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Keywords:

  • dimerization;
  • ladderanes;
  • self-assembly;
  • supramolecular chemistry;
  • topochemistry

An [n]ladderane

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is a molecule that consists of n edge-sharing cyclobutane rings (where n≥2) that define a molecular equivalent of a macroscopic ladder.1 Ladderanes are considered promising building blocks in optoelectronics2 and, very recently, have been identified in biological systems (n=3 and 5), in the form of ladderane lipids,3, 4 which are integral components in the microbiological conversion of ammonium and nitrite ions to dinitrogen gas.3, 4 In the simplest case, a cis-fused [n]ladderane (n=3, 5, 7…) can be constructed by photochemical dimerization of two all-trans-poly-m-enes (m=2, 3, 4…). Despite the apparent simplicity of this intermolecular process, however, such a transformation generally fails.1 This can be attributed to the lack of a method that overcomes the energetic cost, due to solvent5 and entropy1, 5 effects, of organizing two polyene molecules in a suitable geometry in the liquid phase for photoreaction, although a covalent linker that holds two polyene chains in a parallel orientation for a high-yield, intramolecular photoaddition to give a [n]ladderane (n=3 and 5) has been reported.6

We believe that a supramolecular approach to covalent synthesis7, 8 in the organized, solvent-free environment of the solid state8 can provide a solution to the problem of organizing two polyenes for an intermolecular reaction to give a ladderane. Specifically, by taking an approach to control reactivity in solids9 by using molecules that serve as linear templates,1013 we have anticipated that the cocrystallization of resorcinol (1,3-benzenediol), or a derivative, with an all-trans-bis(4-pyridyl)poly-m-ene (4-pyr-poly-m-ene) would produce a four-component molecular assembly, 2(resorcinol)⋅2(4-pyr-poly-m-ene), in which each resorcinol preorganizes, through two O[BOND]H⋅⋅⋅N hydrogen-bonding interactions, two poly-m-enes for [2+2] photoaddition.14 In this design, the two polyenes (Scheme 1) would be positioned by the templates such that the C[DOUBLE BOND]C bonds of the olefins lie parallel and separated by <4.2 Å, a position suitable for the photoreaction. UV irradiation of the solid would produce the targeted [n]ladderane, with the C[DOUBLE BOND]C bonds reacting to form the fused cyclobutane framework. Herein, we report the application of 2(5-OMe-res)⋅2(4-pyr-poly-m-ene) (where: m=2 (1 a) and 3 (1 b); 5-OMe-res=5-methoxyresorcinol) to construct [n]ladderanes (where n=3 (2 a) and 5 (2 b)) in the solid state. The remarkable efficiency of this intermolecular process is exemplified by the fact that the polyenes are converted to the ladderanes stereospecifically, in gram quantities, and in 100 % yield.11

In a typical experiment, one equivalent of 5-OMe-res11 was cocrystallized with an equimolar amount of a 4-pyr-poly-m-ene15 in methanol. Single crystals of 1 a and 1 b suitable for X-ray analysis formed in the methanolic solution within a period of approximately one day.

Single-crystal X-ray structure analyses of 1 a and 1 b reveal that the linear templates preorganize each polyene into a position for intermolecular photoaddition that is favorable for ladderane formation.6 In each case, the linear templates and polyenes form discrete, four-component molecular assemblies that are held together by four O[BOND]H⋅⋅⋅N hydrogen bonds (Figure 1 a,b1), wherein the templates orient the polyenes in a parallel arrangement. The separation between the stacked C[DOUBLE BOND]C bonds ranges from 3.78 to 3.82 Å and 3.69 to 3.97 Å in 1 a and 1 b, respectively. Nearest-neighbor assemblies of each solid pack in an antiparallel fashion so that the olefins of the hydrogen-bonded assemblies are the sole C[DOUBLE BOND]C bonds organized to undergo reaction (Figure 1 c,d1).

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Figure 1. X-ray crystal structures of 1 a and 1 b: a) ORTEP view of 1 a, b) ORTEP view of 1 b, c) space-filling view of the packing of 1 a, and d) space-filling view of the packing of 1 b. Selected interatomic distances [Å] and angles [°]: a) O1⋅⋅⋅N1 2.761(3), O2⋅⋅⋅N2i 2.736(3), O1-H1O⋅⋅⋅N1 175.5(2), O2-H2O⋅⋅⋅N2i 171.4(2); b) O1⋅⋅⋅N1 2.792(5), O2⋅⋅⋅N3 2.777(6), O4⋅⋅⋅N2 2.782(6), O5⋅⋅⋅N4 2.756(6), O1-H1O⋅⋅⋅N1 173.6(3), O2-H2O⋅⋅⋅N3 173.4(3), O4-H4O⋅⋅⋅N2 176.6(3), O5-H5O⋅⋅⋅N4 175.1(3). Symmetry operator i: −x+1, −y, −z+2. The asymmetric unit of 2(5-OMe-res)⋅2(4-pyr-poly-2-ene) consists of one half assembly, which resides around a crystallographic center of inversion, whereas that of 2(5-OMe-res)⋅2(4-pyr-poly-3-ene) involves two full assemblies, which are virtually identical.

