Mid Sweden University

The existence of off-cycle catalyst cooperativity in amine/metal combined catalysis is disclosed. The experimental and density functional theory study of the amine/metal co-catalyzed enantioselective Michael/carbocyclization cascade reaction between allenes and alpha,beta-unsaturated aldehydes reveals that the dual catalysts can perform off-cycle cooperativity that gives access to stable bicyclo[3.2.0]heptane species that limits the carbocycle product formation. Insight into this mode of co-catalyst cooperativity sheds new light on the chiral amine/metal co-catalyzed reactions of to date and gives deeper understanding for improved future design of this type of enantioselective reactions.

The ability of intermolecular cooperative thiourea/oxime hydrogen-bond catalysis for improving and accelerating asymmetric aminocatalysis is presented. The two readily available hydrogen-bond-donating catalysts operates in synergy with a chiral amine catalyst to accomplish highly stereoselective transformations. The synergistic catalyst systems simultaneously activate both electrophiles and nucleophiles, and make the transformations more chemo- and stereoselective. This was exemplified by performing co-catalytic enantioselective direct intermolecular α-alkylation reactions of aldehydes, direct aldol reactions, and asymmetric conjugate reactions, which gave the corresponding products in high yields and enantiomeric ratios.

An efficient heterogeneous palladium-catalyzed transfer hydrogenolysis of primary, secondary, and tertiary benzylic alcohols using formic acid as hydrogen source has been developed. The resulting hydrocarbon products were obtained in excellent yields. Moreover, the system exhibits high chemoselectivity, reacting only with the hydroxy groups in the presence of other functional groups, and excellent recyclability.

A new eco-friendly approach for the preparation of sustainable heterogeneous palladium catalysts from rice husk-derived biogenic silica (RHP-Si and RHU-Si). The designed heterogeneously supported palladium species (RHP-Si-NH2-Pd and RHU-Si-NH2-Pd) were fully characterized and successfully employed as catalysts for various chemical transformations (C–C bond-forming reactions, aerobic oxidations and carbocyclizations). Suzuki-Miyaura transformations were highly efficient in a green solvent system (H2O:EtOH (1:1) with excellent recyclability, providing the cross-coupling products with a wide range of functionalities in high isolated yields (up to 99%). Palladium species (Pd(0)-nanoparticles or Pd(II)) were also efficient catalysts in the green aerobic oxidation of an allylic alcohol and a co-catalytic stereoselective cascade carbocyclization transformation. In the latter case, a quaternary stereocenter was formed with excellent stereoselectivity (up to 27:1 dr). 

A sustainable strategy for the neat production and surface functionalization of nanocellulose from wood pulp is disclosed. It is based on the combination of organocatalysis and click chemistry ("organoclick" chemistry) and starts with nanocellulose production by organic acid catalyzed hydrolysis and esterification of the pulp under neat conditions followed by homogenization. This nanocellulose fabrication route is scalable, reduces energy consumption and the organic acid can be efficiently recycled. Next, the surface is catalytically engineered by "organoclick" chemistry, which allows for selective and versatile attachment of different organic molecules (e.g. fluorescent probes, catalyst and pharmaceuticals). It also enables binding of metal ions and nanoparticles. This was exemplified by the fabrication of a heterogeneous nanocellulose-palladium nanoparticle catalyst, which is used for Suzuki cross-coupling transformations in water. The disclosed surface functionalization methodology is broad in scope and applicable to different nanocelluloses and cellulose based materials as well.

The present invention relates generally to an eco-friendly methodology for the conversion of alcohols and aldehydes to amines and amides using an integrated enzyme cascade system with metal-and organocatalysis. More specifically, the present invention relates to synthesis of capsaicinoids starting from vanillin alcohol and using a combination of an enzyme cascade system and catalysts. Furthermore, the method also relates to synthesis of capsaicinoids derivatives starting from vanillin alcohol derivatives and using a combination of an enzyme cascade system and catalysts.

The concept of merging enamine activation catalysis with transition metal catalysis is an important strategy, which allows for selective chemical transformations not accessible without this combination. The amine catalyst activates the carbonyl compounds through the formation of a reactive nucleophilic enamine intermediate and, in parallel, the transition metal activates a wide range of functionalities such as allylic substrates through the formation of reactive electrophilic π-allyl-metal complex. Since the first report of this strategy in 2006, considerable effort has been devoted to the successful advancement of this technology. In this chapter, these findings are highlighted and discussed. 

A method of reducing a C--O bond to the corresponding C--H bond in a substrate, which could be a benzylic alcohol, allylic alcohol, ester or an ether bond beta to a hydroxyl group or alpha to a carbonyl group using a recyclable metal catalyst system. The recyclable catalyst system is also applicable to reducing a C.dbd.O bond to the corresponding C--OH bond and then C--H bond. These methodologies can be linked in one-pot to selective oxidation and depolymerizations of aromatic polyols such as lignin.

A mild and efficient synthesis of primary amines and amides from aldehydes or ketones using a heterogeneous metal catalyst and amine donor is disclosed. The initial heterogeneous metal-catalyzed reaction between the carbonyl and the amine donor components is followed by the addition of a suitable acylating agent component in one-pot, thus providing a catalytic one-pot three-component synthesis of amides. Integration of enzyme catalysis allows for eco-friendly one-pot co-catalytic synthesis of amides from aldehyde and ketone substrates, respectively. The process can be applied to asymmetric synthesis or to the co-catalytic one-pot three-component synthesis of capsaicin and its analogues from vanillin or vanillyl alcohol. A co-catalytic reductive amination/dynamic kinetic resolution (dkr) relay sequence for the asymmetric synthesis of optically active amides from ketones is disclosed. Implementation of a catalytic reductive amination/kinetic resolution (kr) relay sequence produces the corresponding optically active amide product and optical active primary amine product with the opposite stereochemistry from the starting ketones.

Tropanes are an important class of alkaloid natural products that are found in plants all over the world. These compounds can exhibit significant biological activity and are among the oldest known medicines. In the early 19th century, tropanes were isolated, characterized, and synthesized by notable chemical researchers. Their significant biological activities have inspired tremendous research efforts toward their synthesis and the elucidation of their pharmacological activity both in academia and in industry. In this chapter, which addresses the developments in this field since 1994, the focus is on the synthesis of these compounds, and several examples of sophisticated synthetic protocols involving both asymmetric and catalytic approaches are described. In addition, the structures of more than 100 new alkaloids are included as well as the applications and pharmacological properties of some tropane alkaloids.