Diels-Alder Cycloaddition of Cyclopentadiene to a Bis-naphthoquinone

Addition of cyclopentadiene to bis-naphthoquinone (1) afforded predominantly the endo-endo [4+2] cycloadduct (2).


Introduction
Work in this research group has focussed on the addition of cyclopentadiene to naphthoquinone dienophiles bearing an electron withdrawing group at C-2 [1].These dienes are of particular interest in that the Diels-Alder adducts can undergo selective fragmentation of the C-4/C-4a bond affording an electrophilic site which can then be trapped by a hydroxyl group to give a cyclopentannulated product (Scheme 1).Development of this Diels-Alder/fragmentation reaction in an asymmetric sense has also been the focus of recent investigations [2] using chiral Lewis acid catalysis.As an extension to our earlier work in this area, bis-naphthoquinone (1) was perceived to be a bisdienophile for a double [4+2] cycloaddition reaction with cyclopentadiene (Scheme 2).The Diels-Alder adduct (2) resulting from addition to the two quinonoid double bonds would undergo fragmentation at both ends of the molecule to afford a bis-cyclopentannulated product (3) (Scheme 3).

Results and Discussion
A study of the Diels-Alder addition of cyclopentadiene to bis-naphthoquinone was initiated.An excess of freshly distilled cyclopentadiene was added under nitrogen -78 o C to a dichloromethane solution of bis-naphthoquinone (1) which was prepared as reported previously [3].After 10 min., no starting material remained and the formation of several new products of similar polarity was evident upon TLC analysis. 1H nmr analysis of the reaction mixture displayed features consistent with formation of adduct (2).The presence of signals resonating at δ 6.0-6.5 were assigned to the vinylic protons whilst a resonance at δ 4.13 was characteristic of the bridgehead proton assigned to H-9a.
When using monomeric quinones as the dienophile exclusive formation of the endo cycloaddition adducts was observed [2].However, the possibility of forming several diastereomeric adducts arises when bis-dienophile (1) is used.In bis-naphthoquinone (1) three modes of addition can potentially result, endo-endo, endo-exo and exo-exo, thus the possibility of diastereomeric adducts is not unexpected.The presence of multiple vinylic, bridgehead and methoxy signals in the 1 H nmr spectrum provided evidence for a mixture of products.
Direct fragmentation of the product mixture using SnCl 4 in dichloromethane was then examined in order to simplify product analysis (Scheme 3).After stirring for 10 min.at 0 o C several new products of lower polarity were evident upon TLC analysis, however, rapid decomposition of the crude reaction mixture in CDCl 3 occurred.The addition of the Lewis acid catalyst (SnCl 4 ) to bis-naphthoquinone (1) prior to addition of cyclopentadiene afforded baseline material due to decomposition of bisnaphthoquinone (1) by the Lewis acid.
Partial characterisation of the original Diels-Alder product mixture (5 mg) was accomplished using preparative HPLC affording four separate products in low yield (0.6-2 mg).Formation of the endoendo adduct (2a) as the major product was confirmed upon spectroscopic analysis.High resolution mass spectrometry established the molecular formula C 36 H 30 O 8 whilst two bands in the IR spectrum at 1725 cm -1 and 1678 cm -1 were attributed to the carbonyls of the ketone and ene-dione respectively.The 1 H nmr spectrum displayed two singlets at δ 2.42 and δ 3.50 assigned to the methyl groups of the acetyl and methoxy, whilst multiplets at δ 3.58-3.60and δ 3.80-3.82were assigned to H-1 and H-4 respectively.A two proton multiplet at δ 6.24-6.26 was assigned to the vinylic protons H-2 and H-3, whilst a doublet at δ 4.13 with coupling constant J 9a,1 3.9 Hz was assigned to the bridgehead proton H-9a.The coupling constant J 9a,1 3.9 Hz is consistent with formation of the bis-endo adduct (2a) [2].A second product (1 mg) displayed features consistent with endo-exo adduct (2b) formation, most noticeably three vinylic multiplets were observed which integrated for one, two and one proton(s) respectively.The two proton multiplet at δ 6.25-6.27was assigned to the endo ring vinylic protons H-2 and H-3.These protons resonated at a similar chemical shift to those reported for the analogous pro-tons in the endo-endo adduct (2a).The remaining one proton multiplets at δ 6.41-6.44 and δ 6.11-6.13were thus assigned to the vinylic protons of the exo adduct portion of the molecule, H-2' and H-3'.Two singlets at δ 2.30 and δ 2.42 were assigned to the acetyl group of the exo and endo rings respectively, whilst multiple aromatic signals provided further evidence for the unsymmetrical diastereomer (2b).
The two remaining products (<1.5 mg) exhibited complex 1 H nmr spectra and the structures to date have not been elucidated.It is not unreasonable to assume that the formation of unsymmetrical dimers arising from reaction of only one half of bis-naphthoquinone (1) may well result in a complicated mixture.A poor mass recovery was obtained from the Diels-Alder addition of bis-naphthoquinone (1) to cyclopentadiene thereby precluding a synthetically useful approach to the bis-cyclopentannulated products (3).

Experimental
General 1 H and 13 C NMR spectra were obtained using a Bruker AM 400 NMR and were recorded at 400 and 10 MHz respectively.Liquid secondary ion mass spectrometry (LSIMS) high resolution mass spectra were recorded at a nominal resolution of 5000 using 4-nitrobenzyl alcohol (NBA) and a 5:1 mix (v/v) of dithiothreitol : dithioerythritol as matrix.High performance liquid chromatography (HPLC) was carried out using a Waters Associates system consisting of, a mdel M-6000A pump, a millipore model U6K injector, a model 440 ultra-violet detector at 256 nm and a R401 differential refractometer.Separation was carried out using the indicated solvents on a Partisil 10 M9 semipreparative column of the following dimensions: outer diameter 12.80 mm, inner diameter 9.40 mm, length 500.0mm, and particle size 10.0 µm.Cyclopentadiene was obtained from Aldrich Chemical Company (USA) and was cracked immediately prior to use.