Halomethyl aryl ketones

Haloacetylation of arenes. The salts react with arenes to give high yields of halomethyl aryl ketones ... 

Figure 6.9 Synthesis of an e.p. arylf" C]oxirane through enantioselective reduction of a halomethyl aryl ketone with BH3 THF mediated by CBS catalyst...

The action of hydrogen bromide or hydrogen chloride on diazo ketones represents a general preparative method (50-90%) for pure halomethyl alkyl, halomethyl aryl, or halomethyl heterocyclic ketones. N ... 

Benzene-1,2-diamine undergoes reaction with halomethyl phenyl ketones to give 3-aryl-l,2-di-hydroquinoxalines 1, ° or after oxidation 2-arylquinoxalines 2. ° 1,2-Dihydroquinoxalines can be readily oxidized with different reagents. 

Haller-Bauer reaction, 525 a-Halo acyl chlorides, 75 2-Haloethyl esters, 553 y-Halo ketones, 524 Halomcthyl aryl ketones, 103 Halomethyl aryl sulfones, 41 Halomethylation, 105 tj-Halo-l-phenyl-l-alkynes, 165 Halopropyl isocyanates, 570 2-Halopyridines, 479 Halo-a,p-unsaturated ketones, 647-648 p-Halovinyl ketones, 644 Haworth succinic anhydride synthesis, 474 Hemithioacetal interchange, 381-382... 

These methods are limited in scope. Direct thiation has been reported for the transformation of vicinal diketones to [3,4]-annelated thiophenes <1996CHEC-II(7)49>. Thionations and selenations of vicinal halomethyl ketones with thioacetamide or iV,iV-diethylselenopropionamide as sulfur and selenium donors, respectively, have also been reported <1996CHEC-II(7)49>. In a recent example, thieno[3,4-f]pyrazoles 160 were readily prepared from aryl 5-bromomethyl-l//-l-phenylpyrazole-4-yl ketones 159 by reaction with thioacetamide (Equation 35) <1998JHC71>. Additionally, an example of an amination cyclization by reaction of 161 with benzylamine to afford pyrrolo[3,4-i/ thiazole 162 has been described (Equation 36) <1998JHC71>. 

Enantioselective reductions. The neat reagent (1), prepared from ( + )-< -pinene, reduces aryl a-halomethyl ketones slowly but in high chemical yield to (R)-halohydrins in 90-96% ee, but optical induction is mediocre in the case of aliphatic a-halo ketones (35-66% ee). The chiral halohydrins are useful precursors to chiral epoxides. 

Itsuno s amino alcohol (70), prepared from L-valine, is an extremely efficient auxiliary for enantioselective reduction of aryl alkyl ketones using BH3. The corresponding alcohols are obtained in up to 100% ee using BH3 and 0.5 equiv. of (70) in THF at 30 °C. Reduction of dialkyl ketones affords (R)-carbinols in 55-73% ee. Halomethyl t-butyl ketones are also converted to the corresponding (5)-carbinols in high optical purity (Scheme 15). Immobilized amino alcohol (70) permits reduction in a continuous flow system. 1-Phenylpentanol of 90% ee was prepared by this catalytic process in almost 1000% chemical yield based on the quantity of chiral auxiliary used. ... 

Reaction of labeled aryl halomethyl ketones with amines furnishes j8-amino[ C] ketones. If e.p. amines are employed, subsequent reduction of the keto group with achiral reducing agents produces diastereomeric mixtures of )8-amino alcohols. The individual diastereomers can usually be separated by achiral chromatographic methods, or if these fail chiral HPLC procedures or salt formation with a chiral acid (e.g. dibenzoyl-L-tartaric acid) may prove successful. This pathway was followed for the preparation of [ C]dilevalol (12), an antihypertensive agent (Figure 6.8). Within this synthetic sequence the reaction of the a-bromomethyl ketone 8 with e.p. (7 )-Wbenzyl-(l-methyl-3-phenyl)propylamine (2)... 

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