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Synthesis 2013; 45(24): 3413-3425
DOI: 10.1055/s-0033-1340305
paper
© Georg Thieme Verlag Stuttgart · New York

The Synthesis of Rigid Chromophore–Spacer–Chromophore Dyads and Three-Armed Triads by the 1,3-Dipolar Reaction of Cyclobutene Epoxides with Aromatic Dipolarophiles

Davor Margetić*
a   Laboratory for Physical Organic Chemistry, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia   Fax: +385(1)4561008   Email: margetid@irb.hr
,
Douglas N. Butler
b   Intelligent Polymer Research Institute, Molecular Architecture Unit, University of Wollongong, Wollongong, NSW 2500, Australia
,
Ronald N. Warrener
b   Intelligent Polymer Research Institute, Molecular Architecture Unit, University of Wollongong, Wollongong, NSW 2500, Australia
› Author Affiliations
Further Information

Publication History

Received: 30 July 2013

Accepted after revision: 23 September 2013

Publication Date:
04 November 2013 (online)

 
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Abstract

A series of polyaromatic hydrocarbons (PAHs) or their aza derivatives were reacted as dipolarophiles with ring-fused cyclobutene epoxides (CEs) in the 1,3-dipolar cycloaddition protocol to form 1:1 cycloadducts. The dihydroforms of the PAH chromophores contained in the rigid alicyclic scaffold were dehydrogenated to regenerate the original PAH chromophore and constituted a new route to rigid chromophore-nσ-PAH dyads separated by an alicyclic scaffold. The anthracene 1:1 adduct derived from the reaction with the 5,8-dimethoxynaphthalene-containing CE was reacted a second time to produce stereoisomeric three-armed triads in which naphthalene chromophores were attached rigidly onto scaffold. Two approaches were used to generate the incipient cyclic 1,3-dipolar intermediates involved in cycloaddition process. The first method employed ring-opening of functionalised CEs, the other method produced the dipolar reagent in situ by loss of dinitrogen from the initially formed adduct resulting from treatment of fused norbornenes with 2,5-bis(trifluoromethyl)-1,3,4-oxadiazole.


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Key words

cycloaddition - arenes - ylides - polycycles - dehydrogenation

Molracs,[1] binanes,[2] norbornalogues,[3] C-clamps,[4] position-addressable nanoscaffolds,[5] and hetero-bridged [n]-polynorbornanes[6] are some of the carbocyclic ring systems used as rigid scaffolds of specific topology and functionality. Such scaffolds, formed by the lateral fusion of carbobicyclic rings or their heteroatom derivatives, have been used to form rigid dyads and triads of extended or cavity geometry as well as for the synthesis of cyclic arrays (beltanes)[7] or alicyclophanes.[8] The inclusion of cyclohexene rings into the scaffold was used to achieve the controlled conformational motion and lateral flexibility in the carbocyclic frame.[9] The use of rigid U-, V- or C-shaped alicyclic scaffolds to separate individual chromophores has played an important role in the study of the mechanism and geometric requirements for energy and electron transfer, especially in regard to long-range through bond and through space alternatives.[10]

Alicyclic scaffolds comprised entirely of syn-fused norbornane rings (the [n]-polynorbornanes) are, in principle, excellent molecular frames; however, the all syn-bridged isomers are very difficult to prepare and the [3]-polynorbornane ring system 1 is the longest array of this type yet produced [Figure [1] (a)].[11]

Zoom Image
Figure 1 Rigid scaffold systems containing norbornane subunits

A modified form of [n]-polynorbornanes, the binanes, in which alternate norbornane units were replaced with bicyclo[2.2.0]hexane subunits could be produced by application of the two-step sequence illustrated in Scheme [1] (a). The cyclobutene-1,2-diester 5 formed by Ru-catalysed addition of dimethyl acetylene dicarboxylate to fused norbornenes such as 4 were important reagents in the extension process. Stereoselective addition of quadricyclane (6) to the π-bond of 5 formed a new norbornene 7 and extended the scaffold frame by 3σ bonds. More importantly, the generation of a new norbornene allowed repetition of the cycle to afford extended binanes without compromising the rigidity of the molecular framework.[2] Binane strategies have found applications in the field of electron and energy transfer using specifically designed binane-based multi-chromophore arrays such as in the preparation of ANTH–spacer–NAPH dyad 9 (ANTH = anthracene; NAPH = naphthalene) from the anthracene-fused 6σ-binane 8 [Scheme [1] (b)]. Extended systems have been prepared by incorporation of more than one bicyclo[2.2.0]hexane subunit into the scaffold, for example, the triad 10 [Scheme [1] (c)].[12] Systems like 9 retained C s-symmetry with the tilted interplanar relationship of the chromophores being governed by the topology of the scaffold.

Zoom Image
Scheme 1 Representative binane chemistry: (a) synthesis strategy; (b) rigid anthracene dyad; (c) extended triad containing two binane subunits

More recently our ‘LEGO’ BLOCK assembly protocol was applied to the synthesis of scaffold dyads.[13] The ACE variant,[14] is illustrated by the formation of the generic dyad 14 [Scheme [2] (a)]. The norbornadiene dipolarophile 13 and the cyclobutene epoxide 11 are the key building BLOCKs, the latter serving as a stable precursor to the 1,3-dipole 12 essential for the cycloaddition process. This method was especially suitable for targeting [n]-polynorbornanes in which the methano bridges were separated by an oxa bridge and has been used to prepare the NAPH–spacer–DAF (DAF = diazafluorene) dyad 15 in which the chromophores are orthogonally related. The Ru–spacer–Os metal complex 16 was formed as a single diastereomer by using chiral BLOCKs, one carrying the chiral Ru-complex­ and the other the chiral Os-complex.[15] These and other heteropolynorbornanes containing additional heterobridges have ring systems that retain the molecular rigidity and Cs-symmetry of the scaffold. Interchromophore tilting could be modified by changing the curvature of the scaffold by introducing specific heteroatoms into the [n]-polynorbornane bridges (C = NR, O).[16]

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Scheme 2 (a) The ACE assembly protocol to naphthalene-containing dyad; (b) orthogonally aligned naphthalene-8σ-diazafluorene dyad; (c) chiral Ru-[5]-polynorbornane-Os dyad

Cycloaddition reactions formed the basis of all these strategies for functionalised scaffold construction and the different strategies could be used in concert. It was important that the timing of the assembly process be considered. While such considerations presented little difficulty in the synthesis of dyads, it was exacerbated in the production of triads (Figure [2]).

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Figure 2 Schematic representations of scaffold dyads and three-armed triads

In this paper, we describe a new application of the ACE cycloaddition reaction to the synthesis of dyads and have introduced a variety of chromophores including polycyclic aromatic hydrocarbons (PAHs) and related heterocycles onto rigid scaffolds. When applied to the synthesis of triads using a dual cycloaddition protocol onto anthracene, a bifurcation point was introduced into the carbocyclic frame to accommodate the separate chromophores and the resultant three-armed triad provided a new topological orientation of the individual chromophores (Figure­ [2]).

The method drew on the use of anthracene as a 1,3-dipolarophile for the dyad and triad formation. Existing examples of anthracene acting as a dipolarophile are rare, but served to demonstrate that addition occurred at the 1,2-position on reaction with 2,4,6-trimethylbenzonitrile oxide[17] or oxamethine ylid.[18] Both reactions formed mixtures of 1:1- and 2:1-adducts although the yields in the nitrile oxide reaction were low. Examples of naphthalene, which also participated in 1,3-dipolar reaction acting as a dipolarophile were even less common and its reaction with tetracyanoethylene oxide to produce a 1:1 adduct was a rare example.[19]

Zoom Image
Scheme 3 ACE additions to PAHs: (a) anthracene, (b) naphthalene, (c) benzo[a]anthracene

The fact that several PAHs reacted with ester-activated cyclobutene epoxides to form 1:1 adducts was not unexpected as we had already reported that acenaphthylene formed adduct with CE-11.[20] We found that anthracene acted as a dipolarophile with CE-11 (CH2Cl2, 140 °C, sealed tube, 2 h) to form 1:1 adducts. The composition of the anthracene adducts 18a,b was shown by 1H NMR spectroscopy to be a 5:1 mixture of endo/exo-isomers, formed by reaction at the 1,2-π-bond of the anthracene dipolarophile [Scheme [3] (a)].

