Synthesis, structure, and transannular pi-pi interaction of multilayered [3.3]metacyclophanes

The synthesis of a series of three- to six-layered [3.3]metacyclophanes ([3.3]MCPs) 3-6 has been successfully accomplished by the (p-tolylsulfonyl)methyl isocyanide (TosMIC) method as a critical coupling reaction. Their important synthetic intermediates are the two- and three-layered bis(bromomethyl) compounds 11, 17, 21, and tetrakis(bromomethyl) compounds 25 and 28. The structures of the three- to six-layered [3.3]MCPs (3-6) as well as three- to six-layered [3.3]MCP-di- (22-24) and tetraones (26, 27, and 29) as the synthetic intermediates have been elucidated based on the 1H NMR data and X-ray structural analysis. These multilayered cyclophanes are constructed with two different geometries, syn-[3.3]MCP and anti-[3.3]MCP-2,11-dione. In principle, their geometries are maintained in the multilayered [3.3]MCPs, but deformation of the dihedral angle of the two benzene rings of the syn-[3.3]MCP moiety is generally observed. In the four-layered MCP 4, the central [3.3]MCP moiety takes an anti geometry. These data indicate the structural flexibility of the [3.3]MCP moiety. In the electronic spectra, rather simple and structureless absorption curves are observed, and the most significant spectral change is observed for the two to three layers and becomes less effective even if it is more layered. In the charge-transfer (CT) bands of the multilayered [3.3]MCPs with tetracyanoethylene (TCNE), the lambdamax gradually shifts to the longer wavelength region, but the extent of the shift is much smaller as the number of layers increases. In the multilayered [3.3]MCP-di- and tetraones, the anti-[3.3]MCP-dione moiety works as an insulator. Therefore, the CT interaction of the four- and five-layered [3.3]MCPs with one anti-[3.3]MCP-dione moiety (23 and 24) shows the almost comparable magnitude of the interaction with the two- and three-layered [3.3]MCPs (2 and 3), respectively. The tetraones of the three and four-layered MCPs (29 and 26) do not show CT interactions except for the six-layered MCP 27.     

Synthesis of (Aza)n[3n]cyclophanes as host molecules

(Aza)_n[3ⁿ]cyclophanes were synthesized by the coupling reaction of p-toluenesulfonamide and bis(halomethyl) derivatives in the presence of a base (K₂CO₃, NaH etc.) using DMF, dioxane etc. as a solvent, in acceptable yields. Tetraaza macrocyclic compound (the dimer in Fig. 1) obtained by the coupling of 2,11-diaza[3.3]metacyclophane with 1,3-bis(bromomethyl)benzene gavea 1:1 adduct with benzene.Presented partly at the 42nd Autumn Annual Meeting of the Chemical Society of Japan, Sendai, September, 1980; Abstr. No. 1J17.     

Synthetic and structural studies of [6]-, [7]- and [10]metacyclophanes

A new preparative sequence from 2,3-polymethylene-2-cyclopentenone 5 to 2,6-polymethylenebromobenzenes 3 (n = 6, 7, 10) and 2,6-polymethylenephenyllithiums 6 has been found. The reaction of 6 with various electrophiles produces a number of new compounds to disclose the unique reactivity of the aryl C-Li moiety surrounded by the polymethylene chain. Photolysis of 3a and 3b provides transannular products 8, 10 and 11, all arising from the proximity between the aromatic bromine and the aliphatic hydrogen intraannularly opposed to be removed as HBr. Spectrometric study gives quantitative data of the dependence of the molecular geometry upon the chain length and the aromatic substituents. The energy barriers ΔG_c^≠ of the conformational flipping are 17·4 kcal/mol (T_c 76·5°) for [6]metacyclophane (7a), 11·5 kcal/mol (T_c ?28°) for [7]metacyclophane (7b), ·8 kcal/mol for [10]metacyclophane (7c). The lower-energy process of the aliphatic chain in [6]metacyclophane derivatives is the pseudorotation with substituent-dependent barrier ΔG_c^≠ 11·1 kcal/mol (T_c ?31·5°) for 7a, 12·4 kcal/mol (T_c ?4·5°) for 3a and 12·7 kcal/mol (T_c 1·0°) for 12a. The rather large rotational barrier is attributed to the compressed structure of each system. The benzene ring distortion of the cyclophanes is deduced from the bathochromic shift of the B-band and the diamagnetic shift of the benzene proton signals in the PMR.     

