Synthesis of Expanded Porphyrinoids with Azulene and Indene

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Synthesis of Expanded Porphyrinoids with Azulene and Indene Subunits and an opp-Dioxadicarbaporphyrin from Fulvene Carbinols and a Dioxacarbatripyrrin Timothy D. Lash, Stacy C. Fosu, Tyler J. Smolczyk, and Deyaa I. AbuSalim J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01929 • Publication Date (Web): 24 Sep 2018 Downloaded from http://pubs.acs.org on September 25, 2018

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The Journal of Organic Chemistry

1 Synthesis of Expanded Porphyrinoids with Azulene and Indene Subunits and an oppDioxadicarbaporphyrin from Fulvene Carbinols and a Dioxacarbatripyrrin Timothy D. Lash,* Stacy C. Fosu, Tyler J. Smolczyk and Deyaa I. AbuSalim Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160

Abstract

In an attempt to prepare quatyrin derivatives, which are hydrocarbon analogues of the porphyrins, azulene-appended fulvene carbinols were self-condensed in the presence of BF3•Et2O. Although these investigations failed to give structures related to quatyrin, expanded porphyrin analogues were obtained instead. In dichloromethane, the major macrocyclic product consisted of three fulvene units, but when chloroform was used as the reaction solvent a tetrafulvene macrocycle could be isolated. Self-condensation of a furan-appended fulvene alcohol gave trace amounts of an opp-dioxadicarbaporphyrin. An alternative route to this novel system was developed where a dioxacarbatripyrrin was condensed with an indene dialdehyde in the presence of HBr. The heterodicarbaporphyrinoid proved to have strong globally aromatic properties as assessed by proton NMR spectroscopy, AICD and NICS calculations. In the presence of excess trifluoroacetic acid, an unstable aromatic cation was formed by C-protonation

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2 of an indene subunit. This species was also highly diatropic and the proton NMR spectrum gave an unusually high ∆δ value of 17.46 ppm. Introduction Quatyrin (1, Figure 1), the hypothetical hydrocarbon analogue of the porphyrins, represents an intriguing bridged annulene structure of great theoretical significance.1-3 In essence, quatyrin has all four of the nitrogen atoms in the porphyrin macrocycle replaced with carbons. Theoretical studies have shown that this structure retains fully aromatic characteristics and has a near planar conformation.2 Fully aromatic tetracarbaporphyrin structures of this type are not currently known, although many examples of mono- and dicarbaporphyrins have been described.4 Carbaporphyrins 2,5 and related macrocycles such as azuliporphyrins 3,6 exhibit diverse properties and commonly generate stable organometallic derivatives under mild conditions.7 Several synthetic strategies have been developed for the preparation of dicarbaporphyrinoids including MacDonald-type condensations of dipyrrylmethanes with fulvene dialdehydes,8 condensations with diazulenylmethane dialdehydes,9 base-catalyzed reactions of bis(1indenyl)methane with dipyrrylmethane dialdehydes,10 and the acid catalyzed condensation of 3,4-diethylpyrrole with 1,3-indanedicarbaldehyde.11 Examples of doubly N-confused porphyrins have also been described.12,13 In an attempt to generate the carbon skeleton of quatyrin, calix[4]azulene 4a was prepared by condensing azulene with paraformaldehyde in the presence of florisil.14 6-tert-Butylazulene and 6-methylazulene also reacted under these conditions to generate substituted calix[4]azulenes 4b and 4c.15 A multi-step synthesis of a related tetrahydroxycalix[4]azulene 4d has been noted16 and meso-tetraaryl calix[4]azulenes were subsequently described.17,18 Treatment of 4b with triphenylcarbenium hexafluorophosphate gave the porphodimethene analogue 5 and this species can be considered to be a dihydroquatyrin with


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3 two fused tropylium ions.15 Furthermore, oxidation of tetraarylcalix[4]azulenes with 2,3dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) afforded tetraazuliporphyrin tetracations 6.17,19 Although X-ray crystallographic data could not be obtained for 6, DFT calculations indicated that these tetracations are highly distorted and while they can formally be considered to be didehydroquatyrins related to the theoretically antiaromatic species 7, these highly distorted structures do not appear to possess global π-electron delocalization pathways.17 Regardless, 5 and 6 do not correspond to quatyrin-type structures as they are either insufficiently oxidized15 or have overshot the required level of π-conjugation.17 Therefore, new synthetic approaches are required to access quatyrin-type structures.



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4 Figure 1. Selected carbaporphyrinoids.

In this paper, attempts to prepare quatyrins from fulvene-carbinols are described. Although this approach failed to give substituted quatyrins, the first examples of hydrocarbon analogues of expanded porphyrins were isolated instead. Attempts were made to use the same approach for the synthesis of dioxadicarbaporphyrins and an alternative route to this system from a dioxacarbatripyrrin was developed.

Results and Discussion Synthesis of Expanded Porphyrinoids Consisting of Azulene and Indene Subunits

Scheme 1. Attempted synthesis of a quatyrin derivative.


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5 A synthesis of azulene-appended fulvene aldehydes 8 was previously developed by reacting azulene-1-carbaldehydes 9 with indene enamine 10 in the presence of di-n-butylboron triflate (Scheme 1).8,20 We speculated that the related carbinols 11 might undergo a head-to-tail selfcondensation in the presence of an acid-catalyst to give fulvene dimer 12. This expectation was based in part on the propensity of azulene to undergo electrophilic substitution at the 1,3positions (position 3’ in 11). It was feasible that oxidation of this macrocycle could then afford quatyrin dication 13 (Scheme 1). Luche reduction of fulvene aldehydes 8 with sodium borohydride and cerium chloride gave the required alcohols 11 in 73-89% yield.

Figure 2. Partial proton NMR spectra for expanded porphyrinoids 14 (A) and 15 (B) in CDCl3. In addition, the methylene bridges (not shown) give rise to singlets at 4.28 and 3.81 ppm, respectively.

The best results for carrying out the self-condensation of fulvene carbinols 11 were obtained using catalytic boron trifluoride etherate with very short reaction times. Although both 11a and 11b were investigated, tert-butyl substituted carbinol 11b gave superior results and pure samples



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6 of macrocyclic products could not be isolated from reactions using 11a. In an early experiment, 11b in dichloromethane was reacted in the presence of BF3•Et2O for 5 min before quenching the reaction with a saturated aqueous solution of sodium bicarbonate. Following workup and chromatography on silica gel, a crude macrocyclic product was isolated. The high-resolution electron impact mass spectrum appeared to show the presence of a molecular ion corresponding to the formula C50H44 (calculated 644.3443, found 644.3442). This result is consistent with the targeted fulvene dimer 12b. Attempts were made to oxidize the product to quatyrin dication 13, but these experiments were unsuccessful. However, further investigations demonstrated that the condensation reaction was far more complicated than had at first been appreciated. Improved results were obtained when 11b was reacted with BF3•Et2O for 1 min in dichloromethane. Following column chromatography and recrystallization, a pure macrocyclic product A was isolated in 12% yield. In an attempt to increase the yield of this macrocycle, the solvent was changed to chloroform. Commercially available chloroform contains ethanol, which is present as a stabilizer, and the alcohol may modify the Lewis acid catalyst by coordinating to the boron atom. This factor has been shown to have a beneficial effect in synthesizing sterically hindered meso-tetraarylporphyrins21,22 and in the preparation of meso-tetraarylazuliporphyrins.23 When the reaction was carried out for 5 min in chloroform and the product purified by column chromatography, two brown bands were collected. While the first band afforded a clean product B in 12% yield, the second band gave a 1:1 mixture of two compounds. The proton NMR spectra for samples A and B were consistent with macrocyclic products such as 12b, although the chemical shifts for these compounds differed considerably from one another (Figure 2). For instance, the internal C-H protons for the azulene and indene units in A showed up at 8.14 and 6.93 ppm, respectively, whereas the corresponding peaks for product B appeared at 7.79 and


