Introduction

Ancient pottery vessels were made by coiling ropes of clay1, and a similar method can be used for constructing large three-dimensional structures from flexible strings. Flexible carbon chains can similarly play a crucial role in the synthesis of various organic architectures in molecular science because they can adopt various conformations without giving rise to large strain energies.2 Structurally flexible frameworks generated from flexible components have attracted attentions because they can change structures and properties in response to guest accommodation and other stimuli3,4,5. In the construction of high-order structures with flexible chain components, the main difficulties come from the large entropy losses caused by fixation of conformations and orientations. Flexible carbon chains such as alkyl groups have therefore been embedded in large organic nanostructures and assemblies often merely as hinges, linkers, aggregation agents and solubilizing groups6,7,8. Given recent developments in synthetic reactions using transition-metal-catalyzed functionalization of aliphatic compounds9, the inducement of various conformations, and the construction of two- and three-dimensional assemblies with flexible carbon chains (Fig. 1a) become more important for synthesis of a new class of structurally flexible organic architectures with various size and shape. This prompted us to design and synthesize flexible, yet shapable, carbon chains.

Fig. 1
figure 1

Construction of large organic architectures using flexible polyketone chains. a Strategy for construction of various higher-order organic assemblies. After the conformations of the carbon chains are induced by ketone-related reactions and interactions, the chains are assembled with the aid of metal coordination and other intermolecular interactions. b Design of a flexible and isolable polyketone chain composed of a sequence of alternating 1,3-diketones and 1,4-diketones. c Natural-type sequence of polyketone chains. These readily undergo intramolecular cyclization through enolization

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We focused on aliphatic polyketones as flexible scaffolds. Carbonyl group is one of the most well-studied functional groups in organic chemistry, and various conversions and interactions derived from the lone pair of oxygen atom and electrophilic carbon atom are known. Biological systems also use polyketone chains as a common precursor for the production of a wide range of secondary metabolites known as polyketides10. Natural polyketones, which consist of repeated 1,3-diketones, readily undergo intramolecular cyclization reactions through enolization to form stable six-membered rings, which often aromatize after dehydration (Fig. 1c)11, 12. These characteristics have prevented the synthesis and isolation of long polyketone chains without the aid of enzymes, except oligomers and polymers with repeating 1,4-diketone units13, 14.

Here, we design a new polyketone sequence consisting of alternating 1,3-diketones and 1,4-diketones. These polyketones can be synthesized by oligomerization of an acetylacetone derivative, 3,3-dimethylpentane-2,4-dione (1) (Fig. 1b). Despite the dense arrangement of carbonyl groups on the chain, none of them are located at the sixth position from any of the α-carbons that become nucleophilic on enolization. The arrangement of carbonyl groups enables synthesis and isolation of polyketone chains of various lengths, up to tetracontane (C40) with 16 carbonyl groups, as stable all-keto forms. The 1,3-diketone and 1,4-diketone subunits can undergo various types of reaction, enabling modulation of the chain lengths and conformations. We also achieve construction of sheet-like and cylindrical assemblies of flexible and shapable carbon chains with the aid of metal ion coordination after the conversion of the carbonyl groups to imine groups.

Results

Synthesis of polyketone chains

Polyketone chains composed of alternating 1,3-diketone and 1,4-diketone subunits were prepared by enol silyl ether formation at the terminal carbonyl group and subsequent stepwise oxidative homo-coupling (Fig. 2). When acetylacetone 1 was treated with chlorotrimethylsilane (1.2 equiv) in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)15, enol trimethylsilyl ether 2 was obtained in 93% yield. Excellent selectivity for the mono-silylated product was only observed for DBU, and bis-silylation concomitantly occurred when other amines such as triethylamine were used as a base. Pure enol trimethylsilyl ether 2 can be prepared on a 150 g scale by vacuum distillation. We, therefore, optimized the oxidative coupling conditions using compound 2.

Fig. 2
figure 2

Synthetic scheme for acetylacetone 1-based polyketone chains. Enol trimethylsilyl ethers are formed at the terminal ketone of acetylacetone monomer and oligomers. The enol silyl ethers are then homo-coupled using silver(I) oxide

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For the oxidative coupling of silyl enol ether 2, we examined suitable oxidants to prevent side reactions of unprotected carbonyl groups in the substrate and the products. Among the oxidants reported for 1,4-diketone synthesis with enolate synthons, silver(I) oxide16 was found to mediate the homo-coupling reaction to give dimer 3 without forming major side products other than the desilylated product 1. Reactions with other oxidants17,18,19 such as copper(II) triflate, ammonium cerium(IV) nitrate, and hypervalent iodine gave complicated mixtures including a small amount of dimer 3 (<10% yield), presumably because of reactions at the carbonyl groups. Aprotic polar reaction media were suitable for the silver(I) oxide-mediated coupling reaction, and dimer 3 was obtained in 70% yield in a mixture of dimethylsulphoxide/dimethyl sulphone. It is worth noting that desilylation of substrate 2 was the major reaction in nonpolar and protic solvents because of deceleration of the coupling reaction and acceleration of desilylation, respectively.