Evidence for homo-conjugation between two revolving 14pi-electron systems in 10b-methyl-10c-[2-(10b,10c-dimethyl-10b,10c-dihydropyrenyl)]-10b,10c-dihydropyrene

Ring contraction followed by an elimination reaction on anti-9-methyl-18-trans-2-(10b,10c-dimethyl-10b,10c-dihydropyrenyl)-2,11-dithia[3,3]metacyclophane gave the desired compound 10b-methyl-10c-[2-(10b,10c-dimethyl-10b,10c-dihydropyrenyl)]-10b,10c-dihydropyrene. 1H NMR spectroscopic analysis indicated a ring current effect over a considerable distance from the macro-molecular plane of each of the aromatic rings with the two pi systems freely rotating. Bathochromic shifts and peak broadening in its electronic spectrum clearly supports the presence of through-space pi-pi interactions between the two aromatic rings. This should serve as a good model to verify homo-conjugation effect in such a novel system where the two pi systems are freely revolving.     

Stereocontrolled route to vicinal diamines by [3.3] sigmatropic rearrangement of allyl cyanate: asymmetric synthesis of anti-(2R,3R)- and syn-(2R,3S)-2,3-diaminobutanoic acids

A stereocontrolled route via allyl 1,2-diols to vicinal diamines based on the [3.3] sigmatropic rearrangement of allyl cyanate has been developed. Our approach consists of two consecutive steps: stereoselective construction of allyl anti- and syn-1,2-diols followed by [1,3]-chirality transfer by sigmatropic rearrangement, which allow an access to anti-(2R,3R)- and syn-(2R,3S)-2,3-diaminobutanoic acids. [reaction: see text]     

Conformational analysis—XIII: Syn and anti [3.2]-, [3.3]-, [4.2]-, and [4.3]-metacyclophanes

While in [3.3]metacyclophane (19) the aromatic rings preferentially adopt the syn arrangement, its lower and higher homologues, i.e. [2,2]-, [3.2]-, [4.2], and [4.3]-metacyclophane (1, 6, 26 and 30), adopt the anti conformation. Substituted [m,n]metacyclophanes do not necessarily behave similarly to the parent hydrocarbons. Substituted compounds exhibiting a different conformation are [3.2]metacyclophane-1,11-dione (7) (syn), [3.3]metacyclophane-2,11-dione (24) and the corresponding bis[propylene thioacetal] (25) (anti), [4.2]metacyclophane-2,12-dione (27) (syn), and [4.3]metacyclophane-2,13-dione (31) (syn). Thus, the solution conformation of an [m.n]metacyclophane is sensitive both to chain length [m.n.] of the bridges and substitution. The ring inversion barriers determined by variable temperature ¹H NMR decrease with increasing length of the bridges and qualitatively correlate with the transanular strain present in the pertinent system.     

Synthese von 15-Hydroxy[9]metacyclophan

Synthesis of 15-Hydroxy[9]metacyclophane 3-(1-Nitro-2-oxocyclododecyl)propanal ( 1 ) was converted to 15-hydroxy[9]metacyclophane ( 3 ) on two different routes. In the first case the internal aldol reaction product of 1 was treated with K₂CO₃/THF to give 3 in 29 % yield with regard to cyclododecanone. Alternatively, the aldehyde 1 reacted with a primary amine to form e.g. 4 which gave 3 in the presence of CH₃I/K₂CO₃ in 48 % yield.     

Structural properties of five- and six-layered [3.3]metacyclophanes

We performed X-ray structural analyses of the five- and six-layered [3.3]metacyclophanes (MCPs) 1 and 2 and the six-layered [3.3]MCP tetraone 3. In the solid state, the MCP moieties of 1, 2, and 3 adopt different conformations from those of the free MCPs in solution. In the five-layered [3.3]MCP 1, all the [3.3]MCP moieties adopt anti (chair/boat) conformations. In the six-layered [3.3]MCP 2, two three-layered [3.3]MCPs are connected by a [3.3]MCP in the anti conformation with completely parallel benzene rings. In the six-layered [3.3]MCP tetraone 3, the outer [3.3]MCP moieties and diones adopt general syn and anti geometries, respectively. However, the inner [3.3]MCP moiety adopts an anti geometry. Based on density functional theory (DFT) calculations, the most stable conformers of 1, 2, and 3 are syn (chair/chair) in the [3.3]MCP moieties and anti (twist boat/twist boat) in the dione moieties.     

MNDO Calculations on [n]metacyclophanes

MNDO calculations on [n]metacyclophanes and a variety of related compounds are reported. An analysis of the strain, imposed by the oligomethylene bridge, and its distribution over the distorted benzene ring and the oligomethylene bridge is presented. The effect of strain and bending of the benzene ring on aromatic delocalization is investigated by a comparison of ΔH^o_f of the bent benzene systems with that of a correspondingly bent, but localized 1,3,5-cyclohexatriene. The results indicate that, even in the case of the highly bent [4]metacyclophane ( 1a ), localization is unfavorable by about 10 kcal/mol.     

