Jan-E. Bäckvall

Enantioselective copper-catalyzed conjugate addition and allylic substitution reactions

Departament of Organic Chemistry, University of Geneva, 30 Quai Ernest Ansermet, 1211 Geneve 4, Switzerland, Department of Organic Chemistry, Stockholm University, Arrhenius Laboratoriet, 106 91 Stockholm, Sweden, Organic Chemistry II, Dormund University of Technology, Otto-Hahn-Strasse 6, D-44227 Dortmund, Germany, and Departament de Quimica Fisica i Inorganica, Universitat Rovira i Virgili, C/ Marcel · li Domingo s/n, 43007 Tarragona, Spain

Racemisation in asymmetric synthesis. Dynamic kinetic resolution and related processes in enzyme and metal catalysis

Dynamic kinetic resolution (DKR) has recently become not only an alternative to the traditional kinetic resolution, but also a new procedure for asymmetric synthesis. Enzymes are usually the tools to effect this methodology (DKR), although new techniques have emerged through the use of asymmetric transition metal catalysis. All of these methods need two supplementary steps: racemisation together with a consecutive asymmetric transformation. A breakthrough in this area appeared with the powerful combination of enzymatic resolution and transition metal-catalysed racemisation. Thus, new procedures for efficient dynamic kinetic resolution became available. This review covers the concept of dynamic kinetic resolutions emphasizing the most representative examples as well as new developments in this area. Special effort has been made to show the importance of the racemisation step in the whole asymmetric transformation process.

Photosensitized water oxidation by use of a bioinspired manganese catalyst

In an artificial version of photosynthesis, sunlight and water are used to produce fuels. Our research focuses on the bottleneck in this process, the photooxidation of water. In the course of developing a water oxidation catalyst, a number of metal complexes have been synthesised, characterised, and studied for catalytic activity. Three of them are dinuclear complexes (Ru, Co and Cu) of 2,6-bis[(2-hydroxybenzyl)-(2-pyridylmethyl)aminomethyl]-4-methylphenol (H3bbpmp). The fourth is a dimeric Ru complex with a ligand containing imidazole and phenol motifs. Additionally, a dinuclear Mn complex with a ligand that contains benzimidazoles and carboxylates coordinating to the metal atoms was also developed. This Mn complex was then covalently linked to [Ru(bpy)3]2+-type photosensitisers, resulting in three different bimetallic dyads. Finally, a dinuclear Fe complex containing the same ligand as the dinuclear Mn complex was synthesised.The potential of the three H3bbpmp complexes as catalysts for oxidation of organic compounds was investigated and it was found that the Ru complex catalyses the oxidation of alcohols to the corresponding ketone or aldehyde using (diacetoxyiodo)benzene as oxidant. The Co complex functions as an electron transfer mediator in a coupled catalytic system for allylic oxidation using oxygen gas. The oxidation of 3,5-di-tert-butylcatechol to the corresponding ortho-quinone with oxygen gas using the copper complex proved that it can be considered as a model of catecholase. The dimeric Ru complex and the dinuclear Mn and Fe complexes proved to catalyse water oxidation when employing stoichiometric amounts of the oxidant [Ru(bpy)3](PF6)3. Furthermore, using [Ru(bpy)2(deeb)](PF6)2 as photosensitiser together with Na2S2O8 as sacrificial electron acceptor in aqueous phosphate buffer at pH = 7.2, photochemical water oxidation was demonstrated. The bimetallic dyads however, did not show catalytic activity for the oxidation of water.

