Enantioselective oxidations catalyst

It had been known for a long time that CFIMO can also be used as catalysts in the enantioselective air-oxidation of some but not all prochiral thioethers [97]. Therefore, directed evolution of the CFIMO from Adnetohacter sp. NCIMB 9871 was applied in those cases in which the WT fails [32]. An example is substrate (40), which reacts with an enantiomeric excess of only 14% in slight favor of (R)-41 (see Scheme 2.12). 

The allylic acyloxylation of alkenes, the Kharasch-Sosnovsky reaction, Eq. 81, would be an effective route to nonracemic allylic alcohol derivatives, if efficient, enantioselective catalysts were available. The reaction is mediated by a variety of copper salts, and as such, has been the target of considerable research in an attempt to render the process enantioselective. The original reaction conditions described by Kharasch require high temperatures when CuBr is used as the catalyst (93). However, the use of CuOTf (PhH)0 5 allows the reaction to proceed at temperatures as low as -20°C. Unfortunately, long reaction times are endemic in these processes and the use of excess alkene (2-100 equiv) is conventional. Most yields reported in this field are based on the oxidant. 

Sunden, H., Dahlin, N., Ibrahem, I., Adolfsson, H. and Cordova, A. Novel Organic Catalysts for the Direct Enantioselective a-Oxidation of Carbonyl Compounds. Tetrahedron Lett., 2005, 46, 3385-3389. 

It was clear that 1 would be derived from a Diels-Alder adduct. There has been a great deal of work in recent years around the development of enantioselective catalysts for the Diels-Alder reaction, but the catalysts that have been developed to date only work with activated dienophile-diene combinations. For less reactive dienes, it is still necessary to use chiral auxiliary control. One of the more effective of those was the known camphor-derived tertiary alcohol, so that was used in this project. Diels-Alder cycloaddition of the diene 4 with the enantiomerically-pure enone 5 led to the adduct 6 with high diastereocontrol. Oxidative cleavage led to the acid 7, which was carried on to the bis-enone I. 

Feringa reported an enantioselective allylic oxidation of cyclohexene to optically active 2-cyclohexenyl propionate 25 by using a chiral copper complex prepared from Cu(OAc)2 and (S)-proline, as chiral catalyst (Scheme 9.14) [32], In the absence of additives, a negative NLE was observed, whereas in the presence of a catalytic amount of anthraquinone, a positive NLE (asymmetric amplification) was observed. Moreover, higher enantioselectiv-ity was attained when enantiopure (S)-proline was used. However, the role of the additive remains elusive. 

A similiar approach was performed by van de Velde (1999), using incorporation of vanadate into an acid phosphatase (phytase) to create a semi-synthetic peroxidase similar to the heme-dependent chloroperoxidase. The latter is a useful enzyme for the asymmetric epoxidation of olefins, but less stable due to oxidation of the porphyrin ring and difficult to express outside the native fungal host. The authors exploited the structural similarity of active sites from vanadate-dependent halo-peroxidases and acid phosphatases and have shown the useful application as an enantioselective catalyst for the synthesis of chiral sulfoxides (van de Velde, 1999). 

Scheme 2.31 Direct enantioselective a-oxidation of aldehydes using nitrosobenzene as the oxygen donor and L-proline as the catalyst.

Schwab et al. (46, 47) showed that nickel, copper and platinum supported on optically-active quartz behave as enantioselective catalysts for the dehydrogenation and oxidation of racemic sec-butyl alcohol. At low conversion, a measurable optical rotation of the reaction solution is observed, showing that one enantiomer has reacted... 

Discussion Point DPS The Sharpless enantioselective catalyst system has some substantial disadvantages with respect to other enantioselective systems name at least two. Enantioselective oxidation is to some extent underdeveloped with respect to e.g. hydrogenation can you establish logical connections with i) the stability of catalysts in the reaction medium ii) the nature of the oxidants used and their environmental impact Hi) the number of reactions that can successfully be accomplished. 

As pointed out in the introduction, a particular feature of hydrosilylation reactions is that they require catalysis. Arguably the most valuable of enantioselective synthetic methods are those in which asymmetric induction occurs from small quantities of enantiomerically pure catalysts. It is natural, therefore, that considerable effort has been directed towards the catalytic enantioselective hydrosilylation-oxidation of C —C double bonds. Some degree of success has been met in the hydrosilylation of simple alkenes and 1,3-dienes, and in intramolecular hydrosilyla-tions. Also, as discussed at end of this section, a catalytic enantioselective disilylation (effectively the same as a hydrosilylation) has been developed for a,)3-unsaturated ketones. 

Oxidations. A widely used method for allylic oxidation is the Kharash-Sosnovsky reaction using a peroxide and a copper(I) salt system. Enantioselective allylic oxidations of cycloalkenes such as cyclopentene, cyclohexene and cycloheptene with tert-butyl peibenzoate were investigated with a variety of catalysts derived from bis(oxazoline) ligands and copper(I) triflate complexes (eq 18). The ligand-copper(I) complexes from the /-Bu-... 

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