Arylboronic bromination

The medicinal importance of 2-aryltryptamines led Chu and co-workers to develop an efficient route to these compounds (130) via a Pd-catalyzed cross-coupling of protected 2-bromotryptamines 128 with arylboronic acids 129 [137]. Several Suzuki conditions were explored and only a partial listing of the arylboronic acids is shown here. In addition, boronic acids derived from naphthalene, isoquinoline, and indole were successfully coupled with 128. The C-2 bromination of the protected tryptamines was conveniently performed using pyridinium hydrobromide perbromide (70-100%). 2-Phenyl-5-(and 7-)azaindoles have been prepared via a Suzuki coupling of the corresponding 2-iodoazaindoles [19]. 

Extensive use of Pd-catalyzed reactions was included in the synthesis of 2,6,8-trisubstituted purines (Fig. II).33 The synthesis started by anchoring dichloropurine to Rink resin via N9 linkage. Polymer-bound 2,6-dichloropurine (63) was selectively substituted at C6 via acid-catalyzed SNAr substitutions. In the absence of Pd catalysis, the substitution on C2 could be performed only with strongly nucleophilic amines. To expand the scope of C2 substitution, catalytic amounts of Pd were used. Under these reaction conditions arylboronic acids and amines successfully substituted the chloro atom on C2 to afford C2-C and C2-N bonds. Subsequently, the C8 position was brominated with a bromine-lutidine complex33 (66) to give resin 67. 

These palladium-catalysed reactions involve insertion of the palladium into the carbon-bromine or carbon-triflate bond, reaction with the organometallic species (alkenyl stannane in a Stille reaction, arylboronic acid in a Suzuki reaction, or alkynyl copper species in a Sonogashira reaction) and reductive elimination to give the products shown below. 

Mention may be made of the Suzuki coupling of aryl halides and arylboronic acids. In earlier days, TPPMS could be used to convert the brominated or iodinated aromatics nowadays, cheaper chlorinated aromatics and catalysts based on Pd/TPPTS are used in an aqueous procedure on a commercial scale [Eq. (2)] [5]. 

The palladium-catalysed reaction of aryl triflates with arylboronic acids has also been used to produce biaryls. Reaction of the bis(triflate) of 4-methyl-6,7-dihydroxycoumarin results in selective substitution at the 7-position to produce derivatives (133), which can undergo substitution of the second triflate group at higher temperatures. " Site selectivity in the reaction of the methyl naphthoate derivative (134), resulting in substitution of the triflate group, has been attributed to electronic ortho-effects. Further replacement of the bromine substituent may yield diarylated derivatives. The palladium-catalysed... 

The 5-arylated imidazoles 23 thus obtained can be subjected to a second arylation by bromination with NBS (—>25) followed by Pd-catalyzed Suzuki-Miyaura coupling with arylboronic acids to give l-alkyl-4,5-diarylimidazoles 24. 

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