Computational study about through-bond and through-space interactions in [2.2]cyclophanes

An analysis of the electron density, obtained by B3PW91/6-31+G(d,p), B3LYP/6-31+G(d,p), and MP2/6-31+G(d,p) for [2,2]cyclophanes isomers, [2.2]paracyclophane, anti-[2.2]metacyclophane, syn-[2.2]metacyclophane, and [2.2]metaparacyclophane, was made through natural bond orbitals (NBO), natural steric analysis (NSA), and atoms in molecules (AIM) methods and through analysis of frontier molecular orbitals (MOs). NBO indicates that all compounds present through-bond interactions, but only the conformers of [2.2]metacyclophane present significant through-space interactions. The last interactions are observed in AIM analysis and by the plots of MOs. AIM indicates that these through-space interactions are closed-shell ones, and they stabilize the conformers. In contrast, all isomers present through-bond and through-space repulsive interactions. In addition, the atomic properties, computed over the atomic basins, showed that the position of the bridges and the relative displacement of the rings can affect the atomic charges, the first atomic moments, and the atomic volumes.     

14][14]Metaparacyclophane: first example of an [m][n]metaparacyclophane

The synthesis of [14][14]metaparacyclophane, the first [m][n]metaparacyclophane ever known, is described. The reaction sequence began with the bis-chloromethylation of [14]paracyclophane in refluxing CS(2), which yielded a nonseparable mixture of 16,19- and 16,20-bis(chloromethyl)[14]paracyclophane in an 8:1 ratio. Acetolysis of these dichlorides gave the corresponding diacetate mixture from which the minor component 16,20-bis(acetoxymethyl)[14]paracyclophane was isolated and elaborated into the desired cyclophane via the disulfone of 2,15-dithia[16][14]metaparacyclophane and subsequent sulfur dioxide extrusion by a one-flask Ramberg-B?cklund reaction procedure followed by hydrogenation.     

Tricarbonylchromium complexes of [5]- and [6]metacyclophane: an experimental and theoretical study

Tricarbonylchromium complexes of [5]- and [6]metacyclophane were prepared and the interaction between the Cr(CO)₃ tripod and the cyclophane fragment was evaluated by both an experimental and a theoretical study. The tricarbonylchromium complex of [5]metacyclophane could only be obtained in solution and was characterized by its ¹H NMR spectrum. The tricarbonylchromium complex of [6]metacyclophane was isolated and an X-ray crystal structure was obtained, which reveals that no significant geometric changes occur upon coordination of the severely distorted aromatic ring. Computations on the tricarbonylchromium complexes of m-xylene, [5]- and [6]metacyclophane furthermore demonstrate that the corresponding complexation energy is remarkably unaffected by the degree of distortion of the aromatic ring. Theoretical analyses of the above model systems as well as complexes of planar and artificially deformed benzene with Cr(CO)₃ show that this is primarily the result of two counteracting effects: (i) a stabilization due to an increased back-donation from the metal center to the benzene and (ii) a destabilization due to the increasing strain in the aromatic ring.     

Synthesis and Diels-Alder reactions of 1,2-dimethylene[2.n]metacyclophanes

The Diels-Alder reaction of 1,2-dimethylene[2.n]MCPs (MCP = metacyclophane) with suitable dienophiles followed by aromatization and photoinduced or FeCl(3)-induced transannular cyclization afforded phenanthrene-anellated polycyclic aromatic hydrocarbons, which were found to adopt helical chirality in the solid state.     

Zur frage transanularer II-II-wechselwirkungen im [2.2]metacyclophan, [2.2]Paracyclophan und 2,2′-spirobiindan

Concerning the question of transanular II-II-interactions in [2.2]metacyclophane, [2.2]paracyclophane and 2,2′-spirobiindane.From the quotient of the two dissociation constants (K₁/K₂) of [2.2]metacyclophane-bis-chromtricarbonyl (9·0 ± 1·9) it was concluded that there are no transanular II-II-interactions between the two benzene rings. The corresponding values for the bis-chromtricarbonyl-complexes of 2,2′-spirobiindane and [2.2]paracyclophane are 8·0 ± 1·5 and 10⁴, resp. These results are supported by IR-spectroscopical data of the CO-frequencies of the Cr(CO)₃-complexes of [2.2]metacyclophane and some derivatives, of 2,2′-spirobiindane and [2.2]paracyclophane.Moreover, UV-spectroscopic studies of tetracyanoethylene complexes of arenes are shown to be insignificant with regard to transanular II-II-interactions.     

