Halides, aryl, arylation coupling

In addition to sodium, other metals have found application for the Wurtz coupling reaction, e.g. zinc, iron, copper, lithium, magnesium. The use of ultrasound can have positive effect on reactivity as well as rate and yield of this two-phase reaction aryl halides can then even undergo an aryl-aryl coupling reaction to yield biaryls. ... 

In a Kumada-Corriu reaction, an aryl halide is oxidatively coupled with a homogeneous nickel(ll)-phosphine catalyst [2], This species reacts with a Grignard reagent to give biaryl or alkylaryl compounds. Later, palladium-phosphine complexes were also successfully applied. By this means, stereospecific transformations were achieved. 

These results were significantly improved by the same authors using the well-defined pre-catalyst 16 (PEPPSl-lPr), that is able to promote the coupling of alkyl halides, aryl halides or alkyl sulphonates with alkylzinc chlorides or bromides [83,84]. 

The synthesis of 1-alkenylboronic acids from l-alkenylmagnesiums or -lithiums suffers from difficulty in retaining the stereochemistry of 1-aikenyl halides, but the palladium-catalyzed coupling reaction of diboron 82 with 1-aikenyl halides or tri-flates directly provides 1-alkenylboronic esters (Scheme 1-43) [157, 158]. Although the reaction conditions applied to the aryl coupling resulted in the formation of an... 

There are many other transition-metal catalyzed coupling reactions that are based on organic halides in aqueous media. One example is the coupling of terminal alkyne with aryl halides, the Sonogashira coupling, which has been discussed in detail in the chapter on alkynes (Chapter 4). An example is the condensation of 2-propynyl or allyl halides with simple acetylenes in the presence of copper salts. 

Benzylmanganese halides, prepared by the insertion of Rieke s manganese into benzylic halides, undergo cross-coupling with aryl iodides in the presence of Pd(PPh3)4.175... 

The pyrrole component can also be employed as the aryl halide in Suzuki coupling with aryl boronic acids. Thus, Chang has effected several such reactions using phenylboronic acid and halopyrroles such as 70 and 71 [60]. 

Halogenated pyrroles can serve as the aryl halide in Stille couplings with organotin reagents. Scott has used this idea to prepare a series of 3-vinylpyrroles, which are important building blocks for the synthesis of vinyl-porphyrins, bile pigments, and indoles [77]. Although 3-chloro-and 3-bromopyrroles fail completely or fared poorly in this chemistry, 3-iodopyrroles 101 work extremely well to yield 3-vinylpyrroles 102. 

Unlike normal all-carbon aryl halides, regioselective Negishi coupling reaction of 2,3-dibromofuran 27 with 2-furylzinc chloride was achieved at C(2) to afford bisfuran 28 [35]. 

Arylation of cycloalkenes.1 Aryl halides undergo Heck coupling with cy-cloalkenes in the presence of a palladium catalyst. The reaction involves addition of an arylpalladium intermediate to the double bond followed by elimination of a palladium hydride. 

Catalytic processes based on the use of electrogenerated nickel(O) bipyridine complexes have been a prominent theme in the laboratories of Nedelec, Perichon, and Troupel some of the more recent work has involved the following (1) cross-coupling of aryl halides with ethyl chloroacetate [143], with activated olefins [144], and with activated alkyl halides [145], (2) coupling of organic halides with carbon monoxide to form ketones [146], (3) coupling of a-chloroketones with aryl halides to give O -arylated ketones [147], and (4) formation of ketones via reduction of a mixture of a benzyl or alkyl halide with a metal carbonyl [148]. 

The Pd(0)-catalyzed electroreductive coupling of aryl halides (303) is a currently relevant topic. In the electroreduction of aryl halides (307) the replacement of the halogen atom by hydrogen predominantly takes place giving (306). Difficulties are encountered, however, when aryl-aryl coupling products (305) via (304) are wanted (Scheme 116). An efficient electroreductive coupling of aryl bromides (307) (X = Br) and iodides (307) (X = I) into biaryls (310) has been shown to occur in a DMF/Et4NOTs/(Pb cathode) system in the presence of Pd(0) and/or Pd(II) catalysts (Scheme 117) [440]. 

Cross coupling between an aryl halide and an activated alkyl halide, catalysed by the nickel system, is achieved by controlling the rate of addition of the alkyl halide to the reaction mixture. When the aryl halide is present in excess, it reacts preferentially with the Ni(o) intermediate whereas the Ni(l) intermediate reacts more rapidly with an activated alkyl halide. Thus continuous slow addition of the alkyl halide to the electrochemical cell already charged with the aryl halide ensures that the alkyl-aryl coupled compound becomes the major product. Activated alkyl halides include benzyl chloride, a-chloroketones, a-chloroesters and amides, a-chloro-nitriles and vinyl chlorides [202, 203, 204], Asymmetric induction during the coupling step occurs with over 90 % distereomeric excess from reactions with amides such as 62, derived from enantiomerically pure (-)-ephedrine, even when 62 is a mixture of diastereoisomcrs prepared from a racemic a-chloroacid. Metiha-nolysis of the amide product affords the chiral ester 63 and chiral ephedrine is recoverable [205]. 

In addition to aryl-aryl coupling, the Stille reaction can be used with alkenylstan-nanes and alkenyl halides and triflates.125 The reactions occur with retention of configuration at both the halide and the stannane. These reactions have become very useful in stereospecific construction of dienes and polyenes, as illustrated by some of the examples in Scheme 8.10. 

Palladium-catalyzed aryl-aryl coupling, 66, 70 PALLADIUM-CATALYZED COUPLING OF ARYL HALIDES, 66, 67 Palladium sponge, 66, 54... 

These aryl—aryl couplings are applications of the Ni(O) and Ni(II)-catalyzed cross-couplings of unreactive oiganic halides with Grignard reagents. This work has been extensively reviewed (90). 

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