The structures of the anthracene adducts were determined by NMR spectroscopy (Figure [3]). The 1H NMR spectrum of the dominant endo-isomer 18a features the presence of four singlets for the methyl resonances of the methoxy groups (δ = 4.02, 4.09) and the esters (δ = 3.96, 3.55) confirmed the lack of Cs-symmetry. The cross-frame couplings between H-17, H-30 (J = 6.9 Hz) on the exo-face of the scaffold provided further confirmation of the asymmetry of the adduct, while the chemical shifts of H-15, H-2 (J = 9.6 Hz) on the endo-face of the scaffold displayed additional W-coupling with H-32a were in keeping with the assignments and typical of norbornene systems. The endo-stereochemistry of the dihydroanthracene was assigned by NOESY spectroscopy which linked H-15 with the olefinic proton H-18. A significant feature of those adducts derived from CE-11 was the significant differential shift between the methylene-bridge protons (H-32a, δ = 1.41; H-32b, δ = 2.76) caused in large part by the downfield shift of proton H-32b caused by it being adjacent to the oxa bridge.[21]

Zoom Image
Figure 3 The key NMR structural information of 18a

The ability of the 1,3-dipole 12 to react with aromatic systems was further demonstrated by its reaction with naphthalene (but not with benzene, quinoline, isoquinoline, biphenyl) to form related 1:1 adducts 21a,b (HRMS, m/z = 538.1984), this time as a mixture (10:1) of endo/exo­-stereoisomers [Scheme [3] (b)]. The stereochemical assignments were again based on 1H and 13C NMR data, backed up by COSY and NOESY spectroscopy. Some of the 1H NMR spectra seem to show a certain degree of aggregation, which may be related to the aromatic π–π stacking. Reaction of epoxide CE-11 with benzo[a]anthracene (22) occurred site-selectively at the phenanthrene-like π-bond (site c) rather than at the anthracene-like positions (site a, site b) [Scheme [3] (c)]. Only the endo­-adduct 23a was observed and the site selectivity of the cycloaddition was in accord with the AM1 calculated orbital energies and symmetry (see Figure S1, Supporting Information). Unsymmetrical cycloadducts shown in Scheme [3] and further in the paper are racemic mixtures and their separation was not attempted, since photophysical properties of optically pure bis-chromophoric isomers are expected to be identical.

The reaction of phenanthrene (25) with CE-11, conducted as a melt at 145–160 °C, was complete after 20 minutes and two isomeric adducts 30a,b (ratio 6:1 favouring the endo-isomer) were isolated by radial chromatography (Table [1]). The Cs-symmetry apparent in the 1H NMR spectra of these products confirmed that 1,3-dipolar reaction had occurred at the Δ5,6-π-bond of the phenanthrene.

Table 1 Yields and Isomer Ratios for Reactions of CE-11 with Phenanthrene (25), Azaphenanthrenes 26–28, and Acenaphthylene (29)

2π Reagent

X

Y

Z

Adduct

endo/exo ratio

Total yield

δ Ha endo-isomer

δ Ha exo-isomer

25

CH

CH

CH

30

6:1

88

1.96

2.83

26

N

CH

CH

31

5:1

63

1.98, 2.03

–

27

CH

CH

N

32

endo- only

not recorded

–

–

28

N

N

CH

33

1.2:1

60

2.04

2.85

29

–

–

–

34

1:1.25

79

1.88

2.82

Similar adducts 31–34 were obtained from reaction of CE-11 with 1-azaphenanthrene (26), 4-azaphenanthrene (27) and 1,10-phenanthroline (28), respectively (Table [1]) in dichloromethane (sealed tube at 140 °C). The yields fell off slightly upon the introduction of nitrogen atoms into the phenanthrene nucleus and the proportion of major endo-isomer in the reaction mixture decreased from 6:1 in the case of phenanthrene to 1.2:1 for 1,10-phenanthroline.

Since the nitrogen sites of the 1,10-phenanthroline nucleus were well known to act as bidentate ligands, this offered the opportunity to attach metal complexes at that site in the resultant dyads. The use of 1,10-phenanthroline metal complexes directly in the cycloaddition was not investigated in this study; however, we had shown [Scheme [2] (c)] that metal-complexed chromophores could be accommodated in either the dipolarophile or cyclobutene epoxide.[15]

The reaction between acenaphthylene (29) and cyclobutene epoxide CE-11 (140 °C, stainless steel vessel, 3 h) yielded an isomeric mixture of endo- and exo-adducts 34a,b, in which the exo-isomer was dominant (1:1.25), a result that contrasted in stereoselectivity with the phenanthrenes where the endo-isomer was favoured (Scheme [4]). This reaction was reported in a preliminary communication dealing with photochemically-induced cycloadditions between CE-11 and alkenes,[20] and the isomer distribution was essentially the same as that obtained in the present thermal process. Dehydrogenation of 30a,b gave a single phenanthrene product 35 (Scheme [4]).

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Scheme 4 Cycloadducts of CE-11 with acenaphthylene and dehydrogenation of phenanthrene adducts 30
Zoom Image
Scheme 5 Methods for introducing dibenzobarrelene end units to dyads using the ACE strategy

The thermal method was equally successful with other ester­-activated cyclobutene epoxides, for example, 38, derived from the methano-bridged tetrahydrotriptycene 36 [22] using the standard two-step reaction sequence illustrated in Scheme [5]. Reaction of CE-38 with anthracene yielded the endo-adduct 40 formed by trapping of the 1,3-dipole intermediate 39, while similar reaction of CE-38 with phenanthrene produced the endo-1:1 adduct 41. Again, the chemical shifts of the methano bridge protons (Ha, Hb) in this series were structurally informative. The Ha protons were positioned in the face of one of the benzene rings and upfield shifted above TMS. This shift was even more pronounced in those adducts in which the methano bridge was flanked by an oxa bridge, for example, adducts 40–42 where it peaked at δ = –0.70 in 41. In regard to the Hb protons, the downfield shift caused by the the oxa bridge (see above) was less pronounced since it was offset by the long range upfield shift associated with the benzene ring proximate to Ha. Adduct 43 presented an interesting situation since it contained two methano bridges in different environments. That with the adjacent oxa bridge (Ha, Hb) displayed the characteristic downfield shift of Hb at δ = 1.35 and the upfield proton shift for Ha at δ = –0.41 again positioned in the face of the benzene ring. The other methano bridge (Ha′, Hb′), which lacked the juxtaposed oxa bridge, retained an upfield Ha′ proton (δ = –0.56) while the partner Hb′ now resonated at δ = 0.45. This indicated that the downfield shift caused by the oxa bridge was around 1 ppm. Reference to the other compounds in this series as well as the CF3-series (Scheme [6], see below) showed that these effects were reliable probes for the presence of an oxa bridge adjacent to the methano bridge. In particular, they all displayed downfield shift of Hb as well as a the smaller geminal coupling constant (J = 9.8–11.8 Hz) compared to those lacking oxa bridge feature (J = 12–12.6 Hz).

The formation of adducts from the reaction of cyclobutene epoxides with cyclobutene-1,2-diesters has been reported in our earlier work,[20] and reconfirmed in the present study by a chance observation in the reaction of CE-38 with phenanthrene. In practice, the sample of epoxide 38 used in the reaction was contaminated with its precursor cyclobutene-1,2-diester 37 and this reacted competitively with CE-38 to form stereoselectively the 1:1 adduct 43 in which the cyclobutene π-bond served as the dipolarophile (Scheme [5]).

In those cases where the presence of ester groups in the adducts was undesireable, then adducts containing trifluo­romethyl substituents in their stead were prepared using an indirect route (Scheme [6]). The method involved generating the corresponding bis(trifluoromethyl)-1,3-dipole 46 in situ, by treatment of the functionalised norbornene 36 with 2,5-bis(trifluoromethyl)-1,3,4-oxadiazole (44).[23] Inverse-electron demand Diels–Alder addition of 44 to the alkene 36 to form transient adducts 45a and/or 45b was considered to be the first step and these intermediates spontaneously ejected dinitrogen to produce 1,3-dipole 46.[24]

Zoom Image
Scheme 6 Scaffold assembly involving formation of the 1,3-dipole 46 by reaction of 2,5-bis(trifluoromethyl)-1,3,4-oxadiazole (44) with norbornenes­

In the absence of competing dipolarophiles, the symmetrically coupled product 47 was produced by reaction of the putative 1,3-dipole 46 with excess starting norbornene derivative 36, the latter acting as the dipolarophile. In the presence of anthracene, a mixture of homocoupled product 47 and the mixed anthracene adduct 48 was obtained while a similar reaction conducted in the presence of phenanthrene gave endo-adduct 49 as well as the ubiquitous homocoupled product 47.

A feature of this new approach to PAH dyad formation was the ability to dehydrogenate the dihydro chromophore present in the 1:1 adduct to one containing the chromophore used in adduct formation. Thus, DDQ dehydrogenation of the anthracene adducts 18a,b produced the unsym-DMN-4σ-ANTH dyad 19 (DMN = 1,4-dimethoxynaphthalene). In a similar way, the phenanthrene-derived adducts 30 and 41 regenerated the phenanthrene chromophore on treatment with DDQ to form the new sym-DMN-4σ-PHEN dyad 35 (PHEN = phenanthrene) and sym-BNZ-6σ-PHEN dyad 42 (BNZ = benzene), respectively (Scheme [5]). The benzo[a]anthracene (BaA) chromphore was introduced into the sym-BNZ-6σ-BaA dyad 24 by dehydrogenation of adduct 23a (Scheme [3]).

Restoration of aromaticity in dyads 19, 24, 35, and 42 was reflected in the proton chemical shifts of the ester methyl substituents, which were moved to lower field by up to δ = 0.76 relative to their respective adduct precursors. This shift, which was not apparent in the methoxyl resonances, was attributed to the increased ring current of the aromatic components and the realignment of the ester substituents to a more coplanar geometry relative to the aromatic ring. The differential shifts in the ester groups of the anthracene dyad 19 reflected the asymmetry of the dyad and the positioning of the esters relative to the ring current of the anthracene ring.

Not all adducts could be dehydrogenated and the stereoisomeric 1,10-phenanthroline adducts 33a,b failed to produce aromatised products on treatment with DDQ or other oxidising agents such as PhI(OAc)2.

