Thermal transformation of 1α− and 1ß-endo and exo- dicyclopentadienyl vinyl ethers (competitive Claisen and Cope systems)

1α-endo-Dicyclopentadienyl vinyl ether undergoes Claisen rearrangement at 110°C, whereas at higher temperatures it suffered a tandem Claisen and Cope rearrangement. In contrast, the epimeric 1ß-vinylether undergoes only Cope, and no Claisen rearrangement. In exodicyclopentadienyl series where there is no possibility of Cope rearrangement, only the αvinylether underwent a smooth Claisen rearrangement.


Introduction
The stereochemical and regiochemical control of carbon -carbon bond formation offered by the Claisen rearrangement has made this named reaction a powerful synthetic tool.Many variants of this fundamental reaction have been developed to include hetero atoms, lower temperature conditions and better stereo control in the bond forming step.We wanted to exploit the Claisen rearrangement methodology for the stereospecific generation of new chiral centres in the synthesis of linear triquinanes.Linear triquinanes are an important class of sesquiterpene natural products possessing the fused cis-anti-cis [6.3.0.0 2,6 ]-undecane carbon skeleton.Some of these compounds have antitumour and antibiotic properties and hence there are many reports on their synthesis 1 .As one of the approaches for the synthesis of linear triquinanes, cis-anti-cis and cissyn-cis, we sought to investigate the Claisen rearrangement of vinylethers 1a and 1b.

1a 1b
The activation energy for Claisen rearrangement is lower than that for Cope rearrangement 2 .In the light of this fact, one could expect that Claisen rearrangement should occur preferentially in systems where competition between Claisen and Cope rearrangement exists.Indeed this has been observed by Cookson et.al 3 in acyclic systems.We have encountered an unusual reverse preference viz., a facile Cope migration in preference to Claisen rearrangement, which we describe herein.
While many examples can be found for tandem Claisen -Cope or sequential Claisen rearrangements, only a few examples are known where Claisen and Cope rearrangement mutually compete 2, 3. Hence, it was of interest to investigate the thermal rearrangement of the vinyl ethers 1a and 1b.The vinylethers were prepared from the respective alcohols 4 by mercuric acetate catalyzed trans etherification using n-butyl vinyl ether.

Results and Discussions
Thermolysis of 1α− vinyl ether 1a 5 in refluxing xylene for 3 h furnished a mixture of two aldehydic products 2a and 2b in 2:1 ratio in 70% yield, which are closely resolved in tlc.When 1a was refluxed in toluene for 6 h, it gave exclusively only the aldehyde 2a 5 in 70% yield (based on recovery of starting material).Attempts to force this reaction to completion by prolonged heating led to the formation of 2b viz., product of sequential Claisen -Cope rearrangement demonstrating that Claisen rearrangement is preferred over Cope rearrangement in this system, which parallels literature reports 3 .When pure 2a was refluxed in xylene for 3 h, it furnished a mixture of 2a and 2b in a ratio of 2:1.It is evident from the above experiment that the aldehyde 2b formed in the thermolysis of vinyl ether 1a at 140 o C, is due to the sequential Claisen and Cope rearrangement Scheme 1.

Scheme 1
In remarkable contrast to the behavior of 1a, the epimeric vinyl ether 1b 5 under identical conditions exhibited an exclusive preference for the Cope pathway furnishing the anti ether 2c 5 .No Claisen product could be observed Scheme 2. The structure of the anti ether 2c was confirmed by synthesizing it from the literature 4 .The structure of 2c can be easily distinguished from the starting 1β-vinyl ether 1b.The upfield shift 0.8 ppm in the case of H10 (δ 3.8) viz, CH-O-CH=CH 2 in 2c is due to the shielding of this proton by the norbornene double bond and in 1b the signal due to the corresponding proton viz, H3 appears at δ 4.7.The signals due to H10 and H10' protons of the methylene bridge in 1b, which resonated at δ 1.4 and 1.2 are absent in 2c.The signals due to allylic methylene (H3 and H3') protons of 2c resonated at δ 1.6 and 2.2 (Scheme 2).