Silylation of acetylacetone dimer 3 occurred selectively at the terminal carbonyl groups under mild conditions. When dimer 3 was treated with chlorotrimethylsilane, triethylamine, and sodium iodide in acetonitrile at 0 °C20, the terminal enol silyl ethers 4 and 5 were obtained in 42 and 26% yields, respectively, along with the recovery of unreacted 3 (16%). For silylation of acetylacetone oligomers, conditions using DBU were not suitable because complicated mixtures were obtained presumably due to intramolecular aldol reactions. Enol silyl ether 4 also underwent a silver(I) oxide-mediated homo-coupling reaction to give tetramer 6 in 47% yield. Similar terminal-selective silylation of tetramer 6 took place, furnishing the mono-silylated product 7 in 26% yield along with 41% of bis-silylated product. Although the ratio of terminal/internal carbonyl groups was 1:3, formation of enol silyl ethers of the internal carbonyl groups was not detected using 1H nuclear magnetic resonance (NMR) spectroscopy. The coupling reaction using silver(I) oxide and compound 7 gave acetylacetone octamer 8, bearing 16 carbonyl groups on the tetracontane (C40) main chain, as a colourless solid in 17% yield after high-performance liquid chromatography (HPLC) separation.

Oligoacetylacetone chains 3–8 were obtained as single tautomers, which enabled full characterization of their pure forms. The high-resolution electrospray-ionization time-of-flight (ESI–TOF) mass spectrum showed the ion peak at m/z = 1033.5496, which is assignable to [8 + Na]+ (calculated for C56H82O16Na m/z 1033.5495). The 1H NMR spectrum of octamer 8 in CDCl3, showed the terminal acetyl proton signal at 2.15 p.p.m. as a singlet, but no signal was observed in the olefinic region at 4.0–7.0 p.p.m. This clearly shows that enolization is effectively suppressed by two methyl substituents in the 1,3-diketone subunits, even for octamer 8, which still has 16 carbonyl groups and 34 α-CH protons. Other polyketone chains 3 and 6 were also detected as all-keto forms, on the basis of their NMR spectra. These polyketone chains are thermally stable at least up to 120 °C and did not undergo intramolecular aldol cyclization in solution under neutral conditions. On heating in the solid state, compounds 3, 6, and 8 melted at 78, 94, and 119 °C, respectively, without any decomposition. It should be emphasized that the two main problems in handling long polyketone chains, namely enolization and intramolecular cyclization, can be avoided by using an oligoacetylacetone sequence.

Length and conformation changes of chains

Single-crystal X-ray diffraction analysis revealed that the acetylacetone-based chains adopt unique conformations caused by interactions at carbonyl groups in the solid state. In particular, the main carbon chain conformations vary widely according to the torsion angles of the 1,4-diketone subunits. The central ethylene unit of dimer 3 adopts a gauche conformation with a torsion angle of 68.8°, making the decane (C10) main chain twisted (Fig. 3b). A similar tendency is observed in the crystal structure of tetramer 6, in which two terminal 1,4-diketone subunits adopt gauche conformations (Fig. 3c). Only the central ethylene unit adopts a sterically favoured anti-periplanar conformation, therefore the icosane (C20) main chain of compound 6 is folded into an S-shape. In addition to hydrogen bonding interactions in the crystal packing, dipole–dipole and n–π* interactions21, 22 are known to govern the conformation of the 1,4-diketone structure. These weak but favourable interactions in the diketone units are useful for inducing complex conformations of flexible chains.

Fig. 3
figure 3

Modulation of chain length and favourable conformations of flexible carbon chains. a Synthetic schemes for the chemoselective conversion of 1,3- and 1,4-diketone subunits. b X-ray crystal structure of dimer 3. c X-ray crystal structure of tetramer 6. d X-ray crystal structure of 2,5-furylene-bridged chain 9. e X-ray crystal structure of compound 10. f X-ray crystal structure of isopyrazole dimer 11. g X-ray crystal structure of octaimine chain 12. All the thermal ellipsoids are drawn at the 50% probability level

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The alternating 1,3-diketone and 1,4-diketone sequence is convenient for adjusting the lengths and conformations of the flexible polyketone chains through chemoselective reactions (Fig. 3a). When a toluene solution of tetraketone 3 was refluxed in the presence of p-toluenesulfonic acid (p-TsOH), the ethylene proton signals of 3 disappeared and a new aromatic peak appeared at 6.14 p.p.m. in the 1H NMR spectrum. Single-crystal X-ray analysis confirmed the formation of a planar 2,5-furylene bridge, which connects two dimethylmethylene subunits with a distance of 4.87 Å (Fig. 3d). The distance is ~1 Å shorter than that in 1,4-diketone 3 (5.81 Å), resulting in a decrease in the chain length. The two terminal acetyl groups are located in parallel, and the decane (C10) carbon chain takes a U-shape.

