A-heteroarylation

Remarkably, one year later Leadbeater described that biaryls can be synthesized via a Suzuki-type coupling under transition-metal free conditions [51, 52]. The reaction conditions were almost identical to those reported for the ligand-free process, with the difference being that a larger amoimt of Na2C03 and arylboronic acid were used. Only one successful example of a heteroaryl haUde substrate is shown namely, the coupling of 2-bromopyridine with phenylboronic acid (Scheme 32). 3-Bromothiophene did not couple under the same reaction conditions. Unfortimately, attempts to use heteroarylboronic acids such as 3-pyridinylboronic acid, 3-thienylboronic acid, and lH-indol-5-ylboronic acid on 4-bromoacetophenone completely failed. 

A mild and efficient a-heteroarylation of simple esters and amides via nucleophilic aromatic substitution has been described <06OL1447>. Treatment of 2-chloro-benzo[//Jthiazole 99 with tert-butyl propionate in the presence of NaHMDS under nitrogen furnishes tert-butyl 2-(benzo[c(jthiazol-2-yl)propanoate 100. When the same reaction is preformed initially under nitrogen and then exposed to air, the hydroxylation product 101 is obtained. This method offers two desirable features that are either complementary or improvements to the palladium-catalyzed a-arylation reactions. First, heteroaryl chlorides... 

A practical a-heteroarylation of simple esters or amides has been developed via nucleophilic aromatic substitution. Exposure of chlorothiadiazoles 317 and 319 to NaHMDS and tert-butyl acetate or iV-dimethylacetamide leads to the formation of functionalized... 

Palladium chemistry involving heterocycles has its unique characteristics stemming from the heterocycles inherently different structural and electronic properties in comparison to the corresponding carbocyclic aryl compounds. One example illustrating the striking difference in reactivity between a heteroarene and a carbocyclic arene is the heteroaryl Heck reaction (vide infra, see Section 1.4). We define a heteroaryl Heck reaction as an intermolecular or an intramolecular Heck reaction occurring onto a heteroaryl recipient. Intermolecular Heck reactions of carbocyclic arenes as the recipients are rare [12a-d], whereas heterocycles including thiophenes, furans, thiazoles, oxazoles, imidazoles, pyrroles and indoles, etc. are excellent substrates. For instance, the heteroaryl Heck reaction of 2-chloro-3,6-diethylpyrazine (1) and benzoxazole occurred at the C(2) position of benzoxazole to elaborate pyrazinylbenzoxazole 2 [12e]. 

A particularly elegant domino Heck reaction involving 4-bromoindole and bromo(indolyl)maleimide 251 to give N-methylarcyriacyanin A (252) in one operation was reported by Steglich [173]. This alkaloid could also be prepared from triflate 253 in higher yield in a heteroaryl Heck reaction. 

Miura s group carried out a heteroaryl Heck reaction of bromobenzene and 1-methylimidazole and isolated both mono-arylation (53%) and bis-arylation products [45], In accord with Ohta s observation, the first arylation took place at the electron-rich C(5) and the second arylation occurred at the more electron-poor C(2). 

Walker and associates described a heteroaryl Heck reaction of 2,4-dimethoxy-5-iodopyrimidine with thiophene [78], They found that it was advantageous to carry out the thienylation in the presence of water as opposed to anhydrous conditions. Thienylation of less reactive 2,4-dimethoxy-5-bromopyrimidine gave the product in a lower yield (38%). 

As a class, these pigments include 1-aminoanthraquinone compounds which bear free amino groups, and also derivatives in which the primary amino group is substituted by an aryl or a heteroaryl moiety. Only very few representatives are industrially important. 

Intermolecular or intramolecular Heck reaction that occurs onto a heteroaryl recipient. 

A recent review on four-membered heterocycles formed from imino-phosphoranes concentrates on the preparation and the reactivity of 2,4-diimino-l,3-diazetidine and related compounds (93JPR305). As an example, the synthesis via bisiminophosphorane 85 is described in Scheme 42. The bisiminophosphorane has both a heteroaryl and a styryl site. From a mechanistic view, the reaction of the bisiminophosphorane proceeds with aryl isocyanate formation via an aza-Wittig mechanism. Intermediate car-bodiimide formation (86) occurs directly on the iminophosphorane moiety... 

TABLE 6.2. 2-[2-(a-HETEROARYL)ETHENYL]-4(5//)-OXAZOLONIUM PERCHLORATES FROM OXAZOLONIUM SALTS AND ALDEHYDES ... 

Transamination reactions have also been described for 4-(aminomethylene)-2-substituted-5(47T)-oxazolones. As an example, displacement of the A-methyl-heteroarylamino group of a 4-[(A-heteroaryl-A-methyl)aminomethylene]-2-phen-yl-5(47T)-oxazolone 420 by an a-amino acid derivative produces p-amino-a,(3-dehydro-a-amino acid precursors 421 (Scheme 7.137). ... 

Formation of the antiasthmatic imidazoquinoline compound was achieved through the closure of the central pyridine ring in a heteroaryl Heck reaction (4.28.), The best results were obtained in the presence of tetrabutylammonium chloride without any added ligand (Jeffery s ligand free variant).32... 

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