Strain-based design, direct macrocyclization, and metal complexation of thiazole-containing calix[3]pyrrole analogues

Abstract

The coordination chemistry of ring-contracted porphyrinoids, such as subporphyrins and calix[3]pyrroles, has been largely unexplored owing to the synthetic difficulty of their free-base analogues. Here, we report strain-based molecular design and high-yield synthesis of thiazole-containing calix[3]pyrrole analogues for metal complexation. The artificial force induced reaction and StrainViz analysis methods were used to perform a conformational search and evaluate/visualize the ring strain. The results indicated that the thiazole-containing analogues are less strained than the parent calix[3]pyrrole, while incorporation of imidazole or oxazole unexpectedly leads to an increase in the total strain. Calix[1]furan[2]thiazole was obtained in 60% yield by the direct macrocyclization between α-bromoketone and bis(thioamide), whereas the meso-N(sp²)-bridged analogue, which was calculated to be 5.1 kcal mol⁻¹ more strained, was only obtained in a 2% yield. Calix[1]furan[2]thiazole was converted to calix[1]pyrrole[2]thiazole to investigate metal complexation. Through the reaction with Et₂Zn, calix[1]pyrrole[2]thiazole bound a Zn(II) ion in a tridentate fashion adopting a cone conformation, giving a water/air stable organozinc complex that catalyzes polymerization of lactide. Conversely, Ag(I) and Pd(II) ions coordinated to the partial cone conformation of calix[1]pyrrole[2]thiazole in a bidentate fashion. Strain-based molecular design expands the synthetic access to contracted porphyrinoids and provides the opportunity to take advantage of their rich coordination chemistry.