Hydroxyketone cleavage

Mild base does not effect isoxazolidine ring cleavage by fission of the N—O bond rather, C—O bond cleavage takes place <77AHC(2l)207). The reaction of iV-trimethyl-silylisoxazolidine (185) with KOH produced a /3-hydroxyketone oxime (Scheme 59) (74DOK109). 

Most diaziridines are not sensitive towards alkali. As an exception, diaziridines derived from 2-hydroxyketones are quickly decomposed by heating with aqueous alkali. Acetaldehyde, acetic acid and ammonia are formed from (162). This reaction is not a simple N—N cleavage effected intramolecularly by a deprotonated hydroxy group, since highly purified hydroxydiaziridine (162) is quite stable towards alkali. Addition of small amounts of hydroxybutanone results in fast decomposition. An assumed reaction path — Grob fragmentation of a hydroxyketone-diaziridine adduct (163) — is in accord with these observations (B-67MI50800). 

FIGURE 18.18 Thiamine pyrophosphate participates in (a) the decarboxylation of n-keto acids and (b) the formation and cleavage of n-hydroxyketones. 

Oxidation with mepba — -hydroxyketones, using the reaction of isophorone dienol ether (detailed preparation given), and Et3N.HF cleavage of the intermediate silyl ether. 

Both the diketone and the cleavage products were shown to arise from an a-hydroxyketone intermediate (benzoin) 9. 

Over the past several years, Mascarenas and co-workers (150-153) utilized the oxidopyrylium ion with variously hetero-substituted olefin tethers. Mascarenas has used this methodology in tandem with a Diels-Alder reaction to prepare tricyclic cycloheptanoid substrates. Further, Mascarenas and co-workers (154—156) achieved the synthesis of optically active oxabicyclic[3.2.1]octane derivatives through the addition of a homochiral p-tolylsulfinyl group substituted at the olefin tether. The Mascarenas group has also used this methodology to prepare the THF portion of ( )-nemorensic acid via oxidative cleavage of the substituted a-hydroxyketone moiety (157) (Scheme 4.78). 

TPP is utilized as a coenzyme in reactions involving the decarboxylation of a-keto acids and the formation and cleavage of a-hydroxyketones. 

This explains, for example, the tendency of some 1,2-diols to suffer oxidative carbon-carbon bond breakage under the action of PDC. Thus, although many 1,2-diols can be uneventfully oxidized to a-hydroxyketones with PDC,176 very often a cleavage of a carbon-carbon bond occurs, resulting in two carbonyl functionalities.177 Vicinal tertiary diols, sometimes, are smoothly oxidized to diketones by PDC.178... 

PCC reacts with epoxides, resulting in cleavage either generating two carbonyl compounds or transformation into a a-hydroxyketone. 

The aldol addition of Figure 13.47 can also be carried out in such a fashion that the crude silyl ether-containing aldol adducts are treated directly with periodic acid without prior aqueous workup. In that case, the silyl ether and oc-hydroxyketone cleavages both occur in one operation. 

Periodic acid is a selective reagent for the cleavage of 1,2-dioIs and related substances, such as l-amino-2-hydroxy compounds, 1,2-diketones and a-hydroxyketones. With periodic acid, corticosteroid compounds (where R= H, OH), can be transformed into 17(Lcarboxylic acids and formaldehyde. 

An analogous reaction occurred with oxiranes which underwent mainly carbon-oxygen bond cleavage, with formation of a-hydroxyketones. In some instances byproducts arising from carbon-carbon bond cleavage were also formed in triphenyl-oxirane this mode dominated and the sole product was the hydroxyketone Ph2C(OH)COPh (80%) [54],... 

A2-l,3,4-Oxadiazolines readily undergo ring cleavage in acid to carbonyl compounds and hydrazines (B-61MI42300). The acyloxadiazolines (54) form hydrazine derivatives in acid, and on treatment with alkali yield acylhydrazones (55) which are useful intermediates in the preparation of a-hydroxyketones (Scheme 8) (77CL245). 

Hydroxyketones can be generated by an aldol reaction, for example between two ketones. This reaction is reversible, that is, the 3-hydroxyketones can be transformed back into the two ketones by a carbon, carbon bond cleavage. Such an aldol system as part of a ring system is shown in the general structure VIII/1, Scheme VIII/1. The aldol is incorporated in the bicycle in such a way that the carbon, carbon bond, cleaved in a retro aldol reaction, is the zero bridge of the... 

I) is a /(-hydroxyketone. Loss of a proton from the —OH affords an alkoxide (IV) that undergoes a retroaldol condensation by cleavage of the Ca—bond. 

Reactions of 68 or 170 with a-benzyl-a-hydroxyketones resulted in decarbonylated cleavage products 144). Based on deuterium labelling studies, it appears that the initial step involves abstraction of a hydroxylic hydrogen atom. 

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