Petr Slavík

Unprecedented meta-substitution of calixarenes: direct way to inherently chiral derivatives.

Electrophilic aromatic substitution in the calix[n]arene series is a well-established procedure leading exclusively to para-substituted derivatives. An unprecedented regioselectivity of the mercuration reaction leading to the meta-substituted calix[4]arenes is described. These compounds represent a new type of substitution pattern in classical calixarene chemistry and open the door for the straightforward synthesis of inherently chiral receptors based on calixarenes.

meta-Bridged calix[4]arenes: a straightforward synthesis via organomercurial chemistry

The regioselective mercuration of tetraalkylated calix[4]arenes with Hg(OCOCF3)2 leads to the formation of meta-substituted products which enabled Pd-catalysed intramolecular bridging within the calixarene skeleton. Bridged derivatives represent a completely novel substitution pattern in calixarene chemistry with extremely distorted cavities and possible applications in supramolecular chemistry.

Intramolecularly Bridged Calix[4]arenes with Pronounced Complexation Ability toward Neutral Compounds

Regioselective derivatization via an organomercury intermediate allowed for the introduction of carboxylic acid functionality into the meta position of the calix[4]arene skeleton. Intramolecular Friedel-Crafts cyclization led to a novel type of calixarene containing a ketone bridging moiety. Subsequent attack of the ketone by organometallic compounds occurred selectively from outside providing tertiary alcohols with the OH group oriented inside the cavity. These compounds can complex neutral molecules both in the solid state (X-ray) and in solution (NMR) using the cooperative effect of hydrogen bonding (OH) and CH-π interactions from within the cavity.

Inherently Chiral Upper-Rim-Bridged Calix[4]arenes Possessing a Seven Membered Ring

The mercuration of calix[4]arene immobilized in the cone conformation allowed the introduction of an amino group at the meta position of the basic skeleton. Acylation and subsequent intramolecular Bischler-Napieralski-type cyclization led to a novel type of bridged calixarene containing a seven-membered ring. These compounds with an enlarged and rigidified cavity represent a unique and inherently chiral system that may potentially be applicable for the design of chiral receptors. The absolute configuration of one enantiomer, obtained by resolution of the racemate using chiral HPLC, was assigned by single-crystal structure determination.

Shaping of calix[4]arenes via double bridging of the upper rim

Direct double meta-mercuration can be used for subsequent bridging of a calix[4]arene skeleton via the installation of ketone moieties. This unprecedented substitution pattern in calixarene chemistry possesses a heavily distorted and rigid cavity capable of interactions with selected molecular guests as documented by binding of a CH2Cl2 molecule held in place by an intricate net of 10 specific (halogen bonding and hydrogen bonding) interactions from two neighbouring calixarene molecules.

meta-Bridged calix[4]arenes prepared by Friedel–Crafts alkylation

By applying electrophilic aromatic mercuration of calix[4]arene the introduction of substituted hydroxymethyl groups at the meta position of the basic skeleton has been achieved. Subsequent intramolecular Friedel–Crafts alkylation led to a novel type of bridged calix[4]arenes with additional symmetrically substituted methylene bridges connecting to the neighbouring aromatic units. Additionally, this new efficient synthetic pathway was also used for the preparation of a double bridged analogue. These compounds with rigidified cavities can complex cations and neutral compounds using CH–π and/or cation–π interactions as demonstrated by 1H NMR titration experiments.

Introducing an amine group to calix[5]arene: comparison of several methods

Abstract Chemists often use an amine group as an intermediate in syntheses of imines, amides and ureas; however, in the case of syntheses of p-aminophenol type compounds, several problems might occur. In this article, we prepared p-aminocalix[5]arene-pentaol by reduction of both nitro and azo derivatives, and compared four methods of the amine preparation, focusing mainly on its gramme scale and time-consuming issues.

meta-Bridged calix[4]arenes with the methylene moiety possessing in/out stereochemistry of substituents

meta-Substituted organomercury calix[4]arenes and their corresponding iodo derivatives have been used for lithiation followed by a reaction with various aldehydes or ketones. The resulting diastereomers were in some cases separable using simple column chromatography. Subsequent intramolecular Friedel–Crafts alkylation led to calix[4]arenes with an additional methylene bridge bearing two different substituents with in/out (relative to the cavity) stereochemistry. Our results indicate that the stereochemistry of the final cyclised product does not depend on the structure/stereochemistry of the starting compound, but rather it is influenced by the stability of the products. The relationship between the positions of these substituents and the complexation properties was demonstrated by 1H NMR titration experiments with N-methylpyridinium iodide.

CCDC 1542922: Experimental Crystal Structure Determination

Related Article: Martin Tlustý, Petr Slavik, Michal Kohout, Vaclav Eigner, and Pavel Lhotak|2017|Org.Lett.|19|2933|doi:10.1021/acs.orglett.7b01170