Organocatalysts Fold To Generate an Active Site Pocket for the Mannich Reaction

Catalysts containing urea, thiourea, and tertiary amine groups fold into a three-dimensional organized structure in solution both in the absence as well as in the presence of substrates or substrate analogues, as indicated by solution NMR and computational studies. These foldamer catalysts promote Mannich reactions with both aliphatic and aromatic imines and malonate esters. Hammett plot and secondary kinetic isotope effects provide evidence for the C–C bond forming event as the turnover-limiting step of the Mannich reaction. Computational studies suggest two viable pathways for the C–C bond formation step, differing in the activation modes of the malonate and imine substrates. The results show that the foldamer catalysts may promote C–C bond formation with an aliphatic substrate bearing a cyclohexyl group by enhanced binding of the substrates by dispersion interactions, but these interactions are largely absent with a simpler catalyst. Additional control experiments demonstrate the ability of simple thiourea catalysts to promote competing side reactions with aliphatic substrates, such as reversible covalent binding of the thiourea sulfur to the imine which deactivates the catalyst, and imine to enamine isomerization reactions. In foldamer catalysts, the nucleophilicity of sulfur is reduced, which prevents catalyst deactivation. The results indicate that the improved catalytic performance of foldamer catalysts in Mannich reactions may not be due to cooperative effects of intramolecular hydrogen bonds but simply due to the presence of the folded structure that provides an active site pocket, accommodating the substrate and at the same time impeding undesirable side reactions

The effects of environmental pollutants on human cells

Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Facies organiche nel Giurassico inferiore del dominio tetideo: sedimentologia organica e biostratigrafia a cisti di dinoflagellati

Dottorato di ricerca in scienze della terra. 7. ciclo. A.a. 1991-95. Relatore M. Nocchi. Coordinatore G. Pialli. Correlatori U. Biffi e S. CirilliConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Metal-Free sp²‑C–H Borylation as a Common Reactivity Pattern of Frustrated 2‑Aminophenylboranes

C–H borylation is a powerful and atom-efficient method for converting affordable and abundant chemicals into versatile organic reagents used in the production of fine chemicals and functional materials. Herein we report a facile C–H borylation of aromatic and olefinic C–H bonds with 2-aminophenylboranes. Computational and experimental studies reveal that the metal-free C–H insertion proceeds via a frustrated Lewis pair mechanism involving heterolytic splitting of the C–H bond by cooperative action of the amine and boryl groups. The adapted geometry of the reactive B and N centers results in an unprecedentently low kinetic barrier for both insertion into the sp²-C–H bond and intramolecular protonation of the sp²-C–B bond in 2-ammoniophenyl­(aryl)- or -(alkenyl)­borates. This common reactivity pattern serves as a platform for various catalytic reactions such as C–H borylation and hydrogenation of alkynes. In particular, we demonstrate that simple 2-aminopyridinium salts efficiently catalyze the C–H borylation of hetarenes with catecholborane. This reaction is presumably mediated by a borenium species isoelectronic to 2-aminophenylboranes

Chiral Molecular Tweezers: Synthesis and Reactivity in Asymmetric Hydrogenation

We report the synthesis and reactivity of a chiral aminoborane displaying both rapid and reversible H₂ activation. The catalyst shows exceptional reactivity in asymmetric hydrogenation of enamines and unhindered imines with stereoselectivities of up to 99% ee. DFT analysis of the reaction mechanism pointed to the importance of both repulsive steric and stabilizing intermolecular non-covalent forces in the stereodetermining hydride transfer step of the catalytic cycle

Cross-Dehydrogenative Couplings between Indoles and β‑Keto Esters: Ligand-Assisted Ligand Tautomerization and Dehydrogenation via a Proton-Assisted Electron Transfer to Pd(II)

Cross-dehydrogenative coupling reactions between β-ketoesters and electron-rich arenes, such as indoles, proceed with high regiochemical fidelity with a range of β-ketoesters and indoles. The mechanism of the reaction between a prototypical β-ketoester, ethyl 2-oxocyclopentanonecarboxylate, and <i>N</i>-methylindole has been studied experimentally by monitoring the temporal course of the reaction by ¹H NMR, kinetic isotope effect studies, and control experiments. DFT calculations have been carried out using a dispersion-corrected range-separated hybrid functional (ωB97X-D) to explore the basic elementary steps of the catalytic cycle. The experimental results indicate that the reaction proceeds via two catalytic cycles. Cycle A, the dehydrogenation cycle, produces an enone intermediate. The dehydrogenation is assisted by <i>N</i>-methylindole, which acts as a ligand for Pd­(II). The computational studies agree with this conclusion, and identify the turnover-limiting step of the dehydrogenation step, which involves a change in the coordination mode of the β-keto ester ligand from an <i>O</i>,<i>O</i>′-chelate to an α-C-bound Pd enolate. This ligand tautomerization event is assisted by the π-bound indole ligand. Subsequent scission of the β′-C–H bond takes place via a proton-assisted electron transfer mechanism, where Pd­(II) acts as an electron sink and the trifluoroacetate ligand acts as a proton acceptor, to produce the Pd(0) complex of the enone intermediate. The coupling is completed in cycle B, where the enone is coupled with indole. Pd­(TFA)₂ and TFA-catalyzed pathways were examined experimentally and computationally for this cycle, and both were found to be viable routes for the coupling step

Stereocontrol in Diphenylprolinol Silyl Ether Catalyzed Michael Additions: Steric Shielding or Curtin–Hammett Scenario?

The enantioselectivity of amine-catalyzed reactions of aldehydes with electrophiles is often explained by simple steric arguments emphasizing the role of the bulky group of the catalyst that prevents the approach of the electrophile from the more hindered side. This standard steric shielding model has recently been challenged by the discovery of stable downstream intermediates, which appear to be involved in the rate-determining step of the catalytic cycle. The alternative model, referred to as the Curtin–Hammett scenario of stereocontrol, assumes that the enantioselectivity is related to the stability and reactivity of downstream intermediates. In our present computational study, we examine the two key processes of the catalytic Michael reaction between propanal and β-nitrostyrene that are relevant to the proposed stereoselectivity models, namely the C–C bond formation and the protonation steps. The free energy profiles obtained for the pathways leading to the enantiomeric products suggest that the rate- and stereodetermining steps are not identical as implied by the previous models. The stereoselectivity can be primarily controlled by C–C bond formation even though the reaction rate is dictated by the protonation step. This kinetic scheme is consistent with all observations of experimental mechanistic studies including those of mass spectrometric back reaction screening experiments, which reveal a mismatch between the stereoselectivity of the back and the forward reactions