have been described.Intramolecular C-H insertion of the -ketocarbene derived from diazoketone 5 can not lead to a five-membered ring, although it might give a three-or four-membered ring.Insertion at the bridgehead positions leading to a six-membered ring must be very unfavorable for steric reasons.Consequently, it appeared to us that there was a real chance for the -ketocarbene derived from 5 to insert into the C-Hsyn bond of the methylene bridge leading to the tetracyclo[7.2.1.0 2,6.0 5,11]dodecane skeleton with formation of a seven-membered ring competing with the other possible intramolecular C-H insertions.
The configuration of alcohol 2 could not be unambiguously determined by 1 H and 13 C NMR in spite of the absence of NOE between 4-H and 10-Hsyn, however, it was clearly established by X-ray diffraction analysis (Figure 1).Oxidation of alcohol 2 with Jones reagent 9 gave the corresponding carboxylic acid 3 in good yield.Reaction of acid 3 with thionyl chloride followed by reaction with an excess of an ethereal solution of diazomethane, prepared as described, 10 gave diazoketone 5 in 58% yield, after column chromatography.Photochemical decomposition of diazoketone 5 in n-pentane solution using a quartz reactor and a 125 W low pressure mercury lamp gave a mixture of compounds, none of them having the expected molecular mass (GC/MS) for the tetracyclic ketone 6.A similar result was obtained when diazoketone 5 was decomposed at room temperature in CH2Cl2 in the presence of the complex dirhodium tetra(perfluorobutyrate)([Rh(pfb)2]2).The new compounds 2, 3 and 5 were fully characterized through their spectroscopic data (IR, MS, 1 H and 13 C NMR) and elemental analysis.Worthy of note, the MS spectra (electron impact, 70 eV) of compounds 3 and 5 showed a base peak with m/z = 91 Da, an ion which was also abundant in the MS spectrum of compound 2.Although this ion could correspond to [C6H5N] •+ , it might also correspond to the tropilium ion [C7H7] + .This assumption was supported by the fact that many sandalwood odorants containing the same tricyclo[5.2.1.0 2,6]decane skeleton and lacking any aniline group also show abundant peaks of m/z = 91 Da, which in one case was the base peak. 11A possible pathway for the formation of the tropilium ion by fragmentation of the parent ion of compounds 2, 3 or 5 is given in Scheme 2.

Scheme 2. Possible pathway for the formation of tropilium ion in the MS spectra of compounds 2, 3 and 5.
A tentative structure for the main ions observed in the MS spectra of acid 3 and diazoketone 5 as well as possible mechanistic pathways for the formation of most of them is given in Schemes 3 and 4, respectively.Fragmentation of alcohol 2 essentially parallels that of acid 3, although in this case the parent peak is the base peak.

Scheme 3 .Scheme 4 .
Scheme 3. Possible structures and pathways for the formation of the main ions in the MS spectrum of compound 3.
a b Maximum peaks in final difference synthesis.c Minimum peaks in final difference synthesis.