Sulfur-bridged molecular racks: O,S -sesquinorbornadienes, CNS -[3] and CNOS -[4]polynorbornanes

Thiophene has been reacted under high-pressure (10 kbar) and temperature (100 0 C) with N - methylmaleimide and N -phenylmaleimide to produce Diels-Alder exo - and endo -adducts in modest yields (25-36%). Reaction of 7-oxanorbornadiene-2,3-dicarboxylic anhydride 6 , a highly reactive dienophile, with thiophene occurred under high-pressure (10 kbar) at 100 o C to yield stereoisomeric 1:1-adducts by site selective attack at the maleic anhydride type of π -bond. This approach afforded the first examples of syn-and anti-heterobridged sesquinorbornadiene anhydrides 8 and 9 containing a sulfur bridge. Similar reaction of isobenzothiophene with 6 was even more facile as reaction occurred at room temperature and atmospheric pressure to yield benzo-analogues 12 and 13 . Thermal fragmentation involving loss of furan and sulfur occurred from both classes of adducts under FVP (370 0 C, 0.005 mbar) to produce phthalic anhydride or naphthalene-2,3-dicarboxylic anhydride respectively. The putative 7-thianorbornadiene intermediates 20 and 22 , generated by loss of furan, were not detected. Reaction of exo-N -methyl 7-thianorbornene-5,6-dicarboxylic imide 4a with the ester-activated cyclobutenoaziridine 16 provided access to CNS-[3]polynorbornane 18 , while similar addition of the exo,endo -isomer of O,S -benzosesquinorbornadiene 13 to 16 afforded the CNOS-[4]polynorbornane 19 . These are the first S -bridged [n]polynorbornanes to be reported. Molecular modelling (AM1) has shown that S n - [n]polynorbornadienes have a curved topology greater than O n - [n]polynorbornadienes but less than N n - [n]polynorbornadienes.


Introduction
The use of [n]polynorbornanes and related molracs as scaffolds for vectorially positioning functionality has been realized through the syntheses of V-and U-shaped bis-porphyrin cavity systems. 1 The value of their metalated derivatives as supramolecular building blocks has been exploited in the co-ordinative assembly of pyridyl components to form universal joints, 2 as noncovalently linked donor/acceptor electron transfer agents 3 and more recently for self-assembly into large container molecules. 4In other applications, [n]polynorbornanes have served as spacer molecules for separating attached intercalators in order to promote optimal DNA/substate binding. 5

Results and Discussion
The choice of specific [n] polynorbornanes 6 or related molracs 7 has been predicated on scaffold topology meted by synthetic accessibility.Systems containing polyoxygen or polynitrogen bridges, as well as repeating combinations of C,O and C,N bridges have been described by our group. 8This has opened the way to produce a number of novel [n]polynorbornanes, the curvature of which was governed by the various combinations of C,N,O bridge components.In a natural extension of this series, we sought to add systems with sulfur bridges to the repertoire, an area that has been little investigated here-to-fore. 9n this paper, we explore ways to redress this deficiency and report on the synthesis of OSsequinorbornadienes, a CNS- [3]polynorbornane, a COS- [3]polynorbornane and a CNOS- [4]polynorbornane in which four different atom bridges are incorporated.Our approach commenced with the preparation of the sulfur-bridged norbornenes 3 and 4 and a study of their dienophilicity.In spite of the reluctance of thiophene to participate as a 1,3-diene in Diels-Alder reactions, there was a report on the addition of maleic anhydride to thiophene at high-pressure and temperature. 11That report also noted that dimethyl maleate, dimethyl fumarate, acrolein and other common dienophiles failed to add under the high-pressure conditions.

