Radostan Riedel

Asymmetric Radical–Radical Cross‐Coupling through Visible‐Light‐Activated Iridium Catalysis

Combining single electron transfer between a donor substrate and a catalyst-activated acceptor substrate with a stereocontrolled radical-radical recombination enables the visible-light-driven catalytic enantio- and diastereoselective synthesis of 1,2-amino alcohols from trifluoromethyl ketones and tertiary amines. With a chiral iridium complex acting as both a Lewis acid and a photoredox catalyst, enantioselectivities of up to 99% ee were achieved. A quantum yield of <1 supports the proposed catalytic cycle in which at least one photon is needed for each asymmetric C-C bond formation mediated by single electron transfer.

Tailored Synthetic Polyamines for Controlled Biomimetic Silica Formation

Organic compounds isolated from diatoms contain long-chain polyamines with a propylamine backbone and variable methylation levels and chain lengths. These long-chain polyamines are thought to be one of the important classes of molecules that are responsible for the formation of the hierarchically structured silica-based cell walls of diatoms. Here we describe a synthetic route based on solid-phase peptide synthesis from which well-defined long-chain polyamines with different chain lengths, methylation patterns, and subunits can be obtained. Quantitative silica precipitation experiments together with structural information about the precipitated silica structures gained by scanning and transmission electron microscopy revealed a distinct dependence of the amount, size, and form of the silica precipitates on the molecular structure of the polyamine. Moreover, the influence of the phosphate concentration was elucidated, revealing the importance of divalent anions for the precipitation procedure. We were able to derive further insights into the precipitation properties of long-chain polyamines as functions of their hydrophobicity, protonation state, and phosphate concentration, which may pave the way for better control of the formation of nanostructured silica under ambient conditions.

Silica precipitation with synthetic silaffin peptides

Silaffins are highly charged proteins which are one of the major contributing compounds that are thought to be responsible for the formation of the hierarchically structured silica-based cell walls of diatoms. Here we describe the synthesis of an oligo-propyleneamine substituted lysine derivative and its incorporation into the KXXK peptide motif occurring repeatedly in silaffins. N(ε)-alkylation of lysine was achieved by a Mitsunobu reaction to obtain a protected lysine derivative which is convenient for solid phase peptide synthesis. Quantitative silica precipitation experiments together with structural information about the precipitated silica structures gained by scanning electron microscopy revealed a dependence of the amount and form of the silica precipitates on the peptide structure.

Octahedral Ruthenium Complex with Exclusive Metal-Centered Chirality for Highly Effective Asymmetric Catalysis

A novel ruthenium catalyst is introduced which contains solely achiral ligands and acquires its chirality entirely from octahedral centrochirality. The configurationally stable catalyst is demonstrated to catalyze the alkynylation of trifluoromethyl ketones with very high enantioselectivity (up to >99% ee) at low catalyst loadings (down to 0.2 mol%).

Octahedral rhodium(III) complexes as kinase inhibitors: Control of the relative stereochemistry with acyclic tridentate ligands.

Octahedral metal complexes are attractive structural templates for the design of enzyme inhibitors as has been demonstrated, for example, with the development of metallo-pyridocarbazoles as protein kinase inhibitors. The octahedral coordination sphere provides untapped structural opportunities but at the same time poses the drawback of dealing with a large number of stereoisomers. In order to address this challenge of controlling the relative metal-centered configuration, the synthesis of rhodium(III) pyridocarbazole complexes with facially coordinating acyclic tridentate ligands was investigated. A strategy for the rapid synthesis of such complexes is reported, the diastereoselectivities of these reactions were investigated, the structure of several complexes were determined by X-ray crystallography, the high kinetic stability of such complexes in thiol-containing solutions was demonstrated in (1)H-NMR experiments, and the protein kinase inhibition ability of this class of complexes was confirmed. It can be concluded that the use of multidentate ligands is currently maybe the most practical strategy to avoid a large number of possible stereoisomers in the course of exploiting octahedral coordination spheres as structural templates for the design of bioactive molecules.

Catalytic asymmetric synthesis of a nitrogen heterocycle through stereocontrolled direct photoreaction from electronically excited state

The reactivity of photoexcited molecules has been extensively studied for decades but until today direct bond-forming reactions of such excited states in a catalytic and asymmetric fashion are restricted to the synthesis of cyclobutanes via [2 + 2] photocycloadditions. Herein, we demonstrate a previously elusive visible-light-induced catalytic asymmetric [2 + 3] photocycloaddition of alkenes with vinyl azides. A wide range of complex 1-pyrrolines are obtained as single diastereoisomers and with up to >99% enantiomeric excess using a simple reaction setup and mild reaction conditions. The reaction is proposed to proceed through the photoexcitation of a complex out of chiral rhodium catalyst coordinated to α,β-unsaturated N-acylpyrazole substrates. All reactive intermediates remain bound to the catalysts thereby providing a robust catalytic scheme (no exclusion of air necessary) with excellent stereocontrol. This work expands the scope of stereocontrolled bond-forming reactions of photoexcited intermediates by providing catalytic asymmetric access to a key nitrogen heterocycle in organic chemistry.Despite intensive research on photoexcited molecules, stereocontrol of direct bond formation upon photoexcitation remains limited. Here the authors expand the research on stereocontrolled bond forming photochemistry and introduce the catalytic asymmetric synthesis of chiral nitrogen heterocycles.

Visible-Light-Activated Asymmetric β-C–H Functionalization of Acceptor-Substituted Ketones with 1,2-Dicarbonyl Compounds

We report a visible-light-activated asymmetric β-C(sp3)-H functionalization of 2-acyl imidazoles and 2-acylpyridines with 1,2-dicarbonyl compounds (typically α-ketoesters) catalyzed by a tailored stereogenic-at-rhodium Lewis acid catalyst. The C-C bond formation products are obtained in high yields (up to 99%) and with excellent stereoselectivities (up to >20:1 dr and up to >99% ee). Experimental and computational studies support a mechanism in which a photoactivated Rh-enolate transfers a single electron to the 1,2-dicarbonyl compound followed by proton transfer and a subsequent stereocontrolled radical-radical recombination.