Ruthenium-Catalyzed Transfer Hydrogenation of Imines by Propan-2-ol in Benzene

Transfer hydrogenation of a variety of different imines to the corresponding amines by propan-2-ol in benzene catalyzed by [Ru2(CO)4(mu-H)(C4Ph4COHOCC4Ph4)] (1) has been studied. The reaction is highly efficient with turnover frequencies of over 800 per hour, and the product amines were obtained in excellent yields. A remarkable concentration dependence of propan-2-ol was observed when the reaction was run in benzene as cosolvent. An optimum was obtained at 24 equivalents of propan-2-ol to imine, and further increase of the propan-2-ol led to a dramatic decrease in rate. Also the use of polar cosolvents with 24 equivalents of propan-2-ol gave a low rate. It was found that ketimines react faster than aldimines and that electron-donating substituents on the imine increase the rate of the catalytic transfer hydrogenation. Electron-withdrawing substituents decreased the rate. An isomerization was observed with imines having an alpha-hydrogen at the N-alkyl substituent, which is in accordance with a mechanism involving a ruthenium-amine intermediate. It was demonstrated that the ruthenium-amine complex from alpha-methylbenzylamine, corresponding to the postulated intermediate, can replace 1 as catalyst in the transfer hydrogenation of imines. A primary deuterium isotope effect of kCH/CD = 2.7 +/- 0.25 was observed when 2-deuterio-propan-2-ol was used in place of propan-2-ol in the transfer hydrogenation of N-phenyl-(1-phenylethylidene)amine.

Chemoenzymatic dynamic kinetic resolution: a powerful tool for the preparation of enantiomerically pure alcohols and amines.

Chemoenzymatic dynamic kinetic resolution (DKR) constitutes a convenient and efficient method to access enantiomerically pure alcohol and amine derivatives. This Perspective highlights the work carried out within this field during the past two decades and pinpoints important avenues for future research. First, the Perspective will summarize the more developed area of alcohol DKR, by delineating the way from the earliest proof-of-concept protocols to the current state-of-the-art systems that allows for the highly efficient and selective preparation of a wide range of enantiomerically pure alcohol derivatives. Thereafter, the Perspective will focus on the more challenging DKR of amines, by presenting the currently available homogeneous and heterogeneous methods and their respective limitations. In these two parts, significant attention will be dedicated to the design of efficient racemization methods as an important means of developing milder DKR protocols. In the final part of the Perspective, a brief overview of the research that has been devoted toward improving enzymes as biocatalysts is presented.

Ruthenium-catalysed aerobic oxidation of alcohols via multistep electron transfer

Aerobic oxidation of primary alcohols to aldehydes occurs under mild conditions at 20 °C via a triple catalytic system consisting of RuCl(OAc)(PPh3)3–hydroquinone–Co(salophen)(PPh3)[H2salophen =N,N′-bis(salicylidene)-o-phenylenediamine].

An efficient and mild ruthenium-catalyzed racemization of amines: application to the synthesis of enantiomerically pure amines

An efficient and mild Ru-catalyzed racemization of amines under transfer hydrogenation conditions is reported. A significant advantage of this new procedure is that the ruthenium hydrogen transfer catalysts allow high functional group tolerance. Interestingly, both primary and secondary amines were efficiently racemized under these conditions. We also report on the combination of this new amine racemization with an enzymatic kinetic resolution of primary amines.

Efficient ruthenium-catalysed transfer hydrogenation of ketones by propan-2-ol

In the presence of the co-catalyst NaOH (2. 4 mol%), RuCl2(PPh3)3(0.1 mol%) catalyses efficient transfer hydrogenation of both aliphatic and aromatic ketones by propan-2-ol with rates up to 900 turnovers per hour at 82 °C; no hydrogenation occurs in the absence of sodium hydroxide.

CHIRAL ARENETHIOLATOCOPPER(I) CATALYZED SUBSTITUTION REACTIONS OF ACYCLIC ALLYLIC SUBSTRATES WITH GRIGNARD REAGENTS

Abstract Asymmetric induction can be achieved in the γ-selective substitution reaction of allylic substrates (R′CHCHCH 2 Y) with n -BuMgI catalyzed by the chiral arenethiolatocopper(I) complex 1b . It was found that the enantiomeric excess of the γ-substituted product (R′CH( n -Bu)CHCH 2 ) is influenced by the coordinating ability of the leaving group Y, and e.e.s of up to 42% (R′ = Cy, Y = OAc) have been obtained.

Multi-step catalysis for the oxidation of oleftns to ketones by molecular oxygen in chloride free media

Abstract A multi-step catalytic system consisting of Pd(II)/Pd(0) - benzoquinone/hydroquinone -Fe(Pc) ox /Fe(Pc) was utilized to achieve a mild and selective aerobic oxidation of terminal olefins to methyl ketones in chloride free media.