Cyclophanes precursors

Figure 3.25. Catenane synthesis from a polyether ring and a C-shaped cyclophane precursor...

With the idea of creating a more rigid chiral bis-NHC ligand, Veige and coworkers linked the wingtips of independent NHCs to a tra s-9,10-dihydroetha-noanthracene backbone [59]. The dibenzimidazolium cyclophane precursor exhibited a fluxional process in solution, but was static once bounded to Pd. Evidence of spatial distinction in the chiral pocket was the observation of a 1 4 ratio of endolexo conformers in both solid state and solution. 

Simons RS, Garrison JC, Kofron WG et al (2002) Synthesis and structural characterization of two bis-imidazolium-linked cyclophanes precursors toward carbeneporphyrinoid ligands. Tetrahedron Lett 43 3423-3425... 

A potential drawback of all the routes discussed thus far is that there is little control over polydispersity and molecular weight of the resultant polymer. Ringopening metathesis polymerization (ROMP) is a living polymerization method and, in theory, affords materials with low polydispersities and predictable molecular weights. This methodology has been applied to the synthesis of polyacctylcne by Feast [23], and has recently been exploited in the synthesis of PPV. Bicyclic monomer 12 [24] and cyclophane 13 [25) afford well-defined precursor polymers which may be converted into PPV 1 by thermal elimination as described in Scheme 1-4. 

Macrocycles containing isoxazoline or isoxazole ring systems, potential receptors in host—guest chemistry, have been prepared by multiple (double, triple or quadruple) 1,3-dipolar cycloadditions of nitrile oxides, (prepared in situ from hydroxamoyl chlorides) to bifunctional calixarenes, ethylene glycols, or silanes containing unsaturated ester or alkene moieties (453). This one-pot synthetic method has been readily extended to the preparation of different types of macrocycles such as cyclophanes, bis-calix[4]arenes and sila-macrocycles. The ring size of macrocycles can be controlled by appropriate choices of the nitrile oxide precursors and the bifunctional dipolarophiles. Multiple cycloadditive macrocy-clization is a potentially useful method for the synthesis of macrocycles. 

In more recent works, Zhu and coworkers synthesized a variety of para-cyclophanes and biarylether containing macrocycles (14c and d) using a reaction sequence consisting of an Ugi reaction followed by an intramolecular Sj Ar cyclization (Scheme 14) [76-78]. Many linear precursors (14a and b) were achieved with the Ugi reaction by employing varied primary amines. This synthetic planning allowed the introduction of four points of diversity within the resulting scaffolds, thus producing a small library of cyclopeptoids. 

From this important subgroup of cyclophanes [2.2]metacyclophane (5) and its derivatives (including [3.3]precursors for synthetic purposes) as well as some related carbo- and heterophanes have attracted much attention. Syntheses 30), the stereochemistry as well as several reactions and spectra 12) have been reviewed earlier. 

Cyclophanes are known to be efficient receptors for aromatic compounds in protic solvents. Thus, linking a cyclophane unit to a porphyrin, like in 193, provides an excellent way to study the oxidation of aromatic hydrocarbons [117]. The synthesis of 193 took advantage of an earlier protocol for the preparation of strapped porphyrins [118] using the bis-dipyrromethane 194 already linked to the cyclophane as a valuable precursor for an acid catalyzed condensation leading to the porphyrin in 9% yield (Fig. 32). 

The Palauan deep-water (500 m) marine actinomycete Salinispora pacifica has yielded cyanosporasides A (1731) and B (1732), which feature a chlorine on an unactivated benzene ring (1658). The authors suggest a novel biosynthesis from an enediyne precursor. Related to the previously known nosto-cyclophanes (1) are the new carbamidocyclophanes A-E, of which A (1733), B (1734), C (1735), and D (1736) are chlorinated, being isolated from the Vietnamese cyanobacterium Nostoc sp. (1659). These compounds exhibit cytotoxicity against MCF-7 (breast) and FI (amniotic epithelial) human cancer cells. 

It was converted to the phthalimide via a Mitsunobu reaction, reduced to the amine, and the amine was coupled with />-nitrophenylacetic acid to give the precursor to the macrocycle. Macrocylization was done via Troger s base formation using Johnson s method, which resulted in two isomers of the amide macrocycle. These were separated and reduced to give the cyclophane host. This was the first time two diastereomers were observed in these syntheses and the separation of these diastereomers was very difficult. 

Even the distorted boat-like deck in [2.2]metacyclophanes can be constructed by an intramolecular version of the benzannulation. A suitable precursor bears a chromium vinylcarbene and an allcyne moiety linked to a meta-phenylene core by two-atom bridges, as shown for complexes 80. Benzannulation under the typical conditions affords hydro-quinonophanes 81 in fair yields (Scheme 31) [73]. Interestingly, the intramolecular benzannulation approach even tolerates heteroatom bridges, which impose both additional strain and helicity on the cyclophane skeleton [73b]. 

Many cyclophanes are conformationally mobile, and the study of their behavior in solution has proved to be most intriguing. A particularly striking example of conformational analysis was recently reported by Fukazawa [28]. The [4.4]paracyclophane derivative 34 was synthesized by a photoinduced double S l reaction of the precursors 32 and 33 (Scheme 9). In the low-temperature H NMR spectrum of 34, signals due to three distinct conformers were observed. Assignment of the structure of the major conformer was then accomplished in a unique way. The crystal structure was determined, and this corresponded to the calculated lowest energy... 

Control experiment indicated that template effect (in the presence of different metal salts) [108] was not operating for this transformation. The presence of NH function in 86 that could potentially form a H-bond with oxazole ring, thus preorganizing the cyclization precursor [109], was not an obligation. Indeed, compound 86 (R = H) and 87 (R = Et, Fig. 2) was obtained in essentially identical yield. Aliphatic diamines are suitable substrates, as cyclophane 88 and 89 can be prepared in reasonable yield. It is interesting to note that a 47% yield of 89 meant 88% yield per chemical bond created, including the macrocyclization step. 

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