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To evaluate the reactivity of the solid-state molecular assemblies, powdered crystalline samples of 1 a and 1 b were subjected to UV irradiation (broadband Hg lamp) for periods of approximately 120 and 72 h, respectively. As evidenced by 1H NMR spectroscopy (in [D6]DMSO), 2 a and 2 b formed stereospecifically and in 100 % yield (Figure 2). Each ladderane is characterized by the complete disappearance of the olefinic protons and the emergence of cyclobutane protons in the δ=3.0–4.3 ppm range.6, 16 The three fused cyclobutane rings of 2 a produced two broad signals at δ=3.49 and 4.30 ppm (1:1 ratio), while the five fused cyclobutane rings of 2 b produced three broad signals at δ=3.12, 3.27, and 4.27 ppm (1:1:1 ratio).

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Figure 2. 1H NMR spectra of the solid-state assemblies before and after photoreaction: a) 1 a (before), b) 1 a (after), c) 1 b (before), and d) 1 b (after).

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To confirm the structures of the ladderanes, the reactions were repeated in gram quantities. The linear templates were then separated from each photoproduct by solvent extraction. Single-crystals of 2 a and 2 b⋅2(benzene) were grown, over a period of approximately three days, by way of slow solvent evaporation from ethanol and benzene, respectively.

Single-crystal X-ray structure analyses confirm the structures of 2 a and 2 b (Figure 3). Each photoproduct consists of a cis-fused cyclobutane framework with ends that are functionalized with four 4-pyridyl groups. The C[BOND]C bond lengths and C-C-C bond angles of the fused cyclobutane units compare well to both calculated and experimentally related structures.6, 16

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Figure 3. ORTEP perspectives of the ladderanes: a) 2 a and b) 2 b. Selected interatomic distances [Å] and angles [°]: C6-C7 1.593(5), C13-C14 1.566(5), C15-C16 1.575(5); b) C6-C7 1.585(3), C13-C14 1.567(3), C15-C16 1.585(3), C16-C15ii 1.526(3). Symmetry operator ii: −x+2, −y, −z+1. The asymmetric unit of 2 a contains two full ladderanes, which are virtually identical, while that of 2 b⋅2(benzene) contains one half ladderane, which resides around a crystallographic center of inversion, and an included benzene molecule, respectively.

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The ladderanes 2 a and 2 b appear to form within 1 a and 1 b through stepwise [2+2] photodimerizations. 1H NMR spectra obtained 24 and 48 h into each reaction reveal that lower-order [n]ladderanes form during the generation of each final product. Thus, a product consistent with a single cycloaddition (i.e., “[1]ladderane”) precedes 2 a while products consistent with single and double cycloadditions (e.g., [3]ladderane) precede 2 b. Such observations contrast reactivity experiments involving 1,4-butadienes,14, 17 which exhibit similar packing in the solid state and react, via a single photodimerization, to produce cis-vinyl cyclobutanes and rearrange thermally, via a Cope rearrangement,18 into ciscis cyclooctadienes.19 Here, the relatively strong O[BOND]H⋅⋅⋅N hydrogen bonds between the templates and reactants may serve to force divinyl groups from a first photoaddition into a conformation suitable for a second and third photoaddition, thus leading to each ladderane product.20 In the case of 2 b, such stepwise transformations may occur either randomly or by way of a “zipper” process in the solid.6 Experiments are underway to determine the structures of the lower-order ladderanes and the sequence by which the photocycloadditions occur.21

In this report, we have demonstrated that a linear template may be used to position two polyenes for an intermolecular reaction to produce [n]ladderanes (n=3 or 5). The template preorganizes the polyenes, through hydrogen-bonding interactions, for [2+2] photodimerizations in the solid state. By using the organized, solvent-free environment of the solid state9 for reaction, the ladderanes can be formed in gram quantities and in 100 % yield. We believe that these results illuminate the utility of applying concepts of supramolecular chemistry and self-assembly to address a problem of covalent synthesis7, 8 and we are now exploring whether such template molecules can be used to construct ladderanes of increasing size and complexity in the solid state.8

Experimental Section

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  2. Experimental Section

1 a and 1 b: 4-pyr-poly-2-ene and 4-pyr-poly-3-ene were prepared according to a literature procedure.22 5-OMe-res was commercially available. Cocrystals of 1 a were obtained by evaporation of a solution of 4-pyr-poly-2-ene (0.058 g, 0.28 mmol) and 5-OMe-res (0.039 g, 0.28 mmol) in hot methanol (3.0 mL). Co-crystals of 1 b were obtained in a similar manner using 4-pyr-poly-3-ene (0.030 g, 0.13 mmol) and 5-OMe-res (0.018 g, 0.13 mmol).