Conformational changes of 2,11-dithia[3.3]metacyclophane. A new look using VT NMR and calculation

The conformational changes of 2,11-dithia[3.3]metacyclophane are reexamined utilizing VT NMR data and calculations (ab initio, semiempirical, density functional, and molecular mechanics) to show that the syn to syn' inversion that occurs with exchange of the benzylic hydrogens proceeds most easily through bridge wobbles of the anti isomers and that the critical barrier is the conversion of the syn - chair - chair isomer to the anti-chair-chair isomer, barrier (found) = 9.3-9.6 kcal/mol, barrier (calc) = 10.3 kcal/mol, such that when this conversion is slow on the NMR time scale, the benzylic hydrogens no longer exchange, and the syn-chair-chair isomer becomes frozen. The syn-boat-chair isomer, however, can continue to invert to the anti-boat-chair isomer until lower temperatures, and thus, the benzylic hydrogens continue to exchange for this isomer. Thus, while bridge wobbles of the syn isomers have the largest barriers, bridge wobbles of the anti isomers have the smallest barriers, and so the barriers of the syn-to-anti conversions play a much greater role than previously determined.     

Quasi-octahedral complexes of pentamethylcyclopentadienyliridium(III) bearing bis(diphenylphosphinomethyl)phenylphosphine (dpmp)

Reaction of [Cp*IrCl2]2 (1) with dpmp in the presence of KPF6 afforded a binuclear complex [Cp*IrCl(dpmp-P1,P2;P3)IrCl2Cp*](PF6) (2) (dpmp =(Ph2PCH2)2PPh). The mononuclear complex [Cp*IrCl(dpmp-P1,P2)](PF6) (4) was generated by the reaction of [Cp*IrCl2(BDMPP)](BDMPP =PPh[2,6-(MeO)2C6H3]2) with dpmp in the presence of KPF6. These mono- and binuclear complexes have four-membered ring structures with a terminal and a central P atom of the dpmp ligand coordinated to an iridium atom as a bidentate ligand. Since there are two chiral centers at the Ir atom and a central P2 atom, there are two diastereomers that were characterized by spectrometry. Complexes anti-4 and syn-4 reacted with [Cp*RhCl2]2 or [(C6Me6)RuCl2]2, giving the corresponding mixed-metal complexes, anti- and syn- [Cp*IrCl(dppm-P1,P2;P3)MCl2L](PF6) (6: M = Rh, L = Cp*; 7: M = Ru, L = C6Me6). Treatment with AuCl(SC4H8) gave tetranuclear complexes, anti- and syn-8 [[Cp*IrCl(dppm-P1,P2;P3)AuCl]2](PF6)2 bearing an Au-Au bond. Reaction of anti- with PtCl2(cod) generated the trinuclear complex anti-9, anti-[[Cp*IrCl(dppm-P1,P2;P3)]2PtCl2](PF6)2. These reactions proceeded stereospecifically. The P,O-chelated complex syn-[Cp*IrCl(BDMPP-P,O)] (syn-10)(BDMPP-P,O = PPh[2,6-(MeO)2C6H3][2-O-6-(MeO)C6H3]2) reacted with dpmp in the presence of KPF6, generating the corresponding anti-complex as a main product as well as a small amount of syn-complex, [Cp*Ir(BDMPP-P,O)(dppm-P1)](PF6) (11). The reaction proceeded preferentially with inversion. The reaction processes were investigated by PM3 calculation. anti- was treated with MCl2(cod), giving anti-[Cp*Ir(BDMPP-P,O)(dppm-P1;P2,P3)MCl2](PF6)(14: M = Pt; 15: M = Pd), in which the MCl2 moiety coordinated to the two free P atoms of anti-11. The X-ray analyses of syn-2, anti-2, anti-4, anti-8 and anti-11 were performed.     

Synthesis of naphtho[2',3':4,5]imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3]-thiazole-5,10-dione and naphtho[2',3':4,5]imidazo-[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3]benzothiazole-7,12-dione

The reaction of 2,3-dibromo-1,4-naphthoquinone with 2-aminothiazole in MeONa/MeOH at 60oC for 3 h gave naphtho[2',3':4,5]imidazo[2,1-b][1,3]thiazole-5,10-dione in 64% yield. The reaction of 2,3-dibromo-1,4-naphthoquinone with 2-aminobenzothiazole under the above-mentioned conditions gave 2-(benzo[d]thiazol-2-ylamino)-3-bromonaphthalene-1,4-dione in 64% yield, which on treatment with Na/THF or NaN₃/acetone under reflux conditions gave naphtho[2',3':4,5]imidazo[2,1-b][1,3]- benzothiazole-7,12-dione in 69 and 56% yields, respectively.     