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7 6.14 ppm. Similarly, the two macrocycles showed the CH2 bridging protons at 4.28 ppm for A and 3.81 ppm for B, while the methine bridges appeared at 7.78 (A) and 7.27 ppm (B). The second band from the chloroform experiment consisted of a mixture of A and B. While 12b is one of the possible macrocyclic products that can be derived from carbinol 11, larger structures such as fulvene trimer 14 or tetramer 15 could also be generated (Figure 3). Although significant amounts of B could be seen when dichloromethane was used as a solvent, much higher yields of B were produced using chloroform. Macrocycles A and B were isolated as dark brown powders that were reasonably stable but somewhat insoluble. However, hydrocarbon B did show some signs of decomposition when chromatographed more than once on silica. Due to the intrinsic symmetry for these structures, the identity of these condensation products could not be deduced from the NMR data. The proton and carbon-13 NMR spectra for A and B were both consistent with 12b but could also just as easily correspond to 14 or 15. The mass spectra for these compounds were carefully assessed. Using high resolution fast atom bombardment (FAB) mass spectrometry, a molecular ion corresponding to the molecular formula C75H66 (calculated 966.5164, found 966.5181) was observed for macrocycle A, and these data demonstrate that this compound is trimer 14. High resolution FAB MS analysis of B gave a molecular ion corresponding to C100H88 ([M+H]+ calculated 1289.6964, found 1289.6987), thereby confirming that this product is tetramer 15. Importantly, 14 and 15 are the first examples of hydrocarbon analogues of expanded porphyrins.24,25 The formation of these very large ring systems was unexpected as oligomerization of the intermediates might be expected to occur more easily. It was also unclear whether dimer 12b was actually generated in these reactions. The initial study gave impure material and the observed ion at m/z 620.3401 could possibly have corresponded to a doubly charged ion derived from tetramer 15. A reevaluation of the NMR data



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8 for the initial product showed that it primarily consisted of trimer 14 that was contaminated with approximately 20% of tetramer 15. Therefore, it is doubtful that dimer 12b was a significant product in any of these experiments.

Figure 3. Hydrocarbon analogues of expanded porphyrins. Relative energies per fulvene subunit are given relative to fulvene dimer 12b.

It was difficult to rationalize the favorability for the formation of expanded porphyrinoids 14 and 15 over dihydroquatyrin derivative 12 given the entropic penalty for achieving this type of arrangement. In order to gain further insights, density functional theory (DFT) was employed to


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9 probe the potential cause(s) for the predominance of 14 and 15 over 12. To this end, geometry optimizations, with the M06-2X functional,26 were performed for 12, 14, and 15. Although these macrocycles are not fully conjugated, the individual fulvene units represent conjugated components that connect individual indene units to azulene moieties. Effective conjugation in these subunits obviously requires that these are planar. However, in all three cases the optimized structures show substantial twisting at the methine linkages (Figure 4). The dihedral angles for the indene and azulene components of each fulvene subunit in 12b are 35.7o and 36.9o. In trimer 14, these values were calculated as 22.6o, 25.6o and 35.0o, while tetramer 15 showed dihedral angles of 23.1o, -9.3o, -25.0o and -15.3o. Clearly, in 15 the larger macrocyclic ring accommodates the fulvene subunits with the smallest amount of distortion while these units are subjected to the largest degree of twisting in dimer 12b. Nevertheless, the expanded porphyrinoids are highly folded structures that are twisted around the CH2 bridges. Indeed, tetramer 15 takes on a distinctive Möbius-type conformation. The calculated relative energies per fulvene subunit also indicate that dimer 12b is the least stable while tetramer 15 is the most stable (Figure 3). Hence, these computational results provide an explanation for the preferential formation of 14 and 15.



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10

Figure 4. DFT optimized calculated conformations for fulvene dimer 12b (top left), fulvene trimer 14 (top right) and fulvene tetramer 15 (bottom).


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11

Synthesis of an opp-Dioxadicarbaporphyrin Although

the

self-condensation

of

fulvene

carbinol

11b

failed

to

give

the

tetracarbaporphyrinoid 12b, intriguing examples of expanded macrocycles were generated. The success of this study suggested that other porphyrinoid systems might be generated by using a similar approach. As the crucial carbon-carbon bond forming reactions involve electrophilic aromatic substitution, a suitably reactive aromatic unit would have to be attached to the fulvene intermediate. Examples of adj-dicarbaporphyrins 1610 and the related dioxadicarbaporphyrins 1727 have been described, and an example of an opp-dicarbaporphyrin 18 has also been reported11 (Figure 5). These highly modified porphyrinoids are aromatic compounds and their proton NMR spectra show the presence of strong diamagnetic ring currents. Dicarbaporphyrin 16 has also been shown to be a unique organometallic ligand generating a stable tripalladium sandwich complex.10 Dicarbaporphyrin 18 was found to be somewhat unstable in solution, possibly due in part to a high degree of crowding resulting from the presence of four hydrogens within the porphyrinoid cavity.11 The related dioxadicarbaporphyrin 19 had not been synthesized previously but this system has the potential to retain strongly aromatic properties while possessing improved stability because only two hydrogens would be present within the macrocyclic core. As furan is reasonably reactive towards electrophiles, we speculated that a furan-appended fulvene carbinol 20a could act as a precursor to this new porphyrinoid system (Scheme 2).



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12

H H

O

O

N

N Me

Me Et

Et

R

16

17 a. R = H, b. R = Ph Et Et H

N

N

O

H O

Et Et

19

18

Figure 5. Dicarbaporphyrins and dioxadicarbaporphyrins.

R CHO R

R Bu2BOTf

O

R

22

O 21 CHNMe2

10

CHO NaBH4 CeCl3.7H2O

R R R

R O O

20

CH2OH

a. R = H, b. R = Me

O R R 23

[O] 19

a. R = H, b. R = Me

Scheme 2. Self-condensation of a furan-appended fulvene carbinol.

Fulvene aldehyde 21a28 was synthesized by reacting furfural (22a) with indene enamine 1029 in the presence of the Lewis acid catalyst dibutylboron triflate. The monoaldehyde 21 was


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13 purified by column chromatography to yield a bright orange powder in 53% yield. Luche reduction with cerium(III) chloride and sodium borohydride gave the related alcohol 20a as a bright yellow solid in 81% yield following purification by column chromatography. It was anticipated

that

self-condensation

of

20a

under

acidic

conditions

would

afford

dihydroporphyrinoid 22a, and subsequent oxidation would then yield the aromatic product 19 (Scheme 2). A solution of 20a in dichloromethane was stirred with BF3•Et2O in an attempt to generate macrocyclic products such as 23 or 19. The proton NMR spectrum of the crude product showed the presence of trace amounts of a compound with an upfield resonance at -4 ppm and two downfield singlets between 9.2 and 9.8 ppm that were consistent with the internal CH, and external furan and meso-protons for an aromatic porphyrinoid system. These results are consistent with the formation of the targeted dioxadicarbaporphyrin 19 and presumably spontaneous air oxidation of an intermediary dihydro-porphyrinoid 23a had occurred. Addition of the oxidant DDQ did not improve the yields. We have had some success using aqueous ferric chloride solutions as an oxidizing agent,30 but the use of this reagent did not result in noticeable improvements. The condensation was attempted using hydrobromic acid as a catalyst but again only trace amounts of 19 could be isolated. p-Toluenesulfonic acid failed to give any product, while addition of trifluoroacetic acid resulted in decomposition. In most porphyrin-type syntheses, peripheral substituents are present and these may aid in the cyclization reaction by altering the conformations of the intermediates. Electron-donation from alkyl substituents attached to the aromatic rings may also enhance reactivity. With these possibilities in mind, a dimethylfuranylfulvene carbinol 20b was prepared. 3,4-Dimethylfuran-2carbaldehyde (22b)31 was reacted with 10 in the presence of Bu2BOTf, and following hydrolysis with aqueous sodium acetate, fulvene aldehyde 21b was isolated as an orange solid in 61% yield.



