Impact of Backbone Substitution on Organocatalytic Activity of Sterically Encumbered NHC in Benzoin Condensation.

In this study, we provide a theoretical explanation for the experimentally observed decrease in the organocatalytic activity of N-aryl imidazolylidenes methylated at the C4/5-H positions in the benzoin condensation of aromatic aldehydes. A comparative quantum chemical study of energy profiles for the NHC-mediated benzoin condensation of furfural has revealed a high energy barrier to the formation of the IPrMe-based furanic Breslow intermediate that can be attributed to the negative steric interactions between the imidazole backbone methyl groups and N-aryl substituents.

Adaptive carbonyl umpolung involving a carbanionic carbene Breslow intermediate: an alternative mechanism for NHC-mediated organocatalysis.

Herein, we propose a novel mechanistic model for NHC-mediated carbonyl umpolung which involves the formation of a carbanionic carbene Breslow intermediate (CCBI). We have demonstrated theoretically that this reactive intermediate can be formed by inserting an aldehyde into the C4-H position of an N-aryl-substituted imidazolium-derived NHC via the generation of an H-bonded ditopic carbanionic NHC (dcNHC). Our DFT study on benzoin condensation has revealed that the mechanism of polarity inversion proceeding through the CCBI may be more energetically favorable than the classical mechanism of umpolung that uses the C2 carbene position in NHC. The potential existence of the CCBI highlights the dynamic and adaptive nature of NHC-mediated organocatalysis, particularly in relation to carbonyl umpolung. This finding also sheds light on new pathways in organocatalytic transformations employing the ambident reactivity of NHC, which may be particularly attractive for reactions involving furanic aldehydes and sterically encumbered N-aryl-substituted carbenes.

Intermolecular Diels-Alder Cycloadditions of Furfural-Based Chemicals from Renewable Resources: A Focus on the Regio- and Diastereoselectivity in the Reaction with Alkenes.

A recent strong trend toward green and sustainable chemistry has promoted the intensive use of renewable carbon sources for the production of polymers, biofuels, chemicals, monomers and other valuable products. The Diels-Alder reaction is of great importance in the chemistry of renewable resources and provides an atom-economic pathway for fine chemical synthesis and for the production of materials. The biobased furans furfural and 5-(hydroxymethyl)furfural, which can be easily obtained from the carbohydrate part of plant biomass, were recognized as "platform chemicals" that will help to replace the existing oil-based refining to biorefining. Diels-Alder cycloaddition of furanic dienes with various dienophiles represents the ideal example of a "green" process characterized by a 100% atom economy and a reasonable E-factor. In this review, we first summarize the literature data on the regio- and diastereoselectivity of intermolecular Diels-Alder reactions of furfural derivatives with alkenes with the aim of establishing the current progress in the efficient production of practically important low-molecular-weight products. The information provided here will be useful and relevant to scientists in many fields, including medical and pharmaceutical research, polymer development and materials science.

The Increasing Value of Biomass: Moving From C6 Carbohydrates to Multifunctionalized Building Blocks via 5-(hydroxymethyl)furfural.

Recent decades have been marked by enormous progress in the field of synthesis and chemistry of 5-(hydroxymethyl)furfural (HMF), an important platform chemical widely recognized as the "sleeping giant" of sustainable chemistry. This multifunctional furanic compound is viewed as a strong link for the transition from the current fossil-based industry to a sustainable one. However, the low chemical stability of HMF significantly undermines its synthetic potential. A possible solution to this problem is synthetic diversification of HMF by modifying it into more stable multifunctional building blocks for further synthetic purposes.

Ambident Reactivity of Imidazolium Cations as Evidence of the Dynamic Nature of N-Heterocyclic Carbene-Mediated Organocatalysis.

This work reveals ambident nucleophilic reactivity of imidazolium cations towards carbonyl compounds at the C2 or C4 carbene centers depending on the steric properties of the substrates and reaction conditions. Such an adaptive behavior indicates the dynamic nature of organocatalysis proceeding via a covalent interaction of imidazolium carbenes with carbonyl substrates and can be explained by generation of the H-bonded ditopic carbanionic carbenes.