The potential of the ACE/dehydrogenation method to form dyads of various chromophore combinations can be foreshadowed by inspection of the range of known cyclobutene epoxides. In this way, porphyrins,[25] metal complexes,[15] or crown ethers[26] could each be delivered via the appropriate cyclobutene epoxide BLOCK and linked with PAHs of the type illustrated herein. The distance between the chromophores could be addressed using epoxide reagents with extended scaffold frames, and geometric variants via scaffolds with bent-frames.

There are a large number of triad combinations described in the chemical literature and increasingly they contain C60 as one of the chromophores.[27] Typically, such triads have been formed in a serial sequence and often the chromophores were linked by flexible chains.[28] The triad 10 (Scheme [1]) was representative of those incorporating the chromophores held in a linear sequence on a rigid molecular scaffold.

In the present study, we had the opportunity to prepare triads with the individual chromophores linked at the termini of a three-armed molecular scaffold, thereby offering rigid­ systems with new inter-chromophore geometries. The anthracene-derived adduct 18a played a key role in the synthesis of this new class of triads, since the ‘isolated’ π-bond present in the dihydroanthracene subunit was available for further cycloaddition.

Indeed, reaction of 1:1 adduct 18a with CE-11 produced a pair of stereoisomeric 2:1 adducts 50a and 50b (Scheme [7]).[29] Structural assignments to these isomers were based on facial selectivity considerations in the transition state leading to their formation and the symmetry of the products. Reference to Figure [4] (a) showed that anti-facial attack should be preferred on 18 because the syn-face was screened by the scaffold. This being the case, then the two products would have resulted from the stereoselectivity of the addition, one producing an exo-isomer and the other an endo-isomer.

Zoom Image
Scheme 7 Triad construction by cycloaddition of CE-11 to dihydroanthracene 18a
Zoom Image
Figure 4 Assessment of facial selectivity at the ‘isolated’ π-bond of 18 and its dehydrogenated product 19

The symmetry of the two adducts distinguished between them and was apparent in their 13C NMR spectra: the major adduct 48a having the rotational axis of symmetry displayed only 29 C resonances (two C=O resonances) and the minor adduct 48b, which lacked symmetry, displayed 58 C resonances (four C=O resonances).

The fact that 19, the dehydrogenated derivative of 18, failed to add CE-11 indicated that the reaction was sensitive to geometric crowding, since in this case the oxa bridge of 19 prevented attack on the syn-face and the scaffold hindered attack on the anti-face [Figure [4] (b)]. Additional decrease in reactivity came from the fact that the 2-π system in 19 is the part of aromatic structure.

Triads 50a and 50b each link two identical 1,4-dimeth­oxynaphthalene chromophores with the naphthalene chromophore. Given that the reaction sequence was stepwise, so it should be possible to introduce different chromophores by way of the cyclobutene epoxide reagents (e.g., those displayed in Scheme [2]) using one such reagent to prepare the 1:1 adduct and a different one in the second cycloaddition.

Frontier molecular orbital analysis using semiempirical AM1 calculations (see Figure S1, Supporting Information) demonstrated that the cycloaddition of the 1,3-dipolar species derived by ring opening of ester-activated cyclobutene epoxides with anthracene should be dominated by the anthracene LUMO interacting with the 1,3-dipole HOMO. Further, the orbital symmetry was appropriate for attack to occur at the 1,2-position of the anthracene, which explains experimentally observed site-selectivity. Identical conclusion was reached by FMO analysis of benzo[a]anthracene (see Figure S2, Supporting Information).

In conclusion, new methods for the production of scaffold dyads and triads with novel geometry are reported based on the use of PAHs and some of their azalogues as dipolarophiles in ACE coupling with cyclobutene epoxides. In particular, Δ1,2 π-bond of anthracene and naphthalene, the Δ9,10 π-bond of phenanthrene, the Δ5,6 π-bonds of 1-azaphenanthrene, 4-azaphenanthrene and 1,10-phenanthroline, and the Δ4,5-π-bond of acenaphthalene act as 2π-reagents with 1,3-dipoles to form rigid scaffold structures in stereoselective and site-selective cycloadditions. The fact that the 1:1 adducts formed in the 1,3-dipolar cycloaddition can be dehydrogenated to reform (hetero)-PAH chromophores, coupled with the fact that the 1,3-dipoles can be functionalised with separate chromophores makes this process a rich source of rigid chromophore-nσ-chromophores. The first example of a three-armed scaffold triad is reported by coupling of a cyclobutene epoxide with the 1:1 adduct of anthracene, which should open new avenues for the precise construction of polychromophoric systems. An alternative route to cyclic 1,3-dipoles via [4π+2π] cycloaddition of 2,5-bis(trifluoromethyl)-1,3,4-oxadiazole has further enhanced the synthetic scope of dyad formation reactions.

Petroleum ether (PE) used refers to the fraction boiling at 40–60 °C. Melting points, which are uncorrected, were obtained on a Reichert Micro hot stage melting point apparatus Model YOSCO No. 67885. 1H NMR spectra were recorded at Bruker AMX-300 and Bruker Avance DPX 400 NMR spectrometers. 13C NMR spectra were recorded by using an inverse gated sequence at 75.4 MHz. Unless otherwise stated all data were acquired using CDCl3 solutions with TMS as an internal standard and are reported on the appropriate δH and δC scales. Coupling constants are reported in Hertz (Hz). Merck silica gel 60 (230–400 mesh) was used for column chromatography. TLC analysis was performed on Merck aluminum sheets coated with silica gel 50F254. Radial chromatography was carried out with a Chromatotron, Model No. 7924T, using a 1 mm plates coated with Merck silica gel 60 F254. Mass spectra were obtained by EI or PCI (photochemical ionisation) on a Hewlett Packard 5988A spectrometer or by EI or ESMS (electrospray mass spectrometry) on a Micromass­ Platform II single quadrupole mass spectrometer.


#

Dimethyl (1α,2β,3α,14α,15β,16α,17α,30α)-5,12-Dimethoxy-31-oxanonacyclo[14.14.1.13,14.02,15.04,13.06,11.017,30.020,29.022,27]dotriaconta-4,6,8,18,20,22,24,26,28-nonaene-1,16-dicarboxylate (18a) and Dimethyl (1α,2β,3α,14α,15β,16α,17β,30β)-5,12-Dimethoxy-31-oxanonacyclo[14.14.1.113,14.02,15.04,13. 06,11.017,30.020,29.022,27]dotriacontan-4,6,8,18,20,22,24,26,28-nonaene-1,16-dicarboxylate (18b)

A solution of epoxide 11 (103 mg, 0.251 mmol) and anthracene (17; 178 mg, 1.0 mmol) in CH2Cl2 (0.5 mL) was heated in a sealed glass tube at 140 °C for 2 h. Evaporation of solvent in vacuo yielded a colourless solid. The reaction mixture was subjected to radial chromatography [PE–EtOAc (20:1), then the solvent polarity was gradually increased to EtOAc] to afford products 18a and 18b.


#

18a

Yield: 79 mg (54%); colourless solid; mp 176–178 °C.

1H NMR (CDCl3): δ = 1.41 (d, J = 9.6 Hz, 1 H), 2.10 (d, J = 6.9 Hz, 1 H), 2.71 (d, J = 6.9 Hz, 1 H), 2.76 (d, J = 9.6 Hz, 1 H), 3.51 (ddd, J = 9.6, 2.0, 1.5 Hz, 1 H), 3.55 (s, 3 H), 3.60 (s, 1 H), 3.82 (s, 1 H), 3.96 (s, 3 H), 4.02 (s, 3 H), 4.09 (s, 3 H), 5.94 (dd, J = 10.0, 4.0 Hz, 1 H), 6.52 (dd, J = 10.0, 1.8 Hz, 1 H), 7.34–7.46 (m, 5 H), 7.46 (s, 1 H), 7.63–7.71 (m, 2 H), 7.92 (d, J = 8.2 Hz, 1 H), 8.04 (d, J = 8.2 Hz, 1 H).

13C NMR (CDCl3): δ = 42.9, 43.4, 47.3, 48.9, 51.6, 53.3 (2 C), 61.4, 62.1 (2 C), 91.1, 92.5, 122.7, 122.8, 125.1, 126.7, 126.9, 127.4, 128.2 (2 C), 128.3, 128.5, 128.6, 129.2, 129.8, 133.5, 130.6, 133.6, 134.5, 135.6, 144.4, 144.9, 170.6, 170.9.

HRMS: m/z calcd for C37H32O7: 588.2148; found: 588.2145.


#

18b

Yield: 14 mg (10%); colourless solid; mp 159–160 °C.

1H NMR (CDCl3): δ = 1.46 (d, J = 10,4 Hz, 1 H), 2.69 (d, J = 6.9 Hz, 1 H), 2.75–2.81 (m, 2 H), 3.35 (s, 3 H), 3.49 (ddd, J = 8.9, 3.3, 2.2 Hz, 1 H), 3.67 (s, 1 H), 3.84 (d, J = 9.0 Hz, 1 H), 3.88 (s, 1 H), 4.00 (s, 3 H), 4.03 (s, 3 H), 4.15 (s, 3 H), 5.69 (dd, J = 9.9, 3.8 Hz, 1 H), 6.62 (dd, J = 9.9, 1.3 Hz, 1 H), 7.37–7.41 (m, 4 H), 7.47 (dd, J = 6.4, 3.5 Hz, 4 H), 7.69 (dt, J = 6.6, 2.7 Hz, 2 H), 8.08–814 (m, 4 H).