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14 Subsequent Luche reduction afforded the required alcohol 20b in 88% yield as a yellow solid. However, this species failed to give even trace amounts of identifiable macrocyclic products under any of the reaction conditions investigated.

Scheme 3. Synthesis of carbatripyrrins.

As the fulvene carbinol route had failed to produce significant quantities of dioxadicarbaporphyrin 19, an alternative strategy was investigated. In a recent study, a new approach to carbaporphyrins was developed using a carbatripyrrin as the key intermediate (Scheme 3).32 Pyrrole-2-carbaldehyde (24) reacted with indene and potassium hydroxide in refluxing ethanol to give fulvene 25. Reduction with lithium aluminum hydride gave dihydrofulvene 26 and this reacted with KOH and 24 to give carbatripyrrin 27. Initially isomeric tripyrrenes 28 appeared to have been generated that were in equilibrium with 27. However, when the reaction was conducted under concentrated conditions, the relatively insoluble carbatripyrrin precipitated out of solution and this outcome drove the equilibrium towards the formation of this product. The carbatripyrrin proved to be a versatile intermediate in the synthesis of


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15 heterocarbaporphyrin systems. This methodology was adapted for the synthesis of porphyrinoid 19. Reaction of furfural with KOH and indene in refluxing methanol gave the known fulvene 2933 in 45% yield. Reduction with LiAlH4 in refluxing THF generated the related dihydofulvene 30 and this reacted with furfural in the presence of potassium hydroxide to give dioxacarbatripyrrin 31 in 75% yield (Scheme 3). Similar asymmetrical intermediates such as 32 may be produced in this chemistry but once again 31 proved to be comparatively insoluble in the alcohol solvent and this factor drives the equilibrium towards the formation of this product. The dioxacarbatripyrrin precipitated out in pure form as a yellow solid. Proton and carbon-13 NMR spectroscopy confirmed that 31 has a plane of symmetry. In the proton NMR spectrum, the bridging methine protons and the indene methylene unit produced 2H triplets (J = 2.3 Hz) at 6.47 and 3.94 ppm, respectively, due to allylic coupling (Figure 6). The bridge CHs afforded a comparatively upfield carbon-13 resonance at 107.6 ppm owing to electron-donation from the associated furan rings.

Scheme 4. Synthesis and protonation of a dioxadicarbaporphyrin.



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16

Figure 6. Proton NMR spectrum of dioxacarbatripyrrin 19 in CDCl3. Initial attempts to react 31 with indene dialdehyde 33 in the presence of trifluoroacetic acid failed to give any macrocyclic products. However, when the reaction was carried out with HBr in acetic acid, dioxadicarbaporphyrin 19 could be isolated in 46% yield (Scheme 4). The porphyrin analogue was virtually insoluble in most organic solvents. At 50 oC, a weak proton NMR spectrum could be obtained in CDCl3 and this confirmed that the symmetrical nature of the structure (Figure 7). The meso-protons gave rise to a 4H singlet at 9.76 ppm, while the furan protons appeared as a 4H singlet at 9.25 ppm. The internal indene protons were located at -4.23 ppm, providing further conformation for the presence of a strong diatropic ring current. The porphyrinoid was also slightly soluble in d6-benzene at 60 oC and in this solvent 19 showed the meso-protons at 9.50 ppm, the furan protons at 8.61 ppm and the internal CH units at -3.91 ppm (Figure 7). These results imply that the diatropic ring current is slightly reduced in d6-benzene. A useful measure for assessing diatropicity is the ∆δ value, which corresponds to the difference between the chemical shifts for the upfield and downfield protons. Therefore, it is noteworthy that the ∆δ for 19 in CDCl3 is 13.99 ppm, but in d6-benzene this value falls to 13.41 ppm.


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17 Porphyrinoid 19 was more soluble in d6-DMSO and in this solvent the diatropicity appears to be enhanced as the ∆δ value increases to 14.61 ppm. The external meso- and furan protons gave singlets at 10.12 and 9.61 ppm, respectively, while the inner protons gave a resonance at -4.49 ppm. Solvent induced shifts of this type have been noted previously for other carbaporphyrinoid systems such as azuliporphyrins.34 The carbon-13 NMR spectrum of 19 in d6-DMSO confirmed that the compound has a highly symmetrical structure. The meso-carbons were identified at 100.9 ppm, while the inner CHs gave a resonance at 114.6 ppm.

Figure 7. Proton NMR spectrum of 19 in d6-benzene (A) and CDCl3 (B). The sloping baseline for spectrum A is due to the low solubility of 19 and the presence of a very large C6HD5 peak.



18 12 10

ε x 10-4 M-1cm-1

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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8 6 4 2 0 300

400

500

600

700

800

Wavelength (nm)

Figure 8. UV-vis spectra of dioxadicarbaporphyrin 19 in dichloromethane (free base, red line) and in 10% TFA-dichloromethane (cation 19H+, blue line).

The UV-vis spectrum for 19 in dichloromethane was consistent with an aromatic porphyrinoid showing a strong Soret band at 427 nm, a secondary absorption at 356 nm and Q bands at 499 and 523 nm (Figure 8). Two very weak absorptions were also noted at 675 and 741 nm. Addition of excess TFA led to the formation of a protonated cation 19H+ that gave a slightly weaker red shifted Soret band at 499 nm and a strong absorption at 751 nm (Figure 8). Protonation occurs on an internal carbon and this reduces the symmetry of the system. In principle, a diprotonated dication 19H22+ could be formed but this species does not appear to be generated even in neat TFA (Scheme 4). Although 19 is fairly stable in solution, the protonated species slowly decomposes over several hours at room temperature. The proton NMR spectrum of 19 in 50% TFA-CDCl3 showed the inner methylene protons at -5.26 ppm and the indene CH at -6.78 ppm, while the external meso-protons gave 2H singlets at 9.77 (10,15-H) and 10.68 ppm (5,20-H) (Figure 9). These results indicate that the aromatic character has been enhanced in the protonated form given that the ∆δ value has increased for 19H+ to 17.46 ppm. In addition, the data show that one of the benzo moieties is involved in the macrocyclic delocalization pathway, while the remaining benzo unit remains outside of the global aromatic circuit. This is evident from the


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19 observation that the benzo-protons for the protonated indene ring are strongly shifted downfield to give multiplets at 9.86-9.89 and 8.82-8.85 ppm, while the isolated benzene unit gives the equivalent resonances at 8.28-8.31 and 7.63-7.66 ppm. Unfortunately, the low solubility and instability of 19H+ prevented us from obtaining a carbon-13 NMR spectrum for this species. However, HSQC and DEPT-135 NMR spectra could be acquired as these could be run far more rapidly. These results showed that the carbon resonances for the meso-protons were present at 113.4 (10,15-CH) and 106.8 ppm (5,20-CH). The inner CH2 resonance was identified at 33.5 ppm and the internal indene CH appeared at 129.7 ppm.

Figure 9. Proton NMR spectrum of 19H+ in 50% TFA-CDCl3.

Further insights into the properties and aromatic characteristics of dioxadicarbaporphyrins were obtained by carrying out density functional theory (DFT) calculations on 19, 19H+ and 19H22+. In addition, the free base and protonated forms of isomeric adj-dioxadicarbaporphyrin 17a were investigated. Initially, the structures were optimized using DFT-B3LYP/6311++G(d,p).35 The free bases and the corresponding protonated structures were shown to be



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20 near planar. The relative energies were assessed for the two series and the adjdioxadicarbaporphyrin free base 17a, monocation 17aH+ and dication 17aH22+ were shown to be more stable than the equivalent members of the opp-dioxacarbaporphyrin series (Table 1). These comparisons were made using three different computational methods, all of which gave comparable results. In addition, the ∆G values were also very similar, indicating that entropic factors do not play a significant role.

