Regioselective Baeyer-Villiger

The stereoselective [2+2] cycloaddition between ketenes and enolethers can be used as a key step in the construction of y-butyrolactones (Scheme 14) [45], if the resulting cyclobutanones can subsequently undergo ring enlargement by a regioselective Baeyer-Villiger oxidation. 

Fig. 14.36. Regioselective Baeyer-Villiger rearrangement of an unsymmetrical ketone with HCPBA (meta-chloro-peroxybenzoic acid). The aryl group is [l,2]-shifted in all cases and irrespective of whether the acetophenone is electron-rich or electron-poor.

Fig. 14.37. Regioselective Baeyer-Villiger rearrangement of an electron-poor aromatic aldehyde. This reaction is part of the autoxidation of benz-aldehyde to benzoic acid. Both alternative reaction mechanisms are shown the [1,21-rearrangement (top) and the /3-elimination (bottom).

Fig. 14.38. Regioselective Baeyer-Villiger rearrangement of an electron-rich aromatic aldehyde.

The efficiency of this method was demonstrated in a total synthesis of the antibiotic (-r)-tetrahy-drocerulenin 28 (Scheme 8) and (-h)-cerulenin [11]. Irradiation of complex 22 in the presence of the chiral iV-vinyl-oxazolidinone 24, which is easily prepared from the amino carbene complex 23 [12], leads to the cyclobutanone 25 with high diastereoselectivity. Regioselective Baeyer-Villiger oxidation followed by base-induced elimination of the chiral carbamate yields the butenolide 26 in high enantiomeric purity. This is finally converted, using Nozoe s protocol [13], to the target molecule 28 by diastereo-selective epoxidation (- 27) and subsequent aminolysis. 

The regioselective Baeyer-Villiger oxidation of acyclic aliphatic ketones normally results in the insertion of oxygen next to the bulkier alkyl chain. Since methyl is a poor migrating group, a common use of this reaction is to reduce the chain length of methyl ketones 1 two carbons to provide alcohols, after hydrolysis. The ability to synthesize methyl ketones from acids and med l-sutetituted alkenes (equation... 

Because it is often possible to control the stereochemical orientation of substituents on a cyclic array, Baeyer-Villiger cleavages of substituted cyclic ketones have been used extensively in the stereocon-trolled syntheses of substituted carbon chains. An asymmetric synthesis of L-daunosamine intermediate (30) from a noncarbohydrate precursor employed the cyclopentenol (28), prepared in optically pure form (95% ee) from 2-methylcyclopentadiene using asymmetric hydroboration (Scheme 8). Stereoselective epoxidation, conversion to Ae ketone and regioselective Baeyer-Villiger oxidation afforded lactone (29). 

The ability of silicon to stabilize jS-carbonium ions results in regioselective Baeyer-Villiger oxidations in ketones such as (33) leading to acids (34) after removal of the silane function.The full potential of this observation has yet to be delineated. 

The sphingosine 296 has been prepared from D-mannose in 10 steps Levoglucosenone is the starting material for a synthesis of (25,3S,4i )-2-amino-1,3,4-octadecanetriol 300 (see Scheme 47), by carbonyl reduction, diastereoselec-tive cu-oxyamination and reoxidation to 297. Regioselective Baeyer-Villiger... 

There are other simple transformations that can be performed on the hydrolyzed ketone adduct. One of them is the regioselective Baeyer-Villiger oxidation (Scheme 23a) [23, 33]. This methodology gives access to chiral lactones, which are key intermediates in the preparation of valuable intermediates. Another one is the oxidative ozonolysis (Scheme 23b), which gives access to chiral aldehydes [33]. Finally, there is also the ketone reduction to a primary alcohol (Scheme 23c) [59]. 

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