Asymmetric Baeyer-Villiger reaction

Bolm et al. (130) reported the asymmetric Baeyer-Villiger reaction catalyzed by Cu(II) complexes. Aerobic oxidation of racemic cyclic ketones in the presence of pivalaldehyde effects a kinetic resolution to afford lactones in moderate enan-tioselectivity. Aryloxide oxazolines are the most effective ligands among those examined. Sterically demanding substituents ortho to the phenoxide are necessary for high yields. Several neutral bis(oxazolines) provide poor selectivities and yields in this reaction. Cycloheptanones and cyclohexanones lacking an aryl group on the a carbon do not react under these conditions. 

Scheme 5.35. Co-catalyzed asymmetric Baeyer-Villiger reaction of ketones.

Oxidoreductases are, after lipases, the second most-used kinds of biocatalysts in organic synthesis. Two main processes have been reported using this type of enzymes-bioreduction of carbonyl groups [39] and biohydroxylation of non-activated substrates [40]. However, in recent few years other processes such as deracemization of amines or alcohols [41] and enzymatic Baeyer-Villiger reactions of ketones and aldehydes [42] are being used with great utility in asymmetric synthesis. 

Another method for the asymmetric version of the Baeyer-Villiger reaction was presented by Lopp and coworkers in 1996 . By employing overstoichiometric quantities of Ti(OPr-t)4/DET/TBHP (1.5 eq./1.8 eq./1.5 eq.), racemic andprochiral cyclobutanones were converted to enantiomerically enriched lactones with ee values up to 75% and moderate conversions up to 40% (Scheme 171). Bolm and Beckmann used a combination of axially chiral C2-symmetric diols of the BINOL type as ligands in the zirconium-mediated Baeyer-Villiger reaction of cyclobutanone derivatives in the presence of TBHP (or CHP) as oxidant (Scheme 172) . With the in situ formed catalysts 233a-d the regioisomeric lactones were produced with moderate asymmetric inductions (6-84%). The main drawback of this method is the need of stoichiometric amounts of zirconium catalyst. 

The use of a chiral hydroperoxide as oxidant in the asymmetric Baeyer-Villiger reaction was also described by Aoki and Seebach, who tested the asymmetric induction of their TADOOH hydroperoxide in this kind of reaction98. Besides epoxidation and sulfoxidation, for which they found high enantioselectivities with TADOOH (60), this oxidant is also able to induce high asymmetry in Baeyer-Villiger oxidations of racemic cyclobutanone derivatives in the presence of DBU as a base and LiCl as additive (Scheme 174). The yields and ee values (in parentheses) of ketones and lactones are given in Scheme 174 as... 

An interesting asymmetric Baeyer-Villiger reaction of prochiral ketones via chiral ketals (9) allowed the synthesis of chiral 3-butyrolactones in ees of up to 89%.167 An SnCU mCPBA ratio of >1 in dichloromethane at —100 °C gave the best results and this is attributed to a high 5k 1 character due to lowered nucleophilicity of peracid by coordination to S11CI4. This is mirrored by die beder selectivity of BH3 dian EtjSiH in acetal reductions. 

A Baeyer-Villiger oxidation has the potential of being asymmetric if a regioselective reaction is conducted on a meso-substrate or if a stereodifferentiated stereogenic center is already present. The oxidation can be chemical or enzymatic.213-215 216 An example of a chemical reagent in a Baeyer-Villiger reaction is provided in the synthesis of fragment A 26 from /f-carvone (27) (Scheme 9.38) as part of a synthesis of Cryptophycin A (28).217... 

Although the use of asymmetric Baeyer-Villiger reactions for desymmetrization of several types of prochiral ketone using enzymes or metal-catalyzed systems is well established [81], few studies have been conducted on organocatalytic variants. An interesting organocatalytic Baeyer-Villiger reaction has been reported in which the planar-chiral bisflavin 32 (Fig. 12.12) promotes desymmetrization... 

Murahashi S-I, Ono S, Imada Y (2002) Asymmetric Baeyer-Villiger reaction with hydrogen peroxide catalyzed by a novel planar-chiral bisflavin. Angew Chem Int Ed 41 2366-2368... 

Stewart, J. D. Cyclohexanone monooxygenase a useful reagent for asymmetric Baeyer-Villiger reactions. Curr. Org. Chem. 1998, 2,195-216. 

Bolm, C., Beckmann, O. Baeyer-Villiger reaction, in Comprehensive Asymmetric Catalysis /-///(eds. Jacobsen, E., Pfaitz, A.,Yamamoto,... 

Bolm, C., Luong, T. K. K., Beckmann, O. Oxidation of carbonyl compounds asymmetric Baeyer-Villiger oxidation. Asymmetric Oxidation Reactions). 2001,147-151... 

Scheme 8.29. (a) A generic asymmetric ring-expansion reaction, (b) A kinetic resolution using an asymmetric Baeyer-Villiger catalyst [128]. (c) A synthetic equivalent of an asymmetric Baeyer-Villiger reaction [129]. 

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