Dimerization of confined Brønsted acids in enantioselective organocatalytic reactions.

The formation of Brønsted acid aggregates in the course of asymmetric organocatalytic reactions is often overlooked in mechanistic studies, even though it might have a deep impact on the stereo-controlling factors of the transformations. In this work, we shed light on the influence of the catalyst structure and reaction conditions on the spontaneity of the aggregation process for popular chiral organocatalysts derived from phosphoric acids using high-level quantum mechanical calculations. Our study encompasses small and sterically unhindered chiral phosphoric acids as well as large and "confined" imidodiphosphates and imidodiphosphorimidates. These systems have recently proven particularly effective in promoting a large number of highly relevant asymmetric transformations. While cooperative catalytic effects of sterically less hindered chiral phosphoric acid catalysts are well appreciated in literature, it is found that the formation of catalyst dimers in solution is possible for both standard and confined catalysts. The spontaneity of the aggregation process depends on reaction conditions like solvent polarity, polarizability, temperature, the nature of the interaction with the substrate, as well as the catalyst architecture. Finally, it is shown that, at low temperatures (153 K), the aggregation process can profoundly influence the reaction kinetics and selectivity.

Exploring the Limits of Intramolecular London Dispersion Stabilization with Bulky Dispersion Energy Donors in Alkane Solution.

We present an experimental study of a cyclooctatetraene-based molecular balance disubstituted with increasingly bulky tert-butyl (tBu), adamantyl (Ad), and diamantyl (Dia) substituents in the 1,4-/1,6-positions for which we determined the valence-bond shift equilibrium in n-hexane (hex), n-octane (oct), and n-dodecane (dod). Computations including implicit and explicit solvation support our temperature-dependent NMR equilibrium measurements indicating that the more sterically crowded 1,6-isomer is always favored, irrespective of solvent, and that the free energy is quite insensitive to substituent size.

An induced-fit model for asymmetric organocatalytic reactions: a case study of the activation of olefins via chiral Brønsted acid catalysts.

We elucidate the stereo-controlling factors of the asymmetric intramolecular hydroalkoxylation of terminal olefins catalyzed by bulky Brønsted acids [Science 2018, 359 (6383), 1501-1505] using high-level electronic structure methods. The catalyst-substrate interaction is described using a dispersion-driven induced-fit model, in which the conformational changes of the catalyst and of the substrate in the transition states are governed to a large extent by London dispersion forces. The distortion energy of the catalyst is dominated by the change in the intramolecular dispersion interactions, while intermolecular catalyst-substrate dispersion interactions are the major stabilizing contribution in the transition state. This model provides a new general framework in which to discuss the stereoselectivity of transformations catalyzed by such confined organocatalysts.

A Combined Spectroscopic and Computational Study on the Mechanism of Iron-Catalyzed Aminofunctionalization of Olefins Using Hydroxylamine Derived N-O Reagent as the "Amino" Source and "Oxidant".

Herein, we study the mechanism of iron-catalyzed direct synthesis of unprotected aminoethers from olefins by a hydroxyl amine derived reagent using a wide range of analytical and spectroscopic techniques (Mössbauer, Electron Paramagnetic Resonance, Ultra-Violet Visible Spectroscopy, X-ray Absorption, Nuclear Resonance Vibrational Spectroscopy, and resonance Raman) along with high-level quantum chemical calculations. The hydroxyl amine derived triflic acid salt acts as the "oxidant" as well as "amino" group donor. It activates the high-spin Fe(II) (St = 2) catalyst [Fe(acac)2(H2O)2] (1) to generate a high-spin (St = 5/2) intermediate (Int I), which decays to a second intermediate (Int II) with St = 2. The analysis of spectroscopic and computational data leads to the formulation of Int I as [Fe(III)(acac)2-N-acyloxy] (an alkyl-peroxo-Fe(III) analogue). Furthermore, Int II is formed by N-O bond homolysis. However, it does not generate a high-valent Fe(IV)(NH) species (a Fe(IV)(O) analogue), but instead a high-spin Fe(III) center which is strongly antiferromagnetically coupled (J = -524 cm-1) to an iminyl radical, [Fe(III)(acac)2-NH·], giving St = 2. Though Fe(NH) complexes as isoelectronic surrogates to Fe(O) functionalities are known, detection of a high-spin Fe(III)-N-acyloxy intermediate (Int I), which undergoes N-O bond cleavage to generate the active iron-nitrogen intermediate (Int II), is unprecedented. Relative to Fe(IV)(O) centers, Int II features a weak elongated Fe-N bond which, together with the unpaired electron density along the Fe-N bond vector, helps to rationalize its propensity for N-transfer reactions onto styrenyl olefins, resulting in the overall formation of aminoethers. This study thus demonstrates the potential of utilizing the iron-coordinated nitrogen-centered radicals as powerful reactive intermediates in catalysis.