Aust. J. Chem., 1996, 49, 1263-1272

The Synthesis and Reactivity of 5 H-Cycloprop [f ] isobenzofuran and Related Compounds. A Kinetic Probe for the Mills-Nixon Effect

Ian J. Anthony and Dzeter Wege

Department of Chemistry, University of Western Australia, Nedlands, W.A. 690

5H-Cycloprop[f]isobenzofuran (6) and the sulfur analogue 5H-cyclopropa[f][2]benzothiophen (18) have been prepared by a sequence of reactions involving trapping of 1,2-dibromocyclopropene with 3,4dimethylidenetetrahydrofuran and 3,4dimethylidenetetrahydrothiophen foiiowed by sequential dehydrogenation and di-dehydrobromination. Both cyclopropa-fused heterocycles, like their parents, have limited stability. Several other 5,6-methylene-bridged and 5,6-disubstituted isobenzofurans (32) have been generated and characterized as their adducts with dimethyl fumarate. Second-order rate constants for the reaction of dimethyl fumarate with isobenzofuran, 5H-cycloprop[f]isobenzofuran as well as the series of substituted derivatives have been measured. The reactivity span is only one order of magnitude suggesting that T-bond fixation (the Mills-Nixon effect) does not play a significant role in determining the reactivity of (6).

Introduction

Isobenzofuran (1) and its derivatives are highly reac- tive dienes which find considerable use as synthons for the construction of polycyclic systems, and aspects of the chemistry of isobenzofurans have been the subject of several detailed reviews.'-5 We previously reported that the reactivity of isobenzofuran and a number of its benzannulated derivatives towards maleic anhydride can be correlated with the gain in resonance energy in going from reactants to product.6 Thus angularly benzannulated isobenzofurans (those having benzo- fusion to the 4,5-bond) were found to be less reactive, while linearly benzannulated derivatives (those having benzo-fusion to the 5,6-bond) were predicted to be more reactive than the parent system (1).

It seemed to us that the isobenzofuran ring system could also serve as a probe for structure-reactivity factors pertaining to the cycloproparene ring system. Benzocyclopropene (2) is the parent member of the cycloproparene family and the chemistry of these highly strained 1,2-methylene-bridged aromatic ring systems has been studied e ~ t e n s i v e l y . ~ - ~ ~ One interesting obser- vation in this area is that those cycloproparenes which possess a high T-bond order across the methylene- bridged bond appear to be considerably more reactive than the parent (2), or those derivatives in which bridg- ing is across a bond of lower T-character. Thus, while 1H-cyclopropa[b]naphthalene (3) is relatively stable, the isomeric 1H-cyclopropa[a]naphthalene (4) decomposes violently on melting.12 1H-Cyclopropa[l]phenanthrene (5), in which there is further enhanced T-character across the bridged bond, was only characterized after considerable synthetic effort; (5) is unstable in solution at -60°C and also decomposes in the solid state at -78OC,13,14

In considering 5 H-cycloprop[f lisobenzofuran (6), it is apparent that methylene bridging is across a bond of low T-bond character, while in Diels-Alder adducts of (6), e.g. (8)-see later, the T-bond order of the bridged bond is increased, since it now becomes ben- zenoid in character (the Kekulk structure drawn for (8) emphasizes this). In view of the stability trends discussed above it was therefore of interest to assess what effect such bridging has on the reactivity of the isobenzofuran ring system. This question also pertains to the much-debated Mills-Nixon effect. In order to explain the orientation effects observed in electrophilic

Manuscript received 15 March 1996

1264 I. J. Anthony and D. Wege

substitutions in indan compared to tetralin, Mills and Nixon in 1930 proposed15 that in indan the presence of the fused five-membered ring imparts ring strain which (in modern terminology) results in bond fixation in the direction implied by structure (7a). With the availabilty in recent years of more strained methylene bridged systems such as benzocyclopropene (2) and benzocyclobutene (7; n = 2), as well as ring systems having more than one small-membered ring fused to a benzene ring, considerable effort has been expended in trying to demonstrate the presence or absence of the Mills-Nixon effect. l6 Siege1 has discussed some historical perspectives of this matter17 as well as the recent X-ray crystallographic a.nd compiutational

which indicates that deformations in such systems are the consequence of 'bent' bonds around the positions of small ring-fusion; bond alternation as required by the Mills-Nixon postulate is not observed. Nevertheless in other systems Mills-Nixon type bond length alternation is claimed t o be present despite the existence of 'bent' bonds.21

As most of the probes into the Mills-Nixon effect in cycloproparenes have been computational, crystallo- graphic, or spectroscopic,16-21 we felt that it would be of interest to examine the reactivity of the cyclopropa- fused isobenzofuran (6) and to compare this reactivity with that of other 5,6-methylene-bridged isobenzo- furans. This prompted the current study, part of which has been described briefly in a preliminary c o m m ~ n i c a t i o n . ~ ~

(6) X = 0 Scheme 1 (18) X = S

Synthesis of 5H-Cycloprop[f]isobenzofuran and 5 H-Cyclopropa[f ] [2]benzothiophen

The synthesis of 5H-cycloprop[f]isobenzofuran (6) and the related 5H-cyclopropa[f][2]benzothiophen (18) is outlined in Scheme 1. The key step involved Diels-Alder reaction of 1,2-dibromocyclopropene ( 1 0 ) ~ ~ with 3,4-dimethylidenetetrahydrofuran (12) and 3,4- dimethylidenetetrahydrothiophen (13) to give adducts

(14) and (15) in 92 and 53% yield respectively. A limiting factor in the synthesis concerns the prepara- tion of the dienes (12) and ( 1 3 ) ; ~ ~ in our hands this proved to be somewhat capricious due to the ten- dency of these dienes to undergo ready polymerization and the yields given above represent the best values obtained after several reactions. Adducts (14) and (15) were smoothly dehydrogenated with 2,3-dichloro- 5,6-dicyano-l,4-benzoquinone (ddq), and treatment of the resulting products (16) and (17) with potassium t-butoxide in tetrahydrofuran at -78OC gave the target compounds (6) and (18) as a liquid and low-melting solid respectively. Both compounds have limited stability and like the p r e n t isebenzofwan and benze[c]thinphes readily polymerized at or near room temperature. From a qualitative viewpoint, cyclopropa-fusion across the f-bond does not appear to impart significant stability to these reactive ring systems. The isobenzofuran (6) readily gave adduct (8) with dimethyl fumarate.

The spectroscopic properties of 5H-cycloprop[f]iso- benzofuran (6) and 5 H-cyclopropa[f] [a] benzothiophen (18) have been described in some detail in our pre- liminary c o m m ~ n i c a t i o n ~ ~ and will not be discussed further here. Both compounds possess spectroscopic characteristics typical of cycloproparenes, and (6) and (18) were the first reported examples of heterocyclic cycloproparenes. The synthesis of a cyclopropapyridine was disclosed almost concurrently,25 as were unsuc- cessful approaches to cyclopropapyridazines.26 More recently, the synthesis of a cyclopropisoquinoline has been described,27 as well as an approach to a cyclopropa- fused t h i ~ ~ h e n . ~ ~ Very recently, Muller and Miao have reported the preparation of the gem-difluoro derivative of the cyclopropa-fused benzo[c]thiophen (18) by the general pathway outlined in Scheme 1.29 Contrary to expectation, difluoro substitution did not impart additional stability to the heterocyclic system. The study of the chemistry of heterocyclic cycloproparenes is thus beginning to develop and further growth in this area will undoubtedly take place.