13C NMR (CDCl3): δ = 42.4, 43.9, 44.1, 44.2, 49.5, 51.9, 52.6, 53.1 (2 C), 54.6, 56.4, 62.8 (2 C), 92.8, 96.1, 122.5, 122.8, 122.9, 123.5, 126.2 (2 C), 126.6, 126.7, 126.9, 127.7, 128.0, 128.4, 128.7, 128.8, 128.9, 130.5, 130.8 (2 C), 133.7, 134.7, 144.8, 144.9, 157.7, 169.3, 169.8.

HRMS: m/z calcd for C37H32O7: 588.2148; found: 588.2143.


#

Dimethyl (1α,2β,3α,14α,15β,16α)-5,12-Dimethoxy-31-oxanonacyclo[14.14.1.13,14.02,15.04,13.06,11.017,30.020,29.022,27]dotriaconta-4,6,8,17(30),18,20,22,24,26,28-tetraene-1,16-dicarboxylate (19)

A solution of anthracene adducts 18a,b (34 mg, 0.058 mmol) in CHCl3 (1 mL) and DDQ (60 mg, 0.264 mmol) were heated at 65 °C for 2 days in an NMR tube and the reaction progress monitored by NMR spectroscopy. The reaction mixture was filtered through silica gel/Celite and subjected to radial chromatography [PE–EtOAc (10:1), then the solvent polarity was gradually increased to EtOAc] to afford the anthracene dyad 19 as a colourless solid; yield: 11 mg (32%); mp 150–153 °C.

1H NMR (CDCl3): δ = 1.74 (d, J = 9.9 Hz, 1 H), 2.50 (d, J = 7.1 Hz, 1 H), 2.57 (d, J = 7.1 Hz, 1 H), 3.09 (d, J = 9.9 Hz, 1 H), 3.79 (s, 1 H), 3.96 (s, 3 H), 4.08 (s, 3 H), 4.14 (s, 3 H), 4.15 (s, 3 H), 4.29 (s, 1 H), 7.36–7.39 (m, 2 H), 7.46–7.49 (m, 2 H), 7.68–7.69 (m, 2 H), 7.95–8.03 (m, 4 H), 8.45 (s, 1 H), 8.62 (s, 1 H).

13C NMR (CDCl3): δ = 42.3, 42.7, 42.9, 50.7, 52.3, 53.2, 53.9, 54.4, 56.1, 57.1, 89.7, 90.2, 117.4, 121.3, 122.3, 122.7, 125.7, 125.8, 126.3, 126.5, 128.3, 128.4, 128.5, 128.9, 130.3, 131.7, 131.9, 132.7, 134.,7 135.2, 137.1, 141.1, 142.9, 144.6, 168.8, 170.6.

HRMS: m/z calcd for C37H30O7: 586.1991; found: 586.1993.


#

Dimethyl (1α,2β,3α,14α,15β,16α,17α,26α)-27-Oxaoctacyclo[14.10.1.13,14.02,15,04,13.06,11.017,26.020,25]octacosa-4,6,8,10,18,20,22,24-octaene-1,16-dicarboxylate (21a)

A solution of epoxide 11 (102 mg, 0.246 mmol) and naphthalene (20; 210 mg, 1.641 mmol) in CH2Cl2 (1 mL) was heated in a sealed glass tube at 140 °C for 2 h. Evaporation of the solvent in vacuo yielded a yellow oily residue, which was subjected to radial chromatography [PE–EtOAc (20:1), then the solvent polarity was gradually increased to EtOAc] to afford the endo-adduct 21a as a colourless solid; yield: 39 mg (29%); mp 220–222 °C.

1H NMR (CDCl3): δ = 1.39 (d, J = 9.7 Hz, 1 H), 2.05 (d, J = 6.9 Hz, 1 H), 2.67 (d, J = 6.9 Hz, 1 H), 2.71 (td, J = 9.7, 1.3 Hz, 1 H), 3.48 (ddd, J = 7.8, 4.0, 1.8 Hz, 1 H), 3.58 (s, 1 H), 3.72 (s, 3 H), 3.84 (s, 1 H), 3.95 (s, 3 H), 3.96 (m, 1 H), 3.99 (s, 3 H), 4.03 (s, 3 H), 5.83 (dd, J = 9.9, 1.8 Hz, 1 H), 6.29 (dd, J = 9.9, 1.8 Hz, 1 H), 6.94–6.99 (m, 2 H), 7.07–7.11 (m, 2 H), 7.40–7.44 (m, 3 H), 7.99–8.07 (m, 3 H).

13C NMR (CDCl3): δ = 42.5, 43.3, 43.9, 44.0, 47.1, 48.6, 49.5, 52.1, 52.9, 61.8, 90.9, 91.9, 122.4, 122.5, 124.0, 125.7, 125.8, 128.0, 128.5, 129.1, 129.3, 130.8, 133.8, 129.5, 132.3, 134.4, 135.1, 144.6, 170.3, 170.3 (3 C unaccounted for).

HRMS: m/z calcd for C33H30O7: 538.1992; found: 538.1984.


#

Dimethyl (1α,2β,19α,20α,21β,22α,33α,34β)-24,31-Dimethoxy-35-oxadecacyclo[18.14.1.122,33.02,19.03,12.05,10.013,18.021,34.023,32.025,30]hexatriaconta-3,5,7,9,11,13,15,17,23,25,27,29,31-tridecaene-1,20-dicarboxylate (23a)

A solution of epoxide 11 (38 mg, 0.146 mmol) and benzo[a]anthracene (22; 210 mg, 0.921 mmol) in CH2Cl2 (1 mL) was heated in a sealed glass tube at 140 °C for 2 h. Evaporation of solvent in vacuo yielded a colourless solid. The reaction mixture was subjected to radial chromatography [PE–EtOAc (20:1), then the solvent polarity was gradually increased to EtOAc] to afford product 23a as a colourless solid; yield: 38 mg (41%); mp 312–314 °C.

1H NMR (CDCl3): δ = 1.27 (d, J = 9.7 Hz, 1 H), 1.87 (d, J = 6.6 Hz, 1 H), 1.98 (d, J = 6.6 Hz, 1 H), 2.62 (td, J = 9.7, 1.3 Hz, 1 H), 3.35 (s, 3 H), 3.67 (s, 3 H), 3.73 (s, 3 H), 3.77 (s, 1 H), 4.07 (s, 3 H), 4.10 (s, 3 H), 4.16 (d, J = 5.1 Hz, 1 H), 4.29 (d, J = 5.1 Hz, 1 H), 7.07–7.14 (m, 7 H), 7.54 (s, 1 H), 7.71–8.01 (m, 5 H), 8.25 (s, 1 H).

13C NMR (CDCl3): δ = 42,2, 43.2, 43.3, 47.2, 49.5, 49.6, 49.9, 51.3, 51.4, 53.0, 60.9, 61.2, 92.2, 92.6, 122.2, 122.3, 122.5, 122.9, 124.4, 126.6, 126.8, 127.6, 128.0, 128.1, 128.2, 128.3, 128.5, 128.9, 129.0, 129.5, 129.9, 130.6, 131.9, 132.9, 133.1, 134.7, 144.1, 144.2.

HRMS: m/z calcd for C41H34O7: 638.2304; found: 638.2307.


#

Dimethyl (1α,20α,21β,22α,33α,34β)-24,31-Dimethoxy-35-oxadecacyclo[18.14.1.122,33.02,19.03,12.05,10.013,18.021,34.023,32.025,30]hexatriaconta-2,4,6,8,10,12,14,16,18,23,25,27,29,31-tetradecaene-1,20-dicarboxylate (24)

A solution of adduct 23 (78 mg, 0.122 mmol) in CHCl3 (3 mL) and DDQ (200 mg, 0.881 mmol) were heated at 65 °C overnight in an NMR tube and the reaction progress monitored by NMR spectroscopy. The reaction mixture was filtered through silica gel/Celite and subjected to radial chromatography [PE–EtOAc (20:1), then the solvent polarity was gradually increased to EtOAc] to afford dyad 24 as a brown-coloured solid; yield: 48 mg (46%); mp 138 °C (dec.).

1H NMR (CDCl3): δ = 1.78 (d, J = 9.7 Hz, 1 H), 2.97 (td, J = 9.7, 1.3 Hz, 1 H), 2.68 (s, 2 H), 4.08 (s, 3 H), 4.10 (s, 3 H), 4.13 (s, 3 H), 4.17 (s, 3 H), 4.38 (s, 2 H), 7.46 (dd, J = 6.5, 3.3 Hz, 3 H), 7.55–7.61 (m, 3 H), 7.98–8.09 (s, 6 H), 8.61 (s, 1 H), 8.82 (d, J = 7.9 Hz, 1 H), 9.17 (s, 1 H).

13C NMR (CDCl3): δ = 42.4, 42.6, 53.6, 53.7, 55.5, 57.1, 61.7, 61.8, 61.9, 122.2, 122.4 (2 C), 123.5, 124.2, 124.3, 125.7 (2 C), 126.8 (2 C), 127.7, 127.9, 128.3, 128.6, 128.8, 129.1, 132.2, 132.4, 132.8, 134.9, 135.0, 141.5, 141.6, 144.6, 170.6, 171.1.

HRMS: m/z calcd for C41H32O7: 636.2148; found: 636.2160.


