Eberhard Steckhan

Environmental protection and economization of resources by electroorganic and electroenzymatic syntheses

The electrochemical methodology is an intrinsically environmentally friendly technique. It is especially excellently suited for preventive environmental protection because the practically mass-free electrons are used as reagents. Therefore, it allows the production of organic compounds without the formation of ecologically critical waste which has to be disposed. In addition, toxic waste formation can be prevented by continuous in situ or two-step electrochemical regeneration of heavy metal redox reagents. By using solid polymer electrolytes (ion-exchange membranes), even the use of a supporting electrolyte can be avoided. Thus, product formation can take place in pure methanol without any other chemical present. The consumption of resources can be economized by generating high-value products on both electrodes, anode and cathode (paired electrosynthesis). In certain cases, the same product may be formed on the anode and the cathode (200%-cell). Finally, in electroenzymatic syntheses, two environmentally friendly methods can be combined for the regeneration of the cofactors or the prosthetic groups of redox enzymes.

Efficient indirect electrochemical in-situ regeneration of nadh:electrochemically driven enzymatic reduction of pyruvate catalyzed by d-ldh

Abstract Using [Cp(Me) 5 Rh(bipy)C1]C1 ( 1 ) as redox catalyst for the continous NADH regeneration it was possible to perform an electrochemically driven enzymatic reduction of pyruvate to D-lactate catalyzed by D-LDH at a rate of 5 turnovers per hour. This is by a factor of 20 faster than the best results obtained until now. Current yields of 50 to 70 % may be obtained.

Anodic oxidation of N-acyl and N-alkoxycarbonyl dipeptide esters as a key step for the formation of chiral heterocyclic synthetic building blocks

Abstract The anodic oxidation of N-protected dipeptide esters using chloride as a redox catalyst can be performed regioselectively at the C-terminal amino acid. With methanol as solvent, glycine as the C-terminal, and L-valine or L-proline as N-terminal amino acid methoxylation at the glycine residue takes place. Deprotection of this product leads to the (3S,6RS)-6-methoxy-2,5-piperazinedione(3) which can be applied as a chiral cationic glycine equivalent. The exchange of the methoxy group by C-nucleophiles takes place with high trans-diastereoselectivity under steric control by the substituent in 3-position. With branched amino acids at the C-terminus of the dipeptide ester the anodic oxidation in acetonitrile/methanol (95:5) as solvent with tetraethylammonium chloride as supporting electrolyte and redox catalyst leads to methyl imidazolidin-4-one-2-carboxylates. The cyclization takes place via the intermediate formation of the N-acylimino ester of the C-terminal amino acid.

Investigation of the manganese-substituted α-Keggin-heteropolyanion K6SiW11O39Mn(H2O) by cyclic voltammetry and its application as oxidation catalyst

Abstract The behavior of a manganese substituted α-Keggin silicon tungstoheteropolyanion (K 6 SiW 11 O 39 Mn(II)(H 2 O)) under electrochemical oxidation conditions was investigated by means of cyclic voltammetry in phosphate buffer. Substitution of the water ligand by counter anions (L: H 2 PO − 4 or HPO 2− 4 ) leading to SiW 11 O 39 Mn(II)(L) was observed. Replacement of the counter anion by an aquo ligand was observed in cyclic voltammetry by continuous cycling. After oxidation of SiW 11 O 39 Mn(II)(L) to SiW 11 O 39 Mn(IV)(L), this counter anion L was in turn substituted by OH − . The thus formed complex SiW 11 O 39 Mn(IV)(OH) oxidizes different alcohols, the reactivity of which decreases as follows: 1-phenyl-ethanol, benzylalcohol > iso -propanol > ethanol.

Electrochemically induced [4+2]-cycloadditions - a mechanistic interpretation of the cation radical Diels-Alder reaction based on preparative results☆

Abstract For the first time it was possible to induce the cation-radical Diels-Alder reaction between electronrich dienes and electronrich dienophiles electrochemically, thus providing a clearer view upon the mechanism of this reaction type. In contrast to common explanations it could be demonstrated that this reaction most probably takes place via the cation radical of the diene. A role selectivity towards the cation radical of the dienophile could be ruled out.

Electrochemical oxidation of chiral 5-substituted 2-oxazolidinones: A key building block for dichiral β-amino alcohols

The 4-methoxylation of some chiral 5-substituted 2-oxazolidinones can be performed successfully by direct electrochemical oxidation at 50 mA/cm2 in methanol at graphite electrodes using an undivided or quasi-divided cell and sodium tetrafluoroborate or sodium benzene sulfonate as supporting electrolytes. The yields and selectivities are depending on the pH of the solution and the concentration of the substrate. Thus, (4RS,5S)-chloromethyl-4-methoxy-2-oxazolidinone (7) could be obtained in 76% yield from (5S)-chloromethyl-2-oxazolidinone (3). Through nucleophilic methoxy-group exchange these heterocycles are key intermediates for enantiomerically pure trans-4,5-difunctionalized-2-oxazolidinones in both enantiomeric forms, which are very interesting targets due to their various pharmacological effects and as precursors for β-amino alcohols and protease inhibitors.

Efficient pathways to (R)- and (S)-5-hydroxymethyl-2-oxazolidinone and some derivatives

Abstract 2-Oxazolidinones are a very interesting class of compounds due to their various pharmacological effects. Two new syntheses of enantiomerically pure ( R )- and ( S )-5-hydroxymethyl-2-oxazolidinone have been developed starting with D -mannitol, L -ascorbic acid and ( R )- or ( S )-malic acid. ( R )- and ( S )-5-hydroxymethyl-2-oxazolidinone have been used to synthesize some new homochiral 2-oxazolidinone derivatives.

Indirect electrochemical α-methoxylation of N-acyl and N-carboalkoxy α-amino acid esters and application as cationic glycine equivalents

Abstract Indirect electrochemical methoxylation of N -acyl and N -carboalkoxy α-amino acid esters in α-position to nitrogen is possible, if chloride is used as mediator. The course of the reaction depends upon the protecting group as well as upon the amino acid side-chain. Increased electron withdrawing effects of the protecting group are accelerating the reaction. On the other hand aliphatic side-chains are diminishing the reactivity. High chloride ion concentrations improve the current yields surprisingly strong.

Indirect electrochemical side-chain oxidation of alkyl aromatic compounds - selective synthesis of methyl benzoates or ortho-benzoic acid trimethylesters

Abstract The technically important side-chain oxidation of alkyl aromatic compounds to from either methyl benzoates or orthobenzoic acid trimethylesters can be performed electrochemically at low potentials in methanol solution using an undivided cell and tris(2,4-dibromopheny1)amine as redox catalyst. Under neutral or slightly acidic conditions methyl benzoates are selectively formed while under basic conditions the ortho-esters are predominating. In a similar way ortho benzoic acid trimethylesters are formed selectively starting from benzaldehyde dimethylacetals. The redox catalyst is stable under the reaction conditions so that several thousand cycles can be performed without noticeable loss.

Benzannulation of Axial Chiral Biscarbene Complexes of Chromium: An Approach to Novel C2‐Symmetrical Redox‐Active Bi(phenanthrenequinones)

The axial and planar chiral biphenanthrene complexes 1 are synthesized by benzannulation reactions and have been studied by CD spectroscopy. Oxidation of 1 affords the diquinone 2, which has been characterized by cyclic voltammetry.