Preparation of 6,7-Methylene-Bridged 1,6Dihydro- 1,4-epoxynaphthalenes

In order to assess the reactivity of 5H-cycloprop[f]iso- benzofuran (6) in Diels-Alder additions, it was necessary for comparative purposes to prepare other 5,6-methylene bridged and 5,6-disubstituted isobenzofurans. The requisite 1,4-dihydro-1,4-epoxynaphthalene precursors were prepared by trapping the appropriate benzyne with furan. The benzynes in turn were generated by the dehydrobromination of the requisite bromoarene or by debromination of the appropriate o-dibromobenzene.

With regard to the dehydrobromination of 3,4- disubstituted bromobenzenes (19), two benzynes (22) and (23) can arise by the removal of Ha and Hp respectively (Scheme 2). Halton and cowork- ers have shown that the dehydrobromination of 3-bromobenzocyclopropene (19d) with sodium amidel

sodium t-butoxide (CauberB's base30) in tetrahydrofu- ran is highly regioselective and results in the formation of linear adduct (25d) and angular adduct (24d) in the ratio 98 : 2.31 We have examined the dehydrobromination of 4-bromo-1,2-dimethylbenzene (19a), 5-bromoindan (19b) and 4-bromobenzocyclobutene (19c) under sim- ilar conditions (Scheme 2) and observe the product ratios shown in Table 1.

Scheme 2

The product ratios (angular versus linear) should be determined by an interplay of two factors: (i) by the relative acidities of H, and Hp, and (ii) the relative stabilities of the two possible benzynes (22) and (23). The annulation of progressively smaller rings onto a benzene ring leads to an increased kinetic acidity at the a-position, and the Finnegan-Streitwieser mode132133 proposes that rehybridization of the carbon orbitals at the ring junction results in the a-carbon being bound to an orbital of higher electronegativity. Because of this induced polarization, the a-carbon-hydrogen bond has higher s-character and this is reflected by an increase in the value of J c , ~ and an increase in acidity. Thus since the 13C-lH coupling constant is a quantitative measure of carbon acidity,34 we have measured these J values for 4-bromo-l,2-dimethylbenzene (19a) , 5- bromoindan (19b) and 4-bromobenzocyclobutene (19c)

by examining the fully coupled 13C n.m.r. spectrum of each compound and assigning the relevant resonances with the aid of heteronuclear correlation. The values for 3-bromobenzocyclopropene (19d) are unavailable, but those for the corresponding chloride have been determined35 and are included in Table 1, given that bromo and chloro substituents have similar effects on 13C-lH coupling constant^.^^

It can be seen that for 4-bromo-1,2-dimethylbenzene (19a) Hp ( J c , ~ 166 Hz) is more acidic than H, ( J c , ~ 162 Hz) and the product ratio favours the adduct (25a) from the linear benzyne (23a) which arises from abstraction of Hp. For 4-bromobenzocyclobutene (19c), Ha (JCJ 167 Hz) is more acidic than Hp (Jc,H 164 Hz), and the product ratio strongly favours the adduct (24c) from the angular benzyne (22c) arising from abstraction of Ha. 5-Bromoindan (19b) falls between these two cases. It appears that, for bromoarenes (19a-c), benzyne formation is determined at least in part by the relative acidity of H, and Hp. However 3-bromobenzocyclopropene (19d), in which the acidity of Ha is increased further, no longer follows this trend and there is surprisingly a marked change in behaviour. Apeloig and coworkers (1986)~' have calculated the relative stabilities of the cyclopropabenzynes (22d) and (23d) in order to explain the high regioselectivity in aryne formation. The computational results indicate that the linear aryne (23d) is c. 10 kJ mol-I more stable than the angular aryne (22d) and that this energy difference outweighs the relative kinetic acidi- ties that should favour the formation of (22d). This implies that, if the mechanism for dehydrobromination is a two-step process proceeding via the conjugate base of the bromoarene as shown in Scheme 2, the proton abstraction step must be reversible, a t least for 3-bromobenzocyclopropene (19d), to permit the predominant formation of product (25d) arising from the linear aryne (23d).

The substituted 1,4-dihydro-1.4-epoxynaphthalenes (25a), (25c) and (31) also were prepared by trap- ping with furan the appropriate benzyne generated by treatment of the requisite o-dibromoarene with butyllithium (Scheme 3). The syntheses of the o- dibromoarenes are generally not as straightforward as those of the simple bromoarenes used above, but the unambiguous generation of only one benzyne in each case is an obvious advantage from the synthetic viewpoint.

Table 1. Comparison of one-bond 13c- l~ coupling constants of aryl halides and product distribution of aryne-furan adducts

Halide J C ~ - ~ (Hz) J ~ ~ - ~ (Hz) Ratio of angular to linear adduct

4-Bromo-1,2-dimethylbenzene (19a) 162 166 20 : 80 5-Bromoindan (19b) 164 165 73 : 27 4-Bromober~zocyclobutene (19c) 167 164 97 :3 3-Bromobenzocyclopropene (19d) 170A 1 6 4 ~ 2 : 9gB

A Value for 3-chlorobenzocyclopropene taken from ref. 35 From ref. 31.

I. J. Anthony and D. Wege

(28) X = Br, I (254

Bu&H (29) X = H

Scheme 3

The Reactivity of 5H-Cycloprop[f]isobenzofuran

Isobenzofurans (32a-c,e) were generated in solution by treating the 1,4-dihydro-1,4-epoxynaphthalenes (25) in chloroform with 3,6-(pyridin-2'-yl)-s-tetrazine6>37>38 and characterized as adducts (34) by addition of dimethyl fumarate (Scheme 4). In a parallel series of experiments a solution of each isobenzofuran was diluted quantitatively with cyclohexane and the elec- tronic spectrum of each compound was recorded. The rates of addition of dimethyl fumarate to the isoben- zofurans were then measured under pseudo-first-order conditions by following the decrease in absorbance of the longest wavelength absorption band of the isobenzo- furan in the presence of a known (excess) concentration of dienophile. These first-order rate constants were then converted into second-order values k 2 by dividing by the concentration of dimethyl fumarate.

The k 2 values for the addition of dimethyl fumarate to the linearly ring-fused or disubstituted isobenzofu- rans (32a-e) as well as the angularly cyclobuta-fused derivative (35) are given in Table 2. The rate data reveal

(25) (32)

(b) RR = CH2CH2CH2 (not examined) (c) RR = CH2CH2 (d) RR = CH2

- -

transition state

Scheme 4

that these isobenzofuran derivatives show a reactivity span of only one order of magnitude. According to the concept of T-bond fixation or bond alternation (the Mills-Nixon effect), 5 H-cycloprop[f]isobenzofuran (6) should be less reactive than isobenzofuran (1) because of the reluctance of (6) to accept an increase in double-bond character in going from reactant to tran- sition state (33d) (Scheme 4). The cyclopropa-fused derivative (6) is indeed less reactive than the parent (I), but only by a factor of 4, which corresponds to a difference in free energy of activation AAGt of 3 .4 kJ mol-l. The linearly cyclobuta-fused isobenzofuran (32c) should, according to the concept of bond fixation,

Table 2. Second-order rate constants for the addition of dimethyl fumarate to isobenzofurans at 25OC

Compound --

kz (1. mol-I s-l) Relative rate

5,6-Dimethylisobenzofuran (32a) 5,6-Dihydrocyclobut~]isobenzofuran (32c) 6,7-Dihydrocyclobut[e]isobenzofuran (35) Isobenzofuran (1) 5,6-Dibromoisobenzofuran (32e) 5H-Cycloprop[f]isobenzofuran (6)

also be less reactive than (1). Experimentally it is observed to be more reactive by a factor of 1 .5 . The angularly fused cyclobuta-derivative (35), which loses T-bond order across the bridged bond in going from reactant to transition state, should be more reactive than ( I ) , whereas it actually has the same reactivity as (1). It also is slighty less reactive than the linearly fused isomer (32c), although the operation of the Mills- Nixon effect would demand it to be more reactive. Finally, the presence of the electron-donating methyl groups a t C 5 and C 6 in (32a) leads to a threefold rate enhancement, while dibromo substitution as in (32e) leads to a twofold rate reduction.