When Will 5-Hydroxymethylfurfural, the "Sleeping Giant" of Sustainable Chemistry, Awaken?

Bring on the subs! Biorefining will be realized by using two different approaches: the production of new biobased molecular targets or sustainable access to traditional base and commodity chemicals. Awakening of 5-hydroxymethylfurfural (HMF) can be expected with different probabilities, depending on the approach chosen to create a sustainable future.

Towards Improved Biorefinery Technologies: 5-Methylfurfural as a Versatile C6 Platform for Biofuels Development.

Low chemical stability and high oxygen content limit utilization of the bio-based platform chemical 5-(hydroxymethyl)furfural (HMF) in biofuels development. In this work, Lewis-acid-catalyzed conversion of renewable 6-deoxy sugars leading to formation of more stable 5-methylfurfural (MF) is carried out with high selectivity. Besides its higher stability, MF is a deoxygenated analogue of HMF with increased C/O ratio. A highly selective synthesis of the innovative liquid biofuel 2,5-dimethylfuran starting from MF under mild conditions is described. The superior synthetic utility of MF against HMF in benzoin and aldol condensation reactions leading to long-chain alkane precursors is demonstrated.

Facile Chemical Access to Biologically Active Norcantharidin Derivatives from Biomass.

Reductive amination of 2,5-diformylfuran (DFF) was used to implement the transition from bio-derived 5-hydroxymethylfurfural (HMF) to pharmaceuticals. The synthesized bis(aminomethyl)furans were utilized as building blocks for the construction of new derivatives with structural cores of naturally occurring biologically active compounds. Using the one-pot procedure, which included the Diels-Alder reaction followed by hydrogenation of the double bond, bio-derived analogues of the anticancer drug norcantharidin were obtained. The cyclization process was diastereoselective, and resulted in the formation of tricyclic products with the endo configuration. Analysis of cytotoxycity for the resulting tricyclic amine-containing compounds showed an increase of anticancer activity as compared with the unsubstituted norcantharimide.

Critical Influence of 5-Hydroxymethylfurfural Aging and Decomposition on the Utility of Biomass Conversion in Organic Synthesis.

Spectral studies revealed the presence of a specific arrangement of 5-hydroxymethylfurfural (5-HMF) molecules in solution as a result of a hydrogen-bonding network, and this arrangement readily facilitates the aging of 5-HMF. Deterioration of the quality of this platform chemical limits its practical applications, especially in synthesis/pharma areas. The model drug Ranitidine (Zantac®) was synthesized with only 15 % yield starting from 5-HMF which was isolated and stored as an oil after a biomass conversion process. In contrast, a much higher yield of 65 % was obtained by using 5-HMF isolated in crystalline state from an optimized biomass conversion process. The molecular mechanisms responsible for 5-HMF decomposition in solution were established by NMR and ESI-MS studies. A highly selective synthesis of a 5-HMF derivative from glucose was achieved using a protecting group at O(6) position.

Direct Observation of Self-Organized Water-Containing Structures in the Liquid Phase and Their Influence on 5-(Hydroxymethyl)furfural Formation in Ionic Liquids.

Water-containing organic solutions are widespread reaction media in organic synthesis and catalysis. This type of multicomponent liquid system has a number of unique properties because of the tendency for water to self-organize in mixtures with other liquids. The characterization of these water domains is a challenging task because of their soft and dynamic nature. In the present study, the morphology and dynamics of micrometer- and nanometer-scale water-containing compartments in ionic liquids were directly observed by electron microscopy. A variety of morphologies, including isolated droplets, dense structures, aggregates, and 2D meshworks, have been experimentally detected and studied. Using the developed method, the impact of water on the acid-catalyzed biomass conversion reaction was studied at the microscopic level. The process that produced nanostructured domains in solution led to better yields and higher selectivities compared with reactions involving the bulk system.