Studies in the cycloproparene series: cycloaddition reactions of diarylmethylidenecycloproparenes †1

Diarylmethylidenecyclopropanaphthalenes 4b-d add diphenylisobenzofuran (DPIBF) and α - pyrone across the exocyclic double bond to give ring expanded products 11b-d and 13b-d that result from subsequent relief of ring strain in the non-isolable spirocyclic intermediates 10 and 12 , respectively. The benzene homologues 3b and 3c add DPIBF across the bridge bond to give the norcaradiene adducts 19b and 19c


Introduction
The class of strained aromatic hydrocarbons known as the cycloproparenes, 2   X-ray crystallographic data that confirm the structures of products 18d and 19b are also reported.
The theoretical calculations have employed ab initio quantum mechanical calculations methods at the MP2/6-31G(d)// HF/6-31G(d) level for studying the reactions of the unknown 4 parents 3a and 4a with furan and the semiempirical method was used for calculating the reactions of the diphenyl compounds 3b and 4b with DPIBF as actually examined experimentally.

Results and Discussion
The cycloproparene hydrocarbons 1 and 2 have available two potential sites for cycloaddition, namely the C1a-C5a (or 7a) bridge bond and the three-membered ring σ bond.With the HOMO of 1 located at the bridge and C3-C4 bonds, it is not surprising that the molecule behaves as an electron rich dienophile and adds dienes across the bridge resulting in a range of derivatives that transform into other interesting compounds. 2However, cycloaddition across the strained threemembered ring σ bond can also occur especially with four-electron electrophilic dipolar reagents. 9With DPIBF, 1 displays both reaction modes dependent on the specific conditions employed.Addition to the bridge results in both endo and exo adducts 8 while ring opening gives 9 (Scheme 2). 10 Reagent: i) diphenylisobenzofuran -DPIBF

Scheme 2
In comparison, cyclopropanaphthalene 2 predominantly opens the three-membered ring by addition across the σ bond thereby avoiding the high energy orthoquinodimethane intermediate demanded from loss of aromaticity in both six-membered rings. 9,10 comparison to the above, the methylidene derivatives 3 and 4 offer the exocyclic double bond as an additional site for reaction.It is, therefore, more than idle curiosity that demands an answer to the question of regioselectivity in the cycloadditions of these compounds.The outcome must result in novel products that likely transform into other interesting materials irrespective of the site of addition and we now report on these.

Experimental Study
The readily available and representative diarylmethylidenecyclopropanaphthalenes 4b, 6 4c, 11 and 4d, 12 and the more difficultly obtained benzenoid homologues 3b 6 and 3c 11 were selected for examination and prepared according the published procedures.
When heated with DPIBF in dry degassed toluene for several days 4b provides a pale yellow solid 1:1 addition product the 13 C NMR of which does not show the characteristically shielded C2/7 resonances (105-115 ppm) of the cycloproparene precursor. 2This clearly implies the absence of 4b and any product in which the cycloproparenyl moiety is retained.Moreover, the proliferation of aromatic carbon resonances (Experimental) demands a lack of symmetry.The product is identified as the cyclobutanaphthalene 11b (55%).The 13 C NMR clearly displays three of the four cyclobutarenyl carbons (δ 76.1, sp 3 ; 150.3 and 163.1, aromatic sp 2 )] and the side-chain carbonyl carbon is at δ 198.2;IR absorptions for the side-chain conjugated carbonyl and the exocyclic olefinic bond are recorded at 1665 and 1738 cm -1 , respectively. 13In like manner, reaction of the dimethoxy 4c and bis(trifluoromethyl) 4d lead to the corresponding cyclobutarenes 11c (32%) and 11d (42%).
The formation of the cyclobutarenyl products 11 shows that cycloproparenes 4 resist addition to both the bridge and strained σ bonds and that any addition across the exocyclic double bond must result in subsequent rearrangement of the product.The formation of 11 is best rationalized from initial [2+4] addition across the exocyclic π bond to give the novel spirocycles 10.These highly strained compounds are able to release strain by way of cycloproparenyl-cyclobutarenyl ring expansion 2,7 with concomitant cleavage of the ether bridge and diaryl ketone formation, as depicted in Scheme 3. Analogous ether bridge cleavage has recently been reported by Kitamura et al. for DPIBF adducts of norbornynes. 15While the Diels-Alder cycloaddition with 4 proceeds to a strained (and transient) cycloadduct, it does so without involving the bridge bond and the (presumably) higher energy orthoquinodimethane, cf. 8 (Scheme 2 and below).
The reactions of 4b-d with α-pyrone also provide product that is best rationalized from additon to the exocyclic double bond of the substrate.Again the use of ethylene glycol in place of toluene as solvent is notably beneficial, viz. the reaction period for 4b reduces from days to 7 h and the yield increases from 12 to 50%.The products are identified as the substituted benzindanones 13b-d (Experimental) that arise from comparable rearrangement of the initially formed spirocycles 12.In these cases rapid migration of the three-membered ring σ bond to the carbonyl carbon triggers formation of the (Z)-enal functionality with ring expansion from three to five-members (Scheme 3).Opening of the lactone moiety in this way is presumed to be facile as diene products resulting from the more traditional decarboxylation 16 were not observed.The proposal is supported by isolation of the methoxy analogue of enol ether 17b when the reaction was performed in the presence of methanol.

