Aryl halides reaction patterns

The value of alkyl halides as starting materials for the preparation of a variety of organic functional groups has been stressed many times In our earlier discussions we noted that aryl halides are normally much less reactive than alkyl halides m reactions that involve carbon-halogen bond cleavage In the present chapter you will see that aryl halides can exhibit their own patterns of chemical reactivity and that these reac tions are novel useful and mechanistically interesting... 

A second general reaction that proceeds by an SrnI mechanistic pattern involves aryl halides. Aryl halides undergo substitution by eertain nueleophiles by a ehain mechanism of the SrnI class.Many of the reactions are initiated photochemically, and most have been conducted in liquid ammonia solution. 

Reaction Patterns of Aryl, Alkenyl and Benzyl Halides and Pseudohalides... 

Reaction patterns of aryl, alkenyl and benzyl halides and pseudohalides... 

The reactivity of the aryl halide decreases in the halide order I > Br, with chlorides failing to react. The reactivity of substituted aryl halides increases upon going from electron-donating substituents through unsubstituted aryl halides to electron-withdrawing substituents. Both reactivity patterns of Arl > ArBr and activation of aryl halides with electron-withdrawing substituents follow the general reactivity of aryl halides in Pd(0) oxidative addition reactions [3],... 

Ring closure reactions taking place by intramolecular addition of an aromatic radical to a double bond have been widely studied on both their regio- and stereochemical aspects [93]. Aryl halides and diazonium salts substituted at ortho- position with a 0-allyl or TV-allyl chain were used for the preparation of 2,3-dihydrobenzofuranes and 2,3-dihydro-1/7-indoles under different reaction conditions. The reaction pattern involves the generation of an aryl radical 20, which reacts with the double bond in a 5-exo trig fashion to afford the exocyclic radical 21, plausible of reduction by a hydrogen donor to obtain the reduced-cyclized product 22 (Sch. 23) [93d,94]. 

The basic pattern of the Heck reaction in its classical form is depicted in Scheme 1. It involves, for instance, the reaction of an aryl halide (1) with an olefin in the presence of a base and a catalytic amount of a palladium complex to give a styrene derivative (2) under elimination of HX. 

The stabilities of the metal-carbon bond formed from oxidative additions are as varied as their mechanistic pathways. Metal-carbon bond strengths increase going down a triad in an isostructural series of complexes. Alkyl migration to CO ligands on the metal to form acyl derivatives is more facile in first-row transition metals because of their lower metal-carbon bond energies. The thermal stability of alkyls vs. acyls does not follow any pattern, except that the availability of a sixth coordination site in ML (acyl) complexes favors the alkyl carbonyl isomer. The corresponding acyl, which can be made by running the reaction of the alkyl or aryl halide in CO (at 1-3 atm), is more stable by... 

Arylmetals can be coupled with alkenyl and alkynyl halides. In these cases, the reverse polarity affinity patterns, i.e., the alkenyl-aryl and alkynyl-aryl coupling reactions... 

The examples described here demonstrate that a variety of aryl halides or triflates with differing substitution patterns, electronic properties, and functional groups can be coupled with primary and secondary amines in high yield. The reactions are only modestly air sensitive, require no special equipment or techniques, and are amenable to large scale synthesis. 

The first example of an o/t/20-alkylation/Mizoroki-IIcck coupling was reported by Catellani [4] in 1997. Using the PNP dimer as a catalyst in the presence of an aryl halide, norbomene, an alkyl iodide, a terminal olefin and a base at room temperature, 1,2,3-trisubstituted benzenes (Scheme 16), were synthesized through alkylation of a palladacycle of type 35, followed by Mizoroki-Heck coupling with an arylpalladium(II) species of type 36. Although the synthetic scope of the reaction was limited, the importance of the report reveals an unprecedented catalytic transformation where two aryl C-H bonds are converted to sp2-sp3 C-C bonds followed by a standard Mizoroki-Heck coupling. The 1,2,3-trisubstitution pattern generated in the products would be very difficult to obtain via conventional methods. 

Cobalt(II) catalyses the coupling of Grignard reagents with chloropyridines"° and of aryl cuprates with aryl halides. This reaction shows unusual substrate reactivity patterns and the mechanism is thought to involve a radical intermediate at the oxidative addition step. 

This reaction displays a diverse functional group tolerance. This reaction showed no significant differences in yields when comparing electron-donating groups and electron-withdrawing groups. The substitution pattern of the aryl halide displayed minimal effects on the isolated yields of the products. 

Allenes undergo facile carbopalladation and are used extensively in organic synthesis. The general reaction patterns of allenes with aryl halides are as follows. In carbopalladation of allene, an Ar group attacks the central sp carbon of the allene system to generate 367 and then the 7r-allylpalladium 368 as an intermediate. Then the attack of a nucleophile mainly on a less substituted terminus yields the alkene 369. Thus 1,2-addition to one of the double bonds in the allene occurs. In the absence of nucleophiles, y3-H elimination gives 2-substituted 1,3-dienes... 

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