High pressure addition of dienophiles to thiophene
We have now found that N-substituted maleimides also add to thiophene at high-pressure and temperature.Reaction of N-methyl maleimide 2a with thiophene 1a occurred under highpressure (10 kbar) and temperature (100 o C) to give a 1.4:1 mixture of endoand exo-[4π+2π] adducts 3a and 4a respectively (Scheme 1).This reaction was general and similar mixtures of stereoisomers were formed in the reaction of thiophene 1a with N-phenyl maleimide 2b and of 2,5-dimethylthiophene 1d with N-methyl maleimide (see Table 1, Scheme 1).In all cases, the endo-isomers were the preferred product although significant quantities of the exo-isomers were also obtained.In comparison, the high-pressure reaction (100 o C, 15 kbar) between thiophene and maleic anhydride, first reported by Kotsuki et al., 11 was reported to produce almost exclusively the exo-adduct 4c.We have repeated this reaction and found that careful evaluation of the reaction mixture by 1 H-NMR showed that the endo-isomer 3c was also present, but it could not be isolated, possibly because of cycloreversion to starting materials at atmospheric pressure. 12tructural assignments to the various cycloadducts were made on the basis of chemical shifts and coupling constants (see Table 2) We have reported elsewhere that 7-oxanorbornadiene-2,3-dicarboxylic anhydride 6 was especially reactive in Diels-Alder reactions, 13 eg, we find that anthracene added at room temperature and ambient pressure to form adduct 7 (Scheme 2).Reaction between dienophile 6 and thiophene was more difficult but could be achieved at 100 o C by working under high pressure (10 kbar) to afford adducts 8 and 9 by site selective, exo-face addition to the maleic anhydride type of π-bond of 6.The structures of these adducts were assigned on the basis of NMR data (see Table 3).
The syn O,S-sesquinorbornadiene 8 and its anti-isomer 9 are the first examples of this ring system, although S-oxides related to the anti-isomer 9 have been reported in the bridgehead methyl series derived from 2,5-dimethylthiophene sulphoxide. 14The reduced Diels-Alder reactivity of 7-thianorbornenes compared with the 7oxanorbornenes was illustrated by the reaction of 9, a compound containing both sub-units, with excess cyclopentadiene which yielded adduct 10 by site selective addition at the 7oxanorbornene π-bond, albeit in very low yield.The activated dienophile 6 reacted with isobenzothiophene (IBT) 11, generated in situ, 15 under even milder conditions (ambient temperature and pressure) to form 1:1-adducts 12 and 13 in a reaction that exhibited the same site selectivity as that observed for thiophene (Scheme 3).

O
That this reaction occurred at room temperature within 30 minutes whereas the reaction between 6 and thiophene required high pressure and temperature, reinforced the improved Diels-Alder reactivity of isobenzothiophene relative to thiophene.In another example, IBT 11 was reacted (70 o C, CHCl 3 ,12 hr) with the less dienophilic dimethyl 7-oxanorbornadien-2,3-dicarboxylate 14 to form the 1:1 adduct 15.In this case, the site-selectivity changed to favor reaction at the unsubstituted π-bond 18 while the stereoselectivity was such that only the exo, anti-adduct 15 was observed.Li et al. have reported 14 that tetramethylthiophene-S-oxide reacted with 14 to yield an adduct with the corresponding site and stereoselectivity. 18he olefin π-bonds in adducts 3a-d and 4a-d were extremely reluctant to enter into [4π+2π] cycloaddition reactions.No cycloaddition occurred between 4a and inverse electron-demand heterocycles such as 3,6-di(2-pyridy1)-s-tetrazine, 2,5-bis(trifluoromethyl)-1,3,4-oxadiazole or regular electron-demand 1,3-dienes including cyclopentadiene (trace of product detected by NMR), cyclopentadienones or ester-activated cyclobutane epoxides under thermal, high pressure or photochemical conditions.By comparison, all these reactions have been reported to proceed with 7-oxanorbornenes. 19