Table 1. Relative energies in kcal/mol of opp-dioxacarbaporphyrins compared to their adjdioxadicarbaporphyrin counterparts. Therefore 19 is contrasted with 17a, 19H+ is compared to 17aH+ and 19H22+ is compared to 17aH22+. In every case, the opp-dioxadicarbaporphyrin series is higher in energy. ∆G(B3LYP) ∆E(B3LYP) ∆E(M06-2X) ∆E(B3LYP-D3)

19 7.24 7.16 8.01 7.92

+

19H 6.47 6.07 7.24 6.82

2+

19H2 3.87 3.12 1.91 3.83

Nucleus independent chemical shift (NICS) calculations36 were performed and these confirmed that all of the structures are highly diatropic (Table 2). In NICS calculations, large negative values within a given ring implies that the structure is an aromatic compound. A large positive result may indicate that the system is antiaromatic or that the region being assessed is external to the aromatic ring current. Values that are close to zero imply that the system is nonaromatic. Standard NICS calculations incorporate effects due to σ and π electrons and do not always reliably assess aromatic characteristics. However, NICSzz calculations primarily measure the effects due to the π system. In order to obtain rigorous insights into these structures, NICS and NICSzz calculations were performed. The latter measurement were made 1 Å above the ring (NICS(1)zz). The two sets of data were consistent, although the values obtained using NICSzz


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21 were much larger than those produced using standard NICS calculations. In order to simplify the analysis, only the results for the NICS calculations are discussed, but it is noteworthy that the two methods showed the same trends in all of the calculations. opp-Dioxadicarbaporphyrin 19 gave a NICS(0) value of -13.37 ppm, demonstrating that the structure possesses a strong diamagnetic ring current. The furan rings (b and d) also gave large negative values, but rings a and c afforded large positive values. These results are consistent with the presence of an 18π electron delocalization pathway that bypasses the two benzo-units. Similar results were determined for adj-dioxodicarbaporphyrin 17a, although the NICS(0) value was slightly lower. Again, the results show that the 18π electron pathway runs around the furan rings but avoids the two fused benzene rings. Monocation 19H+ retains strongly aromatic properties and has a NICS(0) value of -11.25 ppm. In this case, benzo-unit e has a NICS value of -10.35 ppm, although the calculated NICS for the remaining benzene ring is only -3.62 ppm. Rings a, b and d all give large negative values, but ring c afforded a large positive result. The data suggest that this species favors a 23-atom 22π electron circuit that passes around ring e, as illustrated in structure 34 (Figure 10). The cationic species 17aH+ for the adj-dioxadicarbaporphyrin also appears to incorporate one of the indene rings into the favored aromatic circuit to give a similar 23-atom 22π electron pathway as illustrated in structure 35 (Figure 10). The calculated NICS(0) value for dication 19H22+ was -12.91 ppm but in this case rings a, b, c, d, e and f all gave large negative NICS values as well. These data indicate that this species would be highly diatropic due to presence of a pathway that resembles a bridged [28]annulene dication (see structure 36). The NICS(0) value for the related dication 17aH22+ is reduced but nevertheless all of the individual rings appear to be within the confines of the global aromatic pathway. Hence, this species also appears to favor a delocalized structure that runs around the periphery of the whole system and



Page 22 of 43

22 involves a 28-atom 26π electron circuit of the type illustrated in structure 37.

Table 2. NICS values for dioxadicarbaporphyrins and related protonated species. Negative values denoting strongly shielded regions are highlighted in bold, while highly deshielded values are labeled in red.

Molecule NICS(0)/NICS(1)zz NICS(a)/NICS(1a)zz NICS(b)/NICS(1b)zz NICS(c)/NICS(1c)zz NICS(d)/NICS(1d)zz NICS(e)/NICS(1e)zz NICS(f)/NICS(1f)zz

Molecule NICS(0)/NICS(1)zz NICS(a)/NICS(1a)zz NICS(b)/NICS(1b)zz NICS(c)/NICS(1c)zz NICS(d)/NICS(1d)zz NICS(e)/NICS(1e)zz NICS(f)/NICS(1f)zz

19 -13.37/-32.67 +9.02/+18.74 -16.83/-41.62 +9.02/+18.74 -16.83/-41.62 -3.99/-15.53 -3.99/-15.53

17a -11.90/-29.88 +8.48/+16.53 +8.48/+16.53 -16.42/-41.33 -16.42/-41.33 -4.01/-15.64 -4.01/-15.64

19H+ -11.25/-25.97 -11.34/-34.38 -15.54/-38.80 +11.14/+23.68 -15.53/-38.78 -10.35/-33.01 -3.62/-14.50

19H22+ -12.91/-29.83 -14.22/-42.38 -15.74/-40.71 -14.19/-42.34 -15.75/-40.71 -11.75/-37.79 -11.78/-37.86

17aH+ -10.39/-25.08 +15.42/+34.47 -11.59/-35.84 -15.41/-38.61 -14.78/-37.26 -1.42/-9.35 -10.72/-34.15

17aH22+ -8.56/-19.41 -9.54/-31.44 -9.53/-31.43 -13.72/-34.98 -13.72/-34.98 -10.85/-35.11 -10.85/-35.11


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23

O O

O

O

34

35

O O

2+

O

36

2+

O

37

Figure 10. Favored conjugation pathways in protonated dibenzo dioxadicarbaporphyrins. The calculated bond lengths for these structures were also consistent with these interpretations (Figures 11 and 12). The free base form of 19 showed an absence of significant bond length alternation around the proposed 18-atom delocalization pathway. However, the bonds connecting the [18]annulene unit to the benzo subunits were longer (1.48 Å). In the related monocation 19H+, the length of the corresponding bonds connected to the benzo-unit that is incorporated into the global conjugation pathway is reduced to 1.44 Å. However, the remaining indene unit essentially retains the original bond lengths because they do not contribute to the macrocyclic delocalization pathway (Figure 11). Similar results were obtained for the adjdioxadicarbaporphyrin free base and monocation (Figure 12). Further support for the proposed aromatic pathways were obtained using anisotropy of induced current density (AICD).37 The AICD plots for 19 and 19H+ are given Figure 13 and related results of this type are provided in the Supporting Information section. The AICD plot for 19 clearly shows the proposed [18]annulene delocalization pathway, while the plot for 19H+ demonstrates that a 23-atom 22π electron pathway is favored.



Page 24 of 43

24

Figure 11. Calculated bond lengths for dibenzo opp-dioxadicarbaporphyrin 19 (left) and the related monoprotonated cation 19H+ (right).

Figure 12. Calculated bond lengths for dibenzo adj-dioxadicarbaporphyrin 17a (left) and the related monoprotonated cation 17aH+ (right).


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25

Figure 13. AICD plots (isovalues = 0.07) for dibenzo opp-dioxadicarbaporphyrin 19 and the related monoprotonated cation 19H+. The free base structure shows the presence of an 18π electron delocalization circuit that bypasses the benzo-units, while the AICD plot for cation 19H+ demonstrates that one of the fused benzene rings facilitates an extended aromatic pathway.

Conclusions Azulene-appended fulvene carbinols have been shown to self-condense in the presence of boron trifluoride etherate to form large macrocyclic structures consisting of 3 or 4 fulvene subunits, although cyclic difulvenes could not be isolated. The new macrocycles can be considered to be hydrocarbon analogues of expanded porphyrins. However, this approach does



Page 26 of 43

26 not appear to be compatible with the synthesis of quatyrin (tetracarbaporphyrin) derivatives. A similar self-condensation of a furan-appended fulvene carbinol gave only trace amounts of a dioxadicarbaporphyrin. An alternative synthesis to this new porphyrinoid system was achieved by reacting a dioxacarbatripyrrin with an indene dialdehyde in the presence of HBr. The dioxadicarbaporphyrin was shown to be fully aromatic in the free base and protonated forms by proton NMR spectroscopy, AICD and NICS calculations. These results demonstrate that new synthetic approaches of this type can provide access to novel porphyrinoid systems that further extend our understanding of these important aromatic structures.

