Hydroxy ketones Baeyer-Villiger reaction

The Dakin reaction proceeds by a mechanism analogous to that of the Baeyer-Villiger reaction. An aromatic aldehyde or ketone that is activated by a hydroxy group in the ortho or para position, e.g. salicylic aldehyde 12 (2-hydroxybenzaldehyde), reacts with hydroperoxides or alkaline hydrogen peroxide. Upon hydrolysis of the rearrangement product 13 a dihydroxybenzene, e.g. catechol 14, is obtained ... 

The peracid oxidizes secondary hydroxy groups to ketones, which then undergo the Baeyer-Villiger reaction. 

Several of the seminal routes to the lactone, as devised by Corey, are summarized in Fig. 5. Diels-Alder reaction of (methoxymethyl)cyclo-pentadiene [15] with chloroacrylonitiile and then basic hydrolysis gave the bicydic ketone [16] (20). Ring expansion in a selective Baeyer-Villiger reaction led to lactone [17] that was then hydrolyzed to hydroxy add [18],... 

The Baeyer-Villiger reaction of hydroxy ketones and unsaturated diketones is very common in steroids, where it occurs preferentially at the keto group on C-17 and leaves the carbonyls in position 3 intact. 

The Baeyer-Villiger reaction is regioselective — the more substituted group migrates—and stereospecific — it does so with retention. Hydroxy ketone (22) was needed for insect pheromone synthesis and is a 1,6-difunctionalised compound. It could be made by nucleophilic displacement by an organo-metallic reagent (R ) on lactone (23), the Baeyer-Villiger product from (24) which can be made from aromatic (26). 

In a typical Knof procedure, 3jS-hydroxyandrost-5-en-17-one acetate is epoxidized with perbenzoic acid (or m-chloroperbenzoic acid ) to a mixture of 5a,6a- and 5)5,6)5-epoxides (75) in 99 % yield. Subsequent oxidation with aqueous chromium trioxide in methyl ethyl ketone affords the 5a-hydroxy-6-ketone (76) in 89% yield. Baeyer-Villiger oxidation of the hydroxy ketone (76) with perbenzoic acid (or w-chloroperbenzoic acid ) gives keto acid (77) in 96% yield as a complex with benzoic acid. The benzoic acid can be removed by sublimation or, more conveniently, by treating the complex with benzoyl chloride and pyridine to give the easily isolated )5-lactone (70) in 40% yield. As described in section III-A, pyrolysis of j5-lactone (70) affords A -B-norsteroid (71). Knof used this reaction sequence to prepare 3)5-hydroxy-B-norandrost-5-en-17-one acetate, B-noran-... 

Baeyer-Villiger oxidation has been used to selectively oxidize one of two methyl ketones (to esters) in the final step of a stereoselective synthesis of (—)-acetomycin, an antibiotic with potential anti-leukemia activity (equation 25)135. This reaction was accomplished using MCPBA as oxidant, with an excess of sodium bicarbonate and 5-/er/-bulyl-4-hydroxy-2-melhyl phenyl sulfide as a radical inhibitor. 

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]. 

One of the most important methods for lactone preparation, and hence of the corresponding hydroxy acids (or halogeno acids, Section 5.14.1 above) is the Baeyer- Villiger rearrangment of cyclic ketones by the action of peracids. A wide variety of peracids have been used in this reaction but currently the reagents of choice are pertrifluoroacetic acid, m-chloroperbenzoic acid, and permaleic acid. The mechanism is formulated below for the conversion of an acyclic ketone into an ester. 

NaH, dimethylformamide (DMF), CH3I], undergoes electrophilic nitration (89), Friedel-Crafts acylation (90), and alkylation (91) at the C-9 position. Although attempts to effeet a Baeyer-Villiger oxidation of ketone 90 were successful, the route was laborious since oxidation to amine oxide 92 preceded oxidation of the methyl ketone 90. However, a Dakin reaction of aldehyde 91 gave 9-hydroxy-6-methylellipticine (93) in excellent yield. It remains to be seen if this methodology can be extended to an N-unsubstituted ellipticine. 

Several 21,22-seco-diacids (150) have been prepared in the 20/S,28-epoxy-18a,19/8H-ursane series by oxidation of the corresponding 22-hydroxymethylene-21-ketones (151). Reaction of the 21-ketone (152) with oxygen in an alkaline medium afforded the a-hydroxy-acid (153) and the seco-diacid (150). ° Several interesting reactions were observed during this work. ° While pyrolysis of the a-acetoxy-acid (154) yielded the ketone (155) pyrolysis of the seco-diacid anhydride resulted in loss of carbon monoxide and formation of the lactone (156). Lead tetra-acetate oxidation of the ketone (155) [or the hydroxy-acid (153)] followed a Baeyer-Villiger pathway to the lactone (156). The ketone (155) was very susceptible to reduction in the presence of alcoholic alkali. The mass spectral fragmentation of a series of compounds based on 20/8,28-epoxy-18a,19/8H-ursane has been examined. ... 

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