The cleavage of alkenes to the corresponding carbonyl products is a widely employed method in organic synthesis, especially to introduce oxygen functionalities into molecules, remove protecting groups and tailor large molecules. Chemical methods available for alkene cleavage include, for instance, ozonolysis, several metal-based variants (KMnO 4 , OsO 4 , RuO 4 , etc.), electrochemical alternatives, singlet oxygen, hypervalent iodine and organic molecules in combination with oxygen. Furthermore, several enzymatic methods for alkene cleavage have been described to establish safe, mild and selective oxidation methods. Various heme and non-heme iron-dependent enzymes catalyse the alkene cleavage at ambient temperature and atmospheric pressure in an aqueous buffer, showing good chemo-and regioselectivities in selected cases. Quite recently some Cu-, Mn-and Ni-dependent enzymes have been identified for this reaction. This review gives an overview of the different chemical and enzymatic methods available for the cleavage of alkenes.

This account focuses on the application of ω-transaminases, lyases, and oxidases for the preparation of amines considering mainly work from our own lab. Examples are given to access α-chiral primary amines from the corresponding ketones as well as terminal amines from primary alcohols via a two-step biocascade. 2,6-Disubstituted piperidines, as examples for secondary amines, are prepared by biocatalytical regioselective asymmetric monoamination of designated diketones followed by spontaneous ring closure and a subsequent diastereoselective reduction step. Optically pure tert-amines such as berbines and N-methyl benzylisoquinolines are obtained by kinetic resolution via an enantioselective aerobic oxidative C–C bond formation.

The oxidation of the renewable diols isosorbide and isomannide was successfully achieved using a TEMPO/laccase system. Furthermore, various TEMPO-derivatives were tested leading to conversions of up to >99% for the oxidation of isosorbide, isomannide, indanol and a halohydrin to the corresponding ketone.Scheme 1 Relative Gibbs free energies (kcal mol −1 ) for the oxidation and hydration of isosorbide 1 and isomannide 2. Energies for oxidations were calculated for the reaction of the alcohol with acetone yielding the ketone plus 2-propanol. The calculations were performed using the MP2/cc-pVTZ//MP2/cc-pVDZ procedure in aqueous solution (IEFPCM solvation model). † Electronic supplementary information (ESI) available: Analytics, sources of chemical and enzymes, computational details. See

New clothes for Mn3+: Aerobic alkene cleavage of styrene‐type substrates by Trametes hirsuta is attributed to an enzyme that is dependent on manganese in oxidation state three. The enzyme has a proteinase backbone and binds Mn3+ exclusively via oxygen atoms, in contrast to all known Mn3+ enzymes.

The first report of a biocatalytic regioselective oxidative mono-cleavage of dialkenes was successfully achieved employing a cell-free enzyme preparation from Trametes hirsuta at the expense of molecular oxygen. Selected reactions 10 were performed on preparative scale affording high to excellent conversions and chemoselectivities.Oxidative alkene cleavage is an important synthetic tool (i) to remove protecting groups; (ii) to tailor large molecules or (iii) to access carbonylic functional groups.1 Among the different 15 methodologies available to perform this reaction, the ones employing ozone 2 or metal-based oxidants 3 are the most frequently used. However, these methods present some disadvantages: for instance, (i) the use of special equipment and reaction conditions or (ii) over-oxidation of aldehyde products 20 leading to by-products such as carboxylic acids. Furthermore, from an environmental point of view, it is desirable to find alternatives for metal catalysts and stoichiometric amounts of peroxides or salts. Consequently, novel greener methodologies have been developed to overcome some of these drawbacks. Chemical oxidative alkene cleavage of compounds bearing more than one (non-aromatic) C=C double bond generally leads to the cleavage of all the alkene groups. One remarkable exception was described by Neumann and co-workers using a ruthenium catalyst in the presence of hydrogen peroxide, showing 45 that a terminal alkene group was regioselectively oxidized in the presence of other more sterically hindered internal (or cyclic) C=C double bonds in different aliphatic polyalkenes, displaying high to excellent selectivities. 12 The lack of more regioselective methods could be due to the fact that oxidative alkene cleavage is 50 highly exothermic (e.g., 47-64 kcal mol -1 for ozonolysis), 13 therefore hampering an easy control of the regioselectivity. To the best of our knowledge, alkene cleaving biocatalysts have not yet been investigated for their ability to differentiate between two alkene groups within the same molecule.