Ketones phenacyl halides

Early work on the asymmetric Darzens reaction involved the condensation of aromatic aldehydes with phenacyl halides in the presence of a catalytic amount of bovine serum albumin. The reaction gave the corresponding epoxyketone with up to 62% ee.67 Ohkata et al.68 reported the asymmetric Darzens reaction of symmetric and dissymmetric ketones with (-)-8-phenylmenthyl a-chloroacetate as examples of a reagent-controlled asymmetric reaction (Scheme 8-29). When this (-)-8-phenyl menthol derivative was employed as a chiral auxiliary, Darzens reactions of acetone, pentan-3-one, cyclopentanone, cyclohexanone, or benzophenone with 86 in the presence of t-BuOK provided dia-stereomers of (2J ,3J )-glycidic ester 87 with diastereoselectivity ranging from 77% to 96%. 

Asymmetric induction using catalytic amounts of quininium or A-methyl-ephedrinium salts for the Darzen s reaction of aldehydes and ketones with phenacyl halides and chloromethylsulphones produces oxiranes of low optical purity [3, 24, 25]. The chiral catalyst appears to have little more effect than non-chiral catalysts (Section 12.1). Similarly, the catalysed reaction of sodium cyanide with a-bromo-ketones produces epoxynitriles of only low optical purity [3]. The claimed 67% ee for the phenyloxirane derived from the reaction of benzaldehyde with trimethylsul-phonium iodide under basic conditions [26] in the presence of A,A-dimethyle-phedrinium chloride was later retracted [27] the product was contaminated with the 2-methyl-3-phenyloxirane from the degradation of the catalyst. 

Compounds, eg, phenacyl halides, benzyl halides, alkyl iodides, or alkyl esters of sulfonic acids, react with DMSO at 100—120°C to give aldehydes (qv) and ketones (qv) in 50—85% yields (eq. 8) (41) ... 

Ring synthesis from non-heterocycles by closure y to the heteroatom are reported. Sulfonium ylides (135) with active methylene compounds such as malononitrile give a C-phenacyl product (136) however, when reacted with /3-diketones and /3-ketonic esters they produce furans quantitatively (74CL101). In these cases O-phenacylation takes place followed by cyclization to give the 3-hydroxydihydrofuran (137), which is dehydrated to the furan (138) (Scheme 30). These furans differ from those formed by the reaction of the diketone or ketonic esters with phenacyl halides. The latter reaction takes place by C-phenacylation, yielding the isomeric furans (139). 

The formation of cyano ketones by this method is illustrated by the conversion of phenacyl halides to the corresponding nitriles. Ring closure to cyclopropane derivatives is a side reaction which has been encountered with y-halo ketones. Benzalacetophenone dibromide is converted by alcoholic potassium cyanide to the fi-cyaao ketone, the a-halogen atom being reduced. Several a-chloro ketones have been found to yield a-cyano epoxides. ... 

The nitrogen of ethyl pyridine-3-acetate becomes a bridgehead atom when the compound is heated with a phenacyl halide. The chemistry of a-halo ketones has been reviewed [B-45]. 

The condensation of the asymmetric oxazoline (125) and 2-propanone is reported to give the adduct (126 equation 40). The Darzens condensation of aromatic aldehydes with phenacyl halides in the presence of catalytic bovine serum albumin affords epoxy ketones in optical yields as high as 62% ee. ... 

In the reaction of 2-hydroxyalkyl halides with cyanide ions the intermediate formation of oxiranes can give rise to rearrangement products. Epoxides may also be encountered if CN ions are reacted with a-halo ketones (Scheme On heating with quaternary ammonium halides in acetonitrile or DMSO at 80-130 C these cyanooxiranes (3) are converted into 2-cyano ketones (4). Phenacyl bromide, in contrast, gives rise to 3-oxo-3-phenylpropionitrile (5) on treatment with cyanide ions. Not much is known about the reaction of the corresponding a-halo sulfides with cyanide ethylthioacetonitrile was obtained from the chloro sulfide by treatment with Hg(CN)2. ... 

The validity of the hypothesis that quaternization favors ring reduction over ketone function is given support in the work on 1-phenacyl-pyridinium halides. Krohnke and Faslod (117) found that in water... 

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