The acid-catalyzed Paal–Knorr type furan synthesis23 is also applicable to tetramer 6. Under the same conditions, all the 1,4-diketone units were converted to furan rings to give compound 10 in 76% yield. Single-crystal X-ray analysis showed that compound 10 had an S-shaped conformation, as in the corresponding octaketone 6, but 10 was clearly smaller than 6 (Fig. 3e). The chain length was shortened by ca. 20% by formation of three furan rings in the chain (Supplementary Table 1). It is also worth noting that similar Paal–Knorr type reactions with poly(1,4-diketone)s often leave isolated ketones between two generated aromatic rings24. The alternating 1,3- and 1,4-diketone system favours full conversion of 1,4-diketone subunits to aromatic rings via Paal–Knorr synthesis25 in high yields, keeping only the terminal acetyl groups intact.

On treatment with hydrazine26, the 1,3-diketone units of polyketone chains 3 and 6 were converted to isopyrazole rings to furnish polyimine chains 11 and 12 in 89 and 80% yields, respectively. Considering that eight imine bonds formed during the reaction with tetramer 6, each reaction at the carbonyl group proceeded in more than 97% yield. The X-ray crystal structures of 11 and 12 show that the steric conformations of the ethylene bridges are all anti-periplanar, making the carbon chains straight, as is often observed in the most stable conformations of unsubstituted alkanes (Fig. 3f, g). All the isopyrazole rings in 11 and 12 are located roughly on the same plane. The distance between the two terminal carbon atoms in 12 was increased to 2.3 nm, as compared with that of 1.0 nm in S-shaped octaketone 6. Octaimine 12 was hydroscopic and crystallized with seven water molecules per chain molecule. The water molecules form clusters that are hydrogen bonded to the nitrogen atoms on compound 12 (Supplementary Fig. 5). As a result, carbon chains 12 are networked each other in the crystal by multiple hydrogen bonds. These multiple interactions on the nitrogen atoms are promising of not only for inducing conformations, but also producing assemblies of flexible carbon chains using hydrogen bonds and coordination bonds.

Assemblies of flexible carbon chains

Once we had achieved the length adjustment and the induction of various conformations of flexible carbon chains, we investigated methods for assembling large organic architectures using metal complexation27. When tetraimine chain 11 was combined with zinc(II) tetrafluoroborate hexahydrate in methanol, colourless crystals were formed. Elemental analysis indicated a ligand 11 to metal ratio of 2:1. The crystals were almost insoluble in common organic solvents such as chloroform and diethyl ether. Single-crystal X-ray diffraction analysis showed a two-dimensional coordination polymer in which each zinc(II) ion has tetrahedral geometry and binds to four ligands 11 at the terminal imine nitrogen atoms. Because the internal imine nitrogen atoms remain uncoordinated, ligand 11 adopts almost the same linear conformation as that of its pure crystal (Figs. 4a and 3f).

Fig. 4
figure 4

Two-dimensional assembly of tetraimine chain 11. a ORTEP diagram of coordination polymer [Zn(11)2(BF4)2] n around the zinc(II) centre with thermal ellipsoids at the 50% probability level. Zn, N, and C atoms are coloured in magenta, light blue, and grey, respectively. b Structural formula of coordination polymer [Zn(11)2(BF4)2] n . c two-dimensional sheet-like coordination network structure viewed along the b axis. The sequence of the closest carbon chains to 11 is highlighted in green. d Orientation of the closest carbon chains 11 highlighted in c viewed along the (1 0 –1) direction. Counter ions and solvent molecules are omitted for clarity

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In the crystal packing structure, the two-dimensional grids are stacked along the b axis to form infinite one-dimensional channels, in which counter anions and solvent molecules were observed (Fig. 4c and Supplementary Fig. 8). On removal of solvent molecules under vacuum, the crystallinity was lost, reflecting the flexibility of the framework components. Two of the four ligand molecules 11 around a zinc centre are located close to each other with a terminal C•••C distance of 3.98 and 4.01 Å. If we focus on the closest chains, the decane (C10) main chains of ligand 11 are one-dimensionally aligned to take wave-like orientations (Fig. 4d). This pre-organization could enable formation of a two-dimensional sheet covalent carbon network by generating terminal C–C bonds between the nearest terminal carbon atoms. These results clearly show the possibility of construction of elaborate carbon frameworks by assembling flexible, conformation-induced carbon chains.

