Oxazolidinones Baeyer-Villiger oxidation

An important feature of this reaction is that in contrast to most other catalytic asymmetric Mannich reactions, a-unbranched aldehydes are efficient electrophiles in the proline-catalyzed reaction. In addition, with hydroxy acetone as a donor, the corresponding syn-l, 2-aminoalcohols are furnished with high chemo-, regio-, diastereo-, and enantioselectivities. The produced ketones 14 can be further converted to 4-substituted 2-oxazolidinones 17 and /i-aminoalcohol derivatives 18 in a straightforward manner via Baeyer-Villiger oxidation (Scheme 9.4) [5]. 

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 Baeyer-Villiger oxidation of oxazolidinone 202 afforded the previously unknown 5-acyloxyoxazolidin-2-one 203. This intermediate allowed an easy access to several other oxazolidinone derivatives by reaction with different nucleophiles <03SL1903>. 

Varied derivatization strategies, including a novel stereospecific dytropic rearrangement allowing access to bridged y-butyrolactones 81 were also demonstrated. A mild Baeyer-Villiger oxidation, DIBAL-H reduction, and ring expansion to form an oxazolidinone 82 were also exhibited (Scheme 3.19). 

To further understand how structure affects the stabihty and reactivity of the ketone, and to search for more robust ketone catalysts, ketone 55 was prepared and investigated (Scheme 3.42) [74]. It was hoped that the replacement of the ketal of 39 with a more electron withdrawing oxazolidinone would reduce the undesired Baeyer-Villiger oxidation (Scheme 3.27), thus providing a more stable ketone catalyst Ketone 55 was indeed found to be highly active. The catalyst loading can be reduced to 5 mol% and even 1 mol% in some cases. 

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