Reactions with a-bromo ketones

Under nonhydrolytic conditions, 2-amino-1,8-naphthyridines (82) do, however, undergo the normal cyclization reactions with a-bromo ketones. Thus, imidazo[l,2- ]naphthyridines (83) are readily obtained.45... 

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. 

Examples of the synthesis of thieno[2,3-Z>]pyridines according to method C are scarce. In this case, the synthesis of the starting 3-cyanopyridine-2(l //)-thione, its -alkylation, and cyclization of an intermediate occur as a multicomponent one-pot process. For example, the reaction of thioamides 28 with l-(4-morpho-lino)cyclohexene (29) in anhydrous ethanol followed by treatment with a twofold excess of KOH and then with a-bromo ketones produced thienoquinolines 30 (1997KGS1384). 

Cyclopentadienes.2 This allylic triphenylphosphorane reacts with a-bromo ketones in the presence of NaHC03 at 25 ° to form cyclopentadienes by a [3 + 2]annela-tion. The reaction may involve intermediates such as a and b. 

P-Hydroxy ketones. a-Bromo ketones undergo a Reformatsky-type reaction with aldehydes which is promoted by R3Sb but which is only possible with iodine as catalyst. The function of I2 is probably for a Br/I exchange, since I2 is not required in reactions with a-iodo ketones. 

The substitution reactions of a-bromo-ketones to give a -acetoxy-ketones are generally considered to proceed vih an enol, with allylic (SN2r) substitution in the cis stereochemical sense.62 A new investigation of the reaction between 4/3-bromo-3-oxo-5/3-steroids (29) and acetate ion shows that the initial product is the 2a-acetoxy-ketone (30), which rearranges rapidly under the reaction conditions to give the stable... 

Treatment of thioacylmorpholines with a-bromo ketones affords the substituted thiophenes 469. The reaction involves A-alkylation of thioacylmorpholines and subsequent cyclization of the intermediates 468 (Scheme 77)... 

A direct and simpler conversion of w-bromoacetophenone into phenylglyoxal is achieved by treatment with dimethyl sulfoxide at room temperature [1003], The reaction of a-bromo ketones with dimethyl sulfoxide can be carried out in anhydrous medium [1003], as well as in the presence of water [1001], The mechanism of the reaction in aqueous medium is more... 

The aldol-type reaction of a-bromo ketones with aldehydes, mediated by CrCh, has been studied by Dubois and coworkers. The reaction is carried out by addition of (241 equation 80) to a solution of (242) and CrCh in THF. The reaction proceeds with high levels of syn selectivity with bulky bromo ketones (241), independent of the substrate aldehyde used (Table 11, entries 1-6). However, the reaction is stereorandom with bromoacetophenone (entry 7) and selectively anti with 2-bromocyclohexanone (entry 8). No explanation of the stereoselectivity has been advanced, but the reaction is believed not to proceed via a simple chromium enolate since no condensation reaction is obtained by addition of (242) to a solution of (241) and CrCh. Moreover, Nozaki and coworkershave demonstrated that chro-mium(II) chloride treatment of 1-bromocyclododecanone followed by treatment with either methyl iodide or TMS-Cl produces only cyclododecanone. 

Table 11 Reaction of a-Bromo Ketones (241) with Aldehydes (242) using CiCh (equation 80) ...

Tin(n) triflate mediated cross aldol reactions between a-bromo ketone (124 Scheme 56) and aldehydes afford iyn-a-bromo-P-hydroxy ketones (125) with high stereoselectivity. The resulting halohydrins are converted to the corresponding (Z)-2,3-epoxy ketones (126). Chiral aldehyde (127) reacts with lithium alkynide (128) followed by mesylation and base treatment to give chirally pure ( )-epoxide (129). The initially formed alkoxide anion should be trapped in situ by mesylation, otherwise partial racemization takes place owing to benzoate scrambling (Scheme 56). ... 

Aluminum enolates can be obtained also by transmetallation of lithium enolates (Scheme 31 ). 3 Diethylaluminum enolates can be produced regiospecifically through reaction of diethylaluminum chloride and zinc dust with a-bromo ketones and esters (Scheme 32). Obviously zinc is involved in this reaction, but the mild conditions are in sharp contrast to the Refoimatsky reaction and support the existence of an aluminum enolate in this process. The same type of enolate can be obtained from r-butyi acetates and diethylaluminum 2,2,6,6-tetramethylpiperidide (DATMP), which is generated in situ from diethylaluminum chloride and LITMP (Scheme 33). ... 

The reaction of a-bromo ketones with diethylzinc leads to an ethylzinc enolate (equation 38). O... 

Halogen can be tolerated either in the carbonyl substrate or in the bromo ester component of the Reformatsky reaction. It is noteworthy that the intermediate zinc aldolate (11) does not internally substitute halogen until HMPA is added (Scheme 7). For reactions with a-halo ketone substrates in a A -buten-... 

Tin(II) enolates can be generated from the reactions of a-bromo ketones with tin(O). The activated metallic tin is typically prepared by the reduction of tin(II) chloride with lithium aluminum hydride. 

In the same report, imidazo(l,2-a]pyrimidines 7 were also prepared through the condensation of 2-amino-4-methylpyrimidine 5 with a-bromo ketone 6 under thermal conditions. No yield was given in this latter reaction. 

A remarkable solvent effect is observed in the reaction of a-bromo ketones with nickel carbonyl. In tetrahydrofuran, dimeric 1,4-diketones are produced, while in dimethylformamide furan derivatives are formed via epoxy ketone intermediates (Yoshisato and Tsutsumi, 1968b,c). Reaction of iron penta-... 

Likewise a-keto and a-aldehydo esters have been prepared by the reaction of potassium phenylacetate with a-bromo ketones or aldehydes by an 18-crown-6 catalyzed displacement reaction in acetonitrile or benzene solution. These compounds could be isolated after short reaction times, or they could be converted on continued heating to 2(5H)furanones, the product of intramolecular aldol condensation and... 

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