Partial OH → Me Replacement in the Calixarene Scaffold:  Preparation, Conformation, and Stereodynamics of Tetra-tert-butyl-25,27-dihydroxy-26,28-dimethylcalix[4]arene and Its Dimethyl Ether Derivative

Abstract

The first example of the replacement of hydroxyl groups of a calixarene by methyls is described. Reaction of the bis(spirodienone) calixarene derivative 3B with MeLi afforded the bis addition product 4 which is derived, as shown by X-ray crystallography, from attack on the face of the carbonyls which is anti to the ether oxygen. The reaction of the alternant bis(spirodienone) calixarene derivative 3A with excess MeLi resulted in addition to the CO groups, but with a concomitant cleavage of the spiro bonds. Ionic hydrogenation (CF3COOH/Et3SiH) of this product (5) yielded 5,11,17,23-tetra-tert-butyl-25,27-dihydroxy-26,28-dimethylcalix[4]arene (6) while ionic hydrogenation of 4 resulted in fragmentation of the macrocyclic ring. Calixarene 6 adopts a 1,3-alternate conformation both in solution and in the solid state. 6 is conformationally flexible, and an inversion barrier of 15.1 kcal mol-1 was measured for it by DNMR. The dimethyl ether derivative of 6 (i.e., 7) exists in a partial cone (paco) conformation and undergoes two distinct dynamic processes possessing barriers of 13.3 and 18.1 kcal mol-1. Molecular mechanics calculations predict correctly the preferred conformation of 6 and 7 and indicate that the topomerization pathways resulting in the mutual exchange of the protons within a methylene group are the following: 1,3-alt → paco(CH3) → 1,2-alt → paco(CH3)* → 1,3-alt* for 6, and paco(CH3) → 1,3-alt → paco(OCH3) → 1,2 alt → paco(OCH3)* →1,3-alt* → paco(CH3)* for 7 with calculated barriers of 15.0 and 16.1 kcal mol-1, respectively.

Conformation and Stereodynamics of Monodioxamethylene Calix[4]arene Derivatives

“…Reduction of the Monospirodienone Derivative. The nucleophilic addition of MeLi to the carbonyl groups of the bis(spirodienone) calixarene derivatives is stereospecific, and in the case of 5B , X-ray analysis indicated that the product derives from the attack to the carbonyl face anti to the spiro oxygen . Reaction of a (racemic) solution of 6 in THF with NaBH 4 proceeded rapidly, and the yellow color of the solution (typical of the spirodienone derivatives) was discharged in minutes yielding 7 .…”

Spirodienone and Bis(spirodienone) Derivatives of Calix[4]naphthalenes

“…As a result, the carbonyl functionalities can be modified by a variety of different methods to effectively result in selective hydroxyl replacements of the parent calix[4]arenes. Biali et al have thus been able to replace the intraannular hydroxyls with hydrogens, amino, halogens, and methyl groups. Besides their synthetic utility, these spirodienones are interesting per se in that up to two stereogenic centers are generated from calix[4]arenes, resulting in the isomerism observed and depicted in compounds 2−4 .…”

Extraannular Fluorinated Calixarenes: Regiospecificity of the Deoxofluorination Reactions of Bis(spirodienol) Derivatives

“…The downfield shift of the OH groups of 3c (compared to those of 3a and 3b ) is also consistent with exo attack, since it suggests an intramolecular hydrogen bond interaction, and only when directed to the central part of the macrocycle can the two OH groups be engaged in such a bond . The observed selectivity of the hydride delivery for the exo face is reasonable, since this is the less hindered face, and reactions of a dioxamethylene monospirodienone derivative with NaBH 4 and of the bis(spirodienone) 2b with MeLi have been shown to proceed via attack at the exo faces of the carbonyl groups.…”