Heteroaromatic bromides

The Heck coupling reaction appeared to be a route of choice to achieve the synthesis of the modified-DIOP ligands. We previously studied the palladium-catalyzed coupling of acrolein and acrolein acetals with several polyaromatic and heteroaromatic bromides either in the presence of homogeneous or heterogeneous catalytic systems (6, 7). After optimization of the reaction conditions, high conversions and selectivities were achieved except with anthracenyl derivatives (8). Based on these results, we developed the synthesis of the desired ligands. The... 

Notably, the presence of iPrI in the reaction medium (generated during the arylzinc preparation or included as an additive) accelerates the cross-coupling reaction, possibly by radical catalysis ]130]. Aromatic and heteroaromatic bromides react with diarylzinc reagents at 25 °C within minutes to yield the corresponding biaryl compounds, as shown with the preparation of 144 from 142 with 143. 

Early in 2007, Letavic and Ly published a letter describing aminocarbonylations of heteroaromatic bromides using Mo(CO)6 as the CO source, thereby further demonstrating the usefulness of this type of reaction for the rapid generation of a series of dmglike stmctures. Heteroaromatic bromides used in these examples were different pyridines and pyrimidines, 3-bromoisoquinoline, 4-bromoindole, 2-bromothiazole, and 5-bromo-l-methyl-lH-imidazole. Sixteen heteroaromatic... 

Letavic, M.A. and Ly, K.S. (2007) Microwave assisted, palladium catalyzed aminocarbonylations of heteroaromatic bromides using solid Mo(CO),s as the carbon monoxide source. Tetrahedron Letters, 48, 2339-2343. 

In the reaction of Q,/3-unsaturated ketones and esters, sometimes simple Michael-type addition (insertion and hydrogenolysis, or hydroarylation, and hydroalkenylation) of alkenes is observed[53,54]. For example, a simple addition product 56 to methyl vinyl ketone was obtained by the reaction of the heteroaromatic iodide 55[S5]. The corresponding bromide affords the usual insertion-elimination product. Saturated ketones are obtained cleanly by hydroarylation of o,/3l-unsaturated ketones with aryl halides in the presence of sodium formate, which hydrogenolyses the R—Pd—I intermediate to R— Pd—H[56]. Intramolecular hydroarylation is a useful reaction. The diiodide 57 reacts smoothly with sodium formate to give a model compound for the afla-toxin 58. (see Section 1.1.6)[57]. Use of triethylammonium formate and BU4NCI gives better results. 

Heteroaromatic esters such as 493 and amides are produced by the carbo-nylation of heterocyclic bromides[347,348]. Even dichloropyrazine (494) and chloropyridine are carbonylated under somewhat severe conditions (120 C, 40 atm)[349]. The carbonylation of trifluoroacetimidoyl iodide (495) proceeds under mild conditions, and can be used for the synthesis of the trifluoromethyl-glycine derivatives 496 and 497(350]. 

The photochemical introduction of a trifluoromethyl group into aromatic and heteroaromatic rings, such as uracil, can be performed also with trifluoromethyl bromide [/5/] (equation 131)... 

Both benzothiazolyl and berizolriazoly] units have been employed as heteroaromatic anion-stabilizing groups for metalated epoxides (Scheme 5.47) [71]. The successful use of a simple alkyl bromide as electrophile with 200 is notable. 

When aqueous solutions of aromatic and heteroaromatic diazonium salts are treated with cuprous chloride, -bromide, or -cyanide, the corresponding aromatic chlorides, bromides, or cyanides are formed, respectively. In many cases the anions mentioned must be present in excess. This reaction, the Sandmeyer reaction, was discovered by Sandmeyer in 1884. A variant carried out with copper powder and HBr or HC1 was for many years called the Gattermann reaction (Gattermann, 1890). As it is often confused with the Gattermann-Koch reaction (ArH + CO + HC1 ArCHO), and as it is mechanistically not significantly different from Sandmeyer s procedure, the name Gattermann reaction should be avoided. 

This is a problem that has been reported by several researchers in other cya-nation methods on heteroaromatic halides. (Hetero)aryl chlorides have also been tackled via in situ halogen exchange to (hetero)aryl bromides followed by sequential cyanation (Scheme 71). For this microwave-assisted process an equimolar amount of NiBr2 and a two-fold excess of NaCN were used. The only heteroaromatic chloride tested was 2-chloropyridine. Although the procedures described involve the use of significant amounts of nickel salts, a clear advantage is that the reactions can be performed in air. Moreover, the cyanat-ing reagents are easily removed since they are water soluble. 

To overcome this drawback, we studied the arylation of diethyl 2-vinyl-[l,3]-dioxolane-4,5-diacetate 2 with several bromo polyaromatic and heteroaromatic substrates (Table 21.1 and Scheme 21.4). In parallel, the Heck coupling of several vinyl dioxolane derivatives with aryl bromides was studied in the presence of homogeneous catalysts (Table 21.1). 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

Furthermore, this protocol can be employed for the highly efficient introduction of two (159) and even three allene entities (161) into an aromatic workbench (Scheme 2.51). Thus, by starting with two different halides, e.g. 162 (or with identical halides in different positions of a heteroaromatic substrate), two diverse allenic groups can be introduced by sequential coupling reactions. Furthermore, a structurally different bisallene 166 was also assembled via a twofold coupling of the bispro-pargyl bromide 165 with the functionalized aryl iodide 164 [85],... 

Finally, polymer 594 has been used as an arene-catalyst to activate nickel from nickel(II) chloride and lithium, in order to perform hydrogenation of different organic substrates such as afkenes, afkynes, carbonyl compounds and their imines, alkyl and aryl halides (chlorides, bromides and iodides), aromatic and heteroaromatic compounds as well as nitrogen-containing systems such as hydrazines, azoxy compounds or Af-amino oxides, giving comparable results to those obtained in the corresponding reaction in solution . 

Anodic addition to an electron-rich heteroaromatic compound is used to transform furan to 2,5-dimethoxy-2,5-dihydrofuran, a valuable synthetic intermediate. Again, an indirect electrochemical process occurs. The bromide ion as redox catalyst is electrochemically oxidized to give bromine, which then acts as chemical oxidant for furan [7] ... 

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