Experimental Melting points are uncorrected. NMR spectra were recorded using a 400 or 500 MHz NMR spectrometer and were run at 302 K unless otherwise indicated. 1H NMR values are reported as chemical shifts δ, relative integral, multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad peak) and coupling constant (J). Chemical shifts are reported in parts per million (ppm) relative to CDCl3 (1H residual CHCl3 δ 7.26,

13

C CDCl3 triplet δ 77.23), d6-

benzene (1H residual C6H5D δ 7.15 ppm) or d6-DMSO (1H residual d5-DMSO pentet δ 2.49, 13C d6-DMSO heptet δ 39.7), and coupling constants were taken directly from the spectra. NMR assignments were made with the aid of 1H-1H COSY, HSQC, DEPT-135 and nOe difference proton NMR spectroscopy. 2D experiments were performed by using standard software. Highresolution mass spectra (HRMS) were carried out by using a double focusing magnetic sector instrument. 1H and

13

C NMR spectra for all new compounds are reported in Supporting

Information.


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27 6-(6-tert-Butyl-1-azulenyl)benzo[a]fulvene-3-carbaldehyde (8b). Dibutylboron triflate (1.2 mL, 1.0 M in dichloromethane) was added to a stirred solution of 6-tert-butylazulene-1carbaldehyde 9b (200 mg, 0.942 mmol) and sodium sulfate (500 mg) in 1,2-dichloroethane (300 mL). A solution of indene enamine 10 (205 mg, 1.20 mmol) in 1,2-dichloroethane (50 mL) was added dropwise over 20 min, and the resulting mixture was allowed to stir under reflux for 4 h. A saturated solution of sodium acetate trihydrate (120 mL) was added, and the solution was allowed to stir for 15 min at room temperature. The solution was extracted with dichloromethane, washed with a saturated sodium bicarbonate solution and dried over sodium sulfate. The organic layers were combined and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with 30% hexanes/70% dichloromethane. A dark purple fraction was collected and the solvent removed under reduced pressure. The product was recrystallized from chloroform-hexanes to give the aldehyde (158 mg, 0.495 mmol, 53%) as a dark purple powder, mp 198-200 °C, dec. (lit.8 mp 198-200 oC). 1H NMR (500 MHz, CDCl3): δ 1.50 (9H, s, t-Bu), 7.31-7.36 (2H, m), 7.48 (1H, d, J = 4.3 Hz), 7.57 (1H, dd, J = 1.8, 10.2 Hz), 7.66 (1H, dd, J = 1.8, 10.6 Hz), 7.86-7.88 (1H, m), 8.04 (1H, s), 8.16-8.18 (1H, m), 8.33 (2H, d, J = 10.2 Hz), 8.38 (1H, s), 8.42 (1H, d, J = 4.3 Hz), 8.69 (1H, d, J = 10.6 Hz), 10.23 (1H, s, CHO).

13

C NMR (125 MHz, CDCl3): δ 32.0, 39.1, 118.7, 121.9, 122.8,

125.26, 125.2, 125.7, 125.8, 125.9, 126.7, 128.3, 133.0, 133.7, 136.5, 137.48, 137.52, 138.9, 140.23, 140.27, 140.4, 144.0, 164.5, 189.0. 6-(1-Azulenyl)benzo[a]fulvene-3-carbaldehyde (8a). Dibutylboron triflate (200 µL, 1.0 M in dichloromethane) was added over 5 min to a stirred solution of 1-azulenecarbaldehyde 9a (31 mg, 0.198 mmol) in dichloromethane. A solution of indene enamine 10 (71 mg, 0.415 mmol) in dichloromethane (15 mL) was added dropwise over 10 min, and the resulting solution was



Page 28 of 43

28 allowed to stir at room temperature overnight. A solution of sodium acetate trihydrate (1.5 g) in water (2 mL) was added and the mixture was refluxed for 15 min. The organic phase was separated and washed with water, 5% sodium bicarbonate and water, and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue purified on a silica gel column eluting with 30% hexanes/70% dichloromethane. The first dark purple band was collected and the solvent was evaporated under reduced pressure. The resulting solid was recrystallized from chloroform-hexanes to yield the fulvene aldehyde (25 mg, 0.088 mmol, 48%) as a dark purple powder, mp 164-165 °C (lit. mp20 166-167 oC). 1H NMR (500 MHz, CDCl3): δ 7.31-7.35 (3H, m), 7.40 (1H, t, J = 9.7 Hz), 7.52 (1H, d, J = 4.2 Hz), 7.73 (1H, t, J = 9.8 Hz), 7.83-7.85 (1H, m), 7.93 (1H, s), 8.14-8.16 (1H, m), 8.30 (1H, s), 8.35 (1H, d, J = 9.4 Hz), 8.43 (1H, d, J = 4.2 Hz), 8.64 (1H, d, J = 9.7 Hz), 10.18 (1H, s, CHO). 13C NMR (125 MHz, CDCl3): δ 118.9, 122.1, 122.8, 126.0, 126.5, 127.0, 127.5, 128.0, 133.8, 134.5, 136.6, 138.3, 138.4, 138.7, 139.9, 140.1, 140.7, 141.2, 145.0, 189.0. 6-(6-tert-Butyl-1-azulenyl)-3-hydroxymethylbenzo[a]fulvene (11b). Fulvene monoaldehyde 8b (100 mg, 0.30 mmol) was added to a solution of cerium(III) chloride heptahydrate (63.8 mg, 0.17 mmol) in ethanol (7.5 mL), methanol (19 mL), and dichloromethane (15 mL). Sodium borohydride (21 mg, 0.55 mmol) was added and the mixture was allowed to stir for 30 min. The solution was quenched with water (40 mL), extracted with dichloromethane, and the organic layers were combined and evaporated under reduced pressure. The residue was purified by column chromatography on silica eluting with chloroform. A purple band eluted initially that corresponded to unreacted fulvene aldehyde, followed by a green product band. Following evaporation of the solvent under reduced pressure, the dark green residue was recrystallized from chloroform-hexanes to yield the carbinol (78 mg, 0.229 mmol, 73%) as a dark green powder, mp


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29 166-168 oC. 1H NMR (500 MHz, CDCl3): δ 1.45 (1H, d, J = 1.1 Hz, OH), 1.48 (9H, s, t-Bu), 4.88 (2H, d, J = 1.1 Hz, CH2OH), 7.26-7.28 (2H, m, 12,22-H), 7.30 (1H, q, J = 1.1 Hz, 4-H), 7..40-7.43 (3H, m, 31,3’,7’-H), 7.49 (1H, dd, J = 1.8, 10.6 Hz, 5’-H), 7.82-7.85 (1H, m, 11-H), 8.04 (1H, s, 6-H), 8.25 (1H, d, J = 10.2 Hz, 8’-H), 8.36 (1H, d, J = 4.2 Hz, 2’-H), 8.60 (1H, d, J = 10.6 Hz, 4’-H).

