Hydrogenation of Calix[4]pyrrole: From the Formation to the Synthesis of Calix[4]pyrrolidine

Abstract

In memory of François Diederich, a dear friend and an inspiring colleague Calix[4]pyrroles can be obtained from the efficient preprogrammed condensation between acetone and pyrrole. This reaction forms the attractive macrocycle resembling in its constitution, but not in its oxidation state, to the porphyrin structure, prominently present in the vital "pigments of life". Calix[2]pyrrolidine[2]pyrrole and calix[4]pyrrolidine, the partially and totally reduced version of the macrocycle, became accessible through the hydrogenation of calix[4]pyrrole, but only under strenuous reaction conditions. The only known hydrogenation, which could give clues for improving the process, was the reduction of the calix[4]furan. To shed light on the process, mixed calix[n]furan[4-n]pyrroles were prepared, and their hydrogenation was studied. After a laborious optimization process, the best conditions were discovered improving the yield of the hydrogenation process from the level of a formation to the level of a complete conversion. The calix [4]pyrrolidine is now accessible in two high yielding synthetic steps. The efforts to understand and to optimize the factors involved in the hydrogenation process of this perazamacrocycle are here reviewed.

Breaking Azacalix[4]arenes into Induline Derivatives

“…Molecules 2023, 28, x FOR PEER REVIEW 6 of 1 competition between degradation and hydrogenation might occur [46]. Here, we screened conditions for hydrogenation in acidic medium and we indeed observed a competin ring-opening reaction.…”

“…When we started to screen reaction conditions with the hope of finding an experimental procedure for the hydrogenation of azacalixarene 6, we first avoided the use of acids and used hydrogenation on Pd/C and direct air-oxidation which led to molecule 7 Previous works on macrocyclic chemistry reported that in the presence of acids, possible competition between degradation and hydrogenation might occur [46]. Here, we screened conditions for hydrogenation in acidic medium and we indeed observed a competing ring-opening reaction.…”

Recent developments in calix[4]pyrrole (C4P)-based supramolecular functional systems

“…[1][2][3][4][5][6][7][8] Among the numerous supramolecular receptors, 9,10 the non-aromatic tetrapyrrolic synthetic macrocyclic receptor (C4P) has emerged as significant receptor and ligand for diverse purposes owing to its structural variety, easy one-pot synthesis, and recognition ability towards anions, ion-pairs, neutral molecules, and metal ions of fundamental importance. [11][12][13][14][15][16][17][18][19][20][21][22][23] Adolf von Baeyer (1835-1917, a German Chemist, Noble Prize in Chemistry, 1905) is credited for the discovery of the parent C4P in 1886 through the acid-mediated condensation of pyrrole with acetone in a single step (Fig. 1).…”

Poisoning and Reuse of Supported Precious Metal Catalysts in the Hydrogenation of N-Heterocycles, Part II: Hydrogenation of 1-Methylpyrrole over Rhodium

“…Rhodium is often used in the heterogeneous catalytic hydrogenation of pyrroles, typically in a supported form: on activated carbon [24][25][26][31][32][33][34][35], on alumina [24,25,34,[36][37][38][39][40][41][42], or on silica [43]. For instance, 2,5-dimethylpyrrole was reduced to cis-2,5-dimethylpyrrolidine over 5% Rh/Al 2 O 3 (7% by weight of substrate) in acetic acid, at 3 bar and room temperature, with 70% yield [36].…”