Aryl with arylzinc reagents

Scheme 14.24 Ni-catalysed cross-coupling of aryl/alkenyl pivalates with arylzinc reagents.

Even if hundreds of chiral catalysts have been developed to promote the enantioselective addition of alkylzinc reagents to aldehydes with enantioselectivities over 90% ee, the addition of organozinc reagents to aldehydes is not a solved problem. For example, only very few studies on the addition of vinyl groups or acetylides and even arylzinc reagents to aldehydes have been published, in spite of the fact that the products of these reactions, chiral allylic, propargylic and aryl alcohols, are valuable chiral building blocks. 

The use of expensive and unstable ZnPli2 in the preparation of chiral di-arylmethanol derivatives, with electronically and sterically similar aryl rings, made this approach less attractive for the enantioselective synthesis. In order to avoid this inconvenience, other alternative preparations of arylzinc reagents were evaluated.As a first choice, Yus et al. proposed the use of arylboronic adds as a viable source of phenyl (Scheme 4.19). Thus, the reaction of various boronic acids with an excess of ZnEt2 at 70 °C gave the corresponding arylzinc intermediates (probably aryl(ethyl)zincs), which were trapped by reaction with dif-... 

Commercially available Pd(PtBu3)2 is a unique, air-stable 14e Pd° complex, an excellent catalyst for cross-coupling reactions of aryl chlorides. The ability of P Bu3 to stabilize such a coordin-atively unsaturated, extremely reactive, and yet easily manageable form of Pd° is one of the most amazing and fruitful recent findings in Pd-based catalysis. The cross-coupling of arylzinc reagents with aryl or vinyl chlorides can be readily accomplished with as little as 0.03% of this catalyst. Both electron-rich and sterically hindered substrates are welcome in this protocol.404... 

Many aryl- and heteroarylzinc reagents have been coupled with halopyridines. Examples include arylzincate 20 derived from ethyl benzoate [3], thienylzinc reagent 21 [16], 2-imidazolylzinc chloride 22 [17], pyrazolylzinc reagent 23 [18], and 2-pyridylzinc reagent 24 [19]. 

Arylzinc reagents can be made from aryl halides with activated zinc118 or from Grignard reagents by metal-metal exchange with zinc salts.119... 

The formation of arylzinc reagents can also be accomplished by using electrochemical methods. With a sacrificial zinc anode and in the presence of nickel 2,2-bipyridyl, polyfunctional zinc reagents of type 36 can be prepared in excellent yields (Scheme 14) . An electrochemical conversion of aryl halides to arylzinc compounds can also be achieved by a cobalt catalysis in DMF/pyridine mixture . The mechanism of this reaction has been carefully studied . This method can also be applied to heterocyclic compounds such as 2- or 3-chloropyridine and 2- or 3-bromothiophenes . Zinc can also be elec-trochemically activated and a mixture of zinc metal and small amounts of zinc formed by electroreduction of zinc halides are very reactive toward a-bromoesters and allylic or benzylic bromides . ... 

Fu s group showed more recently that ot-bromo ketones 6b can be coupled with arylzinc halides catalyzed by 5 mol% NiCl2 DME and 6.5 mol% of PyBOX ligand 5e with good asymmetric induction providing benzylic ketones in 71-93% yield and 72-96% ee (entry 12) [54]. The lower ee values were obtained with orf/io-substituted aryl bromo ketones, while orf/to-substituted arylzinc reagents as well as a-branched bromo ketones did not react. 

Radical addition/cross-coupling products 61 were obtained in 60-91% yield when Ni(dppf)Cl2 was applied as a catalyst in reactions of alkyl halides 60 with 2,3-disubstituted dienes 59 and aryl Grignard or arylzinc reagents (Fig. 12). Competition experiments of n-, sec-, and ferf-butyl bromide with 2,3-dimethylbutadiene... 

The formation of arylzinc reagents can also be accomplished by using electrochemical methods. With a sacrificial zinc anode and in the presence of nickel 2,2-bipyridyl, polyfunctional zinc reagents of type 5 can be prepared in excellent yields (Equation (5)). An electrochemical conversion of aryl halides to arylzinc compounds can also... 

The reaction was exploited very recently in a solid phase synthesis of biaryls. Aryl zinc bromides undergo palladium catalyzed coupling reactions with aryl bromides bound to a polystyrene resin. The product can be released from the resin by transesterification [44]. Ni(0) catalysed homocoupling of arylzinc reagents could also be realised using aryl triflates [45], as well as aryl tosylates and mesylates [46]. 

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