#

Dimethyl (1α,2β,3α,14α,15β,16α,17α,30α)-5,12-Dimethoxy-31-oxanonacyclo[14.14.1.13,14.02,15.04,13.06,11.017,30.018,23.024,29]dotriaconta-4,6,8,10,12,18,20,22,24,26,28-undecaene-1,16-dicarboxylate (30a) and Dimethyl (1α,2β,3α,14α,15β,16α,17β,30β)-5,12-Dimethoxy-31-oxanonacyclo[14.14.1.13,14.02,15.04,13.06,11.017,30.018,23.024,29]dotriaconta-4,6,8,10,12,18,20,22,24,26,28-undecaene-1,16-dicarboxylate (30b)

A mixture of epoxide 11 (103 mg, 0.251 mmol) and phenanthrene (25; 178 mg, 1.0 mmol) was heated in a glass test tube at 145–160 °C for 20 min in an oil bath. 1H NMR analysis showed a mixture of adducts in 6:1 ratio. The mixture was subjected to radial chromatography [PE–EtOAc (20:1), then the solvent polarity was gradually increased to EtOAc] to afford a mixture of endo-30a and exo-adduct 30b; yield: 130 mg (88%). The major endo-adduct 30a was isolated from this mixture by fractional crystallisation from EtOAc as a colourless solid; yield: 12 mg (8%); mp 295–297 °C (Table [1]).


#

30a

1H NMR (CDCl3): δ = 1.29 (td, J = 9.7, 1.6 Hz, 1 H), 1.96 (s, 2 H), 2.61 (td, J = 9.7, 1.6 Hz, 1 H), 3.66 (s, 6 H), 3.81 (s, 2 H), 4.06 (s, 6 H), 4.12 (s, 2 H), 7.03–7.06 (m, 2 H), 7.17–7.26 (m, 4 H), 7.37 (dd, J = 6.2, 3.2 Hz, 2 H), 7.78–7.81 (m, 2 H), 7.97 (dd, J = 6.2, 3.2 Hz, 2 H).

13C NMR (CDCl3): δ = 42.2, 43.1, 49.6, 49.8, 53.0, 61.2, 92.4, 122.4, 123.9, 125.5, 127.9, 128.2, 130.0, 130.8, 132.1, 134.8, 144.2, 170.4 (1 C unaccounted for).

HRMS: m/z calcd for C37H32O7: 588.2148; found: 588.2142.

The mother liquor was subjected to another radial chromatography [PE–EtOAc (10:1), then the solvent polarity was gradually increased to EtOAc] to afford product 30b as a colourless solid; yield: 12 mg (8%); mp 248–251 °C.


#

30b

1H NMR (CDCl3): δ = 1.41 (d, J = 9.7 Hz, 1 H), 2.57 (td, J = 9.7, 1.5 Hz, 1 H), 2.83 (s, 2 H), 3.59 (s, 6 H), 3.84 (s, 2 H), 3.96 (s, 2 H), 4.12 (s, 6 H), 7.16–7.18 (m, 2 H), 7.47 (dd, J = 6.9, 3.3 Hz, 2 H), 7.89 (d, J = 7.9 Hz, 2 H), 8.12 (dd, J = 6.9, 3.3 Hz, 2 H), 7.23–7.29 (m, 4 H).

13C NMR (CDCl3): δ = 41.8, 44.1, 52.5, 52.8, 55.1, 61.8, 122.6, 123.6, 125.9, 127.6, 128.2, 128.4, 129.9, 130.7, 132.7, 134.3, 144.6, 169.4.

HRMS: m/z calcd for C37H32O7: 588.2148; found: 588.2140.


#

Dimethyl (1α,2β,3α,14α,15β,16α)-5,12-Dimethoxy-31-oxanonacyclo[14.14.1.13,14.02,15.04,13.06,11.017,30.018,23.024,29]dotriaconta-4,6,8,10,12,17,19,21,23,25,27,29-dodecaene-1,16-dicarboxylate (35)

A solution of adducts 30a,b (15 mg, 0.026 mmol) in CHCl3 (2 mL) and DDQ (200 mg, 0.881 mmol) were heated at 65 °C for 2 days in an NMR tube and the reaction progress monitored by NMR spectroscopy. Upon completion, the mixture was filtered through silica gel/Celite and the solvent evaporated in vacuo to afford a brown-coloured­ residue, which was subjected to radial chromatography [PE–EtOAc (10:1), then the solvent polarity was gradually increased to EtOAc] to afford the phenanthrene dyad 35 as a brown-coloured solid; yield: 9 mg (60%); mp >330 °C.

1H NMR (CDCl3): δ = 1.73 (td, J = 9.4, 1.3 Hz, 1 H), 2.60 (s, 2 H), 4.07 (s, 6 H), 4.14 (s, 6 H), 7.36 (dd, J = 6.6, 3.3 Hz, 2 H), 7.61 (dq, J = 7.5, 1.3 Hz, 4 H), 7.99 (dd, J = 6.4, 3.5 Hz, 2 H), 8.08 (dd, J = 7.8, 1.6 Hz, 2 H), 8.70 (dd, J = 7.9, 1.6 Hz, 2 H).

13C NMR (CDCl3): δ = 42.4, 42.5, 52.8, 55.3, 61.1, 90.4, 122.4, 123.4, 124.1, 125.6, 125.7, 127.6, 127.9, 128.4, 130.9, 134.9, 141.2, 144.6, 170.6.

HRMS: m/z calcd for C37H30O7: 586.1991; found: 586.1972.


#

Dimethyl (1α,2β,3α,14α,15β,16α,17α,30α)-5,12-Dimethoxy-22-aza-31-oxanonacyclo[14.14.1.13,14.02,15.04,13.06,11.017,30. 018,23.024,29]dotriaconta-4,6,8,10,12,18,20,22,24,26,28-undeca­ene-1,16-dicarboxylate (31a)

A solution of epoxide 11 (100 mg, 0.237 mmol) and benzo[h]quinoline (26; 210 mg, 1.173 mmol) in CH2Cl2 (2 mL) was heated in a sealed glass tube at 140 °C for 2 h. Evaporation of solvent in vacuo yielded a brown-coloured oily residue, which was subjected to radial chromatography [PE–EtOAc (10:1), then the solvent polarity was gradually increased to EtOAc] to afford the endo-adduct 31a as a colourless solid; yield: 79 mg (57%); mp 259–262 °C (Table [1]).

1H NMR (CDCl3): δ = 1.32 (d, J = 9.9 Hz, 1 H), 1.98 (d, J = 7.1 Hz, 1 H), 2.03 (d, J = 7.1 Hz, 1 H), 2.62 (d, J = 9.9 Hz, 1 H), 3.65 (s, 3 H), 3.67 (s, 3 H), 3.70 (s, 1 H), 4.06 (s, 3 H), 4.07 (s, 3 H), 4.11 (d, J = 12.2 Hz, 1 H), 4.12 (d, J = 12.2 Hz, 1 H), 7.07–7.12 (m, 2 H), 7.26–7.27 (m, 2 H), 7.37 (dd, J = 6.2, 3.5 Hz, 2 H), 7.53 (d, J = 7.7 Hz, 1 H), 7.94–7.96 (m, 2 H), 8.44 (d, J = 4.0 Hz, 2 H).

13C NMR (CDCl3): δ = 42.3, 43.1, 48.7, 49.5, 50.3, 53.2, 61.2, 61.3, 91.9, 92.0, 122.3, 122.4, 122.5, 125.7 (2C), 126.0, 126.1, 128.2, 128.3, 128.5, 129.3, 129.6, 132.0, 132.9, 134.3, 134.4, 137.8, 144.2, 144.5, 149.0, 150.3, 170.1, 170.4.

HRMS: m/z calcd for C36H31NO7: 589.2100; found: 589.2096.


#

Dimethyl (1α,2β,3α,14α,15β,16α,17α,30α)-5,12-Dimethoxy-22,25-diaza-31-oxanonacyclo[14.14.1.13,14.02,15.04,13.06,11. 017,30.018,23.024,29]dotriaconta-4,6,8,10,12,18,20,22,24,26,28-un­decaene-1,16-dicarboxylate (33a) and Dimethyl (1α,2β,3α,14α,15β,16α,17β,30β)-5,12-Dimethoxy-22,25-diaza-31-oxa-nonacyclo[14.14.1.13,14.02,15.04,13.06,11.017,30.018,23.024,29]dotriaconta-4,6,8,10,12,18,20,22,24,26,28-undecaene-1,16-dicarboxylate (33b)

A mixture of epoxide 11 (103 mg, 0.251 mmol) and 9,10-phenanthroline (28; 180 mg, 1.0 mmol) was heated in a glass test tube at 145–160 °C for 20 min in an oil bath. NMR analysis showed mixture of adducts endo-33a and exo-33b in a 1:0.8 ratio. The reaction mixture was subjected to radial chromatography [PE–EtOAc (10:1), then the solvent polarity was gradually increased to EtOAc and MeOH, finally washed with aq 5% HCl in MeOH] to afford fractions enriched with products endo-33a (fraction A) and exo-33b (fraction B). Fraction A was evaporated to dryness and subjected to a second radial chromatography (EtOAc, then the solvent polarity was gradually increased to MeOH) to afford product endo-33a as a brown solid; yield: 41 mg (28%); mp 224–226 °C (Table [1]).