Scheme 2
While all the reported examples in the literature bring forth the propensity of the endodicyclopentadienyl derivatives to undergo Cope rearrangement, none of these is a Claisen system and hence there is no possibility for a competition between Claisen and Cope rearrangement 6 .In this context, the 1β-vinyl ether 1b is a unique system wherein competition between Claisen and Cope rearrangement is possible.In order to test the generality of this reverse preference exhibited by 1ß-vinyl ether 1b, various γ− substituted vinyl ethers 6a-6c were prepared as shown in Scheme 3 7,8 No Claisen products were observed in any of these cases.Inspection of the molecular model of these vinyl ethers show that there is a severe interaction between the norbornene double bond and the vinyl ether double bond, when the vinyl ether moiety is brought into the necessary geometry for the Claisen rearrangement.As a result the vinyl ether takes up other conformations, while no such unfavorable steric interactions exist for the formation of Cope geometry.Because of this the Cope rearrangement is favored over Claisen rearrangement.It is interesting to note that in the case of 8,9 dihydro derivatives 1c and 1d which are no longer Cope systems, only 1c 5 underwent a smooth Claisen rearrangement furnishing the aldehyde 2d 5 where as the epimeric βvinyl ether 1d 5 did not undergo any rearrangement even after refluxing for longer time.In the later case the attainment of transition state for Claisen rearrangement is not possible due to steric reasons (Scheme-5).

Scheme 5
Since the ester enolate Claisen rearrangement occurs under relatively milder conditions compared to thermal Claisen rearrangement, it is of interest to find out whether the Claisen rearrangement of the acetate 1e under Ireland conditions would stop at the Claisen rearrangement stage.Indeed the α-acetate 1e, when subjected to Ireland ester enolate Claisen rearrangement 9 , was smoothly transformed to the carboxylic acid 2e in 60% yield (Scheme 6).The epimeric βacetate 1f 10 did not undergo the rearrangement and only starting material was recovered.

Scheme 6
In the case of exo -dicyclopentadiene series two allyl moieties are far away from each other.As a result of this, attainment of a six membered cyclic transition state is geometrically impossible in this system and hence there is no possibility of Cope rearrangement 11 .We observed that the 1α-exo-dicyclopentadienyl vinyl ether 1g underwent a clean Claisen rearrangement and furnished the aldehydic product 2f in 75% yield 5 .Under identical conditions the epimeric 1β-vinyl ether 1h remained inert and only the starting material was recovered while under drastic conditions i.e., refluxing in high boiling solvents like p-cymene, o-dichlorobenzene no clean transformation was observed.The same trend was also observed in the ester enolate rearrangement of two acetates 1i and 1j and only the α acetate 1i underwent the Claisen rearrangement to give the acid 2g in 70 % yield whereas the epimeric β-acetate 1j did not undergo rearrangement Scheme 7.

Scheme 7
Experimental Section General Procedures. 1 H NMR spectra were recorded at 400 MHz except were indicated at 300 MHz.The 13 C NMR were recorded at 100.5 MHz except where indicated otherwise.The chemical shifts of all the NMR spcetra are reported in parts per million relative to tetramethyl silane.

General procedure for Cope and Claisen rearrangements
The respective vinylether 1 m mole was dissolved in 5 ml of toluene and were refluxed under nitrogen atmosphere for 6 hrs.Solvent evaporated under reduced pressure and the products were purified over neutral alumina using hexane as an eluant.For Claisen rearrangements the vinyl ethers were refluxed with xylene for 3 hrs, solvent evaporated under reduced pressure and the products were purified by flash column chromatography on 230-400 mesh silicagel using 3%

Conclusions
Our study has been shown that 1β-vinyl ether 1b undergoes Cope rearrangement in preference to Claisen rearrangement, furnishing the anti ether 2c 5 .This preference for Cope rearrangement has also been observed with a few other γ-substituted vinylethers .In none of these cases, any Claisen rearrangement was observed.In the dihydro series where there is no possibility of Cope rearrangement, the 1α-vinylether 1c underwent Claisen rearrangement, where as the 1βvinylether 1d remained unchanged even after refluxing for a long time .In exodicyclopentadiene series, only the 1α-vinyl ether 1g underwent a smooth Claisen rearrangement.

Scheme 3 ISSN 1424-6376 Page
139 ©ARKAT USA, IncWhen these vinyl ethers were subjected to thermolysis in refluxing toluene, they underwent exclusively Cope rearrangement and furnished the respective anti ethers 7a -7c (Scheme 4 and