Ulf Hanefeld

Renewable Chemicals: Dehydroxylation of Glycerol and Polyols

The production of renewable chemicals is gaining attention over the past few years. The natural resources from which they can be derived in a sustainable way are most abundant in sugars, cellulose and hemicellulose. These highly functionalized molecules need to be de-functionalized in order to be feedstocks for the chemical industry. A fundamentally different approach to chemistry thus becomes necessary, since the traditionally employed oil-based chemicals normally lack functionality. This new chemical toolbox needs to be designed to guarantee the demands of future generations at a reasonable price. The surplus of functionality in sugars and glycerol consists of alcohol groups. To yield suitable renewable chemicals these natural products need to be defunctionalized by means of dehydroxylation. Here we review the possible approaches and evaluate them from a fundamental chemical aspect.

Biocatalysis in non-conventional media—ionic liquids, supercritical fluids and the gas phase

During the last decades much attention has been paid, by both academia and industry, to the development of new solvents. The introduction of ILs, sc-fluids and solid–gas interphase reactions has definitely opened new perspectives. ILs have been introduced into organic chemistry to meet the increasing demand for clean technologies in industrial processes. However, the toxicology of ILs remains unclear and further studies are necessary to assess their sustainability. Use of supercritical fluids is already a mature technique and their power lies less in their number but more in the variety of characteristics that one sc-fluid can have depending on the pressure. Enzyme-catalysed reactions at the solid–gas interphase have undergone a rapid development, and this will definitely find a place in the production of high value added compounds, such as fragrances.

Enantioselective C–C bond synthesis catalysed by enzymes

The enantioselective synthesis of C-C bonds is often the pivotal step of a synthesis. Nature has made a variety of versatile enzymes available that catalyse this type of reaction very selectively under mild conditions. Cyanohydrins, acyloins (alpha-hydroxy ketones), alpha-hydroxy acids and aldols (beta-hydroxy ketones) are very efficiently synthesised enantioselectively with the aid of C-C bond forming enzymes, which we discuss in this tutorial review. In the case of the alpha-hydroxy acids the applications of nitrilases in a synthetic dkr even allows a disconnection that has no enantioselective chemical equivalent.

Reagents for (ir)reversible enzymatic acylations

Commonly, hydrolase-catalysed reactions are used for kinetic resolutions of alcohols, amines and acids. Only a few applications in total syntheses have been described. Most of these examples are for the synthesis of amides and peptides. Here, the synthesis of all the different types of activated acids that can be applied in hydrolase-catalysed acylations is described. The application of these activated acids for both the formation of esters and amides is discussed and the different reactions are compared with the equivalent chemical reactions.

The selective addition of water to CC bonds; enzymes are the best chemists

Water is the liquid of life. Nature has therefore evolved countless enzymes that catalyse the addition of water to C=C bonds, isolated or conjugated. These reactions are regio- and enantioselective, they are part of primary metabolism as well as the secondary metabolism. The enzymes that catalyse these reactions (hydratases or hydro-lyases) are applied industrially in selected cases. However, they are not generally used in the laboratory although they outperform all currently available catalytic chemical methodologies. This feature article highlights the potential that hydratases have for chemistry compared to the acid catalysed addition of water.

Immobilised Burkholderia cepacia lipase in dry organic solvents and ionic liquids: A comparison

Lipase PS from Burkholderia cepacia in its free, commercial form (BCL-PS), immobilised in a sol–gel (BCLxero) and as a CLEA (BCL-CLEA) was tested in dry organic solvents, ionic liquids and their mixtures. Utilising the acylations of secondary alcohols 1–3 the influence of the enzyme preparation on its activity and enantioselectivity was studied. BCL-CLEA displays higher activity (initial rates) than BCLxero for all substrates in the ILs but loses its activity rapidly. Thus, BCLxero is suitable for kinetic resolution in ILs and in their mixtures with organic solvents. It is not possible to label one IL better than the other without taking the nature of the substrate into account. In neat solvents, the nature of the solvent affects enantioselectivity (E) only when furyl-substituted alcohol 2 serves as a substrate while variation in E is more evident for reactions in solvent mixtures.

Enzymatic acylation: assessing the greenness of different acyl donors

The hydrolase-catalyzed esterification of alcohols is the best established enzymatic transformation in todays organic chemistry, along with the corresponding ester hydrolysis. Over the years, various different acyl donors have been proposed to overcome the major limitation of the condensation of an alcohol and an acid, the unfavourable equilibrium. This review aims at screening the actual number of applications of the different acyl donors, and at assessing the “greenness” (or lack thereof) of the most applied among them. Indeed, the use of an enzyme to catalyze an esterification is often regarded as sufficient to define the whole transformation as “green”. However, this definition can easily be misinterpreted if the contribution of the acyl donor to the overall process is overlooked, as is often the case. Aiming at filling this gap, this contribution evaluates the advantages and disadvantages of the acyl donors, and assesses their green credentials using an efficient tool in strategic planning, a strengths-weaknesses-opportunities-threats (SWOT) analysis. A calculation of the atom economy and E-factor for representative acylations involving each donor is included, as well as an analysis of the adherence of each process to the twelve principles of Green Chemistry.

Enantioselective Synthesis of Protected Cyanohydrins

A straightforward process for the preparation of optically active protected cyanohydrins, important building blocks for the synthesis of drugs and agrochemicals, has been established. Lipase B from Candida Antarctica (CAL-B) catalysed the kinetic resolution of racemic cyanohydrin acetates under mild conditions. The resulting labile cyanohydrins were reprotected either by an enzyme-catalysed route involving the addition of vinyl butyrate, or chemically after removal of the enzyme from the reaction mixture. This process gave access to both enantiomers in pure form and in good yields, while considerably reducing the risks due to HCN. A variety of different protection groups have also been introduced. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Chiral catalysts confined in porous hosts: 1. Synthesis

Chiral dirhodium carboxamide catalysts were immobilised inside the pores of MCM-41 and on a low-surface-area silica (Aerosil 200). The catalysts were immobilised via ligand exchange of one chiral ligand with a carboxylate tether group. In part 2 the catalytic activity of these catalysts is reported.

Enantioselective formation of mandelonitrile acetate: investigation of a dynamic kinetic resolution II

Investigations into the separate reactions of a dynamic kinetic resolution and the combined reactions revealed that the overall sequence is highly susceptible to the water content of the reaction mixture. While the racemization and formation of mandelonitrile as well as its kinetic resolution proceeded rapidly when performed independently, the dynamic kinetic resolution was severely hampered by the undesired formation of acetic acid during the reaction. The utilization of drying reagents and neutralizing agents in order to suppress the formation of acetic acid or its consequences were investigated.