The dehydration of glucose and other hexose carbohydrates to 5-(hydroxymethyl)furfural (HMF) was investigated in imidazolium-based ionic liquids with boric acid as a promoter. A yield of up to 42% from glucose and as much as 66% from sucrose was obtained. The yield of HMF decreased as the concentration of boric acid exceeded one equivalent, most likely as a consequence of stronger fructose-borate chelate complexes being formed. Computational modeling with DFT calculations confirmed that the formation of 1:1 glucose-borate complexes facilitated the conversion pathway from glucose to fructose. Deuterium-labeling studies elucidated that the isomerization proceeded via an ene-diol mechanism, which is different to that of the enzyme-catalyzed isomerization of glucose to fructose. The introduced non-metal system containing boric acid provides a new direction in the search for catalyst systems allowing efficient HMF formation from biorenewable sources.

The mechanism for the palladium-catalyzed allylic C–H activation was investigated using a combination of experimental and theoretical methods. A Hammett study revealed a buildup of a partial negative charge in the rate-determining step, and determination of the kinetic isotope effect (KIE) indicated that the C–H bond is broken in the turnover-limiting transition state. These experimental findings were further substantiated by carrying out a detailed density functional theory (DFT)-based investigation of the entire catalytic cycle. The DFT modeling supports a mechanism in which a coordinated acetate acts as a base in an intramolecular fashion during the C–H activation step. The reoxidation of palladium was found to reach an energy level similar to that of the C–H activation. Calculations of turnover frequencies for the entire catalytic cycle for the C–H alkylation were used to acquire a better understanding of the experimental KIE value. The good correspondence between the experimental KIE and the computed KIE values allows discrimination between scenarios where the acetate is acting in an intramolecular fashion (C–H alkylation) and an intermolecular fashion (C–H acetoxylation and C–H amination).

The mechanism of the Kharasch-Sosnovsky reaction has been investigated using B3 LYP/6-31G* calculations on a chiral reaction model [cyclohexene+tert-butyl perbenzoate-->cyclohex-2-enyl benzoate+tert-butyl alcohol, catalyzed by a chiral bisoxazoline-copper(I) complex]. Although two previous reaction mechanisms have been considered, the results are consistent with a new mechanistic pathway. This path involves ligand exchange between the catalyst-cyclohexene complex with tert-butyl perbenzoate to give a catalyst-perester complex, which undergoes an (either one- or two-step) oxidative addition reaction to yield a copper(III) complex. The limiting step of the Kharasch-Sosnovsky reaction consists of an intramolecular step involving the abstraction of an allylic hydrogen from cyclohexene [which is pi-bound to the copper(III) complex]. The resulting allyl-copper(III) complex (subsequent to the loss of tert-butanol) can undergo a haptotropic rearrangement by means of an eta1-allyl/eta3-allyl equilibrium, leading to scrambling between vinylic and allylic positions when an isotopically labeled substrate is used. The allyl-copper(III) ion undergoes a stereospecific reductive elimination involving the pi-bond migration to yield a reaction product-catalyst complex, which can regenerate the alkene-copper(I) complex by ligand exchange. The proposed reaction mechanism is consistent with all known experimental results (including enantioselectivity data).

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The combination of chiral preparative HPLC separation, VCD measurements, and theoretical calculations allows the unambiguous determination of the absolute configuration of the conformationally flexible products of copper-catalyzed carbene insertion reactions. DFT calculations were used to predict the stereochemical outcome of the copper-bis(oxazoline)-catalyzed C-H insertion reaction between methyl diazophenylacetate and tetrahydrofuran and also to predict the absolute configuration of the major stereoisomers derived from the same reaction with different cyclic ethers. These predictions were verified experimentally through NMR and VCD spectroscopy and allowed rationalization of the stereochemical outcome of these reactions without further derivatization of the products, which can be prblematic under certain conditions as described herein.