13

C NMR (125 MHz, CDCl3): δ 32.0 (C(CH3)3), 38.9 (C(CH3)3), 60.3

(CH2OH), 118.9, 119.4, 120.2, 120.8, 123.2, 123.7, 125.1, 126.0, 126.4, 133.4, 134.5, 136.7, 137.2, 138.3, 139.4, 139.8, 142.4, 144.7, 163.3. HRMS (EI) m/z: M+ Calcd for C25H24O: 340.1827; Found 340.1816. 6-(1-Azulenyl)-3-hydroxymethylbenzo[a]fulvene (11a). Fulvene aldehyde 8a (50 mg, 0.18 mmol) and cerium(III) chloride heptahydrate (38 mg, 0.10 mmol) was dissolved in a mixture of ethanol (4.5 mL), methanol (11.5 mL), and dichloromethane (9 mL). Sodium borohydride (14 mg, 0.37 mmol) was added and the mixture stirred for 30 min. Water (25 mL) was added to quench the reaction, the organic phase was separated, and the water layer was back extracted with dichloromethane. The organic layers were combined and solvent was removed under reduced pressure. The residue was chromatographed on silica eluting with chloroform. Recrystallization from chloroform-hexanes gave the carbinol (44.8 mg, 0.16 mmol, 89%) as a green powder, mp 154-156 °C. 1H NMR (500 MHz, CDCl3): δ 1.65 (1H, br s, OH), 4.87 (2H, s, CH2OH), 7.23 (1H, t, J = 9.7 Hz, 5’-H), 7.25-7.30 (4H, m, 11,21,5’,7’-H), 7.40-7.43 (1H, m, 21H), 7.49 (1H, d, J = 4.1 Hz, 3’-H), 7.65 (1H, t, J = 9.8 Hz, 6’-H), 7.83-7.86 (1H, m, 11-H), 8.03 (1H, s, 6-H), 8.30 (1H, d, J = 9.4 Hz, 4’-H), 8.43 (1H, d, J = 4.2 Hz, 2’-H), 8.63 (1H, d, J = 9.8 Hz, 8’-H).

13

C NMR (125 MHz, CDCl3): δ 60.3 (CH2OH), 119.0 (11-CH), 119.4 (21-H), 120.5

(6-CH), 120.6 (3’-CH), 123.1, 124.6, 125.3, 125.6 (5’-CH), 126.4, 126.6, 134.4 (8’-CH), 135.4, 137.6 (4’-CH), 138.2 (2’-CH), 139.1 (6’-CH), 139.26, 139.28, 139.9, 143.5, 145.3. HRMS (ESI)



Page 30 of 43

30 m/z: [M+Li]+ Calcd for C21H16OLi: 291.1356; Found 291.1361. Macrocyclic Trimer 14. Boron trifluoride etherate (30 µL) was added to stirred solution of fulvene carbinol 11b (50 mg, 0.147 mmol) in dichloromethane (250 mL). The solution was stirred for 1 min and immediately washed with saturated sodium bicarbonate solution and back extracted with dichloromethane. The organic layers were combined and concentrated, and the residue purified by column chromatography on silica eluting with 2:1 hexanes/dichloromethane. Recrystallization from chloroform-hexanes gave 14 (8.3 mg, 0.0086 mmol, 12%) as a dark brown powder, mp > 300 °C. 1H NMR (500 MHz, CDCl3): δ 1.41 (27H, s, 3 x t-Bu), 4.28 (6H, s, 3 x bridging-CH2), 6.93 (3H, s, 31,33,35-CH), 7.14 (3H, t, J = 7.4 Hz, 3 x benzo-H), 7.17-7.23 (9H, m, 6 x benzo-H & 82,182,282-H), 7.31 (3H, dd, J = 1.6, 10.6 Hz, 72,172,272-H), 7.71 (3H, d, J = 7.4 Hz, 31,131,231-H), 7.78 (3H, s, 5,15,25-H), 8.14 (3H, s, 32,34,36-H), 8.38 (3H, d, J = 10.6 Hz, 71,171,271-H).

13

C NMR (125 MHz, CDCl3): δ 25.8 (3 x bridge-CH2), 31.9 (3 x

C(CH3)3), 38.7 (3 x C(CH3)3), 118.6 (31,131,231-CH), 118.80, 118.84 (5,15,25-CH), 122.4 (72,172,272), 122.6, 123.8, 124.6, 124.9, 126.0, 130.2, 132.9 (71,171,271-CH), 133.2 (81,181,281CH), 134.7, 137.6 (32,34,36-CH), 138.5, 138.8, 139.5, 141.5, 145.2, 162.7. HRMS (FAB) m/z: M+ Calcd for C75H66 966.5164; Found 966.5181. Macrocycle Tetramer 15. Boron trifluoride etherate (30 µL) was added to stirred solution of fulvene carbinol 11b (50 mg, 0.147 mmol) in chloroform (250 mL) and the solution was stirred for 5 min. The solution was immediately washed with saturated sodium bicarbonate solution and back extracted with dichloromethane. The combined organic layers were dried over sodium sulfate and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica eluting with 2:1 hexanes/dichloromethane. The first band was collected and evaporated under reduced pressure to yield 15 (11 mg, 0.0085 mmol, 12%) as a dark brown


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31 solid, mp >300 °C. 1H NMR (400 MHz, CDCl3): δ 1.37 (36H, s, 4 x t-Bu), 3.81 (8H, s, 4 x bridge-CH2), 6.14 (4H, s, 41,43,45,47-H), 6.93 (4H, dd, J = 1.4, 10.6 Hz, 4 x azulene-H), 7.00 (4H, d, J = 7.4 Hz, 4 x benzo-H), 7.12 (4H, dd, J = 1.6, 10.6 Hz, 4 x azulene-H), 7.15 (4H, t, J = 7.4 Hz, 4 x benzo-H), 7.27 (4H, s, 5,15,25,35-H), 7.39 (4H, t, J = 7.3 Hz, 4 x benzo-H), 7.79 (4H, s, 42,44,46,48-H), 7.97 (4H, d,

J = 10.5 Hz), 8.00 (4H, d, J = 10.7 Hz)

(71,81,171,181,271,281,371,381-H), 8.02 (4H, d, J = 7.6 Hz, 31,131,231,331-H);

13

C NMR (100

MHz, CDCl3): δ 26.0, 32.0, 38.6, 118.45, 188.48, 118.9, 121.8, 122.0, 124.4, 124.6, 124.7, 126.4, 128.4, 132.7, 133.7, 134.7, 138.4, 138.5, 139.2, 140.0, 141.9, 145.2, 162.2. HRMS (FAB) m/z: [M+H]+ Calcd for C100H89: 1289.6964; Found 1289.6987. 6-(2-Furyl)benzo[a]fulvene-3-carbaldehyde (21a). Dibutylboron triflate (1 mL, 1.0 M in dichloromethane) was added to a stirred solution of furfural (86 µL, 99.8 mg, 1.04 mmol) in dichloromethane (150 mL). A solution of indene enamine 10 (196 mg, 1.12 mmol) in dichloromethane (150 mL) was added over 10 min, and the solution was allowed to stir at room temperature overnight. A solution of saturated sodium acetate trihydrate (100 mL) was added and the mixture was allowed to stir for 10 min. The solution was extracted with dichloromethane, washed with saturated sodium bicarbonate solution and brine, dried over sodium sulfate, and the solvent removed under reduced pressure. The oily brown residue was purified by column chromatography (x2) on silica gel eluting with 1:1 hexanes/dichloromethane. A red-orange band was collected and evaporated to give the fulvene aldehyde (123 mg, 0.55 mmol, 53%) as an orange powder, mp 110-112 °C (lit.28 mp 110-112 oC). 1H NMR (500 MHz, CDCl3): δ 6.60 (1H, dd, J = 1.8, 3.5 Hz, 4’-H), 6.85 (1H, d, J = 3.5 Hz, 3’-H), 7.27-7.33 (2H, m, 12,22-H), 7.34 (1H, s, 6-H), 7.64-7.66 (1H, m, 11-H), 7.70 (1H, d, J = 1.7 Hz, 5’-H), 8.08-8.10 (1H, m, 21-H), 8.12 (1H, s, 4-H), 10.20 (1H, s, CHO). 13C NMR (125 MHz, CDCl3): δ 113.3 (4’-



Page 32 of 43

32 CH), 118.9 (3’-CH), 119.4 (11-CH), 120.2 (6-CH), 123.1 (21-CH), 126.5 (12 or 22-CH), 128.0 (12 or 22-CH), 134.8, 137.4, 137.7, 141.3 (4-CH), 142.1, 146.9 (5’-CH), 153.1, 189.3 (CHO). 6-(3,4-Dimethyl-2-furyl)benzo[a]fulvene-3-carbaldehyde

(21b).

