Swern Oxidation of Bicyclo[2.2.1]hept-5-ene-2,3-diol and Its Pyrazine-fused Derivatives: An Improved Synthesis of

An improved synthesis of bicyclo[2.2.1]hept-5-ene-2,3-dione by Swern oxidation of bicyclo[2.2.1]hept-5-ene-2,3-diol, and an unexpected ring-opening reaction by the Swern oxidation of pyrazine-fused congeners are described.


Introduction
Bicyclo[2.2.1]heptane skeletons have been a useful building block for the construction of molecular architectures with a concavity [1].In the course of our studies to synthesize a host molecule utilizing a negative electrostatic potential filed of pyrazine rings, a general method to prepare norobornene-2,3-dione and its pyrazine-fused derivatives was required.We describe here an improved synthesis of bicyclo[2.2.1]hept-5-ene-2,3-dione (3) by Swern oxidation of bicyclo[2.2.1]hept-5-ene-2,3-diol (6).We also report that a similar Swern oxidation reaction of pyrazine-fused congeners 10 and 11 was found to undergo an unexpected rringopening reaction.

Results and Discussion
Previously, bicyclo[2.2.1]hept-5-ene-2,3-dione (3) was prepared by the Diels-Alder reaction of cyclopentadiene with dichlorovinylene carbonate (1) giving the adduct 2, followed by hydrolysis [2].Dichlorovinylene carbonate (1) can be prepared by the reductive dechlorination reaction of tetrachloroethylene carbonate [3].However, the synthesis of tetrachloroethylene carbonate is troublesome because the use of a large amount of chlorine gas is required [3].Furthermore, we could not reproduce the reported yield of the Diels-Alder re-action of 1 with cyclopentadiene: the adduct 2 was obtained only in 40-50% yields whereas 65-70% yields were claimed in the literature [3].Thus, we report here an improved synthesis of 1 starting from more readily available vinylene carbonate (4) [4].
When the exo-cis diol 10 was treated with dimethyl sulfoxide and trifluoroacetic anhydride, (6,7-dihydro-5H-cyclopentapyrazin-5-yl)methanol (12) was obtained in 75% yield.A similar treatment of 11 provided 13) in 63% yield.The Swern oxidation of 11 by the use of oxalyl chloride instead of trifluoroacetic anhydride also produced 13 in 63% yield.We could observe no evidence for the formations of expected α-diketones 14.When we were monitoring the reaction by TLC, a spot initially formed on the TLC plate was disappeared after the work-up with aqueous sodium hydroxide solution.Unfortunately, our attempts to isolate the intermediate corresponding to this spot were unsuccessful.
A plausible mechanism for the present reaction was illustrated in Scheme 3. The initially formed sulfonium ion 15 would undergo the C-C bond cleavage by the abstraction of hydroxyl proton with triethylamine, and the intramolecular Cannizzaro reaction under alkaline conditions followed by decarboxylation could give the products 12 and 13.However, the Cannizzaro reaction is well recognized to proceed for aldehydes with no α-hydrogen [8].Furthermore, the Swern oxidations of vicinal diols 18 [9], 19 [10] and 20 [11] have all been reported to give the corresponding α-diketones, as did the oxidation reaction of 6.Thus, from our results we did not obtain evidence to discriminate between those reaction pathways and other potential mechanisms for the present reaction might be considered.

Conclusion
We have presented a facile route for the synthesis of the norbornenedione 3 and an unusual ring-opening reaction by Swern oxidation of the pyrazine-fused norbornenediols 10 and 11.

General
All the melting points were determined with a Yanagimoto hot-stage apparatus.IR spectra were obtained with a JEOL Diamond-20 spectrometer.NMR spectra were recorded either with JEOL JNM-LA400 ( 1 H: 400 MHz; 13 C: 100 MHz) spectrometer using TMS as internal standard.J-Values are given in Hz.Assignments of the 1 H and 13 C signals are based on DEPT, H-H COSY, and C-H COSY measurements.Mass spectra were measured with a Shimadzu GCMS-QP1000EX spectrometer operating in the electron impact mode (70eV).High-resolution mass spectra (HR-MS) were taken with a JEOL JMS-SX102A spectrometer operating in the FAB+ method.Elemental analyses were performed with a Perkin-Elmer Model 240 apparatus.Solvents were dried and purified by standard methods.Yields are based on isolated products with sufficient purity.