Scheme 4
The exception was reaction of 4a with the aziridine 16 at 100 0 C in the absence of solvents, where the intermediate 1,3-dipole 17, formed from the thermal ring opening of the aziridine 16, was trapped by the π-bond of 4a to yield the CNS- [3]polynorbornane 18 (Scheme 4).
Formation of the first [4]polynorbornane with different atoms in each of the single-atom bridges was obtained by reaction of the major O,S-benzosesquinorbornadiene 13 with aziridine 16 (Scheme 5).The reaction was conducted at 120 0 C for 1 hour in the absence of solvent and produced the CNOS- [4]polynorbornane 19 in 33% yield.There was ample precedent for the exo,exo-coupling of aziridines of type 16 with 7-oxanorbornenes, 22 and this stereochemistry was confirmed by NOESY measurements between Ha and Hb.The reaction of 16 with the sulfurbridged norbornene 13 was the first of its kind, so the assignment of stereochemistry was especially important.Again NOESY measurements in 18 between Ha and Hb confirmed that coupling was again exo,exo-selective.The 1 H NMR data and structural assignments for 18 and 19 are presented in Table 4

Scheme 5
A positive feature of the above results was the fact that a range of aziridines related to 16 has already been reported 22b in which the X-bridges (Scheme 4) have been replaced by spirocyclopropyl, isopropylidene, oxygen or substituted nitrogen.As well, the nitrogen substituent of the aziridine has been also varied, eg methyl, methoxymethyl, p-methoxybenzyl or phenyl, further widening the range of X,N,S-bridged [3]polynorbornanes available by this protocol.Thus, an opportunity to map the role of sulfur as a flanking 'sentinel' may be established in the future.

Scheme 6
The high reactivity of 7-oxanorbornadiene-2,3-dicarboxylic anhydride 6 in Diels-Alder cycloadditions (vide supra) was paralleled by its bridged-nitrogen counterpart. 23On this basis, the S-bridged analogue, 7-thianorbornadiene-2,3-dicarboxylic anhydride 20, should be activated towards cycloaddition relative to 7-thianorbornenes, thereby offering entry to S,Ssesquinorbornadiene anhydrides by reaction with thiophene or isobenzothiophene.Our approach to the preparation of 20 was modeled on the retro-Diels-Alder route used for the preparation of 6 (see, Scheme 2).We reasoned that furan rather than thiophene would be the better dienofuge and FVP of O,S-sesquinorbornadiene anhydride 9 should produce 7-thianorbornadiene-2,3dicarboxylic anhydride 20 by loss of furan.In practice, FVP of 9 at 370 0 C/0.005 mbar produced phthalic anhydride 21 as the main product.Similar FVP of a mixture of O,Sbenzosesquinorbornadienes 12 and 13 yielded naphthalene-2,3-dicarboxylic anhydride 23 in 60% yield (Scheme 6).We consider that 7-thianorbornadienes 20 and 22 were produced but ejected sulfur under the reaction conditions to form the aromatic anhydrides 21 and 23.This proposal for sulfur loss found support in the literature where it has been reported that other attempts to form 7-thianorbornadienes, such as the reaction of benzyne with thiophene, yielded naphthalene rather than the expected 7-thianorbornadiene. 24 In the same vein, we have found that reaction of thiophene with dimethyl acetylenedicarboxylate (DMAD) 24 (100 0 C, 10 kbar) produced dimethyl phthalate 26, a result logically explained by loss of sulfur from the firstformed 7-thianorbornadiene 27 (Scheme 6).Interestingly, reaction of DMAD 24 with 4,9diazaisonaphthothiophene 27 has been reported to give the stable 7-thianorbornadiene 28 in a rare example of this class of sulfur bicycle. 25hese results thwarted our attempts to form dithiasesquinorbornadienes, although the reported stability of 28 does appear to leave open opportunities to form 20 or 22 using milder methods.

