Reactions of Organozinc Compounds

The application of the ketone synthesis has continued. Phenylethynyl and vinylethynyl ketones have been synthesized by the reaction of appropriate acid halides with phenylethynylzinc chloride 521, 522) and vinyl-ethynylzinc chloride 552), respectively. 

The Reformatsky reagent from diethyl bromomalonate reacts with a variety of aldehydes. The resulting alcoholates react with acetyl chloride to give the corresponding acetates 174). 

The reaction of the Reformatsky reagents with a-chloro ethers gives j8-alkoxycarboxylic acid esters 73, 290, 291, 294, 526). For example, 

R OCHaCl + R CHBrCOOR + Zn 0(CHaCl)a + RCHBrCOOR + Zn R OCHsCl + R OOCCHaCHBrCOOR  

A complete product study was reported on the reaction of bis(chloro-methyl) ether with a-bromoisobutyrate in the presence of zinc (557). The reaction of chloromethyl benzoate with a Reformatsky reagent RCH-(ZnBr)COOR gives PhC(OH)(OCH2CHRCOOR )(CHRCOOR ) (296). 

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Perhaps the most investigated reaction of organozinc compounds is their addition to the carbonyl group of aldehydes. A broad range of simple and functionalized diorganozincs and a great variety of aldehydes have been studied in this transformation. The reaction furnishes chiral secondary alcohols, which are essential building blocks in the synthesis of natural products and other important compounds. Recent studies of this transformation have been devoted to its asymmetric catalytic versions (Scheme 103). 

One of the important new directions in the study of addition reactions of organozinc compounds to aldehydes is the use of ionic liquids. Usually, application of these compounds in reactions with common organometallic reagents has a serious problem ionic solvents are usually reactive toward them, particularly Grignard and organolithium derivatives. It has been recently reported that carbonyl compounds react with allylzinc bromide formed in situ from allyl bromide and zinc in the ionic liquid 3-butyl-l-methylimidazolium tetrafluoroborate, [bmim][BF4].285 Another important finding is that the more reactive ZnEt2 alkylates aldehydes in a number of ionic liquids at room temperature.286 The best yields (up to 96%) were obtained in A-butylpyridinium tetrafluoroborate, [bpy][BF4] (Scheme 107). 

The stereocontrolled (at the C—Zn center) preparation and reactions of organozinc compounds are, however, an active field of research. Diastereomeric cyclic secondary organozinc halides were prepared as mixtures of isomers that appear to be configurationally stable under the experimental reaction conditions used, although the distribution of products can be electrophile-dependent Other cyclic and acyclic diastereomerically... 

Palladium and nickel catalysed reactions of organozinc compounds... 

D. Cross-coupling Reactions of Organozinc Compounds in the Presence of... 

The past decade has seen extensive development of cross-coupling reactions of organozinc compounds and organic halides catalyzed by nickel or palladium catalysts. Although nickel-based catalysts are more reactive with respect to the organic halide partner, the number of failures with these catalysts and the greater selectivity realized with palladium-based catalysts have resulted in the almost exclusive use of the latter group of catalysts for these reactions. 

Whereas uncatalyzed substitution reactions of organozinc compounds are limited to very reactive electrophiles, metal-transmetallated organozinc compounds are able to perform substitution reactions on various electrophiles. In the case of conjugated electrophiles, these zinc copper reagents can follow a Sn2 or Sn2 mechanism. 

III. Grignard-Type Addition Reactions of Organozinc Compounds. ... 

Miscellaneous Reactions of Organozinc Compounds which Give Cyclopropane Derivatives from Olefins... 

GRIGNARD-TYPE ADDITION REACTIONS OF ORGANOZINC COMPOUNDS... 

The reaction of cobalt(II) salts with dfganolithiums or -magnesiums leads to a fast decomposition even at low temperature, providing homocoupling products. These transmetallations have therefore found limited applications in organic synthesis [90]. It was recently reported that the reaction of organozinc compounds with cobalt(II) bromide in... 

The direct method (the first one) is preferred because it gives a better yield and it does not proceed through any highly poisonous intermediates ((CH3)2Hg is a very poisonous compound). A good solvent for the preparation and reaction of organozinc compounds is diethyl-ether. 

An interesting feature of the reaction of organozinc compounds is shown in Scheme 4. Reaction of /3-iodozinc derivative 1 with benzoyl chloride in the presence of Pd[P(o-tol)3l4 catalyst gave the iyn-isomer 2, while the anti-isomer 3 was produced by reaction of 1 with benzaldehyde followed by oxidation. The nucleophilic addition to the aldehyde occurs via inversion of the configurations in contrast to the Pd-catalyzed cross-coupling reaction, which proceeds via retention of the configurations. 

The Pd-catalyzed cross-coupling reaction of organozinc compounds is fast and can be carried out under mild conditions. Simple extracting work-up gives the desired products, since the by-product of the reaction is water-soluble Z11X2. When the functional groups present do not easily react with organozinc compounds, this method is the most... 

Palladium-catalyzed coupling reactions of organozinc compounds with acyl halides are the fastest and mildest among the known methods using a variety of organometallic compounds. 

Pd-catalyzed cross-coupling reactions of organozinc compounds with alkenyl and aryl halides can be carried out under mild conditions and are the fastest among all reactions using various organometallics. The reaction with acyl hahdes is not an exception. Usually, the reaction is completed at lower than room temperature within a couple of hours [38,251 - 25 3]. As organozinc compounds are coordinatively unsaturated and sterically less bulky, the transmetallation step is facilitated [29] ... 

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