Arylzinc

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. 

These results were comparable to those obtained for the related additions to aldehydes. Furthermore, it was shown that this ligand was also efficient for the addition of arylzinc reagents, providing enantioselectivities of up to 96% ee, as shown in Scheme 4.12. ... 

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-... 

Organozinc compounds are also useful in palladium-catalyzed coupling with aryl and alkenyl halides. Procedures for arylzinc,156 alkenylzinc,157 and alkylzinc158 reagents have been developed. The ferrocenyldiphosphine dppf has been found to be an especially good Pd ligand for these reactions.159... 

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... 

Low-valent cobalt pyridine complexes, electrogenerated from CoCl2 in DMF containing pyridine and associated with a sacrificial zinc anode, are also able to activate aryl halides to form arylzinc halides.223 This electrocatalytic system has also been applied to the addition of aryl bromides containing an electron-withdrawing group onto activated alkenes224 and to the synthesis of 4-phenylquinoline derivatives from phenyl halides and 4-chloroquinoline.225 Since the use of iron as anode appeared necessary, the role of iron ions in the catalytic system remains to be elucidated. 

During the past decade, the main focus of studies related to the well-known349 CeCl3- or SnCl2-catalyzed reactions of allylzinc and benzylzinc halides with imines was the application of polymer-supported chiral imines.350,351 An example of such reactions is shown in Scheme 135.350 It should be noted that attempts using arylzinc reagents in... 

Arylzinc bromides are also capable of reacting with functionalized primary alkyl iodides in the presence of Ni(acac)2-410 The couplings readily occurred in the presence of an equimolar amount of 4-trifluoromethylstyrene at -15 °C. 

A general method for the Pd-catalyzed cross-couplings of alkyl- and arylzinc chlorides with aryl, heteroaryl, and vinyl chlorides was reported by Dai and Fu.420 They determined that the commercially available and air stable complex Pd(PBut3)2 catalyzed these reactions leading to the formation of an sp2)C - sp2)C bond (Scheme 164). Remarkably, bulky biaryls with two, three, or even four 0/7/fo-substituents (e.g., 323) were obtained in very high yields (76-96%). 

Sequential arylzinc formation and Negishi cross-coupling. 

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]. 

The aryl bromide 40, prepared from cross-coupling between 1,2-dibromobenzene and (trimethylsilyl)acetylene, was converted to the corresponding arylzinc halide 41a and arylboronic acid 41b for subsequent coupling with the haloallenes 42 to produce the benzannulated enyne-allene 43 in -40% yield (Scheme 20.10) [38]. Desilylation with tetrabutylammonium fluoride (TBAF) then afforded 44 in 67% yield. 

Similarly, the benzannulated enyne-allenes 172 and 173 were prepared from the propargylic acetates 171 by cuprate addition or by Pd-catalyzed addition of arylzinc chloride (Scheme 20.35) [49]. The presence of a butyl group and a p-anisyl group at the allenic terminus of 173a and 173b permits competition between a formal ene reaction and a formal Diels-Alder reaction leading to 174 and 175, respectively. 

Arylzinc compounds electrochemically generated in the presence of Ni-bpy and zinc salts, already mentioned in Sect. 3.1, can also react with (CF3C0)20 to give the corresponding aryltrifluoromethylketones [55]. 

Sehemc4.t t. Catalytic cycle for the reduction of 317 halides by palladium complexes. Outer circle represents the electrochemical process, I. = Hly,P and. some anionic ligands are omitted for clarity. Tlie inner shunt is the non-elcciroehemieal reaction with arylzinc halides. 

They tried Ni catalysts with chelating amine and phosphine ligands in the reaction of phenylzinc bromide with A-benzoyloxymorpholine 2a and observed that in the presence of NiCl2(PPh3)2, n-alkyl, aryl and functionalized arylzinc chlorides can be aminated with A,A-disubstituted O-benzoylhydroxylamines in good yields (Schemes 20 and 21). Attempted amination of secondary and tertiary alkylzinc chlorides failed to yield the expected product. 

Theuseof DMPU (l,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidmone) as acosolvent in THF has been reported to increase the amination yield of arylzinc chlorides with Erdik and Omiir also reported competitive kinetic studies for the amination of substituted phenylmagnesium bromides and CuCN-catalyzed phenylzinc chlorides with acetone 0-(mesitylenesulfonyl)oxime 6f in THF and analyzed the rate data via the Hammett... 

---