Strain-Based Design, Direct Macrocyclization, and Metal Complexation of Thiazole-Containing Calix[3]pyrrole Analogues

Coordination chemistry of ring-contracted porphyrins, such as subporphyrin and calix[3]pyrrole, has been largely unexplored due 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 AFIR method and StrainViz analysis were used to perform a conformational search and evaluate/visualize ring strain, respectively. The results indicated that thiazole-containing analogues are less strained than the parent calix[3]pyrrole, while incorporation of imidazole or oxazole unexpectedly leads to an increase in total strain. In fact, calix[1]furan[2]thiazole was obtained in 60% yield by direct macrocyclization between α-bromoketone and bis(thioamide), whereas meso-N(sp2)-bridged analogue, which was calculated to be more strained by 5.1 kcal/mol, was obtained only in a 2% yield. Calix[1]furan[2]thiazole was converted to calix[1]pyrrole[2]thiazole for investigation of metal complexation. Through reaction with Et2Zn, calix[1]pyrrole[2]thiazole bound a Zn(II) ion in a tridentate fashion adopting a cone conformation, furnishing water/air stable organozinc complex that catalyzes polymerization of lactide. Whereas, Ag(I) and Pd(II) ions were chelated by partial cone conformation of calix[1]pyrrole[2]thiazole in a bidentate fashion. Strain-based molecular design has expanded the synthetic access to contracted porphyrinoids and opened up the opportunity of their rich coordination chemistry

Zn(OTf)(2)-mediated annulations of N-propargylated tetrahydrocarbolines: divergent synthesis of four distinct alkaloidal scaffolds

Intramolecular hydroarylations of N-propargylated tetrahydrocarbolines were efficiently mediated using a unique combination of Zn(OTf) 2 with t-BuOH under neutral conditions. Use of the artificial force induced reaction method in the global reaction route mapping strategy provided insights into the Zn(OTf) 2-mediated hydroarylations and the associated intriguing solvent effects of t-BuOH facilitating a protodezincation process without a Bronsted acid activator. We systematically implemented three distinct hydroarylations as well as an unanticipated a-alkenylation of a carbonyl group to obtain the four alkaloidal scaffolds 2-4, and 18. Zn(OTf) 2-mediated annulation of 1c proceeded through kinetic formation of the spiroindole 3c followed by an alkenyl shift and concomitant retro-Mannich-type fragmentation to furnish azepino[ 4,5-b] indole 2 framework. Substituents on substrate 1 in the vicinity of the reaction sites substantially affected the mode of the divergent annulations. Judicious choices of the substituents, solvent and reaction conditions enabled programmable divergent synthesis of the four distinct skeletons

Mechanism of 2,6-Dichloro-4,4 '-bipyridine-Catalyzed Diboration of Pyrazines Involving a Bipyridine-Stabilized Boryl Radical

The mechanism of 4,4'-bipyridine-catalyzed diboration of pyrazines was studied by experimental observation of the inter-mediates and by theoretical calculations. Intermediary radical species were detected by ESR measurement of the reactions of 2,6-dichloro-4,4'-bipyridines with bis(pinacolato)diboron and identified by simulation. Based on these observations, radical processes involving 4,4'-bipyridine-stabilized boryl radicals were evaluated by DFT calculations combined with singlecomponent artificial force induced reaction (SC-AFIR). The results of calculations indicate that a radical transfer process from 4,4'-bipyridine-stabilized boryl radical to pyrazine is a major pathway in the catalytic reaction. The origin of the high catalytic efficiency of 2,6-dichloro-4,4'-bipyridine is ascribed to the effect of the chlorine atom on the stability of the corresponding N,N'-diboryl-4,4'-bipyridinylidene

Convergent evolution of the UbiA prenyltransferase family underlies the independent acquisition of furanocoumarins in plants

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