Kinetic and Binding Studies Reveal Cooperativity and Off-Cycle Competition for H-Bonding Catalysis with Silsesquioxane Silanols.

The catalytic activity, kinetics, and quantification of H-bonding ability of incompletely condensed polyhedral oligomeric silsesquioxane (POSS) silanols are reported. POSS-triols, a homogeneous model for vicinal silica surface sites, exhibit enhanced H-bonding compared with other silanols and alcohols as quantified using a 31 P NMR probe. Evaluation of a Friedel-Crafts addition reaction shows that phenyl-POSS-triol is active as an H-bond donor catalyst whereas other POSS silanols studied are not. An in-depth kinetic study (using RPKA and VTNA) highlights the concentration-dependent H-bonding behavior of POSS-triols, which is attributed to intermolecular association forming an off-cycle dimeric species. Binding constants provide additional support for reduced H-bond ability at higher concentrations, which is attributed to competitive association. POSS-triol self-association disrupts H-bond donor abilities relevant for catalysis by reducing the concentration of active monomeric catalyst.

NMR Quantification of Hydrogen-Bond-Activating Effects for Organocatalysts including Boronic Acids.

The hydrogen-bonding activation for 66 organocatalysts has been quantified using a 31P NMR binding experiment with triethylphosphine oxide (TEPO). Diverse structural classes, including phenols, diols, silanols, carboxylic acids, boronic acids, and phosphoric acids, were examined with a variety of steric and electronic modifications to understand how the structure and secondary effects contribute to hydrogen-bonding ability and catalysis. Hammett plots demonstrate high correlation for the Δδ 31P NMR shift to Hammett parameters, establishing the ability of TEPO binding to predict electronic trends. Upon correlation to catalytic activity in a Friedel-Crafts addition reaction, data demonstrate that 31P NMR shifts correlate to catalytic activity better than p Ka values. Boronic acids were investigated, and 31P NMR binding experiments predicted strong hydrogen-bonding ability, for which catalytic activity was confirmed, resulting in the greatest rate enhancement observed in the Friedel-Crafts addition of all organocatalysts studied. A detailed investigation supports that boronic acid activation proceeds through hydrogen-bonding interactions and not coordination with the Lewis acidic boron center. Using 31P NMR spectroscopy offers a simple and rapid tool to quantify and predict hydrogen-bonding abilities for the design and applications of new organocatalysts and supramolecular synthons.

Reaction Progress Kinetics Analysis of 1,3-Disiloxanediols as Hydrogen-Bonding Catalysts.

1,3-Disiloxanediols are effective hydrogen-bonding catalysts that exhibit enhanced activity relative to silanediols and triarylsilanols. The catalytic activity for a series of 1,3-disiloxanediols, including naphthyl-substituted and unsymmetrical siloxanes, has been quantified and compared relative to other silanol and thiourea catalysts using the Friedel Crafts addition of indole to trans-ß-nitrostyrene. An in-depth kinetic study using reaction progress kinetic analysis (RPKA) has been performed to probe the catalyst behavior of 1,3-disiloxanediols. The data confirm that the disiloxanediol-catalyzed addition reaction is first order in catalyst over all concentrations studied with no evidence of catalyst self-association. 1,3-Disiloxanediols proved to be robust and recoverable catalysts with no deactivation under reaction conditions. No product inhibition is observed, and competitive binding studies with nitro-containing additives suggest that 1,3-disiloxanediols bind weakly to nitro groups but are strongly activating for catalysis.

Synthesis of Structurally Varied 1,3-Disiloxanediols and Their Activity as Anion-Binding Catalysts.

A series of new 1,3-disiloxanediols has been synthesized, including naphthyl-substituted and unsymmetrical siloxanes, and demonstrated as a new class of anion-binding catalysts. In the absence of anions, diffusion-ordered spectroscopy (DOSY) displays self-association of 1,3-disiloxanediols through hydrogen-bonding interactions. Binding constants determined for 1,3-disiloxanediol catalysts indicate strong hydrogen-bonding and anion-binding abilities with unsymmetrical siloxanes displaying different hydrogen-bonding abilities for each silanol group.