From the data in Table 2 it is clear that only small effects are in operation. We agree with the general sentiment^^^.^' that chemists should ignore small differences in reaction rates in comparing sys- tems since many rationalizations often can be devised. Such rationalizations can result in overinterpretation of results, or invalid conclusions, given, for example, that small differences in ground state energies could be responsible for the small difference^.^^ In the current system it is clear that the absence of substantzal rate dzfferences indicates that there is no significant destabilization of the transition states (33c,d) resulting from annulation of a four- or three-membered ring to the f-bond of isobenzofuran. Although it could be argued that the cycloadditions in Scheme 4 all involve early transition states that are very much reactant-like and hence would not reflect much of the consequence of bond fixation effects, this seems unlikely given that substantial rate effects are observed in the cycloaddi- tions of benzannulated is~benzofurans.~ The transition state must reflect at least part of the character of the product.

In summary we conclude that, although the Diels- Alder reaction of 5 H-cycloprop [f] isobenzofuran (6) involves the conversion of a dimethylidenecyclopropane moiety in (6) into a cycloproparene system in adduct (8), and hence an increase in bond order across the C 5-C 6 bond, this does not manifest itself in significant destabilization of transition state (33d). Hence the kinetic probe used in this study rules out that T-bond fixation in the direction indicated by general structure (7a) is significant for adduct (8). The similarity in reac- tivity of the cyclobuta-fused isobenzofurans (32c) and (35) also rules against the operation of a Mills-Nixon effect in these systems.

Experimental General details have been given previously.6

A mixture of the 1,4-dibromo-2,3-bis(bromomethy1)but-2- ene4' (12.0 g, 30 mmol), potassium iodide (17.0 g, 102 mmol) and sodium thiosulfate pentahydrate (27.0 g, 109 mmol) in acetone (200 ml) was heated a t 45' with mechanical stirring for 1 . 5 h. The colour of the reaction mixture changed from orange to dark red to pale yellow. The resultant suspension was poured

into water (100 ml) and extracted with ether (2 x 100 ml). The combined ether extracts were washed with saturated NaCl solution (100 ml) and water (100 ml), dried and the solvent evaporated to give the diiodide (11) as a yellow crystalline solid (12.7 g). This material was dissolved in ether (60 ml) and added in one portion to a mixture of potassium hydroxide (10 g) in water (15 ml) and dimethyl sulfoxide (100 ml). The reaction mixture was stirred vigorously at 60' for 3 . 5 h , cooled to room temperature, diluted with water (50 ml) and extracted with ether (3x70 ml). The combined ether extracts were washed with water (4x50 ml), dried and solvent was distilled off a t atmospheric pressure, to give crude product as a yellow liquid (2.12 g). Kugelrohr distillation (70'122 mm Hg) gave 3.4-dimethylidenetetrahydrofuran (12) as a colourless liquid (480 mg, 17%). There was a substantial amount of polmerized residue. The 'H n.m.r. spectrum was identical with that reported in the literature.'*

4a, 5a-Dibromo-3,4,4a, 5,5a, 6-hexahydro-1 H- cycloprop[f] isobenzofuran (14)

Tetrabutylammonium fluoride trihydrate (1 .8 g, 5 .71 mmol) was dissolved in anhydrous benzene (40 ml). The benzene was then removed under vacuum, and the tetrabutylammonium fluoride residue was dissolved in anhydrous tetrahydrofuran (10 ml). This solution was then added dropwise to a solution of 1,1,2-tribrorno-2-trimethylsilylcyc1opropane (9)23 (1.35 g, 3 .85 mmol) and dimethylidenetetrahydrofuran (12) (370 mg, 3.85 mmol) in anhydrous tetrahydrofuran (10 ml) cooled to -30'. The reaction mixture was stirred at -30' for 1 h! then allowed to slowly warm to room temperature over 21 h. The reaction mixture was then poured into water (40 ml) and extracted with dichloromethane (2x40 ml). The combined dichloromethane extracts were washed with water (30 ml), dried and the solvent was evaporated to give a brown solid (1.55 g) that was preadsorbed onto silica gel. Flash chromatography on a short column of silica gel (50% dichloromethane/light petroleum) gave the adduct (14) as a colourless crystalline solid (1.05 g, 92%) which was recrystallized from light petroleum as colourless rhombs, m.p. 116.5-117.5' (Found: C, 36.8; H, 3.4. CgHloBrzO requires C: 36.8; H, 3.4%). 'H n.m.r. (300 MHz, CDC13) 6 4.54-4.38, rn, 4H, H1!3; 3 .00, s, 4H, H4,6; 1 .56 and 1.51, AB, J 7 . 9 Hz, 2H, H5. 13c n.m.r. (75 MHz, CDC13) S 128.7, C3a,6a; 76.7, C l,3; 37.7, C4a,5a; 33.9, C4:6; 26.7: C5 . Mass spectrum m/z 296, 294, 292 (M; 11, 21, l l % ) , 215, 213 (M-Br; 33, 35), 185 (20), 183 (16), 134 (36), 133 (48), 106 (42), 105 (100): 104 (46), 103 (28), 91 (37), 79 (31), 78 (27); 77 (52), 66 ( l l ) , 65 (20).

4a,5a-Dibromo-4a,5,5a,6-tetrahydro-4 H- cycloprop[f] isobenzofuran (1 6)

A solution of the adduct (14) (200 mg, 0 .68 mmol) and ddq (252 mg, 1 .11 mmol) in anhydrous benzene (10 ml) was heated at reflux under a nitrogen atmosphere until t.1.c. analysis (50% dichloromethane/light petroleum) showed all the starting mate- rial had reacted (4 h). The reaction mixture was then filtered through a short column of silica gel (20% dichloromethane/light petroleum) to give the furan (16) as a colourless oil (187 mg, 94%) that crystallized upon standing, m.p. 37-38.8' (Found: C, 37.2; H, 2.8. CgHsBraO requires C, 37.0; H, 2.8%). 'H n.m.r. (300 MHz, CDC13) 6 7.16, d , J 1 . 5 Hz, 2H, H1!3; 3.55, d , J 15.3 Hz, 2H, H4,6; 3.42, dd, J 15.3: 1 . 5 Hz, 2H, H4,6; 1.46 and 1.38, AB, J 8 . 3 Hz, 2H, H5. 13c n.m.r. (75 MHz. CDC13) S 137.8, C 1,3; 118.7, C3a,6a; 38.2, C4a,5a; 31.4, C4,6; 24.2, C5. Mass spectrum m/z 294, 292, 290 (M; 7, 14, 7%): 213, 211 (M-Br; 23, 23), 133 (8), 132 (82), 131 (loo), 118 (lo), 104 (40), 103 (35); 102 (15), 78 (21), 51 (41).