To assemble a large, discrete architecture by coiling poly(acetylacetone)-based chains, we examined coordination assembly of octaimine chain 12 with a metal oxide cluster28. Treatment with nickel(II) nitrate hexahydrate in chloroform/ethanol caused broadening of peaks in the 1H NMR spectrum of compound 12 because of coordination of paramagnetic nickel(II) ions. After the solution had been allowed to stand at room temperature for 1 d, purple crystals, formulated as [Ni4(12)2(OH)2(NO3)6•4H2O•(solvents)], were formed in 55% yield. The ESI–TOF mass spectrum indicated cation peaks attributable to a nickel tetranuclear complex [Ni4(12)2(OH)2(NO3)4]2+ at m/z = 748.1988 (calculated for [C56H86N16Ni4O2]2+ m/z 748.1995) as a result of dissociation of hydrated water molecules and nitrate ions. The crystal structure shows that a pair of crystallographically equivalent ligands 12 twined around a hydroxo-bridged tetranuclear nickel cluster (Fig. 5 and Supplementary Fig. 10). Four nickel(II) ions are coordinated by two bridging hydroxo ligands, four aqua ligands and two imine ligands 12 to form a hexacationic complex. Each ligand 12 serves as a bidentate ligand for three of four nickel ions in an octahedral coordination geometry. The terminal imine nitrogen atoms of ligand 12 do not coordinate to a nickel ion, but they act as hydrogen-bond acceptors for hydrated water molecules on a nickel ion. The torsion angles of ethylene bridges in the icosane (C20) main chain of ligand 12 vary from 54.9 to 90.0°. The carbon chain of ligand 12 is therefore considerably curved, and adopts a horseshoe-like conformation. Two horseshoe-shaped ligands are closely twined around the nickel cluster, and the icosane (C20) main chains were arranged in a cylindrical assembly (Fig. 5b). It should be emphasized that the flexibility of, and multiple interaction sites on, the carbon chain enabled the cylindrical assembly of coiled carbon chains, as in the case of pottery made from clay ropes.

Fig. 5
figure 5

Cylindrical assembly of coiled octaimine chain 12. a Structural formula of nickel complex [Ni4(12)2(OH)2(NO3)6•4(H2O)]. b The conformation of the twined carbon chain ligand 12 in the nickel complex. The icosane (C20) main carbon chain of the upper ligand is highlighted in orange. Solvent molecules and counter ions are omitted for clarity

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Discussion

We have achieved the synthesis, chain length modulation, conformation induction, and formation of assemblies of flexible carbon chains based on oligo(acetylacetone)s. The alternate repetition of 1,3-diketone and 1,4-diketone subunits is the key to the suppression of intramolecular cyclization and to efficient functionalization of chains to induce various conformations. The terminal-selective silylation and subsequent homo-coupling reaction using silver(I) oxide provided a reliable method for obtaining long polyketone chains up to a tetracontane (C40) bearing 16 ketones. Although many carbonyl groups neighbour each other, the 1,3-diketone and 1,4-diketone positions are independently converted to furan and isopyrazole rings in high yields, leading to the formation of shorter chains and multidentate polyimine ligands, respectively. Polyketone and polyimine chains combine structural flexibility and multiple interaction sites, therefore they can be suitable framework components for various types of complex carbon architectures. While generation of further huge and elaborate structures and investigation of their properties are next challenges, our approach using shapable carbon chains provided a new route to construct structurally flexible assemblies. Furthermore, given that many carbonyl or imine groups and α-carbons are embedded in the main carbon chains, our results promise fixation of the induced conformations by forming C–C covalent bonds.

Methods

Experimental data and procedures

For the experimental procedure, HPLC chromatogram, 1H and 13C NMR, high-resolution ESI–TOF mass spectra, infrared spectroscopy and elemental analysis data, detailed crystallographic data, and chain lengths data, see Supplementary Methods, Supplementary Figs. 1–10 and Supplementary Table 1.

Data availability

The X-ray crystallographic coordinates for the structures of compounds 3, 6, 9, 10, 11, 12, [Zn(11)2(BF4)2·(MeOH)2·H2O] n and [Ni4(12)2(OH)2(NO3)6·(H2O)4] are available as Supplementary Data 1–8, respectively. These data have also been deposited at Cambridge Crystallographic Data Centre (CCDC), under deposition numbers CCDC1587959, CCDC1587960, CCDC1587961, CCDC1587962, CCDC1587963, CCDC1587964, CCDC1587965, and CCDC1587966, respectively. These data can be obtained free of charge from the CCDC via http://www.ccdc.cam.ac.uk/data_request/cif. All other data are available from the authors upon reasonable request.