Ruthenium porphyrin catalyzed tandem sulfonium/ammonium ylide formation and [2,3]-sigmatropic rearrangement. A concise synthesis of (+/-)-platynecine

meso-Tetrakis(p-tolyl)porphyrinatoruthenium(II) carbonyl, [Ru(II)(TTP)(CO)], can effect intermolecular sulfonium and ammonium ylide formation by catalytic decomposition of diazo compounds such as ethyl diazoacetate (EDA) in the presence of allyl sulfides and amines. Exclusive formation of [2,3]-sigmatropic rearrangement products (70-80% yields) was observed without [1,2]-rearrangement products being detected. The Ru-catalyzed reaction of EDA with disubstituted allyl sulfides such as crotyl sulfide produced an equimolar mixture of anti- and syn-2-(ethylthio)-3-methyl-4-pentenoic acid ethyl ester. The analogous "EDA + N,N-dimethylcrotylamine" reaction afforded a mixture of anti- and syn-2-(N,N-dimethylamino)-3-methyl-4-pentenoic acid ethyl esters with a diastereoselectivity of 3:1. The observed catalytic activity of [Ru(II)(TTP)(CO)] for the ylide [2,3]-sigmatropic rearrangement is comparable to the reported examples involving [Rh(2)(CH(3)CO(2))(4)] and [Cu(acac)(2)] as catalyst. Similarly, cyclic sulfonium and ammonium ylides can be produced by intramolecular reaction of a diazo group tethered to allyl sulfides and amines under the [Ru(II)(TTP)(CO)]-catalyzed reaction conditions. The subsequent [2,3]-sigmatropic rearrangement of the cyclic ylides furnished 2-allyl-substituted sulfur and nitrogen heterocycles in good yields (>90%). By employing [Ru(II)(TTP)(CO)] as catalyst, the cyclic ammonium ylide [2,3]-sigmatropic rearrangement reaction was successfully applied for the total synthesis of (+/-)-platynecine starting from cis-2-butenediol.     

Conformational behavior and coordination chemistry of 2,11-dithia[3.3]orthocyclophane with platinum group metals

The compound 2,11-dithia[3.3]orthocyclophane (L) is a mesocyclic dithioether that can act as a bidentate ligand in different conformations. In the ionic heteroleptic complexes [PtL(eta(4)-cod)][CF(3)SO(3)](2) (1), [RhL(eta(4)-cod)][CF(3)SO(3)] (2), and [IrL(eta(4)-cod)][CF(3)SO(3)] (3) (cod = 1,5-cyclooctadiene), L is coordinated in the anti I conformation both in solution and in the solid state, as revealed by an X-ray diffraction study of complex 1. However, in complexes [PdL(PPh(3))(2)][SO(3)CF(3)](2) (4) and [PtL(PPh(3))(2)][SO(3)CF(3)](2) (5), L exhibits two different conformations: anti I and anti II in a 40:60 ratio, as observed by (1)H and (31)P NMR spectroscopy, with no exchange up to 90 degrees C. The homoleptic complexes [PdL(2)][SO(3)CF(3)](2) (6) and [PtL(2)][SO(3)CF(3)](2) (7), with two ligands bound to the metal, display two isomers in solution, one of them with L in conformations anti I-anti II and the other with conformations anti II-anti II with a 75:25 ratio. The X-ray structure of 6 showed only the presence of the anti II-anti II isomer in the solid state. All complexes were synthesized by the reaction of a suitable chloride complex with 2 equiv of silver triflate and 1 equiv of L.     

Structural properties of charge-transfer complexes of four- and five-layered [3.3]metacyclophanes

In the solid state, the cyclophane (CP) moieties of the charge-transfer (CT) complexes of four- and five-layered [3.3]metacyclophanes (MCPs) 1 and 2 with tetracyanoethylene (TCNE) take different conformations from those in the solid state of the free MCPs. In the four-layered [3.3]MCP 1-TCNE complex, the CP moiety takes an s-shaped syn-anti-syn geometry, whereas the inner three benzene rings take the all-syn geometry and the two outer [3.3]MCP moieties have deformed anti-conformations in the five-layered [3.3]MCP 2-TCNE complex. In the crystal-packing diagrams of each complex, intermolecular CH/π-type interactions are observed between adjacent molecules.