I. J. Anthony and D. Wege

To a stirred solution of freshly sublimed potassium t- butoxide (200 mg, 1 .78 mmol) in anhydrous tetrahydrofuran (5 ml), cooled to -78'! was added slowly a solution of the furan (16) (80 mg, 0.27 mmol) in anhydrous tetrahydrofuran (5 ml) over 5 min. The reaction mixture was stirred for a further 15 min, whereupon t.1.c. analysis (50% dichloromethane/light petroleum) showed the presence of only one product. The reaction mixture was poured into water (20 ml) and extracted with pentane (2x20 ml). The combined pentane extracts were washed with water (20 ml), dried and the solvent evaporated to give 5 H-cycloprop[f]isobenzofuran (6) as a near colourless oil (19 mg, 55%). When stored a t 0' under argon, this compound polymerized over 2-4 h. Microanalytical data could not be obtained. 'H n.m.r. (300 MHz, CDC13) 6 7.87, s , 2H, H 1,3; 7.00, s, 2H, H4,6; 3.33: s, 2H, H5. 13C n.m.r. (75 MHz, CDCls) 6 134.2, C 1:3; 127.3, C3a,6a; 121.6, Z4a,5a; 101.9: C4,6; 20.8, C 5 . Electronic spectrum (cyclohexane) A,,, 209, 248, 254, 260, 280; 292, 306sh: 313, 320, 329, 338, 348nm (this spectrum is reproduced in ref. 22).

Adduct of 5H-Cycloprop[f]zsobenzofuran (6) and Dimethyl Fumarate

To a stirred solution of freshly sublimed potassium t- butoxide (329 mg, 2 .93 mmol) in anhydrous tetrahydrofuran (8 ml), cooled to -50°, was added slowly a solution of the furan (16) (200 mg, 0.68 mmol) in anhydrous tetrahydrofuran (8 ml) over 5 min. The reaction mixture was stirred for a fur- ther l h, whereupon t.1.c. analysis (50% dichloromethane/light petroleum) showed the presence of only one product. The reaction mixture was diluted with water (5 drops) and allowed to warm to -30°, then a solution of dimethyl fumarate (186) in tetrahydrofuran (5 ml) was added. The reaction mixture was stirred at -30' for a further 5 min, poured into water (30 ml) and extracted with dichloromethane (2x30 ml). The combined extracts were washed with water (40 ml), dried, and the sol- vent was evaporated to give a nearly colourless oil (180 mg). Preparative radial chromatography (50% dichloromethane/light petroleum) gave the adduct (8)* (102 mg, 55% based on furan (6)) as a colourless solid, m.p. 109-112°. This material decom- posed within 48 h whilst under an argon atmosphere at room temperature and microanalytical data could therefore not be obtained. 'H n.m.r. (300 MHz, CDC13) 6 7.21, d , J 2.0 Hz, lH , H2/7; 7.07, d , J 2.0 Hz, 1H, H7/2; 5.67, s, l H , H3; 5.61, d , J 5 . 3 HZ, 1H! H6; 3.89, dd, J 5 .3 , 4 . 1 HZ, lH, H5; 3.79, s, 3H, C02Me; 3.55, s! 3H, C02Me; 3.35 and 3.27, AB, J 3 . 5 Hz, 2H, H I ; 3.04, d , J 4 . 1 Hz, lH , H4. 13C n.m.r. (75 MHz, CDC13) 6 172.4, C; 170.3, C; 146.2, C; 144.3, C; 126.4, C; 125.9, C; 109.0, CH; 107.9, CH; 82.5; CH bridgehead; 80.0, CH bridgehead; 52.6; CH3; 52.1, CH3; 49.2, CH; 49.1, CH; 23.2, CH2.

A mixture of 1,4-dibromo-2,3-bis(bromomethyl)but-2-ene41 (12.0 g, 30 mmol), potassium iodide (17.0 g: 102 mmol) and sodium thiosulfate pentahydrate (27.0 g, 109 mmol) in acetone (200 ml) was heated at 45' with mechanical stirring for 1 h. The colour of the reaction mixture changed from orange to dark red to pale yellow. The resultant suspension was poured into water (100 ml) and extracted with ether (2x100 ml). The combined ether extracts were washed with saturated NaCl solution (100 ml) and water (100 ml), dried and the solvent was evaporated to give the diiodide (11) as a yellow crystalline solid. This material was dissolved in ethanol (200 ml) and sodium sulfide nonahydrate (18.0 g, 75 mmol) was added. The mixture was heated at reflux with mechanical stirring for 3 h, poured into water (200 ml) and extracted with pentane (3x 100 ml).

The combined extracts were washed with water (150 ml), dried and the solvent was removed by rotary evaporation without external heating, to give 3,4-dimethylidenetetrahydrothiophen (13) as acolourless liquid (1.55 g, 46%). The 'H n.m.r. spectrum was identical with that reported.24 The tetrahydrothiophen was immediately diluted with anhydrous tetrahydrofuran (20 ml) and refrigerated until used to minimize polymerization.

4a, 5a-Dibromo-3,4,4a, 5,5a, 6-hexahydro-1 H- cyclopropa[f] [2]benzothiophen (15)

Tetrabutylammonium fluoride trihydrate (6.5 g, 20.6 mmol) was dissolved in anhydrous benzene (40 ml). The benzene was then removed under vacuum and the residue was dis- solved in anhydrous tetrahydrofuran (20 ml). This solution was then added dropwise to a solution of l,l,2-tribromo-2- trimethylsilylcyclopropane (9)23 (3.0 g, 8.55 mmol) and 3,4- dimethylidenetetrahydrothiophen ( i3) (950 mg: 8.48 mmol) in anhydrous tetrahydrofuran (30 ml) cooled to -30'. The reaction mixture was allowed to warm slowly to room temperature over 30 min, and was then stirred a t room temperature for a further 20 h. The reaction mixture was poured into dichloromethane (120 ml), washed with water (2x100 ml), dried and the solvent evaporated to give a brown solid (3.33 g) that was pread- sorbed on silica gel. Flash chromatography on a short column of silica gel (20% dichloromethane/light petroleum) gave the adduct (15) as a colourless crystalline solid (1.40 g, 53%) which was recrystallized from light petroleum as colourless needles, m.p. 124.5-125.5' (Found: C, 34.8; H, 3.2. CSHIOB~ZS requires C, 34.8; H: 3.2%). 'H n.m.r. (300 MHz, CDC13) 6 3.69-3.49, m, 4H, H1,3; 3.08-2.95, m, 4H, H4,6; 1.56 and 1.47, AB, J 7 . 8 Hz, 2H, H 5. 13C n.m.r. (75 MHz, CDC13) 6 130.1, C3a,6a; 41.2, C4,6; 37.7, C4a,5a; 37.7, C 1:3; 26.5, C5. Mass spectrum m / z 312, 310, 308 (M; 6, 13, 5%), 231. 229 (M-Br; 17, 14); 185, 183 (12, 11), 150 (53), 149 ( l oo ) , 135 (23), 134 (35), 117 (17), 116 (23). 115 (36), 105 (19), 104 (42); 103 (17).