#

endo-33a

1H NMR (CDCl3): δ = 1.26 (d, J = 10.4 Hz, 1 H), 2.62 (td, J = 10.4, 1.8 Hz, 1 H), 2.04 (s, 2 H), 3.63 (s, 6 H), 3.69 (s, 2 H), 4.08 (s, 6 H), 4.14 (s, 2 H), 7.38 (dd, J = 6.2, 3.3 Hz, 2 H), 7.61 (d, J = 7.7 Hz, 2 H), 7.93 (dd, J = 6.2, 3.3 Hz, 2 H), 8.65 (d, J = 3.5 Hz, 2 H), 7.23–7.26 (m, 4 H).

13C NMR (CDCl3): δ = 42.4, 43.1, 48.4, 49.4, 53.4, 61.3, 91.4, 123.5, 124.3, 126.9, 128.5, 129.1, 135.3, 137.9, 144.5, 146.1, 149.7, 170.1.

HRMS: m/z calcd for C35H30N2O7: 590.2053; found: 590.2045.


#

exo-33b

The minor adduct exo-33b was isolated from the fraction washed with aq 5% HCl in MeOH. This fraction was taken up in H2O (10 mL), basified with aq NaOH, and extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were dried (MgSO4), then solvent removed in vacuo to afford 33b as a yellow-coloured solid; yield: 48 mg (32%); mp 248–251 °C.

1H NMR (CDCl3): δ = 1.42 (dd, J = 10.2, 1.3 Hz, 1 H), 2.58 (td, J = 10.2, 1.3 Hz, 1 H), 2.85 (s, 2 H), 3.62 (s, 6 H), 3.83 (s, 2 H), 4.06 (s, 2 H), 4.10 (s, 6 H), 7.22–7.32 (m, 2 H), 7.49 (dd, J = 6.3, 3.4 Hz, 2 H), 7.59 (d, J = 7.7 Hz, 2 H), 8.12 (dd, J = 6.4, 3.3 Hz, 2 H), 8.78 (d, J = 3.5 Hz, 2 H).

13C NMR (CDCl3): δ = 41.8, 44.0, 51.7, 52.7, 55.3, 61.9, 94.9, 113.3, 122.6, 123.6, 126.0, 128.2, 128.5, 33.9, 137.9, 144.7, 149.9, 168.9.

HRMS: m/z calcd for C35H30N2O7: 590.2053; found: 590.2054.


#

Dimethyl (1α,2β,3α,14α,15β,16α,17α,30α)-5,12-Dimethoxy-28-oxanonacyclo[14.12.1.13,14.118,22.02,15.04,13.06,11.017,27.025,30]hentriaconta-4,6,8,10,12,18,20,22,24,26(30)-decaene-1,16-dicarboxylate (34a) and Dimethyl (1α,2β,3α,14α,15β,16α,17β,30β)-5,12-Dimethoxy-28-oxanonacyclo[14.12.1.13,14.118,22.02,15.04,13.06,11.017,30.025,30]hentriaconta-4,6,8,10,12,18,20,22,24,26(30)-decaene-1,16-dicarboxylate (34b)

A solution of epoxide 11 (60 mg, 0.146 mmol) and acenaphthylene (29; 33 mg, 0.220 mmol) in CH2Cl2 (0.5 mL) was heated in a stainless steel reactor at 140 °C for 3 h. Evaporation of solvent in vacuo yielded a yellow-coloured solid, which was subjected to radial chromatography [PE–EtOAc (10:1), then the solvent polarity was gradually increased to EtOAc] to yield a mixture of isomeric adducts endo-34a and exo-34b. Final separation was achieved by HPLC (inverse phase column, 90% MeOH, 10% H2O) to afford products 34a and 34b in inverse order of elution (Table [1]).


#

endo-34a

Yield: 28 mg (34%); colourless solid; mp 239–240 °C.

1H NMR (CDCl3): δ = 1.40 (d, J = 9.6 Hz, 1 H), 1.88 (s, 2 H), 2.92 (d, J = 9.6 Hz, 2 H), 3.52 (s, 2 H), 3.71 (s, 6 H), 4.09 (s, 6 H), 4.56 (s, 2 H), 7.32–7.38 (m, 2 H), 7.41 (d, J = 7.9 Hz, 2 H), 7.48 (d, J = 6.8 Hz, 2 H), 7.57 (d, J = 8.0 Hz, 2 H), 7.89–7.94 (m, 2 H).

13C NMR (CDCl3): δ = 42.7, 42.9, 50.4, 52.6, 58.9, 61.1, 89.4, 121.6, 121.9, 124.7, 125.3, 127.8, 127.9, 131.5, 134.1, 139.2, 140.6, 144.3, 168.9.

HRMS: m/z calcd for C35H28O7: 562.1992; found: 562.1986.


#

exo-34b

Yield: 35 mg (43%); colourless solid; mp 230–232 °C.

1H NMR (CDCl3): δ = 1.47 (d, J = 9.8 Hz, 1 H), 2.79 (d, J = 9.7 Hz, 2 H), 2.82 (s, 2 H), 3.71 (s, 2 H), 3.92 (s, 6 H), 4.08 (s, 6 H), 4.22 (s, 2 H), 7.22 (d, J = 6.9 Hz, 2 H), 7.42 (d, J = 7.9 Hz, 2 H), 7.46–7.50 (m, 2 H), 7.65 (d, J = 8.3 Hz, 2 H), 8.10–8.13 (m, 2 H).

13C NMR (CDCl3): δ = 41.9, 43.1, 52.1, 54.9, 58.0, 61.5, 91.2, 120.2, 122.2, 124.4, 125.6, 127.9, 128.1, 131.6, 134.2, 140.6, 140.9, 143.9, 170.2.

HRMS: m/z calcd for C35H28O7: 562.1992; found: 562.1989.


#

Dimethyl (1α,2β,3α,4β,7β,8α,9β,10α)-Heptacyclo[8.6.6.13,8.02,9.04,7.011,16.017,22]tricosa-5,11,13,15,17,19,21-heptaene-5,6-dicarboxylate (37)

A mixture of alkene 36 [22] (3.50 g, 12.96 mmol), RuH2CO(PPh3)3 catalyst (150 mg), and DMAD (6.05 g, excess) in benzene (25 mL) was heated at 70 °C for 3 days under a N2 atmosphere. The catalyst was removed by filtration through a short silica gel column, which was then eluted with benzene. The solvent was evaporated under reduced pressure and the excess DMAD removed under high vacuo to afford a brown-coloured oily residue. Trituration with cold MeOH afforded a colourless precipitate, which was collected by filtration and washed with cold MeOH (10 mL) to yield the cyclobutene 37 as a colourless solid; yield: 3.10 g (58%); mp 199–201 °C.

1H NMR (CDCl3): δ = –0.23 (d, J = 12.3 Hz, 1 H), 0.91 (d, J = 12.3 Hz, 1 H), 1.57 (s, 2 H), 2.41 (s, 2 H), 2.68 (s, 2 H), 3.76 (s, 6 H), 4.33 (s, 2 H), 7.02 (dd, J = 5.3, 3.1 Hz, 2 H), 7.17 (dd, J = 5.3, 3.1 Hz, 2 H), 7.24–7.29 (m, 4 H).

13C NMR (CDCl3): δ = 29.3, 41.3, 47.4, 48.4, 48.8, 52.6, 53.0, 120.8, 122.9, 125.6, 142.6, 144.7, 166.1.

HRMS: m/z calcd for C27H24O4: 412.1674; found: 412.1671.


#

Dimethyl (1α,2β,3α,4β,5α,7α,8β,9α,10β,11α)-6-Oxaheptacyclo[9.6.6.13,9.0210.04,8.012,17.018,23]tetracosa-2,14,16,18,20,22-hexaene-5,7-dicarboxylate (38)

A solution of cyclobutene 1,2-diester 37 (3.50 g, 8.495 mmol) in anhydrous THF (20 mL) was treated with t-BuOOH (3 M in toluene, 4.2 mL, 12.5 mmol) under N2 atmosphere, cooled to 0 °C, and t-BuOK (317 mg, 2.82 mmol) was added. After 5 min, the reaction mixture was brought to r.t. and stirred for 3 h under N2 atmosphere. The mixture was quenched with aq 10% Na2SO3 (20 mL) and extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were washed with aq 10% Na2SO3 (20 mL) and H2O (20 mL), and dried (MgSO4). The solvent was removed in vacuo and the residue was recrystallised from MeOH to afford the epoxide 38 as a colourless solid; yield: 1.80 g (50%); mp 282–283 °C.

1H NMR (CDCl3): δ = –0.17 (d, J = 12.6 Hz, 1 H), 0.94 (d, J = 12.6 Hz, 1 H), 1.77 (s, 2 H), 2.21 (s, 2 H), 2.56 (s, 2 H), 3.73 (s, 6 H), 4.27 (s, 2 H), 7.07 (dd, J = 5.5, 3.3 Hz, 2 H), 7.12 (dd, J = 5.5, 3.3 Hz, 2 H), 7.21–7.26 (m, 4 H).

13C NMR (CDCl3): δ = 28.3, 40.3, 48.2, 48.4, 51.7, 53.1, 64.9, 123.7, 124.8, 126.6, 142.3, 144.8, 165.0.

HRMS: m/z calcd for C27H24O5: 428.1623; found: 428.1626.


