Displacement of bromine from 1 bromo

Dipolar cycloadditkm reactions of nitrones to olefins, 46, 1,3-Dipolar cycloadditions with 3-phenylsydnone, 45, 98 Dispiro[5 1 5 l]tetradecane-7,14-dione, photolysis to cyclohexylidene-cyclohexane, 47, 34 preparation from cyclohexanecarbonyl chlonde and triethylamine, 47,34 Displacement of bromine from 1-bromo-2-fluoroheptane to give 2-fluoro-heptyl acetate, 46, 37... 

Displacement of bromine from 1-bromo-2-fluoroheptane to give 2-fluoro-heptyl acetate, 46, 37... 

Chemical analysis of the polymer from 2-bromo-4,6-dichloro-phenoxide revealed that somewhere between one half and two thirds of the available bromine was displaced. The presence of residiaal bromine in the polymer is also manifest by the sharp resonance at 118.6 ppm. This residual bromine is also the lilcely cause of the characteristic difference in the 130 ppm region between polymers derived from 2-bromo-4,6-dichloro (2 peaks) and 2,4,6-trichlorophenoxide (3 peaks). In addition to the units 1 and 2, the 2-bromophenoxide could also contain units 3 and 4. ... 

The aldehyde was then used in an aldol reaction with the anion from 3-isopropylbut-2-enolide. [The lactone was prepared in the following way bromination of 3-methyl-2-butanone under kinetic conditions (-15 °C) afforded the 1-bromo derivative. The bromine was displaced by acetate on refluxing a solution in acetone with anhydrous KOAc. Reaction of the resulting keto-acetate with the anion from triethylphosphonoacetate afforded the desired butenolide in 55% yield.] The anion was generated in tetrahydrofuran from the butenolide and lithium diisopropylamide and was cooled to -78 °C before addition of the aldehyde. The temperature was maintained below -70 °C for 5h and the reaction was quenched with ammonium chloride at this temperature. Under these conditions (kinetic) the 22R23R intermediate (3) was obtained in 65% yield (26). 

This methodology was extended by Cardillo et al. to the synthesis of chiral a-benzylamino- S,y-unsaturated acids, starting from a-bromo-a,l -unsaturated chlorides. The treatment of these latter compounds with (i )-pantolactone in the presence of triethylamine (TEA) allowed the in situ formation of the deconjugated ketenes and their direct transformation into the corresponding chiral esters. The substitution of bromine with benzylamine, followed by add hydrolysis, produced enantiomerically enriched a-benzylamino-/ ,y-unsaturated acids (Scheme 1.14). The displacement of the bromine with other nitrogen nucleophiles, such as / -methoxybenzylamine and allylamine, also occurred with good yields with complete diastereoselectivity. 

Examples 1 to 5 in Table 1.1 illustrate simple displacement of a bromide (reactions 1 and 4) or a chloride (reactions 2,3, and 5). Reaction 1 illustrates a radical chain extension reaction that reacts ethylene and methyl bromoacetate 1.17), with AIBN (flzofeis-isobutyronitrile) as a catalyst, to produce the requisite bromo-cster. The reaction is not very selective, however, since it produced a mixture of 1.18 and 1.19. The reaction was not very selective and the observed products arose from addition of one and two equivalents of ethylene, respectively, to 1.17. Subsequent treatment with ammonia, the key reaction for this section, led to a mixture of 4-aminobutanoic acid and 6-aminohexanoic acid, 1.2 and 1.4. In reaction 2, ethyl 4,4,4-trifluoropropanoate (J.20) reacted with PCI3 and bromine to give ethyl 3-bromo-4,4,4-trifluorobutanoate, which reacted with ammonia to give 3-amino-4,4,4-trifluorobutanamide, 1.21. Reaction 3 shows the reaction of P-halo lactic acid (3-chloro-2-hydroxypropanoic acid, 1.22) with 28% aqueous ammonia, in an autoclave, to give isoserine (3-amino-2-hydroxypropanoic acid, 1.23). Both halo-acids l and halo-esters 2 have been converted into hydroxy amino acids typical products are 3-... 

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