Ketones, reductive cleavage reagents

Among other methods for the preparation of alkylated ketones are (1) the Stork enamine reaction (12-18), (2) the acetoacetic ester synthesis (10-104), (3) alkylation of p-keto sulfones or sulfoxides (10-104), (4) acylation of CH3SOCH2 followed by reductive cleavage (10-119), (5) treatment of a-halo ketones with lithium dialkyl-copper reagents (10-94), and (6) treatment of a-halo ketones with trialkylboranes (10-109). 

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. 

Reductive cleavage of a-ketol acetates can also be effected in moderate yield by Fe(CO)s. Ketones, esters and alkenes are unreactive toward this reagent. 

A very convenient hydroxymethylation process has been developed based on the Sml2-mediated Bar-bier-type reaction. Treatment of aldehydes or ketones with benzyl chloromethyl ether in the presence of Smh provides the alkoxymethylated products in good to excellent yields. Subsequent reductive cleavage of the benzyl ether provides hydroxymethylated products. Even ketones with a high propensity for enolization can be alkylated by this process in reasonable yields. The method was utilized by White and Soners as a key step in the synthesis of ( )-deoxystemodinone (equation 27). This particular ketone substrate resisted attack by many other nucleophilic reagents (such as methyllithium) owing to conpeti-tive enolate formation. 

Rearrangements of several ketones and alcohols containing the tricyclo[5.3.0.0 ]decane, and related structures, promoted by various reagents, have been examined. Reductive cleavage with lithium metal in liquid ammonia yielded spiroalkanones (see Section 2.4.1.5.2.6.). By way of contrast, fused ring systems were formed in reactions catalyzed by, for the ketones, e.g. 28 8. /7-toluenesulfonic acid or, for the corresponding alkanols, e.g. 30, perchloric... 

Since utilization of the ketone carbonyl was now complete, its removal was implemented via an efficient three-step sequence involving reductive cleavage of the derived selenocarbonate with tris(trimethylsilyl)silane [12] under free radical conditions [13]. With the acquisition of 17 in this manner, the serviceability of the reagent produced by adding sodium borohydride to cobaltous chloride for chemoselective reduction of the nitrile group [14] was assessed. Indeed, treatment of 17 in this manner, followed directly by basification with potassium hydroxide in methanol, secured 18. In this step as well as in the subsequent progression to the N-methyl derivative 19, no epimerization was seen within ring A. 

SUylated 2-oxidienes and bis-silylated 2,3-dioxidienes are prepared from a , -unsaturated ketones and 1,2-dicarbonyl compounds, respectively in the latter case, the reagent employed for the first silylation is tiimethylsilyl bromide while TMSOTf is required for the second silylation. 1,3-Bis-silyloxydienes are prepared by direct silylation of 1,3-dicarbonyl compounds with TMSOTf(Et3N. They also can be obtained as mixtures of Z/E-isomers by lithium reductive cleavage of isoxazoles followed by the slow addition of an excess of TMSOTfKEt3N (eq 38). ... 

Aluminum chloride hexahydrate An efficient and versatile reagent in organic synthesis (reductive cleavage of2,l-benzisoxazoles and isoxazo-hdines, chemoselective reduction of ketones and of C=C bonds in a,P-unsaturated carbonyl compounds, deoxygenation of N-oxides, dehydration) 13ARK(1)243. 

Lithium aluminium hydride modified with some chiral 1,2-aminodiols, for example (106), gives enantiomeric excesses of up to 82% in the reduction of aromatic ketones," and lithium tris[(3-ethyl-3-pentyl)oxy]aluminium hydride has been introduced as a chemoselective reagent (98—100%) for the reduction of aldehydes in the presence of ketones." Finally, the reagents AlCL-EtSH and AlBrs-EtSH have found further application in the cleavage of esters and lactones. 

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