3,4-Dimethylfuran-2-

carbaldehyde35 (85%, 146 mg, 1.00 mmol) was reacted with indene enamine 1030 (196 mg, 1.15 mmol) and dibutylboron triflate (1 mL, 1.0 M in dichloromethane) under the foregoing conditions to give the fulvene aldehyde (152 mg, 0.61 mmol, 61%) as an orange solid, mp 167.5168.5 oC. 1H NMR (500 MHz, CDCl3): δ 2.02 (3H, s, 4’-CH3), 2.20 (3H, s, 3’-CH3), 7.26-7.31 (2H, m, 12,22-H), 7.31 (1H, s, 6-H), 7.44 (1H, s, 5’-H), 7.67-7.69 (1H, m, 11-H), 8.09-8.11 (1H, m, 21-H), 8.14 (1H, s, 4-H), 10.18 (1H, s, CHO). 13C NMR (125 MHz, CDCl3): δ 8.3 (4’-CH3), 9.3 (3’-CH3), 118.4 (6-CH), 119.0 (11-CH), 123.0 (21-CH), 124.0, 126.2 (12 or 22-CH), 127.5 (12 or 22-CH), 131.1, 132.8, 137.1, 138.0, 141.1, 142.1 (4-CH), 143.6 (5’-CH), 149.8, 189.3 (CHO). HRMS (EI) m/z: M+ Calcd for C17H14O2 250.0994; Found 250.0993. 3-Hydroxymethyl-6-(2-furyl)benzo[a]fulvene (20a). Sodium borohydride (16 mg, 0.42 mmol) was added to stirred solution of fulvene aldehyde 21a (50 mg, 0.26 mmol) and cerium(III) chloride heptahydrate (47 mg, 0.13 mmol) in dichloromethane (10 mL) and methanol (20 mL). The solution was stirred for 30 min and then quenched with water (30 mL). The mixture was extracted several times with dichloromethane, the organic layers combined and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with dichloromethane. A yellow band was collected and evaporated to give the carbinol (46 mg, 0.21 mmol, 81%) as a yellow powder, mp 128-129 oC. 1H NMR (500 MHz, CDCl3): δ 1.64 (1H, br, OH), 4.83 (2H, s, CH2OH), 6.51 (1H, dd, J = 1.8, 3.4 Hz, 4’-H), 6.66 (1H, d, J = 3.4 Hz, 3’-H), 7.07 (1H, s, 6-H), 7.21-7.27 (2H, m, 12,22-H), 7.34-7.36 (2H, m, 21 & 4-H), 7.58 (1H, d, J = 1.7 Hz, 5’-H), 7.60-7.62 (1H, m, 11-H).


13

C NMR (125 MHz, CDCl3): δ

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33 60.2 (CH2OH), 112.5 (4’-CH), 114.0 (6-CH), 115.0 (3’-CH), 119.3 (11-CH), 119.5 (21-CH), 123.5 (4-CH), 125.6 (12 or 22-CH), 127.4 (12 or 22-CH), 135.7, 138.5, 140.5, 144.9 (5’-CH), 146.4, 153.5. HRMS (EI) m/z: M+ Calcd for C15H12O2 224.0837; Found 224.0831. 6-(3,4-Dimethyl-2-furyl)-3-hydroxymethylbenzo[a]fulvene (20b). Fulvene aldehyde 21b (65 mg, 0.26 mmol) was reduced with sodium borohydride (16 mg, 0.42 mmol) and CeCl3•H2O (47 mg, 0.13 mmol) under the previous conditions giving alcohol 20b (58 mg, 0.23 mmol, 88%) as a yellow powder, mp 148-149 oC. 1H NMR (500 MHz, CDCl3): δ 1.59 (1H, br, OH), 1.99 (3H, d, J = 1.1 Hz, 4’-CH3), 2.15 (3H, s, 3’-CH3), 4.82 (2H, d, J = 1.0 Hz, CH2OH), 7.04 (1H, s, 6-H), 7.20-7.26 (2H, m, 12,22-H), 7.33 (1H, s, 5’-H), 7.36-7.38 (1H, m, 21-H), 7.39 (1H, s, 4-H), 7.647.66 (1H, m, 11-H). 13C NMR (125 MHz, CDCl3): δ 8.4 (4’-CH3), 9.0 (3’-CH3), 60.3 (CH2OH), 112.3 (6-CH), 119.0 (11-CH), 119.4 (21-CH), 123.0, 124.3 (4-CH), 125.2 (12 or 22-CH), 126.9 (12 or 22-CH), 133.7, 138.7, 140.3, 141.4 (5’-CH), 145.1, 149.7. HRMS (EI) m/z: M+ Calcd for C17H16O2 252.1150; Found 252.1155. 6-(2-Furyl)benzo[a]fulvene (29). Technical grade indene (5.58 g, 90%, 48 mmol) and freshly distilled furfural (4.60 g, 48 mmol) were dissolved in 1% KOH-methanol (200 mL) and stirred under reflux for 1 h. The mixture was diluted with ethyl acetate, washed with water, and the aqueous layer back extracted with ethyl acetate. The organic solutions were dried over sodium sulfate, filtered and evaporated under reduced pressure. The crude product was purified on silica gel eluting with 4:1 hexanes-dichloromethane to give the fulvene (4.22 g, 22 mmol, 45%) as a red-orange solid, mp 83-84 oC (lit.32a mp 86-86.5 oC; mp32b 91 oC). 1H NMR (500 MHz, CDCl3): δ 6.51 (1H, dd, J = 1.8, 3.4 Hz, 4’-H), 6.66 (1H, d, J = 3.4 Hz, 3’-H), 6.97 (1H, dd, J = 1.3, 5.5 Hz, 4-H), 7.09 (1H, s, 6-H), 7.16-7.24 (2H, m, 12,22-H), 7.29-7.31 (1H, m, 21-H), 7.37 (1H, d, J = 5.5 Hz, 3-H), 7.58 (1H, d, J = 1.7 Hz, 5’-H), 7.59-7.61 (1H, m, 11-H).


13

C NMR (125 MHz,


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34 CDCl3): δ 112.5, 114.4, 115.1, 119.2, 121.3, 125.1, 125.49, 125.51, 133.8, 136.9, 137.6, 142.3, 144.9, 153.5. 3,6-Dihydro-6-(2-furyl)benzo[a]fulvene (30). The foregoing fulvene (2.80 g, 14 mmol) was dissolved in THF (70 mL) and a suspension of LiAlH4 (568 mg) in THF (20 mL) was added dropwise. The resulting mixture was stirred under reflux for 16 h. Water was cautiously added and mixture was extracted several times with ether. The combined organic solutions were dried over sodium sulfate, filtered, and evaporated under reduced pressure. The residue was purified on a silica gel column eluting with dichloromethane. Evaporation of the solvent from the product fraction gave the dihydrofulvene (1.36 g, 6.94 mmol, 48%) as a red-brown oil. 1H NMR (500 MHz, CDCl3): δ 3.37 (2H, q, J = 1.9 Hz, 6-CH2), 3.93 (2H, m, 3-CH2), 6.08-6.09 (1H, m, 3’-H), 6.28 (1H, pentet, J = 1.7 Hz, 4-H), 6.30 (1H, dd, J = 1.8, 3.2 Hz, 4’-H), 7.20 (1H, dt, J = 1.2, 7.4 Hz, 22-H), 7.26-7.29 (1H, m, 12-H), 7.33-7.35 (2H, m, 11-H and 5’-H), 7.45-7.47 (1H, m, 21-H), 7.45-7.47 (1H, m, 21-H). 13C NMR (125 MHz, CDCl3): δ 27.4 (6-CH2), 38.0 (3-CH2), 106.5 (3’CH), 110.5 (4’-CH), 119.4 (11-CH), 124.0 (21-CH), 124.9 (22-CH), 126.3 (12-CH), 130.5 (4-CH), 140.7, 141.5 (5’-CH), 144.6, 144.9, 153.4. HRMS (ESI) m/z: M+ Calcd for C14H12O 196.0888; Found 196.0891. Dioxacarbatripyrrin 31. Dihydrofulvene 30 (0.911 g, 4.65 mmol) and freshly distilled furfural (0.462 g, 4.8 mmol) were dissolved in ethanol (10 mL) containing 0.257 g of potassium hydroxide and the solution was stirred under reflux for 30 min. The resulting precipitate was suction filtered, washed with ethanol, and dried in vacuo to give the pure dioxacarbatripyrrin (0.961 g, 3.51 mmol, 75%) as a yellow solid, mp 130-131 oC. 1H NMR (500 MHz, CDCl3): δ 3.94 (2H, t, J = 2.3 Hz, 16-CH2), 6.47 (2H, d, J = 3.3 Hz, 3,12-H), 6.52 (2H, dd, J = 1.8, 3.3 Hz, 2,13-H), 6.89 (2H, t, J = 2.3 Hz, 5,10-H), 7.26-7.29 (2H, m, 72,82-H), 7.52 (2H, d, J = 1.8 Hz,