To a stirred solution of the adduct (15) (481 mg, 1 .55 mmol) in anhydrous dichloromethane (5 ml) was added ddq (390 mg, 1.72 mmol) in one portion. An immediate mild exothermic reaction occurred with the hydroquinone precipitating out. After 10 min, there was only one product spot by t.1.c. analysis (20% dichloromethane/light The reaction mix- ture was filtered through a short column of silica gel (20% dichloromethane/light and the solvent evaporated to give the thiophen (17) as a colourless amorphous solid (462mg, 97%), m.p. 115-116' (Found: C, 35.0; H, 2.6. CgHsBrzS requires C, 35.1; H, 2.6%). 'H n.m.r. (300 MHz: CDC13) 6 6.91, s, 2H, H lJ; 3 .67 and 3.54, AB, J 15.5 Hz, 4H, H4,6; 1,33, s, 2H, H5. 13C n.m.r. (75 MHz, CDCI3) 6 134.3, C3a,6a; 120.8, C1,3; 3 8 2 , C4a,5a; 36.6: C4,6; 24.0, C5 . Mass spectrum m / z 310, 306 ( M ; I%)! 149 (14), 148 (100: M - 2Br), 147 (23), 121 ( l l ) , 76 (29), 75 (55), 73 (53). Electronic spectrum (cyclohexane) A,,, (log t) 243 nm (3.69).

To a stirred solution of freshly sublimed potassium t-butoxide (480 mg, 4.28 mmol) in anhydrous tetrahydrofuran (10 ml), cooled to -78'; was slowly added a solution of the thiophen (17) (235 mg, 0.76 mmol) in anhydrous tetrahydrofuran (2 ml) over 10 min. The reaction mixture was stirred for a further 10 min, whereupon t.1.c. analysis (20% dichloromethane/light petroleum) showed the presence of only one product. The reac- tion mixture was poured into water (20 ml) and extracted with dichloromethane (30 ml). The organic extract was washed with

* Dimethyl (3a,4cr,5/7,6cr)-3,4,5,6-tetrahydro-3,6-epoxy-l H-cyclopropa[b]naphthalene-4!5-dicarboxylate.

water (20 ml), dried and the solvent evaporated to dryness, and the residue preadsorbed on silica gel. Flash chromatography on a short column of silica gel (20% dichIoromethane/light petroleum) gave 5H-cyclopropa[f]/2]benzothiophen (18) as an off-yellow semicrystalline solid (90 mg, 81%). When stored at 0' under argon, this compound slowly polymerized over 24 h. Microanalytical data could therefore not be obtained. 'H n.m.r. (300 MHz, CDC13) 6 7.49, s, 2H, H1,3; 7.24, s, 2H, H4,6; 3.47, s: 2H, H5. 13c n.m.r. (75 MHz: CDC13) 6 141.8, C3a,6a; 122.3, C4a,5a; 114.7, C1,3; 106.1, C4,6; 22.1, C5. Mass spectrum m / z 146 (M, loo%), 145 (57), 120 (7), 102 (60). Electronic spectrum (cyclohexane) A,,, (loge) 210 (4.22), 221 (4.32), 295 (3.76), 300 (3.75), 308 (3.84), 327 nm (3.56).

Complex Base F ~ r m a t i o n ~ ~ for Comparative Dehydrobrominations of Aryl Bromides (19a-c)

A solution of t-butyl a!cohol (1 4 g, 20.3 mmol) in anhy- drous tetrahydrofuran (5 ml) was added dropwise to a stirred suspension of sodium amide (2 .3 g, 57.5 mmol) and anhy- drous tetrahydrofuran (5 ml) under an argon atmosphere. The mixture was heated at 40-45' for 1 . 5 h, cooled to room temperature, then used directly in the dehydrobrominations.

To the stirred complex base was added a solution of 4- bromobenzocyclobutene ( 1 9 ~ ) ~ ' (700 mg, 3 . 8 mmol) in dry furan (10 ml). Stirring was continued for 2 11, then the reac- tion mixture was poured into water (100 ml) and extracted with dichloromethane (2 x 75 ml). The combined extracts were washed with water (2x50 ml), dried and the solvent was evap- orated to give a brown oil, which was preadsorbed on silica gel. Flash chromatography on a short column of silica gel (50% dichloromethane/light petroleum) gave starting material (19c) (71 mg, 10% recovery) in the first fractions. Further elution gave a yellow crystalline solid (385 mg), m.p. 78-79' (lit.43 80-81' for 1,2,5,8-tetrahydro-5,8-epoxycyclobuta[a]naphthalen the angu- lar adduct (24c)). By 13c n.m.r. analysis, the solid was approximately a 97 : 3 mixture of the angular adduct (24c) and the linear adduct (25c) as indicated by the underlined signals due to (25c) (see later). The yield for the reaction was 59% (or 66% based on amount of bromide consumed). 'H n.m.r. (60 MHz, CDC13) 6 7.02 and 6.52, AB, J 7.0 Hz, 2H, H3/4; 6.89, m, 2H, H6,7; 5.58; m, 2H: bridgehead H5,8; 3.12, s, 4H, H1,2. 13C n.m.r. (20.1 MHz, CDC13) 6 148.1, C; 143.7, CH; 143.0, C; 142.6, C; 142.2, CH; 137.2, C; 119.1, CH; 117.5, CH; 116.1, CH; 82.5, CH; 80.2: CH; 29.9; CH2; 28.9, CH2; 284, CH2. Mass spectarurn m / z 170 (25%), 144 (23), 142 (42), 141 (100); 115 (69), 89 ( lo ) , 63 (10).

Dehydrobromination of 5-Bromoindan ( l9b)

To the stirred complex base was added a solution of 5- bromoindan ( 1 9 k 1 ) ~ ~ (750 mg. 3.81 mmol) in dry furan (8 ml). Stirring was continued for 6 h , then the reaction mixture was poured into water (100 ml) and extracted with dichloromethane (2x75 ml). The combined extracts were washed with water (2x50 ml), dried and the solvent was evaporated to give a brown oil, which was preadsorbed on silica gel. Flash chromatography on a short column of silica gel (10% dichloromethane/light petroleum) gave starting material (19b) (380 mg, 51% recov- ery). Further elution (20% ethyl acetatellight petroleun~) gave a colourless crystalline solid (315 mg), m.p. 100-108'. By 'H n.m.r. analysis, the solid was approximately a 73: 27 mixture of the angular and linear adducts (24b) and (25b) respectively. The yield of adducts was 45% (or 92% based on amount of bromide consumed). Separation by t.1.c. was not possible. By g.1.c.-m.s. analysis, the adducts had very close retention times (Found: C, 85.2; H, 6 .7 . C I ~ H ~ ~ O requires C: 84.7; H, 6.6%). 'H n.m.r. (300 MHz, CDC13) 6 7.11, s, 2H, vinyl (linear); 7.04-6.99, m, 4H, aromatic; 7.04 and 6.82, AB, J 7.2 Hz,

vinyl (angular); 5.72, s, 1H, epoxy methine (angular); 5.69, s, lH , epoxy methine (angular); 5.66, s, 2H, epoxy methines (linear); 2.93-2.78, m, 8H, benzylic methylenes; 2.11-2.06, m, 4H, P benzylic methylenes. 13C n.m.r. (75.5 MHz, CDC13) 6 147.6, C; 146.9, C; 144.1, C; 143.4, CH; 143.2, CH; 142.4, CH; 142.3, C; 140.7, C; 136.5, C; 120.0, CH; 118.1, CH; 117.0, CH; 82.4, CH; 82.3, CH; 81.1: CH; 32.5, CHz; 32.4, CH2; 30.3, CH2; 25.8, CH2; 25.6, CH2. Mass spectrum m / z (angular) 184 (47%), 167 ( lo) , 165 (16), 158 (32), 157 (17), 156 (75), 155 (loo), 153 (42), 152 (28), 141 (37), 129 (25), 128 (57), 127 (22), 115 (41); (linear) 184 (55), 165 ( lo) , 158 (42), 157 (18), 156 (59), 155 (loo), 153 (38), 152 (25), 141 (29); 129 (18), 128 (51), 127 (21), 115 (34).