#

Dimethyl (1α,2β,3α,4β,5α,6α,19α,20α,21β,22α,23β,24α)-38-Oxaundecacyclo[22.6.6.13,22.15,20.02,23.04,21.06,19.09,18.011,16.025,30.031,36]octatria- conta-7,9,11,13,15,17,25,27,29,31,33,35-dodecaene-5,20-dicarboxylate (40)

A solution of epoxide 38 (100 mg, 0.234 mmol) and anthracene (300 mg, 1.685 mmol) in CH2Cl2 (2 mL) was heated in a sealed glass tube at 140 °C for 2 h. Evaporation of solvent in vacuo yielded a brown-coloured solid, which was subjected to radial chromatography [PE–EtOAc (20:1), then the solvent polarity was gradually increased to EtOAc] to afford a 10:1 mixture of endo- and exo-adducts 40 and 40a (78 mg, 63%).

The following spectral data were obtained from the mixture:

HRMS: m/z calcd for C41H34O5: 606.2406; found: 606.2401.


#

Dimethyl (1α,2β,3α,4β,5α,6α,19α,20α,21β,22α,23β,24α)-38-Oxaundecacyclocyclo[22.6.6.13,22.15,20.02,23.04,21.06,19.07,12. 013,18.025,30.031,36]octatriaconta-7,9,11,13,15,17,25,27,29,31,33, 35-dodecaene-5,20-dicarboxylate (41) and Tetramethyl (1α,2β,3α,4β,5α,6β,7α,8β,9α,10β,17α,17β,18α,19β,20α,21β,22α,23β,24α,25β)-46-Oxapentadecacyclo[24.6.6.610,17.13,24.15.22.18,19.02,25.04,23.06,21.07,20.09,18.011,16.027,32.033,38.039,44]heptatetraconta-10,12,14,25,27,29,31,33,35,37,39,41-dodecaene-5,6,21, 22-tetracarboxylate (43)

A solution of epoxide 38 (containing cyclobutene 37 as an impurity, 100 mg, 0.234 mmol) and phenanthrene (25; 200 mg, 1.124 mmol) in CH2Cl2 (2 mL) was heated in a sealed glass tube at 140 °C for 2 h. Evaporation of solvent in vacuo yielded a yellow-coloured solid, which was subjected to radial chromatography [PE–EtOAc (20:1), then the solvent polarity was gradually increased to EtOAc] to afford, in order of elution, phenanthrene endo-adduct 41 as a colourless solid; yield: 121 mg (85%); mp 303–304 °C.

1H NMR (CDCl3): δ = –0.70 (d, J = 10.2 Hz, 1 H), 1.33 (d, J = 10.2 Hz, 1 H), 1.49 (s, 2 H), 1.51 (s, 4 H), 2.05 (s, 2 H), 3.93 (s, 6 H), 4.09 (s, 2 H), 7.02–7.11 (m, 10 H), 7.21–7.28 (m, 4 H), 7.91 (d, J = 6.1 Hz, 2 H).

13C NMR (CDCl3): δ = 28.5, 42.3, 48.2, 48.9, 49.3, 51.4, 52.8, 92.4, 123.5, 123.7, 124.5, 125.9, 132.3, 142.3, 145.0, 170.5.

HRMS: m/z calcd for C41H34O5: 606.2406; found: 606.2406.


#

Cyclobutene Adduct 43

Yield: 4 mg (2%); colourless solid; mp >350 °C.

1H NMR (CDCl3): δ = –0.56 (d, J = 12.0 Hz, 1 H), –0.41 (d, J = 11.7 Hz, 1 H), 0.47 (d, J = 12.0 Hz, 1 H), 1.35 (d, J = 11.7 Hz, 1 H), 1.68 (s, 2 H), 1.85 (s, 2 H), 1.95 (s, 2 H), 2.12 (s, 2 H), 2.17 (s, 2 H), 2.31 (s, 2 H), 3.62 (s, 6 H), 3.86 (s, 6 H), 4.16 (s, 2 H), 4.18 (s, 2 H), 7.03–7.19 (m, 16 H).

13C NMR (CDCl3): δ = 29.3, 30.1, 42.1, 42.9, 47.1, 47.6, 48.3, 48.4, 49.1, 51.7, 51.9, 52.6, 52.7, 64.1, 92.3, 123.4, 123.5, 124.6 (2 C), 125.9, 126.1, 126.4, 126.8, 142.2, 142.3, 144.6, 144.8, 167.5, 167.6.

HRMS: m/z calcd for C54H48O9 + Na: 863.3196; found: 863.3188.


#

Dimethyl (1α,2β,3α,4β,5α,6α,19α,20α,21β,22α,23β,24α)-38-Oxaundecacyclocyclo[22.6.6.13,22.15,20.02,23.04,21.06,19.07,12.013,18.025,30.031,36]octatria-conta-6(19),7,9,11,13,15,17,25,27,29,31,33,35-tridecaene-5,20-dicarboxylate (42)

A solution of phenanthrene adduct 41 (78 mg, 0.122 mmol) in CHCl3 (2 mL) and DDQ (150 mg, 0.661 mmol) were heated at 60 °C for 6 days in an NMR tube and the reaction progress monitored by NMR spectroscopy. Every day, a new portion of DDQ was added. The mixture was filtered through silica gel/Celite, evaporated to dryness, and the residue was subjected to radial chromatography [PE–EtOAc (10:1), then the solvent polarity was gradually increased to EtOAc] to afford the phenanthrene dyad 42 as a brown-coloured solid; yield: 8 mg (10%); mp 213–214 °C.

1H NMR (CDCl3): δ = –0.45 (d, J = 11.8 Hz, 1 H), 1.55 (d, J = 11.8 Hz, 1 H), 1,76 (s, 2 H), 2.06 (s, 2 H), 2.67 (s, 2 H), 3.97 (s, 6 H), 4.27 (s, 2 H), 6.96 (dd, J = 5.6, 3.3 Hz, 2 H), 7.11 (dd, J = 5.1, 3.0 Hz, 2 H), 7.12 (dd, J = 5.3, 3.3 Hz, 2 H), 7.20 (dd, J = 5.5, 3.3 Hz, 2 H), 7.56–7.58 (m, 4 H), 8.07 (d, J = 8.0 Hz, 2 H), 8.68 (d, J = 8.5 Hz, 2 H).

13C NMR (CDCl3): δ = 30.1, 41.8, 48.6, 49.6, 53.4, 56.2, 90.4, 123.4, 123.5, 123.9, 124.7, 125.9, 126.4, 127.2, 127.7, 128.3, 131.0, 140.7, 142.5, 144.9, 170.8.

HRMS: m/z calcd for C41H32O5: 604.2250; found: 604.2268.


#

Dimethyl (1α,2β,3α,4β,5α,6α,19α,20α,21β,22α,23β,24α)-5,20-Bis(trifluoromethyl)-38-oxaundecacyclo[22.6.6.13,22.15,20.02,23.04,21.06,19.09,18.011,16.025,30.031,36]octatria-conta-7,9,11,13,15,17,25,27,29,31,33,35-dodecaene-5,20-dicarboxylate (47) and (1α,2β,3α,4β,5α,6β,7α,8β,9α,16α,17β,18α,19β,20α,21β,22α,23β,24α)-5,20-Bis(trifluoromethyl)-44-oxatetradecacyclo[22.6.6.69,16.13,22.15.20.17,18.02,23.04,21.06,19.08,17.010,15.025,30.031,35.037,42]pentatetraconta-10,12,14,25,27,29,31,33,35,37,39,41-dodecaene (48)

A solution of alkene 36 (60 mg, 0.222 mmol), anthracene (17; 100 mg, 0.56 mmol) and the 1,3,4-oxadiazole 44 (200 mg, 1.190 mmol, excess) in CHCl3 (1 mL) was heated at 140 °C overnight in a sealed glass tube. The reaction mixture was subjected to radial chromatography [PE–EtOAc (20:1), then the solvent polarity was gradually increased to EtOAc] to afford, in order of elution, anthracene adduct 47 as a colourless solid; yield: 39 mg (25%); mp 187–188 °C.

1H NMR (CDCl3): δ = –0.54 (d, J = 9.8 Hz, 2 H), 1.15 (d, J = 9.8 Hz, 2 H), 1.70 (s, 4 H), 1.78 (s, 4 H), 2.34 (s, 4 H), 4.22 (s, 4 H), 7.06–7.11 (m, 8 Harom), 7.16 (dd, J = 5.3, 3.1 Hz, 4 Harom), 7.22 (dd, J = 5.3, 3.1 Hz, 4 Harom).

13C NMR (CDCl3): δ = 28.6, 42.1, 48.8, 49.2, 57.5, 87.7 (q, J = 31.2 Hz), 123.7, 124.6, 125.7 (q, J = 124.3 Hz), 126.0, 127.2, 142.1, 144.9.

HRMS: m/z calcd for C46H36F6O: 718.2670; found: 718.2667.


#

48

Yield: 3 mg (2%); colourless solid; mp 194–196 °C.