Solid-state photoreactions and isolation of 2 a and 2 b: UV irradiation of powdered crystalline 1 a (500 W Hg lamp) over a period of 120 h resulted in 100 % conversion of poly-2-ene to [3]ladderane. In the case of 1 b, the quantitative formation of the [5]ladderane was achieved after 72 h. In both cases, the irradiation experiments were performed by placing finely ground samples of either 1 a or 1 b between two pyrex plates and turning each sample in eight-hour intervals to ensure uniform irradiation. The irradiated solids were stirred with 1 M KOH solution, then extraction with methylene chloride and evaporation of the organic phase yielded the appropriate ladderane as a white solid in 85 % yield. All procedures were readily scaled up to give the ladderanes in gram quantities. Single crystals of 2 a were grown from ethanol, while single crystals of 2 b were grown from benzene yielding a 1:2 benzene solvate. 1H NMR of 1 a before irradiation (300 MHz, [D6]DMSO): δ=9.15 (br s, 2 H), 8.54 (dd, 4 H), 7.50 (dd, 4 H), 7.40 (dd, 4 H), (dd, 4 H), 5.82 (br t, 1 H), 5.78 (br d, 2 H), 3.61 ppm (s, 3 H). 1H NMR of irradiated 1 a (300 MHz, [D6]DMSO): δ=9.16 (br s, 4 H), 8.26 (dd, 8 H), 7.04 (dd, 8 H), (br t, 2 H), 5.78 (br d, 4 H), 4.30 (br s, 4 H), 3.61 (s, 6 H), 3.49 ppm (br s, 4 H). 1H NMR of 1 b before irradiation (300 MHz, [D6]DMSO): δ=9.16 (br s, 2 H), 8.52 (dd, 4 H), 7.46 (dd, 4 H), 7.33 (m, 2 H), 6.72 (m, 4 H), 5.82 (br t, 1 H), 5.79 (br d, 2 H), 3.61 ppm (s, 3 H). 1H NMR of irradiated 1 b (300 MHz, [D6]DMSO): δ=9.15 (br s, 4 H), 8.25 (dd, 8 H), 7.02 (dd, 8 H), (br t, 2 H), 5.78 (br d, 4 H), 4.27 (br s, 4 H), 3.61 (s, 6 H), 3.27 (br s, 4 H), 3.12 ppm (br s, 4 H).

Crystal data for 1 a: monoclinic, P21/c, a=9.182(5), b=13.381(5), c=15.122(5) Å, β=106.712(5)°, V=1779.5(13) Å3, Z=4, ρcalcd=1.300 g cm−3, R1=0.0441 for 2324 reflections with I>2σ(I). Crystal data for 1 b: triclinic, Pequation image, a=9.081(3), b=21.143(4), c=21.308(18) Å, α=87.92(4), β=79.47(6), γ=78.91(2)°, V=3947(4) Å3, Z=2, ρcalcd=1.260 g cm−3, R1=0.0891 for 6150 reflections with I>2σ(I). Crystal data for the 2 a: triclinic, Pequation image, a=12.534(5), b=12.583(5), c=14.787(5) Å, α=100.388(5), β=106.555(5), γ=89.945(5)°, V=2195.7(14) Å3, Z=2, ρcalcd=1.260 g cm−3, R1=0.0647 for 4018 reflections with I>2σ(I). Crystal data for 2 b⋅2(benzene): monoclinic, P21/c, a=9.475(2), b=15.048(3), c=12.235(2) Å, β=95.95(3)°, V=1735.0(6) Å3, Z=4, ρcalcd=1.196 g cm−3, R1=0.0438 for 1625 reflections with I>2σ(I). All crystal data were measured on a Nonius Kappa CCD single-crystal X-ray diffractometer at 77 K. After anisotropic refinement of all non-hydrogen atoms, aromatic, methine, and hydroxyl hydrogen atoms were placed in idealized positions and allowed to ride on the atom to which they were attached. The structure of 1 b was determined to be a rotational twin, the twinning law being a twofold rotation about the (011) reciprocal lattice direction. All crystallographic calculations were conducted using SHELXL-97.23 CCDC-218101 (1 a), CCDC-218102 (1 b), CCDC-218103 (2 a), and CCDC-218104 (2 b) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or deposit@ccdc.cam.ac.uk).

In memory of Xiuchun Gao