Dehydrobromznatzon of 4-Bromo-1,2-dzmethylbenzene (19a)

To the stirred complex base was added a solution of 4- bromo-1,3-dimethylbenzene ( 1 9 ~ ~ ) ~ ' (720 mg: 3 . 9 mmol) in dry furan (10 ml). Stirring was continued for 6 h! then the reac- tion mixture was poured into water (100 ml) and extracted with dichloromethane (2x75 ml). The combined extracts were washed with water (2x50 ml), dried and the solvent was evaporated to give an orange oil (730 mg). Preparative radial chromatography (10% dichloromethane/light petroleum) of the residue gave: as the first band, starting material (19a) (515 mg, 72% recovery). Further elution (10% dichloromethane/light petroleum) gave a colourless crystalline solid (103 mg). By 13C n.m.r. analysis, the solid was approximately an 80 : 20 mixture of the linear and angular adducts (25a) and (24a) respectively. The yield of adducts was 15% (or 60% based on amount of bromide consumed) (Found: C, 84.0; H, 6.8. C12H120 requires C, 83.7; H: 7.0%). Spectroscopic data for the linear adduct (25a): 'H n.m.r. (80 MHz, CDC13) 6 7.02. s , 2 H , H 5 , 8 ; 6 , 9 6 , s , 2 H , H 2 , 3 ; 5 , 6 2 , ~ , 2 H , H 1 : 4 ; 2 . 1 7 , ~ , 6 H , methyls. 13C n.m.r. (20.1 MHz, CDC13) 6 146.9, C; 143.3, CH; 132.7, C; 122.3, CH; 82.3, CH; 19.7, CH3. Spectroscopic data for the angular adduct (24a): 'H n.m.r. (80 MHz, CDC13) 6 7.04-6.69, m, 4H, H2,3,7,8; 5.79: s! 2H, H1,4; 2.19, s: 6H, methyls. 13c n.m.r. (20.1 MHz, CDC13) 6 147.6, C; 146.3, C; 143.4, CH; 142.7, CH; 133.8, C; 130.0, C; 125.8, CH; 1 1 7 8 ; CH; 82.3, CH; 81.2, CH; 19.4, CH3; 15.5, CH3. Mass spectrum m / z 172 (45%), 157 (14), 146 (34), 144 (49), 143 (21), 141 (14), 130 (10); 129 (loo), 128 (86), 127 (23), 115 (24).

Bromination of 1,2-Dibromo-4,5-dimethylbenzene (26)

A mixture of 1,2-dibromo-4,5-dimethylbenzene (26)46 (5.0 g? 18.9 mmol), N-bromosuccinimide (17.5 g, 98.3 mmol) and benzoyl peroxide (200 mg) in tetrachloromethane (120 ml) was heated at reflux. Further portions of N-bromosuccinimide were added after 15 h (17.5 g) and 20 h (17.5 g). After 24 h, the hot reaction mixture was filtered to remove succinimide, and the solution then concentrated. The concentrate was diluted with chloroform (200 ml), washed with 20% aqueous sodium thiosulfite (2x50 ml), dried and the solvent evaporated to give a yellow solid (11.9 g). The solid was recrystallized from chloroform/light petroleum to give pure 1,2-dibromo-4,5- bis(dibromomethyl)benzene (27) (7.18 g, 66%), m.p. 137-138' (lit.47 137-138').

Tetrahalobenzocyclobutenes (28)

A mixture of the hexabromide (27) (5.9 g, 10.2 mmol) and sodium iodide (9.0 g, 60 mmol) in ethanol (50 ml) was heated at reflux for 48 h. The cooled reaction mixture was diluted with chloroform (100 ml) and washed with water (100 ml). The aqueous layer was extracted with chloroform (2 x 70 ml). The combined chloroform extracts were washed with 20% aqueous sodium thiosulfite (100 ml) and water (2x50 ml), dried and the solvent was evaporated to give a dark brown solid (4.24). This solid was recrystallized from ethanol to give the tetra-

I. J. Anthony and D. Wege

halobenzocyclobutenes (28) as a pale yellow solid (2.16 g). By g.1.c.-m.s. analysis, product (28) was a mixture of tetrabromide, iodo tribromide and diiodo dibromide. This mixture was used as isolated for the next step.

Tributyltin Hydride Reduction of the Tetrahalobenzocyclobutenes (28)

Tributyltin hydride (4.2 ml, 4 .6 g, 15.8 mmol) was added dropwise to a solution of the tetrahalobenzocyclobutene mix- ture (28) (3.0 g, c. 7 . 1 mmol) in anhydrous tetrahydrofuran (45 ml). After an initial slightly exothermic reaction, the reaction mixture was stirred at room temperature for 2.5 h, diluted with light petroleum (100 ml) and washed with water (2x 100 ml). The light petroleum layer was separated, dried and the solvent evaporated to give a pale yellow liquid (8.0 g). Kugelrohr distillation (130°/1 mmHg) gave an oil 1 : 1 wrucrl crystallized (1 .1 g), and which by 'H n.m.r. analysis was predominantly 4,5-dibromobenzocyclobutene (29) with some alkyltin residues. Preparative radial chromatography (4 mm plate; 10% dichloromethane/light petroleum) of the product gave as the first band, pure 4,5-dibromobenzocyclobutene (29) as a colourless crystalline solid (753 mg, 40%), m.p. 66-69' (lit.48 72-72'),

Generation and Trapping of the Cyclobutabenzyne (23c)

To a stirred solution of the dibromide (29) (400 mg, 1.53 mmol) and dry furan (10 ml) in anhydrous tetrahy- drofuran (10 ml), cooled to -78' under an argon atmosphere, was added dropwise 1 . 6 M BuLi (1 .2 ml, 1.92 mmol). The reaction mixture was allowed to warm slowly to room tempera- ture (4.5 h), then quenched with methanol (5 ml). The reaction mixture was then diluted with ether (50 ml), washed with water (2x40 ml), dried and the solvent evaporated to give a pale yellow oil (277 mg) that crystallized within 1 h. Preparative radial chromatography (30% dichloromethane/light petroleum) of the residue gave, as the first band, unreacted dibromide (29) (27 mg, 7%). Further elution with 30% dichloromethane/light petroleum gave as the major band, 1,2,4,7-tetrahydro-4,7- epoxycyclobuta[b]naphthalene (25c) as a colourless crystalline solid (192 mg, 74%), m.p. 82-84' (lit.49 83-84'). 'H n.m.r, (80 MHz, CDC13) 6 6.96, m, 4H, H 3,5,6,8; 5.64, s, 2H, H 4,7; 3.00, s, 4H, H1,2. 13C n.m.r. (20.1 MHz, CDC13) 6 147.8, C; 143.5, CH; 142.1, C; 116.2, CH; 82.6, CH; 28.5, CH2.