Page 35 of 43 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


35 1,14-H), 7.59-7.63 (2H, m, 71,81-H). 13C NMR (125 MHz, CDCl3): δ 37.5 (16-CH2), 107.6 (5,10CH), 109.2 (3,12-CH), 112.1 (2,13-CH), 120.6 (71,81-CH), 128.6 (72,82-CH), 138.2, 142.2 (1,14CH), 143.3, 154.2. HRMS (EI) m/z: M+ Calcd for C19H14O2 274.0994; Found 274.0997. Dibenzo[b,l]-21,23-dicarba-22,24-dioxaporphyrin (19). A solution of dioxacarbatripyrrin 31 (50.0 mg, 0.182 mmol) and indene dialdehyde 33 (31.5 mg, 0.183 mmol) was added dropwise over 15 min to a mixture of 30% HBr-AcOH (5 mL) and acetic acid (20 mL) containing 5 drops of additional conc. hydrobromic acid. The resulting solution was stirred for 1 h. The mixture was diluted with chloroform, washed with water, and then with 5% aqueous sodium bicarbonate and water. The organic solution was dried over sodium sulfate, suction filtered and evaporated under reduced pressure. Recrystallization of the residue from chloroform-hexanes gave the dioxadicarbaporphyrin (34.4 mg, 0.084 mmol, 46%) as a brown solid, mp >300 oC. UV-vis (CH2Cl2): λmax/nm (log ε) 309 (4.26), 337 (sh, 4.39), 356 (4.73), 427 (5.07), 492 (sh, 4.31), 499 (4.39), 523 (4.16), 675 (2.85), 741 (2.78). UV-vis (10% TFA-CH2Cl2): λmax/nm (log ε) 319 (4.62), 368 (4.49), 410 (sh, 4.33), 449 (4.99), 592 (3.76), 638 (3.85), 677 (3.92), 716 (3.72), 751 (4.69). 1H NMR (500 MHz, CDCl3): δ -4.23 (2H, s, 21,23-H), 7.68-7.71 (4H, m, 22,32,122,132H), 8.65-8.68 (4H, m, 21,31,121,131-H), 9.25 (4H, s, 4 x furyl-H), 9.76 (4H, s, 4 x meso-H). 1H NMR (500 MHz, C6D6): δ -3.91 (2H, s, 21,23-H), 7.63-7.66 (4H, m, 22,32,122,132-H), 8.53-8.56 (4H, m, 21,31,121,131-H), 8.61 (4H, s, 4 x furyl-H), 9.50 (4H, s, 4 x meso-H). 1H NMR (500 MHz, d6-DMSO): δ -4.49 (2H, s, 21,23-H), 7.71-7.74 (4H, m, 22,32,122,132-H), 8.81-8.85 (4H, m, 21,31,121,131-H), 9.61 (4H, s, 4 x furyl-H), 10.12 (4H, s, 4 x meso-H). 13C NMR (125 MHz, d6-DMSO): δ 100.9 (4 x meso-CH), 114.6 (21,23-CH), 120.3 (21,31,121,131-CH), 124.9 (4 x furyl-CH), 127.0 (22,32,122,132-H), 134.7, 142.5, 153.2 (4 x α-furyl CH). 1H NMR (500 MHz, cation 19H+, TFA-CDCl3): δ -6.78 (2H, s, 21-CH2), -5.26 (2H, s, 23-H), 7.63-7.66 (2H, m,



Page 36 of 43

36 122,132-H), 8.28-8.31 (2H, m, 121,131-H), 8.82-8.85 (2H, m, 22,32), 9.49 (2H, d, J = 4.1 Hz), 9.63 (2H, d, J = 4.1 Hz) (7,8,17,18-H), 9.77 (2H, s, 10,15-H), 9.86-9.89 (2H, m, 21,31), 10.68 (2H, s, 5,20-H). 13C NMR (cation 19H+, partial data derived from DEPT-135 and HSQC spectra, TFA-CDCl3): δ 33.5 (21-CH2), 106.8 (5,20-CH), 113.4 (10,15-CH), 121.2 (121,131-CH), 123.9 (21,31-CH), 126.0 (7,18- or 8,17-CH), 129.7 (122,132-CH & 23-CH), 133.6 (7,18- or 8,17-CH), 133.8 (22,32-CH). HRMS (EI) m/z: M+ Calcd for C30H18O2 410.1307; Found 410.1302. Computational Studies. Calculations on structures 12, 14 and 15 were performed using the Jagaur Suite of ab initio quantum chemistry programs.38 Geometry optimization of these structures was performed with the M06-2X functional26 by using the 6-31G** basis set. Vibrational frequencies were computed to confirm the absence of imaginary frequencies to confirm that the structures are minima, and to derive zero-point energy and vibrational entropy corrections from unscaled frequencies. Solvation energies were evaluated using SCRF, using a dielectric constant of ε = 4.806 for chloroform. Calculations for all other structures we re performed using Gaussian 0939 Rev D.01. Energy minimization and frequency calculations of the porphyrinoid systems were performed at the Density Functional Theory (DFT) level of theory with the B3LYP functional and the 6-311++G(d,p) triple-ζ basis set.40 Single point energy calculations were performed on the minimized structures using both the B3LYP-D341 and M062X26 functionals with a 6-311++G(d,p) triple-ζ basis set. Two types of NMR calculations were performed, the GIAO method was used to obtain NICS values,42 and CGST to obtain ACID plots.43 NICS(0) was calculated at the mean position of all the four heavy atoms in the middle of the macrocycle. NICS(a), NICS(b), NICS(c), NICS(d), NICS(e) and NICS(f) values were obtained by applying the same method to the mean position of the heavy atoms that comprise the individual rings of each macrocycle. In addition, NICS(1)zz, NICS(1a)zz, NICS(1b)zz,


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37 NICS(1c)zz, NICS(1d)zz, NICS(1e)zz, and NICS(1f)zz were obtained by applying the same method to ghost atoms placed 1 Å above each of the corresponding NICS(0) points and extracting the zz contribution of the magnetic tensor. The resulting Cartesian coordinates, energies, and AICD plots for all the molecules can be found in the supporting information section.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website. Tables giving Cartesian coordinates, calculated energies, selected bond lengths, conformations and AICD plots, and selected 1H NMR, 1H-1H COSY, HSQC, DEPT-135, 13

C NMR, MS, and UV-Vis spectra (PDF).

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]. Notes The authors declare no competing financial interest.

ACKNOWLEDGMENTS



Page 38 of 43

38 Preliminary investigations into the synthesis of 12b were carried out by A. D. Lammer. This work was supported by the National Science Foundation under grants CHE-1212691 and CHE1465049, and the Petroleum Research Fund, administered by the American Chemical Society.

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Synthesis of Expanded Porphyrinoids with Azulene and Indene

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