Nucleophiles dialkylzinc reagents

Dialkylzinc reagents combine with BINOL to generate, in situ, a catalyst for homogeneous epoxidation of (/y)-o /3-enoncs to the corresponding f raws-epoxy ketones. TBHP and cumene hydroperoxide (CHP) are effective terminal oxidants for this process ees of up to 96% have been achieved. Mechanistic investigations point towards an electrophilic activation (Scheme 11) of the substrates by the chiral BINOL-zinc catalyst and a subsequent nucleophilic attack of the oxidant227... 

The slow nucleophilic addition of dialkylzinc reagents to aldehydes can be accelerated by chiral amino alcohols, producing secondary alcohols of high enantiomeric purity. The catalysis and stereochemistry can be interpreted satisfactorily in terms of a six-membered cyclic transition state assembly [46,47], In the absence of amino alcohol, dialkylzincs and benzaldehyde have weak donor-acceptor-type interactions. When amino alcohol and dialkylzinc are mixed, the zinc atom acts as a Lewis acid and activates the carbonyl of the aldehyde. Zinc in this amino alcohol-zinc complex is regarded as a kind of chirally modified Lewis acid. Various kinds of polymer-supported chiral amino alcohol have recently been prepared and used as ligands in dialkylzinc alkylation of aldehydes. 

Comma, P. J. Beck, A. K. Seebach, D., A Simple Batch Reactor for the Efficient Multiple Use of Polymer-bound a,a,a ,a -Tetraaryl-l,3-dioxolane-4,5-dimethanol Titanates in the Nucleophilic Addition of Dialkylzinc Reagents to Aldehydes. Org. Process Res. Dev 1998, 2,18. 

Although the level of enantioselectivity observed in this study was modest, this contribution has documented for the first time the use of a dialkylzinc reagent for the stereoselective addition of a carbon nucleophile to the imine function. 

Finally, a completely new use of planar-chiral ferrocenes has been recently disclosed by Fu and co-workers [24]. Compounds of type 25 and 26 were prepared as racemic mixtures and obtained as pure enantiomers via semipreparative HPLC. Derivatives 25, analogues of 4-(dimethylamino)pyridine, were used as nucleophilic catalysts in the kinetic resolution of chiral secondary alcohols [24a,b]. The ami-noalcohol system 26, on the other hand, is an effective chiral ligand for the asymmetric addition of dialkylzinc reagents to aldehydes (up to 90% ee) [24c]. 

When the p-substituent in the cyclic enone is an ester group, the enantioselective formation of the quaternary stereogenic centre is very effective using ligand L9 (Scheme 65) [99]. The scope of this reaction includes both alkyl (including methyl) and aryl dialkylzinc reagents as nucleophiles and methyl and more sterically... 

Nitrones have a more reactive C=N bond toward nucleophilic addition compared to imines. In spite of this fact, there have been only a limited number of studies on the nucleophilic addition reactions of nitrones, particularly organometallic reagents.352-355 During the last decade, research related to reactions of nitrones with zinc-containing reagents was essentially focused on (i) dialkylzinc-assisted alkynylations356-358 and vinylations359 of nitrones, (ii) catalytic asymmetric nucleophilic additions to the C=N bond,360-364 and (iii) nitrone allylations by allylzinc halides.365,366... 

Compared with aldehydes, ketones and esters are less reactive electrophiles in the addition of dialkylzincs. This makes it possible to perform a unique reaction that cannot be done with alkyllithium or Grignard reagents, which are too reactive nucleophiles. For example, Watanabe and Soai reported enantio- and chemoselective addition of dialkylzincs to ketoaldehydes and formylesters using chiral catalysts, affording enantiomerically enriched hydroxyketones 30 (equation 12)43 and hydroxyesters 31 in 91-96% , respectively (equation 13). The latter are readily transformed into chiral lactones 3244. 

The reaction of LVII" and some related heterocycles with a large number of nucleophiles has been investigated thoroughly. Among the nucleophiles, which with few exceptions form sulfonium salts by their reaction with LVII", are water [194, 195], carboxylate ions [196, 197], pyridine [198], organometallic compounds like dialkylmercury and dialkylzinc [199], and Grignard reagents [200], alkenes and alkynes [201], and various aromatic compounds [202-204]. 

The intrinsic difficulty in preparing various titanium derivatives with die desired alkyl group may be overcome by using reagent systems consisting of TiCU as the chelating agent, and a suitable nucleophile like dialkylzinc, allylsilanes, allylstannanes, etc. The utilization of other nucleophiles, like silyl enol ethers will be covert in Part 1 of Volume 2. 

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