Halogen-metal exchange reaction, acidic

For the halogen-metal exchange reaction of bulkier halopyrimidines, steric hindrance retards the nucleophilic attack at the azomethine bond. As a consequence, halogen-metal exchange of 5-bromo-2,4-di-r-butoxypyrimidine (43) with n-BuLi could be carried out at -75 °C [20]. The resulting lithiated pyrimidine was then treated with n-butylborate followed by basic hydrolysis and acidification to provide 2,4-di-f-butoxy-5-pyrimidineboronic acid (44). 5-Bromopyrimidine 43 was prepared from 5-bromouracil in two steps consisting of a dehydroxy-halogenation with phosphorus oxychloride and an SnAt displacement with sodium r-butoxide. 

Nucleophilic addition to a ketone by a pyrazole-3-one can also take place via a pyrazolon-4-yl anion generated from a halogen-metal exchange reaction. Akgiin and Pindur (84M197) (Scheme 106) reported one such example, namely the addition of pyrazole-3-one lithium salt 342, obtained by treating 4-bromopyrazol-3-one 341 with n-BuLi in THF at —78 °C, to benzophenone. The addition product 343 was quenched with tetrafluoroboric acid-diethyl ether complex to afford, after loss of water, (3-oxopyrazol-4-yl) (diphenyl)methylium tetrafluoroborate 344. 

The halogen-metal exchange reaction has been used almost exclusively for the formation of dithienylmethanes lithiated at thiophene /(-positions these derivatives give acceptable yields of aldehydes77 on reaction with dimethylformamide and of acids on carbonation.66 Particular use has been made of bis-J -lithiated compounds for the preparation (via oxidative coupling) of thiophene analogs of fluorenes.3,67 The synthesis of cyclopenta-[ 1,2-b 4,3-b]dithiophene (67) is typical (Eq. 23). 

Rousseau et al. reported the preparation of the water-soluble cryptopahne-111 31 for xenon biosensing application [32]. The synthesis of this compound (Scheme 21.5) first requires the introduction of a reactive function on compound 25 that can be used for subsequent reactions. Thus, a single bromine atom was introduced on the cryptophane-111 skeleton to give rise to cryptophane 32. In turn, a halogen-metal exchange reaction allowed for the introduction of a carboxylic acid... 

Since Li2Zn Bu4 could weU tolerate substrates bearing an acidic proton (Fig. 12), the protection-free synthesis of poly[3-(6-hydroxyhexyl)thiophene] (P3HHT), with hydroxyhexyl side chains, was also successful (Fig. 29). After halogen-metal exchange reaction of 2-bromo-3-(6-hydroxyhexyl)-5-iodothiophene with... 

Simple 5-pyrimidineboronic acid is not trivial to make because the requisite lithiopyrimidine would add to the azomethine bond. The tendency towards these side reactions is less severe in case of 2,4-di-fert-butoxy-5-bromopyrimidine (20) and the halogen-metal exchange can be conducted at -75 °C [29], The nucleophilic attack towards the azomethine bond is retarded due to the steric hindrance. Therefore, the halogen-metal exchange of 2,4-di- -butoxy-5-bromopyrimidine (20) followed by quenching with n-butylborate, basic hydrolysis and... 

Dichloromethane is first deprotonated with "BuLi in tetrah>drofur-an at -10U C. The reaction of dichloromethane with "BuLi represents a competition between deprotonation and halogen-metal exchange. When reaction is carried out at very low temperature only deprotonation occurs. The at complex 16 forms after addition of the methanohoronic acid pinanediol ester 15.10 Upon introduction ofZnCl2 this complex rearranges to compound 3.11... 

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