Calix arenes rearrangement

CHART 8. Ethylene rearrangements over a W-oxo surface modeled by W-calix[4]arene. 

The reason these reactions occur can be found in the relative stabilities of the anions involved. This approach could be of general use for the synthesis of inherently chiral calix[4]arenes. The stabilization of the monoanion of a mono-0-alkyl/-acyl calix[4]arene by two intramolecular hydrogen bonds explains the usually easy access to 1,3-derivatives. However, upon further deprotonation the monoanion of a 1,2-O-alkyl (1,2-O-acyl) derivative is stabilized by an intramolecular hydrogen bond (unlike the analogous 1,3-derivative) and rearrangement occurs if there is a reaction pathway available. For the phosphorotropic rearrangement the authors assume a cyclic intermediate with five-coordinated phosphorus, which is not unreasonable although an intermolecular mechanism is not strictly ruled out. 

The synthesis of the carbamoyl derivative and the subsequent rearrangement have to be carried out simultaneously at four centres [91]. In an analogous manner, the same observations have been carried for the mercaptothia-calix[4]arene [92,93]. Interestingly, in systems where multiple functionalities are present, the metal counterion for the deprotonation of the phenols plays an important role. 

Middel, O., Greff, Z., Taylor, N. J., Verboom, W., Reinhoudt, D. N., Snieckus, V. The First Lateral Functionalization of Calix[4]arenes by a Homologous Anionic Ortho-Fries Rearrangement. J. Org. Chem. 2000, 65, 667-675. 

As an alternative to electrophilic substitution as a means for introducing functional groups into the calixarenes, a reaction sequence has been developed that involves the conversion of calix[4]arene (59) to the tetraallyl ether 63. When 63 is heated in diethylaniline it undergoes a four-fold p-Claisen rearrangement to afford p-allyl-calix[4]arene (62) in excellent yield 126). From the tetra-tosyl ester of 62 (i.e. compound 66 a) a variety of functionalized calixarenes have been obtained, including the aldehyde 66b, alcohol <56 c, bromide 66 d, azide 66 e, amine 66f, and nitrile 66g. Removal of the tosyl group occurs under mildly basic conditions to yield, for example, p-(2-hydroxyethyl)calix[4]arene (66 h). 

Reaction sequences similar to those portrayed in Scheme 7 should also be applicable to the other calixarenes obtained by de-ferf-butylation of 67 (n = 5, 6, 7, 8), as depicted in Scheme 8. Some of these transformations have already been demonstrated 12S), while others remain to be investigated. De-terf-butylation of />-/err-butylcalix[6]-arene (67, n = 6) and p-/< rt-butylcalix[8]arene (67, n = 8) proceed fairly smoothly to afford the corresponding calix[6]arene (68, n = 6) and calix[8]arene (68, n = 8). Conversion of 68 (n = 6) to the hexa-allyl ether (69b, n = 6) followed by Claisen rearrangement produces a modest yield of p-allylcalix[6]arene (70, n = 6). Similar reactions have been shown to take place in the calix[8]arene series as well125), although the yields are much lower and the products have not yet been fully characterized. 

A reaction involving the narrow and the wide rim of a calixarene is the Claisen rearrangement of allyl ethers. In the pioneering times of calixarene chemistry it was regarded as one of the most favourable ways to introduce functionalities onto the wide rim via subsequent modification of the p-allyl groups . Due to its strict intramolecular course it was appropriate also for a selective p-substitution (see Scheme 14, reaction d)), and the first calix[4]arene, monosubstituted at the wide rim, was obtained by Claisen rearrangement of the monoaUyl ether obtained from the tribenzoate of Meanwhile,... 

SCHEME 24. Tandem Claisen rearrangement of doubly bridged calix[4]arenes. The intramolecular pathway is indicated by dashed arrows. BTMSU = bistrimethylsilylurea... 

The ability to create molecular level actuators has been taken even further in the example of thiophene-based molecular muscles by Madden and Hunter. Conformational rearrangement of the polymer backbone in molecules such as calix[4]arene-bithiophene was created at the molecular level [118]. This work has recently been reviewed and prospects for future research in this area considered [119]. 

Lateral functionalization of calix[4]arenes using a homologous anionic ortAo-Fries rearrangement... 

A novel approach for the preparation of the calix[4]arene scaffold involves ring contraction via rearrangement of a macrocycle incorporating pinacol subunits (5). By this approach Sawada and coworkers synthesized a calix[4]arene derivative with two distal methylene bridges functionalized (6) (Eq. 4.3) [7]. 

In contrast to the parent calix[4]arenes, selective functionalization of the resorcinol-based calix[4]arenes [ 18] has hardly been studied. Partly functionalized cavi-tands have only been isolated as side products in the synthesis of tetrafunctionalized cavitands [19, 20]. Although such dissymmetric cavitands have been used in the synthesis of chiral cavitands [21] and hemicarcerands [20] with promising applications [22], their synthesis was never studied in detail. While our work was in progress [23], Sorrell and Richards showed that cavitands can be selectively functionalized at the upper rim by means of a Claisen rearrangement [24]. In this paper we describe the synthesis of partly bridged octols [25] together with a novel route to functionalize these cavitands selectively in a proximal way. 

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