Generation and Trapping of 45-Dimethylbenzyne (23a)

To a stirred solution of 1,2-dibromo-4,5-dimethylbenzene (26)46 (2.64 g, 10.0 mmol) and dry furan (25 ml) in anhydrous tetrahydrofuran (50 ml), cooled to -78' under an argon atmo- sphere, was added dropwise 1 .6 M BuLi (7.5 ml, 12.0 mmol). The reaction mixture was allowed to warm slowly to room tem- perature (5 h), and was then quenched with methanol (10 ml). The reaction mixture was diluted with ether (50 ml), washed with water (3x 100 ml), dried and the solvent evaporated to give a pale brown oil (1.98 g). Preparative radial chromatography (4 mm plate, 30% dichloromethane/light petroleum) gave as the major band, 6,7-dimethyl-l,4-dihydro-1,4-epoxynaphthalene (25a) as a colourless crystalline solid (1.29 g, 75%), m.p. 72-75' (lit.50 72.5-73'). 'H n.m.r. (300 MHz, CDC13) 6 7.02, s, 2H, H5,8; 6 . 9 6 : s , H2,3; 5 . 6 2 , s , 2H, H1,4; 2 .17 , s , 6H, methyls. 13C n.m.r. (75.5 MHz, CDC13) 6 146.5, C 4a,8a; 143.1, C 2,3; 132.4, C6,7; 122.1, C5,8; 82.2, C 1,4; 19.7, methyls. Mass spectrum m / z 172 (M, 45%), 157 (14), 146 (34), 144 (49), 143 (21), 141 (14), 130 (lo), 129 (loo), 128 (86), 127 (23), 115 (24).

Generation and Trapping of 4,5-Dibromobenzyne

To a stirred solution of 1,2,4,5-tetrabromobenzene (30)~ ' (4.0 g, 10.2 mmol) and dry furan (10 ml) in anhydrous toluene (100 ml), cooled to -30' under an argon atmosphere, was added 1 .6 M BuLi (7 .0 ml, 11.2 mmol) dropwise by syringe pump over 3 h. The reaction mixture was allowed to warm slowly to room temperature overnight and was then quenched with methanol (2 ml). The mixture was washed with water (2x 100 ml), dried and the solvent evaporated to give a yellow solid residue (3.26 g). Flash chromatography on a short column of silica gel (30% dichloromethane/light petroleum) gave, as the first band, unreacted tetrabromide (30) (850 mg, 21%). Further elution with 50% dichloromethane/light petroleum gave the adduct (31) (2.12 g, 88% based on amount of tetrabromide consumed) as a colourless solid, m.p. 117-118' (lit.51 115-117')

Deoxygenated chloroform (5 ml) was added to a mixture of the dihydroepoxynaphthalene (25) (0.30 mmol) , dimethyl fumarate (186) (0.30 mmol) and 3,6-di(pyridin-2'-y1)-s-tetrazine (0.33 mmol) under an argon atmosphere. The reaction mixture was stirred at room temperature for 45 min, then heated at 50-55' for 1 h. The reaction mixture was cooled to room temperature, filtered through a short column of silica gel (50% dichloromethane/light petroleum eluant) and the solvent evap- orated to give a white solid. Preparative radial chromatography (1 mm plate, 50% dichloromethane/light petroleum) gave, as the first band, unreacted dimethyl fumarate (<5%). Further elution with the same solvent gave each adduct.

The reaction of 1,2,4,7-tetrahydro-4,7-epoxycyclobuta[b]- naphthalene (25c) gave the adduct (34c)* (83%), m.p. 97-99' (Found: C, 66.7; H, 5.6. ClsHlsOs requires C, 66.7; H, 5.6%). 'H n.m.r. (300 MHz, CDC13) 6 7.03, s, lH, H3/8; 6.90, S, 1H, H8/3; 5.64, s, 1H, H7; 5.58, d , J 5 . 3 Hz, lH, H4; 3.86, dd, J 5.3, 4 . 1 Hz, 1H, H5; 3.79, s , 3H, C02Me; 3.57, s, 3H, C02Me; 3.07: m, 4H, H1,2; 3.02, d , J 4 . 1 Hz, lH, H6. 13c n.m.r. (75.5 MHz, CDC13) 6 172.6 and 170.5, C02Me; 144.9 and 144.5, C 2a,8a; 142.6 and 140.7, C3a,7a; 115.6 and 114.5, C3,8; 83.0, C4/7; 80.6, C7/4; 52.6 and 52.0, C02Me; 49.4, C5/6; 49.2, C6/5; 28.8, C1/2; 28.7, C2/1. Mass spectrum m / z 257 (M- 31, 2%), 225 ( I ) , 170 ( I ) , 169 ( I ) , 145 (11), 144 (loo), 141 (5), 128 ( I ) , 116 (3), 115 (20). Infrared spectrum (Nujol) v,,, 1718 cm-l.

The reaction of 6,7-dimethyl-l,4-dihydro-l,4-epoxynaph- thalene (25a) gave (34a)t (74%), m.p. 103-104' (Found: C, 66.2; H, 6.1. C16H1805 requires C, 66.2; H, 6.2%). 'H n.m.r. (300 MHz, CDCl3) 6 7.10, s, 1H, H 518; 6.96, s, lH , H8/5; 5.61, S, 1H, H I ; 5.55, d , J 5 . 3 HZ, 1H, H4; 3.86, dd, J 5.3, 4 . 1 Hz, lH, H3; 3.77, s, 3H, C02Me; 3.55, s, 3H, C02Me; 3.02, d , J 4 . 1 Hz, lH, H2; 2.22, s, 3H, methyl; 2.20, s, 3H, methyl. 13c n.m.r. (75.5 MHz, CDC13) 6 172.5 and 170.4, C02Me; 141.9 and 140.1, C4a,8a; 135.8 and 135.3, C6,7; 121.7 and 120.6, C5,8; 82.8 and 80.3, C1,4; 52.5 and 52.0, C02Me; 49.6 and 49.4, C2,3; 20.0 and 19.9, methyls. Mass spectrum m / z 259 (M - 31, I%), 199 (I) , 172 ( I ) , 147 (5), 146 (loo), 143 (3), 131 (4), 128 (4), 115 (3), 113 (6). Infrared spectrum (Nujol) v,,, 1725 cm-l.

The reaction of 1,2,5,8-tetrahydro-5,8-epoxycyclobuta[a]- naphthalene (24c) gave an inseparable 1 : 1 mixture of diastereoisomers (36)$ (86%) as a colourless oil (Found: C, 66.3; H, 5.6. C16H1605 requires C, 66.7; H, 5.6%). l H n.m.r. (300 MHz, CDC13) 6 7.17, d , J 7 . 3 Hz, lH, H3/4; 7.03, d , J 7 . 3 Hz, 1H, H4/3; 6.85, d, J 7 . 3 HZ, lH, H3/4; 6.81, d , J 7 . 3 Hz, 1H, H4/3; 5.64: s, lH , H8; 5.62, s, 1H, H8; 5.60, d, J 5 . 4 HZ, 1H, H5; 5.56, d, J

* Dimethyl (4~,5cu,6~,7~)-1,2,4,5,6,7-hexahydro-4,7-epoxycyclobuta[b]naphthalene-5,6-dicarboxylate. t Dimethyl (lcu,2cu,3P,4cu)-6,7-dimethyl-l,2~3,4-tetrahydro-l,4-epoxynaphthalene-2,3-dicarboxylate. $ Dimethyl 1,2,5,6,7,8-hexahydro-5~8-epoxycyclobuta[a]naphthalene-6,7-dicarboxylate.