Scheme 5
In contrast to the foregoing, we find that the methylidenecyclopropabenzenes 3 are more reluctant to undergo cycloaddition.While ethylene glycol again facilitates the reactions in comparison to toluene, the cycloadditions of 3b and 3c to DPIBF still require 24 h at 120 o C rather that the 7 h at 110 o C for 4b-d.These reactions return some unchanged DPIBF but both 3b and 3c give a single crystalline 1:1 cycloadduct in a yield of 48 and 27%, respectively.That these compounds are propelladienes 19 or 20 (Scheme 5) is immediately obvious from the 1 H NMR spectra as they each exhibit an AA'BB' pattern in the olefinic region (δ 5.65 and 6.11), and they do not show a carbonyl stretching frequency in the IR.However, the orientation of these Diels-Alder adducts as endo 19 or exo 20 with respect to the fused benzenoid ring of 3 (cf. Scheme 2) is not obvious and there are no in-built structural features that allow for easy differentiation.As noted above, 1 adds DPIBF across the bridge bond to give both endo and exo [2+4] products as well as the unsymmetrical adduct from addition to the strained σ bond (Scheme 2); 10 it provides no precedent.Determination of the structure of product from 3b depended upon X-ray crystallographic methods and these show the compound to be endo 19b with the oxygen atom and the three-membered ring syn (see Fig. 2 and below); that from 3c is assigned as 19c by analogy.
Unlike DPIBF, α-pyrone fails to add to 3. In either toluene or THF (used as solvent in the reaction with 1) starting materials are returned unchanged.In comparison, ethylene glycol intercepts substrates 3b and 3c to give products whose structures have yet to be resolved. 19e must ask why the regioselectivity exhibited by 3 and 4 is so different.Unfortunately FMO analysis 20 cannot rationalize the experimental findings as the HOMO and LUMO of both 3 and 4 are concentrated at the exocyclic bond.To gain some insight into the different regioselectivity, the interaction of furan and DPIBF with the unknown parent methylidene compounds 3a and 4a as well the diphenyl derivatives 3b and 4b actually employed in the study have been examined using ab initio and semiempirical PM3 methods.
The dramatic changes calculated with substituent incorporation on one reactant are mirrored when the PM3 method is applied to the actual substrates employed, viz. the diphenyl derivatives 3b and 4b with DPIBF.In the case of 3b marked preference is for bridge addition (∆Hrxn endo/exo/exocyclic: -19.8/-18.0/+4.2kcal mol -1 ) and the endo transition states that are involved.
We conclude, therefore, that the observed experimental regioselectivity in these reactions is governed by a combination of steric effects and solvent influences that dictate the precise transition structure involved.This failure of theory is rather unexpected (and disappointing) in view of the general success of ab initio calculations to reproduce reliably the transition state energies (and thus relative reactivity, regioselectivity, etc.) of a wide variety of Diels-Alder and other cycloaddition reactions. 23 will be interesting to study if density functional theory (DFT) calculations will provide better agreement with experiment.

X-ray Crystallographic Analyses
In order to provide unambiguous proof of the formation of the naphthyliodonium triflates 18, the crystal structure of 18d has been determined.A suitable crystal was obtained by slow crystallization from a saturated MeCN/C6H14 solution and the X-ray determination performed using a CAD4 four circle diffractometer with Mo-Kα radiation.Relevant data pertaining to the analysis are in Table 1, an elipsoid plot for the cationic component of 18d (crystallographic numbering appended) is shown in Figure 1, and selected bond lengths and angles appear in Table 2.The structure is confirmed as 1-(2'-naphthyl-3'-phenyliodonium)-2,2-bis(3''trifluoromethylphenyl)ethanone triflate (18d).In similar vein, a crystal of 19b was obtained (acetonitrile/hexane) and the X-ray determination performed using a Nicolet R3m/V diffractometer with Mo-Kα radiation.Relevant data pertaining to this analysis appear in Tables 1  and 3, and the elipsoid plot with numbering scheme is Figure 2. The compound is confirmed as [4aα,9α,9aα,10α]-9,10-diphenyl-11-diphenylmethylidene-4a,9,9a,10-tetrahydro-9,10-epoxy-4a,9a,-methanoanthracene (19b).a Numbers in parenthesis are the estimated standard deviations in the least significant digit.a Numbers in parenthesis are the estimated standard deviations in the least significant digit.