Scheme 7
Extrusion of the sulfur bridge was also implicated in the high-pressure reaction of thiophene with N-methyl maleimide at 100 0 C, which gave a sulfur-free product as well as the 1:1-adducts 3a and 4a (vide supra).This by-product was assigned the bis(maleimide) structure 30 on the basis of 1 H and 13 C NMR data and high resolution mass spectrometry (found m/z = 274.0954).It was considered to arise by N-methyl maleimide addition to the intermediate 1,2dihydrophthalimide 29, itself formed by loss of sulfur from 1:1-adducts 3a and 4a.Subjecting a mixture of 1:1-adducts 3a and 4a to the same thermal and high-pressure conditions, but with no added N-methyl maleimide, also yielded bis-maleimide 30.This result indicated that retro-Diels-Alder reaction of adducts 3a and 4a must have occurred under the reaction conditions competitively with loss of the sulfur-bridge to form cyclohexadiene 29.Reaction of N-methyl maleimide with 1,3-diene 27 to form symmetrical adduct 30 has precedent in the reaction of maleic anhydride with 1,2-dihydrophthalic anhydride. 26he simple endo-stereoisomeric 1:1-adducts 3a-c can be readily distinguished from their exoisomers 4a-c on the basis of vicinal H,H-coupling between Ha and Hb, since the former are coupled whereas the latter show no coupling (Table 2).The chemical shifts of the N-methyl substituents in 3a and 4a also provided a reliable stereo-marker, since the endo-stereochemistry placed the N-methyl group in the shielding zone of the olefinic π-bond. 27This caused an upfield shift of about 0.2 ppm relative to the exo-isomer.It was this chemical shift feature which allowed stereo-assignment for 3d, 4d, in which the bridgehead methyl groups precluded the use of vicinal H,H-coupling data.

NMe
In the sesquinorbornadiene anhydrides (Table 3a), the use of vicinal H,H coupling was again precluded by the presence of the anhydride moiety at the stereo-defining positions.Further, the lack of N-methyl groups precluded the second method used above.In this case, we have used another NMR argument based on the chemical shift of the bridgehead protons.The basis for this method resulted from the shielding by the newly formed π-bond on the adjacent bridgehead protons in sesquinorbornadienes with exo,endo-geometry.The method was typified by model compounds 5 and 31 in the O,O-sesquinorbornadiene anhydride system (Table 3a).The C2vsymmetry of the syn-facial isomer 5 was defined by two chemical shifts: the bridgehead protons at δ 5.22 and the olefinic protons at δ 6.71.In the anti-isomer 31, there are two sets of bridgehead protons, which display significantly different chemical shifts (∆δ = 0.48 ppm).The upfield shift of Ha relative to Hb, being attributed to shielding of Ha by the through-space related olefinic bond.Such shifts were a reliable method for stereochemical assignments, and the 0.39 ppm upfield shift of bridgehead proton Ha in 9 relative to bridgehead proton Ha in 8 has allowed the syn-stereochemistry to be assigned to 8 and the anti-stereochemistry to 9. Table 2. 1 H-NMR Chemical shift assignments for adducts formed in the high-pressure reaction of thiophenes 1a, 1d with N-substituted maleimides 2a, 2b and maleic anhydride 2c   With the O,S-benzosesquinorbornadienes 12 and 13, a similar shielding effect on bridgehead protons Ha was apparent (Table 3b) and was attributed to the anisotropy of the benzene ring.The observed effect was even more pronounced in this case with a shift difference between bridgehead protons Ha in 12 and 13 of 0.58 ppm.The similarity between bridgehead protons Ha in model compound 7 (where there must be similar shielding from the benzene ring), with bridgehead protons Ha in 13 was in keeping with the bent-frame stereochemistry assigned to 13.The second set of model compounds 33 and 34 (Table 3c) confirmed that there was little difference in chemical shift at the bridgehead protons Hb of the sulfur bridge.This observation ruled out a role for the imide ring irrespective of its configuration and confirmed that shift differences in the compounds discussed above, eg 8 v 9 or 12 v 13 were the result of anisotropy from another source, viz olefinic π-bond in the former pair or aryl ring in the latter pair.The proton chemical shift of the N-methyl group was again diagnostic of stereochemistry with the endo-isomer 33 being shifted upfield by 0.56 ppm relative to 34, owing to the shielding influence of the aryl ring.Chemical shift assignments for [n]polynorbornanes 18 and 19 have been determined on the basis of coupling data, comparison of chemical shift data with other [n]polynorbornanes derived from aziridine 16 or chemical shift data collected in this paper.Noteworthy features include: i) the significant downfield shift (steric compression) 28 of the methano-bridge protons (He) adjacent to the nitrogen bridge in compounds 18 and 19 ii) the large upfield shift of the oxa-bridge bridgehead proton (Hc) in 19 caused by anisotopic shielding of the aryl ring as discussed above.iii) a similar upfield shift of Hc in 10 of reduced magnitude has been ascribed to olefinic π-bond shielding iv) the downfield shift (δ 4.85) of the sulfur bridgehead protons Hd in 19 consistent with their benzylic nature and in keeping with model structures 33 and 34.The related bridgehead protons Hd in 18 lack the fused aromatic ring and occur at δ 4.11.

