Hydroxy ketones cleavage

Another common type of C—C cleavage is a-cleavage of an a-hydroxy-ketone ... 

A 11011-addition procedure based on a tandem retroaldol/epoxide-opening/cycli-zation sequence has been utilized for the elaboration of the dihydrofuran ring of the reduced furanochroman subunit of phomactin A. The strategy utilizes the O-TBS-protected 3-epoxy-(3 -hydroxy ketone 201. Cleavage with TBAF starts the retro-... 

Oxidative cleavage of the terminal double bond of 49 by ozonolysis to the aldehyde followed by permanganate oxidation to the acid and esterification with diazomethane produced the methyl ester 50. Dieckmann cyclisation of 50, following the procedure developed in Holton s laboratory (LDA, THF, -78 °C, 0.5 h, then HOAc, THF), gave the enol ester 5J in 93% yield (90% conversion). Decarbomethoxylation of 5J. was carried out by temporarily protection of the secondary alcohol (p-TsOH, 2-methoxypropene, 100%), and heating the resulting compound 52 with PhSK in DMF, at 86 °C (3 h) to provide 53a or, after an acidic workup, the hydroxy ketone 53b. 92% yield. 

The reduction of diketones is very complex. They can be partially reduced to ketols (hydroxy ketones) or ketones, or completely reduced to hydrocarbons. Depending on the mutual distance of the two carbonyl groups and reagents used, carbon-carbon bond cleavage may occur and may be followed by recyclizations or rearrangements. Some reactions may result in the formation of alkenes. Quinones react in their own specific way. 

Both the diketone and the cleavage products were shown to arise from an a-hydroxy ketone intermediate (benzoin), 5. 

This chapter deals mainly with the 1,3-dipolar cycloaddition reactions of three 1,3-dipoles azomethine ylides, nitrile oxides, and nitrones. These three have been relatively well investigated, and examples of external reagent-mediated stereocontrolled cycloadditions of other 1,3-dipoles are quite limited. Both nitrile oxides and nitrones are 1,3-dipoles whose cycloaddition reactions with alkene dipolarophiles produce 2-isoxazolines and isoxazolidines, their dihydro derivatives. These two heterocycles have long been used as intermediates in a variety of synthetic applications because their rich functionality. When subjected to reductive cleavage of the N—O bonds of these heterocycles, for example, important building blocks such as p-hydroxy ketones (aldols), a,p-unsaturated ketones, y-amino alcohols, and so on are produced (7-12). Stereocontrolled and/or enantiocontrolled cycloadditions of nitrones are the most widely developed (6,13). Examples of enantioselective Lewis acid catalyzed 1,3-dipolar cycloadditions are summarized by J0rgensen in Chapter 12 of this book, and will not be discussed further here. 

Dipolar cycloaddition reactions between nitrile oxides and aUcenes produce 2-isoxazolines. Through reductive cleavage of the N—O bond of the 2-isoxazohnes, the resulting heterocycles can be readily transformed into a variety of important synthetic intermediates such as p-hydroxy ketones (aldols), p-hydroxy esters, a,p-unsaturated carbonyl compounds, y-amino alcohols, imino ketones and so forth (7-12). 

Thiamine pyrophosphate promotes the decarboxylation of a-keto acids and the cleavage of a-hydroxy ketones. 

The reagent is effective for oxidative cleavage of a-glycols to aldehydes, of a-hydroxy ketones to an aldehyde and a carboxylic acid, and of a-diketones and a-keto iicids to acids.3... 

The product of this conjugate addition is a p-hydroxy ketone. It undergoes base-catalyzed cleavage to the observed products. 

Novel nor-seco baccatin 99 was synthesized in 92% yield through oxidative cleavage of the A ring of 14-OH-DAB (75) with periodic acid via the hydroxy ketone intermediate 100 (Scheme 19). Protection of the 7-hydroxyl of 99 as TES ether followed by reduction of the aldehyde with sodium borohydride yielded nor-seco baccatin alcohol 101 in 80% yield. Nor-seco 13-amino-baccatins 102 and 103 were synthesized from 101 and 99a via the Mitsunobu reaction and reductive amination, respectively, in high yields (Scheme 20). 

Because of the catalytic effect of aluminum alkoxides on alcohol exchange in esters, reduction of esters of hydroxy ketones usually is accompanied by cleavage of the ester group and the product is a glycol. Ether and acetal linkages are not affected. Thus, the reduction of the acetate (LII) gave a 94% yield of the glycol (LIII).42... 

Under these conditions cycloheptene derivative 35 also reacts [15]. After cleavage of the silylether, cyclic hydroxy ketone 37 can be isolated in 95 % yield and 71 % ee. 

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