1H NMR (CDCl3): δ = –0.47 (d, J = 11.7 Hz, 1 H), 1.38 (d, J = 11.7 Hz, 1 H), 1.48 (dd, J = 7.7, 2.4 Hz, 1 H), 1.70 (d, J = 7.1 Hz, 1 H), 1.74 (dd, J = 7.7, 2.2 Hz, 1 H), 2.07 (s, 1 H), (s, 1 H), 2.38 (d, J = 7.1 Hz, 1 H), 3.51 (dm, J = 13.1 Hz, 1 H), 4.04 (d, J = 13.1 Hz, 1 H), 4.05 (s, 1 H), 4.21 (d, J = 2.9 Hz, 1 H), 5.68 (dd, J = 10.6, 3.9 Hz, 1 H), 6.58 (dd, J = 9.9, 1.3 Hz, 1 H), 7.01–7.21 (m, 8 H), 7.26–7.46 (m, 2 H), 7.47 (s, 1 H), 7.58 (s, 1 H), 7.72–7.73 (m, 2 H).

13C NMR (CDCl3): δ = 29.1, 30.1, 44.4, 45.0, 48.0, 48.3, 48.7, 49.3, 50.7, 51.9, 89.2 (q, J = 122.0 Hz), 91.6 (q, J = 122.0 Hz), 123.5, 123.6, 123.7, 124.1, 124.6, 124.7, 126.1, 126.4, 126.6, 126.8, 127.3, 127.9, 128.1, 129.3, 129.7, 130.3, 133.3, 133.5, 141.9, 142.0, 144.8, 144.9.

HRMS: m/z calcd for C39H28F6O: 626.2044; found: 626.2042.


#

(1α,2β,3α,4β,5α,6α,19α,20α,21β,22α,23β,24α)-5,20-Bis(trifluoromethyl)-38-oxaundecacyclocyclo[22.6.6.13,22.15,20.02,23.04,21.06,19.07,12.013,18.025,30.031,36]octatria-conta-7,9,11, 13,15,17,25,27,29,31,33,35-dodecaene (49)

A solution of alkene 36 (200 mg, 0.740 mmol), phenanthrene (500 mg, 2.12 mmol), and oxadiazole 44 (358 mg, 2.11 mmol, excess) in CH2Cl2 (2 mL) was heated at 140 °C overnight in a sealed glass tube. A mixture of products 47 and 49 was obtained in 1:2 ratio (470 mg) and subjected to radial chromatography [PE–EtOAc (20:1), then the solvent polarity was gradually increased to EtOAc] to afford product 47 (116 mg, 43%) and the impure phenanthrene adduct 49.


#

Tetramethyl (1α,2α,3β,4β,5α,6β,17β,18α,19β,20β,31α,32α,33β,34α)-8,15,36,43-Tetramethoxy-47,48-dioxahexadecacyclo[30.14.1.14,19.16,17.134,45.02,31.03,20.05,18.07,16.09,14.021,30.023,28.033,45.033,45.035,44.037,42]pentaconta-7,9,11,13,15,21,23,25,27,29,35,37,39,41,43-pentadecaene-1,4,19,32-tetracarboxylate (50a) and Tetramethyl (1α,2α,3β,4α,5β,6α,17α,18β,19α,20β,31α,32α,33β,34α)-8,15,36,43-Tetramethoxy-47,48-dioxahexadecacyclo[30.14.1.14,19.16,17.134,45.02,31.03,20.05,18.07,16.09,14.021,30.023,28.033,45.033,45.035,44.037,42]pentaconta-,9,11,13,15,21,23,25,27,29,35,37,39,41,43-pentadecaene-1,4,19,32-tetracarboxylate (50b)

A solution of CE-11 (73 mg, 0.177 mmol) and adduct 18a (87 mg, 0.148 mmol) in CH2Cl2 (2 mL) was heated in a sealed glass tube at 140 °C for 2 h. Evaporation of solvent in vacuo yielded a brown-coloured­ solid, which was subjected to radial chromatography [PE–EtOAc (20:1), then the solvent polarity was gradually increased to EtOAc] to afford, in order of elution: endo,endo-adduct 50a; colourless solid; yield: 41 mg (23%); mp >340 °C.

1H NMR (CDCl3): δ = 1.30 (d, J = 9.7 Hz, 1 H), 1.39 (d, J = 9.7 Hz, 2 H), 2.20 (d, J = 9.7 Hz, 4 H), 2.65 (d, J = 9.7 Hz, 2 H), 3.11 (s, 6 H), 3.23 (d, J = 12.4 Hz, 2 H), 3.59 (s, 2 H), 3.69 (s, 2 H), 3.82 (d, J = 12.4 Hz, 2 H), 3.97 (s, 6 H), 3.99 (s, 6 H), 4.00 (s, 6 H), 7.29–7.43 (m, 8 H), 7.54 (dd, J = 6.4, 3.1 Hz, 2 H), 7.84 (d, J = 8.2 Hz, 2 H), 8.04 (d, J = 8.2 Hz, 2 H).

13C NMR (CDCl3): δ = 41.0, 42.4, 42.8, 43.5, 46.9, 48.8, 49.6, 52.9, 53.1, 60.6, 61.9, 91.0, 91.9, 122.4, 122.5, 122.6, 128.7, 127.5, 128.2, 128.4, 128.8 (2 C), 128.9, 131.9, 134.2, 134.7, 144.3, 169.6, 169.9.

HRMS: m/z calcd for C60H54O14 + Na: 1021.3411; found: 1021.3397.


#

endo,exo-Dyad 50b

Yield: 5 mg (3%); colourless solid; mp 168–170 °C.

1H NMR (CDCl3): δ = 1.25 (d, J = 9.7 Hz, 1 H), 1.26 (d, J = 9.7 Hz, 1 H), 1.38 (d, J = 9.7 Hz, 1 H), 2.41 (d, J = 9.7 Hz, 1 H), 2.61–2.62 (m, 2 H), 2.63 (d, J = 6.9 Hz, 1 H), 2.66 (dd, J = 12.2, 1.1 Hz, 1 H), 2.05 (d, J = 9.7 Hz, 1 H), 2.99 (s, 3 H), 3.06 (s, 3 H), 3.05 (d, J = 9.2 Hz, 1 H), 3.62 (s, 1 H), 3.63–3.64 (m, 3 H), 3.76 (s, 1 H), 3.89 (s, 3 H), 4.00 (s, 3 H), 4.03 (s, 3 H), 4.04 (s, 3 H), 4.06 (s, 3 H), 4.07 (s, 3 H), 4.13 (d, J = 12.2 Hz, 1 H), 7.28–7.33 (m, 3 H), 7.35 (s, 1 H), 7.46–7.49 (m, 4 H), 7.65–7.66 (m, 2 H), 7.80 (d, J = 7.6 Hz, 1 H), 7.88 (d, J = 7.6 Hz, 1 H), 8.09–8.11 (m, 2 H).

13C NMR (CDCl3): δ = 41.7, 41.9, 42.5, 42.7, 43.3, 43.5, 43.7, 43.9, 46.1, 48.6, 49.4, 52.1, 52.6, 52.8, 53.1, 53.2, 54.3, 55.1, 60.6, 61.7, 61.8, 91.2, 92.3, 93.1, 94.9, 122.3, 122.4 (2 C), 122.7, 25.5 (2 C), 125.9, 126.0, 126.5, 126.7, 127.4, 127.5, 127.7, 128.1, 128.3, 128.4, 128.5, 129.1, 129.2, 130.1, 131.9, 132.6, 133.9, 134.2, 134.3, 135.2, 144.2, 144.3, 144.5, 144.6, 168.4, 169.3, 169.5, 170.5.

HRMS: m/z calcd for C60H54O14 + Na: 1021.3411; found: 1021.3450.


#
#

Acknowledgment

The award of a ARC discovery grant (2001–2003) by the Australian Research Council is gratefully acknowledged. This work was initiated at the Centre for Molecular Architecture at Central Queensland University while RNW was director of that centre (1992–2003) and completed at the University of Wollongong. RNW and DNB acknowledge visiting professorial appointments and DM acknowledges visiting fellowships at the University of Wollongong (2004). Molecular modelling and computational studies were financially supported by Ministry of Science, Education and Sport of the Republic of Croatia (Project No. 098-0982933-3218).

Supporting Information

    for this article is available online at http://www.thieme-connect.com.accesdistant.sorbonne-universite.fr/ejournals/toc/synthesis.
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Zoom Image
Figure 1 Rigid scaffold systems containing norbornane subunits
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Scheme 1 Representative binane chemistry: (a) synthesis strategy; (b) rigid anthracene dyad; (c) extended triad containing two binane subunits
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Scheme 2 (a) The ACE assembly protocol to naphthalene-containing dyad; (b) orthogonally aligned naphthalene-8σ-diazafluorene dyad; (c) chiral Ru-[5]-polynorbornane-Os dyad
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Figure 2 Schematic representations of scaffold dyads and three-armed triads
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Scheme 3 ACE additions to PAHs: (a) anthracene, (b) naphthalene, (c) benzo[a]anthracene
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Figure 3 The key NMR structural information of 18a
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Scheme 4 Cycloadducts of CE-11 with acenaphthylene and dehydrogenation of phenanthrene adducts 30
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Scheme 5 Methods for introducing dibenzobarrelene end units to dyads using the ACE strategy
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Scheme 6 Scaffold assembly involving formation of the 1,3-dipole 46 by reaction of 2,5-bis(trifluoromethyl)-1,3,4-oxadiazole (44) with norbornenes­
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Scheme 7 Triad construction by cycloaddition of CE-11 to dihydroanthracene 18a
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Figure 4 Assessment of facial selectivity at the ‘isolated’ π-bond of 18 and its dehydrogenated product 19