Molecular modeling
In this section we address several issues pursuant to the shape of S-bridged [n]polynorbornanes.In particular, separate sections dealing with i) the 3D geometry of 7-thianorbornenes and Sbridged sesquinorbornadienes, ii) the topology of multi-S-bridged [n]polynorbornanes and iii) the conformational (invertomer) preferences of N-benzyl substituents in XNS-[n]polynorbornanes are presented, in that order.

i) 7-Thianorbornene and S-bridged sesquinorbornadienes
Calculations have been conducted at the AM1 level of theory on endo-7-thianorbornene anhydride 3c and its oxygen heterologue 35 and the energy-minimized structures determined.Aside from selected bond angles and bond lengths, inter-planar angles relating the planes defined by the bridgehead carbons and the heteroatom, the etheno bridge or the ethano bridge were determined.Comparisons between the inter-planar angles (θ3 and θ4) indicated the relationship of the hetero-bridge with the boat-shaped cyclohexene ring that constituted the carbocyclic frame.These angular differences revealed that the oxygen bridges were bent away from the etheno-bridge and towards the ethano-bridge to a larger extent than the sulfur bridges.Reference to the inter-planar angles between the carbocyclic bridges showed that the cyclohexene ring component in the oxygen bridged system 35 was more puckered (by ca 6 o ) than its sulfur counterpart 3c.The separation of the bridgehead carbons C 1 and C 4 in the two systems (2.418 v 2.205 Å) provided an additional measure of the geometrical change in the cyclohexene ring.In spite of the fact that the C-S bonds in 3c are significantly longer than the C-O bonds in 35 (1.84 v 1.47 Å), the shape of the carbocylic frames of the two structures remained similar.This becomes apparent in AMI minimised structures of 3c and 35 and the overlay of the two shown in Figure 1.The inter-planar angles (θ5) between the etheno and the ethano bridges are 117.61o for 3c and 111.70 o for 35 and this largely determines the shape of the fused products, viz the increased curvature of sulfur-bridged systems compared to their oxygen analogues (vide supra).Table 5. Calculated parameters (AM1) for heteronorbornene anhydrides 3c and 35 In the related XY-sesquinorbornadiene anhydride systems, the energy-minimized structures (AM1) for the syn-isomers in the O,O-, S,Sand O,S-systems have been computed (Figure 2 a, b, c respectively) and the parameters for these and the corresponding anti-isomers tabulated in Table 6.As a generalization, it was clear once again that the geometry of all the systems were similar with only small but significant changes.In the syn-series where the two hetero-bridges are juxtaposed, it was possible to determine the role of each heteroatom on the sesquinorbornadiene geometry.S,O-interaction in 8 caused an away movement of the O-bridge and attendant shift of the ethano-bridge towards the anhydride ring.Reference to overlays of 35 on 8 (Figure 2g) and 3c on 8 (Figure 2h) demonstrated that both the S-bridge and the O-bridge had been moved outwards and that both etheno-bridges bent downwards as reflected in the decreased inter-planar angles.That the S-bridge was the cause of the second bridge distortion was confirmed by the outward bending of both S-bridges in the S,S-system 36.In contrast, the O,O-sesquinorbornadiene anhydride 5 showed no O-bridge distortion.
Comparison of the geometries of the O,O-system 5 with the S,S-system 36 demonstrated that despite the differences in bond length (C-O v C-S), cyclohexene interplanar angles (110.88 o for 5 v 116.02 o for 36) as well as the heterobridge interactions (O,O v S,S), these parameters turn out to be compensatory and the frame projections (especially those of the cyclohexene subunits which constitute the zig zag carbocyclic frame) were surprisingly similar.Indeed, the separations of the terminal sp2 carbons of the separate π-bonds were almost identical (4.93 Å in 5 v 4.87 in 36).Of course, these small differences are additive and can be expected to still make substantial differences in curvature to the frames of larger [n]polynorbornadienes.