5.2 Hz, l H , H 5 ; 3 .87, m , 2H, H 6 ; 3.79, s , 6H, COzMe; 3.60, s , 3H, COzMe; 3 .56, s , 3H, COzMe; 3.19, m , 8H, H 1,2; 3.07, d , J 4 .1 , l H , H 7 ; 3 .02, d , J 4 .2 Hz, l H , H 7 . 13c n.m.r. (75.5 MHz, CDC13) b 172.5, 170.5 and 170.4, C 0 2 M e ; 145.7, 145.1, 143.6 and 141.5, C2a,8b; 137.9, 137.8, 136.5 and 136.0, C34a,8a; 120.9, 120.4, 119.0 and 117.9, C2 ,3 ; 83.0, 80.7, 80.5 and 80.4, C5,8; 52.6, 52.1 and 52.0, CO2Me; 49.6 , 49.5 , 49.1 and 48.8 , C6 ,7 ; 30.2, 30.1, 29.1 and 28.8, C 1,2. Mass spectrum m/z 288 ( M , I%) , 257 ( 2 ) , 225 ( I ) , 197 ( I ) , 169 ( 2 ) , 145 ( l l ) , 144 ( loo) , 141 ( 5 ) , 116 ( 3 ) , 115 (16) , 113 ( 6 ) . Infrared spectrum (Nujol) v,,, 1720 cm-' .

T h e reaction o f 6,7-dibromo-1,4-dihydro-1,4-epoxynaph- thalene (31) gave the adduct (34e)" (67%), m.p. 90-92' (Found: C , 39.7; H, 2.8. C14H12Brz05 requires C , 40.0; H, 2.9%). ' H n.m.r. (300 MHz, CDC13) b 7 .61, s, l H , H 5 / 8 ; 7 . 4 7 , s , l H , H 8 / 5 ; 5.64, s , l H , H I ; 5 .57, d , J 5 . 4 Hz, l H , H 4 ; 3 .91, d d , J 5 .4 , 4 .2 Hzj l H j H 3 ; 3.80, s j 3 8 , C 0 2 M e ; 3 .60, s, 3H, C02Me; 3.05, d , J 4 . 2 Hz, l H , H2. 13c n.m.r. (75.5 MHz, CDC13) 6 171.6 and 169.9, s, COzMe; 145.0 and 143.4, C4a,8a; 126.0 and 124.9, C5 ,8 ; 123.8 and 123.4, C6,7; 82.1 , C 114; 79.7 , C 4 / 1 ; 52.8 and 52.4, C 0 2 M e ; 49.0 , C 213; 48.9 , C 3 / 2 . Mass spectrum m/z 316 (3%) , 315 ( 3 ) , 278 (19) , 276 (41) , 274 (23 ) , 198 (26) , 196 (30) , 145 (12) , 144 ( l o o ) , 115 (23) , 113 (30). Infrared spectrum (Nujol) v,,, 1728 c m - l .

Determination of Pseudo-First-Order Rate Constants for the Reaction of Isobenzofuran (1 ) and the Derivatives (32) and (35) with Dimethyl Fumarate

Preparation of isobenzofuran solutions. Deoxygenated chlo- roform ( 5 m l ) was added t o a mixture o f the dihydroepoxy- naphthalene (0 .30 mmol) and 3,6-di(pyridin-2'-yl)-s-tetrazine (0.33 mmol ) under an argon atmosphere. T h e reaction mixture was stirred at room temperature for 45 min, diluted wi th more deoxygenated chloroform (15 m l ) , and heated at 50-55' for 15 min. T h e reaction mixture was then diluted with cyclohexane (25 m l ) , and filtered through a short column o f silica gel. T h e filtrate was transferred without delay t o a volumetric flask (100 ml capacity) and made u p t o the mark wi th addi- tional cyclohexane. A n aliquot (10 ml ) o f this solution was further diluted wi th cyclohexane (90 ml ) . Th i s last solution prepare,d was used t o record the electronic spectrum o f the isobenzofuran, and also t o determine the rate constant o f t he reaction between the isobenzofuran and dimethyl fumarate. T h e following electronic spectra were obtained.

5,6-Dihydrocyclobut[f]isobenzofuran (32c) A,,, (absorb- ance) 224 (2 .74 ) , 308 (0.114), 315 (0 .180) , 322 (0 .182) , 330 (O.277), 338 (0 .171) , 348 n m (0.237).

6,7-Dihydrocyclobut[e]isobenzofuran (35) A,,, (absorbance) 218 (2 .39 ) , 315 (1 .129) , 322 (1 .196) , 328 (1 .577) , 337 (1 .031) , 345 n m (1 .385) .

5,6-Dimethylisobenzofuran (32a) A,,, (absorbance) 220 (2 .25) , 255 (0 .117) , 312sh (0 .325) , 326 (0.411), 342 n m (0.289).

5,6-Dibromoisobenzofuran (32e) A,,, (absorbance) 231 ( 3 . 1 ) , 270 (0 .516) , 295 (0 .382) , 312 (0.558), 318 (0 .652) , 326 (0 .980) , 333 (0 .984) , 342 (1 .390) , 350 (0 .871) , 360 n m (1.125).

T h e spectra o f 5H-cycloprop[f]isobenzofuran ( 6 ) (see also above) and o f isobenzofuran ( 1 ) have been given previously.22152

Determination of rate constants. T h e spectrophotomet- ric determinations o f rate constants were made by using a Hewlett-Packard 8450A instrument. Temperature control in the instrument was achieved wi th a Hewlett-Packard 89100A temperature controller set at 25.0'. T h e temperature did not vary by more than 10.05' for each run, and the rela- tive temperature did not vary b y more than 310.08~ between runs. Cyclohexane solutions o f the isobenzofuran and dimethyl

fumarate were equilibrated in a water bath at 252~0.1' for 0 .5 h prior t o each run. Each run was carried out in a 2 c m quartz cuvette under pseudo-first-order conditions, with at least a 10: 1 molar excess o f dimethyl fumarate over the isobenzofuran. T h e rates were determined by following the absorbance at selected wavelengths for each o f the isobenzo- furans. Data were obtained over at least 5 half-lives, with the infinity spectrum and absorbance recorded after at least 10 half-lives. T h e Hewlett-Packard 8450A instrument was interfaced t o an Apple I1 microcomputer and the experimental data were recorded and stored on disk. Treatment o f data was as given previously.6 T h e value kOb, was determined at least twice by using different concentrations o f dimethyl fumarate solutions t o ensure that pseudo-first-order conditions were being used. T h e second-order rate constant kz for each reaction was derived by dividing the values o f kOb, by the concentration o f the dimethyl fumarate solution. Duplicate values o f kz differed by less than 2%. T h e values for k2 are listed in Table 2.

Acknowledgments

This work was supported by a grant from the Australian Research Council and an Australian Post- graduate Research Award (to I.J.A.).

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