Synthesis of Calix[4]pyrrolidine, Calix[m]tetrahydrofuran[n]pyrrolidine (m+n=4) and Similar Macrocyclic Systems - Elucidation of the Hydrogenation Sequence and Factors Influencing the Stereoselectivity

he first meso-octaalkylporphyrinogen (calix[4]pyrrole) was synthesized by Baeyer more than 120 years ago, mixing pyrrole and acetone in the presence of an acid. 92 First proposed by Chelintzev et al., the correct structure was definitively proven by Rothemund in 1955, 93, 94 followed forty years later by the X-ray analysis. 95 This macrocycle could be obtained in gram scale and in very good yield. We have performed a thorough study of the catalytic hydrogenation of calix[4]pyrrole 1, by using common as well as novel heterogeneous catalysts based on transition metals (Pd, Rh, Ru) supported on solid matrices 129 . During our studies, we were able to isolate and identify two half-hydrogenated products, 12a and 12b. A single, all-cis, fully hydrogenated compound 13 could be obtained in low yields only under drastic reaction conditions (100 atm of hydrogen pressure at 100 °C in acetic acid) (Scheme 11). Gas chromatographic analysis of the heterogeneously catalyzed hydrogenation reactions of calix[4]pyrrole 1 allowed to determine the composition of the reaction mixtures. The relative configuration of the three products has been unequivocally determined by single crystal X-ray diffraction. 129, 130 The reduced calix[4]pyrrole 13 reacts smoothly with transition metals to form new organometallic complexes with a large range of transition metals. The manganese complex has shown to possess interesting catalytic activity for oxidation processes. 131 T