ii)Topology of S-bridged [n]polynorbornanes
Revisiting the role of heteroatom-bridges (N and O systems described earlier) 6,8 in governing the shape of [n]polynorbornadienes, we have calculated (AM1) structures for two hypothetical systems, viz the S 9 -polynorbornadiene 38 and (CS) 4 C-polynorbornadiene 39 (Diagram 1, Figure 4).A comparison of the radii of curvature of these S-bridged systems placed them respectively between the corresponding N 9 -and O 9 -(same atom-bridge series) and the (CN) 4 Cand (CO) 4 Canalogues (alternate atom-bridge series) as shown in the Tables 7a,b.

Diagram 1
A consequence of replacing alternative sulfur bridges in 38 by methano-bridges to form 39 was that the curvature of the carbocyclic frame in 39 became more curved and the inter-planar relationship (angle φ) of the terminal norbornenes changed from being divergent in 38 to convergent in 39.This structural feature was not apparent in the oxygen or nitrogen hetero-[n]polynorbornanes studied earlier: both series are convergent in the N 9 and (CN) 4 C-systems and both divergent in the O 9 and (CO) 4 C-systems.iii) N-Benzyl invertomerisation in XNS-trident polynorbornanes Molecular modeling had not been conducted previously for [3]polynorbornadienes containing a sulfur bridge (XNS-tridents).The molecular model (AM1) of the CNS- [3]polynorbornane 18, revealed that the methylene of the N-benzyl group was positioned on the sulfur side rather than on the side of the methano-bridge.This was not unexpected since our earlier results on the effects of flanking 'sentinel' groups (Y) in CN(Bn)Ytridents had demonstrated the dominance of the CH 2 -sentinel over oxygen and nitrogen sentinels.22b The ONS-trident system offered an interesting comparison since this would be the first example of different hetero-bridge sentinels which are not complicated by substituents.It should be appreciated that the ONO-tridents are dynamic and do not assume a preferred invertomer geometry in solution.Calculations (AM1) indicated that the ONS-tridents exhibited two minimum energies, one for the invertomer adjacent to the O-bridge and another adjacent to the Sbridge with the former being favored by 3.3 kcal/mol.An experimental study relating to this topic is currently under investigation.The model (AM1) of the CNOS- [4]isopolynorbornane 19 where the N-benzyl was positioned between a methano-bridge and an oxygen-bridge, a system with precedent in the CNO-trident series, again favored the invertomer directed towards the O-bridge (see Figure 1b).The critical bridge N-O distance was 2.97Å, typical of such tridentane structures. 22nother structural feature of 19 was the inter-planar relationship of the terminal benzene rings.As a consequence of the S-bridge having an anti-relationship to the other bridges of the polynorbornane the terminal benzene rings are pointing in opposite directions and the modeling shows that they are not far removed from being parallel.Such an orientation should be helpful in molecular design for the orientation of functionality on molecular frames.

