Dialkylzinc compounds addition

Many 1,4-diazabutadiene adducts of dialkylzinc compounds show unusual reactivities (see also Section 2.06.10.7), such as the intramolecular electron transfer from zinc to the chelating ligand and the subsequent dimerization of these radicals.127 In solution, the carbon-carbon coupled dimer [MeZn(ButN=CHCH=NBut)2ZnMe] 71 is in equilibrium with its radical monomers (Scheme 56). Addition of potassium to a THF solution of the dimer produced cleanly 72, the first heteroleptic alkyldiamidozincate. 

Nucleophilic addition of metal alkyls to carbonyl compounds in the presence of a chiral catalyst has been one of the most extensively explored reactions in asymmetric synthesis. Various chiral amino alcohols as well as diamines with C2 symmetry have been developed as excellent chiral ligands in the enantiose-lective catalytic alkylation of aldehydes with organozincs. Although dialkylzinc compounds are inert to ordinary carbonyl substrates, certain additives can be used to enhance their reactivity. Particularly noteworthy is the finding by Oguni and Omi103 that a small amount of (S)-leucinol catalyzes the reaction of diethylzinc to form (R)-l-phenyl-1 -propanol in 49% ee. This is a case where the... 

In another study Feringa et al. [20] reported a catalytic enantioselective three-component tandem conjugate addition-aldol reaction of dialkyl zincs. Here, zinc enolates were generated in situ via catalytic enantioselective Michael addition of dialkylzinc compounds to cydohexenone in the presence of a chiral Cu catalyst. Their diastereoselective reaction with an aldehyde then gave trans-2,3-disubstituted cyclohexanones in up to 92% yields and up to >99% ees (Scheme 9.11). 

Fig. 10.39. Preparation of a dialkylzinc compound B and its subsequent enantioselective addition to an aldehyde.

Reagents of this type are suitable for performing catalytic asymmetric additions to aldehydes. For example, an enantiomerically pure Lewis acid is generated in situ from Ti(OiPr)4 and the enantiomerically pure bis(sulfonamide) C. It catalyzes the enantioselective addition of functionalized (or unfunctionalized) dialkylzinc compounds to widely variable aldehydes. There is no detailed, substantiated rationalization of the underlying addition mechanism in this case. 

A different method for the catalytic asymmetric addition of a dialkylzinc compound—Et2Zn and aromatic aldehydes have almost always been used—is shown in Figure 8.31. With regard to stereoselective synthesis, this method has an importance... 

Protected 1,3-an/i-diols 14 are accessible by the highly stereoselective Lewis acid promoted addition of dialkylzinc compounds to 4-acet-oxy-1,3-dioxanes 13 (Scheme 3) [5]. The two d, -orientated alkyl substituents at C2 and C6 fix the carboxonium ion 15 in the half-chair conformation, which undergoes preferential axial attack by the dialkylzinc under stereoelec-tronic control. The 4-acetoxy-1,3-dioxanes 13 may be synthesized from the Seebach 1,3-diox-an-4-ones 12 by reduction with diisobutylalumi-num hydride (DIBAH) and acetylation. Since dialkylzinc compounds are now readily available and are compatible with many functional groups, this... 

As a result of the Schlenk-type equilibrium (equation 2), alkylzinc halide solutions are believed to contain some amounts of the corresponding dialkylzinc compound and zinc halide salt. The equilibrium usually lies on the left side in such a way that the alkylzinc halide compound is favored. Nevertheless, as already mentioned in Section 2, the equilibrium can be shifted to the right by distillation of the more volatile dialkylzinc derivative or by addition of complexing agents to remove the zinc dihahdes from the solution. 

Some heteroleptic (see Heteroleptic Compound) alkylzinc amides have been prepared by addition reaction of dialkylzinc compounds (ZnR2) on l,4-di-tert-butyl-l,4-diaza-l,3-butadiene (t-BuN=CHCH=N-t-Bu). Extensive studies ... 

In contrast to Grignard reagents, dialkylzinc compounds are inert to carbon monoxide at atmospheric pressure either in the absence of solvents or in solution in THF, diglyme, ether, or benzene. Although Rathke and Yu reported in 1972 that the addition of potassium tert-butoxide in stoichiometric amounts promoted the absorption of carbon monoxide, it is now known that the actual reactive species was the corresponding zincate compound (R2ZnO-t-Bu) K+. The only zinc carbonyl species reported so far has been observed by NMR studies of CO on zeolite ZnY and poly crystalline ZnO, at low temperature. " Before this report, such species were only suggested from infrared and photoelectron studies of CO weakly bound to ZnO. 

The reduction predominates over addition in the reaction of /(-branched dialkylzinc compounds with alkyl aryl ketones the enantiomeric excess ranges from 2.4-15.2% with ( + )-bis[(S )-2-methylbutyl]zinc (11 f)1 °5. 

Commercially available lubricating oils caused relatively little deactivation in comparison with lead and phosphorus contamination from fuel. However, Acres and Cooper (4) demonstrated that when the normal dialkylzinc dithiophosphate additive was replaced by similar compounds without the heavy metal—such as in some forms of ashless oil—catalyst deactivation was rapid. Again the nontoxicity of phosphorus compounds in the presence of heavy metal was associated with formation of inorganic phosphates. 

Even the very efficient enantioselective catalysts used in organozinc addition reactions to carbonyl compounds failed to catalyze the corresponding addition reactions to nonactivated imines such as N-silyl-, N-phenyl-, or A-benzyl-imines. However, enantioselective additions of dialkylzinc compounds to more activated imines, like A7-acyl- or N-phosphinoyl-imines, in the presence of catalytic or stoichiometric amounts of chiral see Chiral) aminoalcohols, have been recently reported. For example, in presence of 1 equiv of (N,N-dibutylnorephedrine) (DBNE) diethylzinc reacts with masked N-acyl imines like A7-(amidobenzyl)benzotriazoles, to give chiral N- -phenylpropyl) amides with up to 76% e.e. (equation 68). 

Seebach, D., Behrendt, L. and Felix, D. 1991. Titanate-catalyzed enantioselective addition of dialkylzinc compounds—Generated in situ from Grignard reagents in ether— To aldehydes. Angm Chem. Int. Ed. 30 1008-1009. 

Other Lewis acid mediated C-C bond forming reactions of silylated C-nucleophiles include the Mukaiyama aldol and Michael additions of enolsilanes ), the related reaction of allylsilanes described by Sakurai ) as well as similar reactions of Me3SiCN ). Other "inert C-nucleophiles such as dialkylzinc compounds also react with carbonyl compounds in the presence of Lewis acids ). We ourselves have utilized many of these processes in performing stereoselective reactions, particularly in achieving diastereofacial selectivity in the reactions... 

Dual enantioselective control in the Cu-catalysed conjugate addition of dialkylzinc compounds to acyclic and cyclic enones has been realized in the presence of functionalized A -heterocyclic carbene ligands. " For example, a high degree of asymmetric catalysis (up to 96% ee) has been achieved using a (hydroxy amide)-functionalized azolium salt (19). Most likely the selectivity appears because of the facial selection of the enone, which is a result of steric repulsion between the alkyl group on the azolium ring and the alkyl substituent at the / -position of the enone. 

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