Tomas Smejkal

All-Carbon Quaternary Centers via Ruthenium-Catalyzed Hydroxymethylation of 2-Substituted Butadienes Mediated by Formaldehyde: Beyond Hydroformylation

Ruthenium-catalyzed transfer hydrogenation of 2-substituted dienes 1a-i in the presence of paraformaldehyde results in reductive coupling at the 2-position to furnish the hydroxymethylation products 3a-i, which embody all-carbon quaternary centers. Reductive coupling of diene 1g to paraformaldehyde under standard conditions, but employing deuterio-paraformaldehyde, 2-propanol-d(8), or both, corroborated a catalytic mechanism involving rapid, reversible diene hydrometalation with incomplete regioselectivity in advance of C-C coupling. The present method provides an alternative to the hydroformylation of conjugated dienes, for which efficient, regioselective catalytic systems remain undeveloped.

Transition‐State Stabilization by a Secondary Substrate–Ligand Interaction: A New Design Principle for Highly Efficient Transition‐Metal Catalysis

A library of monodentate phosphane ligands, each bearing a guanidine receptor unit for carboxylates, was designed. Screening of the library gave some excellent catalysts for regioselective hydroformylation of beta,gamma-unsaturated carboxylic acids. A terminal alkene, but-3-enoic acid, was hydroformylated with a linear/branched (l/b) regioselectivity up to 41. An internal alkene, pent-3-enoic acid was hydroformylated with regioselectivity up to 18:1. Further substrate selectivity (e.g., acid vs. methyl ester) and reaction site selectivity (monofunctionalization of 2-vinylhept-2-enoic acid) were also achieved. Exploration of the structure-activity relationship and a practical and theoretical mechanistic study gave us an insight into the nature of the supramolecular guanidinium-carboxylate interaction within the catalytic system. This allowed us to identify a selective transition-state stabilization by a secondary substrate-ligand interaction as the basis for catalyst activity and selectivity.

Combined transition-metal- and organocatalysis: an atom economic C3 homologation of alkenes to carbonyl and carboxylic compounds.

A combination of regioselective room-temperature/ambient-pressure hydroformylation (transition-metal catalysis) and decarboxylative Knoevenagel reactions (organocatalysis) allowed for the development of an efficient, one-pot C3 homologation of terminal alkenes to (E)-alpha,beta-unsaturated acids and esters, (E)-beta,gamma-unsaturated acids, (E)-alpha-cyano acrylic acids, and alpha,beta-unsaturated nitriles. All reactions proceed under mild conditions, tolerate a variety of functional groups, and furnish unsaturated carbonyl compounds in good yields and with excellent regio- and stereocontrol. Further, an iterative C2 homologation of (E)-alpha,beta-unsaturated carboxylic acids is possible through a combination of decarboxylative hydroformylation employing a supramolecular catalyst followed by decarboxylative Knoevenagel condensation with an organocatalyst.

Stereoselective oxidation of thiacalix[4]arenes with the NaNO3/CF3COOH system

Abstract A series of alkyl substituted thiacalix[4]arene derivatives (being conformationally mobile or immobilised in the cone conformation) was used as the starting point for this study. It was demonstrated that the NaNO3/CF3COOH system can serve as an excellent oxidising agent. The oxidation of the bridging sulphur atoms smoothly leads to the corresponding tetrasulfoxides where alkyl and sulfoxide groups are oriented in the opposite directions in a stereoselective manner.

1.8 Chirality in Agrochemicals

In the chapter agrochemical products, aspects of chirality of fungicides, insecticides, and herbicides reported in the last 30 years are reviewed. The chapter is structured by the respective biochemical modes of actions of the different substance classes discussed. Approaches to enantiomerically enriched chemicals are reported which include asymmetric catalysis, the use of building blocks from the chiral pool, as well as a number of different resolution methods. The authors provide detailed insights into the relevance of the chiral centers for the desired pesticidal activity and discuss, when possible, the molecular architecture in context with the underlying biochemical principles. Although the chapter focuses on the more recent agrochemicals, some of the old chemistries are reviewed when justified by relevant data revealed in the recent literature. Overall, the authors provide a concise overview of the chemistry, biology, and biochemistry of modern agrochemicals possessing one or several stereochemical centers, which should be of relevance to students and professionals interested in the chemical science of modern pesticides.

Herbicidal aryldiones incorporating a 5-methoxy-[1,2,5]triazepane ring

Novel 2-aryl-cyclic-1,3-diones containing a 5-methoxy-[1,2,5]triazepane unit were explored towards an effective and wheat safe control of grass weeds. Their preparation builds on the ease of synthetic access to 7-membered heterocyclic [1,2,5]triazepane building blocks. Substitution and pattern hopping in the phenyl moiety revealed structure-activity relationships in good agreement with previously disclosed observations amongst the pinoxaden family of acetyl-CoA carboxylase inhibitors. In light of basic physicochemical, enzyme inhibitory and binding site properties, the N-methoxy functionality effectively acts as a bioisostere of the ether group in the seven-membered hydrazine ring.

Efficient synthesis of new fluorinated building blocks by means of hydroformylation.

Hydroformylation of fluorinated alkenes is an efficient method for the preparation of fluorinated functionalized building blocks for the synthesis of biologically active target structures. In this article we summarize known hydroformylation reactions of fluorinated olefins and we add new results from our research groups. Particular attention is paid to the remarkable influence of organofluorine substituents on catalyst activity, regio- and stereoselectivity of the hydroformylation reaction.