Conclusions
This study has demonstrated that 7-thianorbornenes were extremely poor as dienophiles or dipolarophiles, a property that severely restricted their use for the building of sulfur-bridged [n]polynorbornanes.However, the ability of 7-thianorbornene 4a to react stereo-selectively at the olefinic π-bond with ester-activated aziridinocyclobutene 16 to yield the cycloadduct 18 has proved the exception to the rule and has opened the way for preparing other XNS- [3]polynorbornanes.By incorporating the sulfur bridge within an O,S-sesquinorbornadiene such as 13 allowed site-selective coupling at the activated 7-oxanorbornene π-bond and accession to the prototype XNOS- [4]polynorbornane 19.This coupling protocol should also be suitable for 7oxanorbornenes such as 9, 12 and 13 and has the potential to be extended to the other aziridinocyclobutene reagents mentioned above.As well, cycloaddition with other 4π-reagents should also be possible, since 7-oxanorbornenes are known to participate in Diels-Alder and 1,3dipolar coupling reactions.
Attempts to produce 7-thianorbornadiene-2,3-dicarboxylic anhydride 20 or its benzoanalogue 22 in order to improve their dienophilicity and dipolarophilicity, via FVP-induced retro-Diels-Alder reactions involving loss of furan from adducts 8, 9 or 12, 13 were thwarted by additional loss of the sulfur bridge under the thermal condition and led only to aromatic products.Clearly, special methods will need to be devised to form 7-thianorbornadienes 20 or 22.
S-Bridged alicycles has remained a challenging area of synthesis and this study has exposed some of the deficiencies of cycloaddition chemistry in this area.Nevertheless, the first S-bridged [n]polynorbornadiene has been prepared, some light has been shone on the way ahead and interesting challenges delineated for those wishing to follow down this road of research.

Experimental Section
General Procedures.Melting points, which are uncorrected, were obtained on a Reinhart Micro hot stage melting point apparatus Model YOSCO No. 67885. 1 H NMR spectra were recorded at 300 or 400 MHz. 13 C NMR spectra were recorded by using an inverse gated sequence at 75.4 MHz.Unless otherwise stated all data were acquired using CDC1 3 solutions with TMS as an internal standard and are reported on the appropriate δ H and δ C scales.Coupling constants are reported in Hz.
The silica gel used for column chromatography was silica gel 60 (230-400 mesh).TLC was performed on Merck aluminium sheets coated with silica gel 50F 254 .Centrifugal radial chromatography was carried out with a Chromatotron, Model No. 7924T, using 1mm plates coated with silica gel 60 F 254 .
Mass spectra were obtained by EI or PCI (photochemical ionisation) on a Hewlett Packard 5988A spectrometer or by EI or ESMS (electrospray mass spectrometry) on a Micromass Platform II single quadripole mass spectrometer.

Reaction of N-methylmaleimide with thiophene.
A solution of N-methylmaleimide (60 mg, 0.54 mmol) and thiophene (excess) in dichloromethane (1 ml) was pressurized at 10 kbar and heated to 100 o C overnight.After cooling, solvent and excess thiophene were removed in vacuo and the residue separated by radial chromatography (petroleum ether -ethyl acetate 10:1, then the solvent polarity was gradually increased to ethyl acetate).Elution order 4a (
Reaction of isobenzothiophene (11) with 7-oxanorbornadien-2,3-dicarboxylic anhydride (6).The instability of 6 required that it be produced immediately prior to reaction.The flash vacuum pyrolysis (FVP) process for the elimination of furan from the syn-O,Osesquinorbornadiene 5 13 was conducted at temperatures in the range 350-390 o C (unpacked pyrex tube, 0.001 mbar) since a compromise was required whereby breakdown of 5 was maximized but not so high that product 6 was subjected to further fragmentation to form furan-3,4-dicarboxylic anhydride by loss of acetylene.The sample used for the production of 12 (11

Table 1 .
Isomer distribution and yields for the reaction of maleimides and maleic anhydride to thiophenes under high pressure * Kotsuki et al. report formation of 4c in 37-47% yield(ref 11) .