Experimental Section
General Procedures: These have appeared previously. 7NMR spectra were recorded at 300 (

Cycloaddition reactions of 3 and 4 with a -pyrone
To a solution of 3 or 4 in dry, degassed, ethylene glycol under nitrogen was added excess of αpyrone.For 4 the mixture was heated to 110 o C for ca. 12 h while 120 o C and 24 h were employed for 3.After cooling, the solvent was removed under reduced pressure and the crude product purified.The indanone product 13 from 4 was obtained from flash column chromatography (silica gel, 9:1 hexane/ethyl acetate elution) while for 3 column chromatography employed ethyl acetate/light petroleum (1:7) elution.With either refluxing toluene for 48 h or THF at 70 o C for 5 days only unchanged starting material were recovered.E. 3c 11 (100 mg, 0.32 mmol) and α-pyrone (61 mg, 0.64 mmol) provided no product until the column was flushed with methanol.A white amorphous solid (53.1 mg, 44%) that has eluded identification was obtained.

A. Benz[f]indanone (13b
With either refluxing toluene for 24 h or THF at 70 o C for 5 days only unchanged starting material were recovered.

Cycloaddition reactions of 4 with acetylenic bis-iodonium triflate (14).
To a solution of 4 in dry, degassed acetonitrile (10 mL) under nitrogen was added the bisiodonium salt 14 18 (1.0 mol.equiv.)and the mixture was stirred at RT for 7 h.The solvent was removed in vacuum and the crude product recrystallized (CH 2 Cl 2 /C 6 H 14 ) to give cycloadduct 18.
All NMR data recorded below are for CD 3 CN solutions.

Figure 1 .
Figure 1.ORTEP diagram of the cation of 18d with crystallographic numbering.

Figure 2 .
Figure 2. ORTEP diagram of the cation of 19b with crystallographic numbering.
Of the possible [4 +2] cycloadditions of 3a with furan the calculations predict that the transition states for exo and endo addition to the bridge bond and addition to the exocyclic double bond have essentially the same activation energy (+18.7,+18.4 and +18.2 kcal mol -1 , respectively).No kinetic preference can be expected and the thermodynamically more stable product will result not from addition to the bridge, but to the exocyclic double bond to give product analogous to 10 (the corresponding reaction energies (∆Hrxn ) are: -11.8, -6.2 and -20.4 kcal mol -1 , respectively).Of the two modes of addition to the bridge endo addition is predicted to give (on the basis of thermodynamics) the furan analogue of 19a in which the oxygen atom and the exocyclic double bond are syn (∆Hrxn: endo, -11.8; exo, -6.2 kcal mol -1 ).It is clear that the calculations do not replicate the experimental observations in which 19b,c are isolated from 3b,c with DPIBF (Scheme 5).In contrast to this, the cyclopropanaphthalene analogue 4a shows a 22ve been studied at the ab initio MP2/6-31G(d)// HF/6-31G(d) (i.e.MP2/6-31G(d) single point energy calculations at the HF/6-31G(d) optimised geometries) level of theory using the programs Gausian 9221and Spartan 3.1.22Vibrationalfrequencieswerecomputed for all structures at the HF/6-31G(d) level of theory in order to characterise them as minima (no imaginary frequencies) or transition state,TS (one imaginary frequency).Zero-point energies (ZPEs) were also calculated at HF/6-31G(d).All ab initio energies reported in the discussion are calculated (unless clear kinetic regioselectivity for furan addition to the exocyclic double bond [∆∆EA (the difference in activation energies) is -14.2 and ∆∆Hrxn -19.6 kcal mol-1, respectively] as is observed for the substituted substrates employed.The calculation also show that exo/endo additions to the bridge have the same activation energy (∆EA +29.4 and +29.0 kcal mol -1 ) but endo addition is again thermodynamically favoured, this time by 5.4 kcal mol -1 .

Table 1 .
Experimental data for structure analyses of 18d and 19b a a Deposited with the Cambridge Crystallographic Data Centre.as:18d: CCDC 160279; 19b CCDC 160957.© ARKAT USA, Inc