Chiral dialkylzincs compounds

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). 

As for the reduction of the ketones, the amphoteric catalysts featuring acidic-basic sites have been found to be very effective for the enantioselective catalysis of C-C bond formation. Thus, Soai et al. were the first to report the enantioselective addition of dialkylzincs to aldehydes using enantiomerically pure phosphin-amides and analogues as chiral catalysts in the presence of titanium tetraiso-propoxide. Numerous chiral organophosphorus compounds have been prepared and applied in a test reaction between benzaldehyde and diethylzinc [48, 49]. An important difference in terms of enantioselectivity was observed between the behavior of P=S (47-48) and P=0 (49) groups. Thus, the enan-... 

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). 

An alternate approach to the asymmetric alkylation of aldehydes with dialkylzinc compounds uses chiral nonracemic titanium-based Lewis add catalysts. This has been primarily achieved using complexes prepared from stoichiometric amounts of Ti(0 Pr)4 and enantiomerically enriched ligands. A variety of BINOL deriva-... 

Benzylic acetates are unreactive toward organozinc compounds. However, various ferrocenyl acetates, such as 236, react with dialkylzinc halides in the presence of BF3 OEt2 with retention of configuration leading to the chiral ferrocenyl derivatives like 237 (Scheme 68) . 

Chirality plays a central role in the chemical, biological, pharmaceutical and material sciences. Owing to the recent advances in asymmetric catalysis, catalytic enantioselective synthesis has become one of the most efficient methods for the preparation of enantiomer-ically enriched compounds. An increased amount of enantiomerically enriched product can be obtained from an asymmetric reaction using a small amount of an asymmetric catalyst. Studies on the enantioselective addition of dialkylzincs to aldehydes have attracted increasing interest. After the chiral amino alcohols were developed, highly enantioselective and reproducible —C bond forming reactions have become possible. 

Nowadays, this chemistry includes a wide range of applications. The organozinc compounds employed in the enantioselective addition include dialkylzincs, dialkenylzincs, dialkynylzincs, diarylzincs and the related unsymmetrical diorganozincs. Electrophiles have been expanded to aldehydes, ketones and imines. Asymmetric amplification has been observed in the enantioselective addition of organozincs. Recently, asymmetric autocatalysis, i.e. automultiplication of chiral compounds, has been created in organozinc addition to aldehydes. 

Much attention has been paid to asymmetric amplification where the enantiomeric excess ( ) of the product is higher than that of the chiral catalyst (equation 35)136. The first experiment on asymmetric amplification was reported by Kagan and coworkers in the Katsuki-Sharpless asymmetric epoxidation of allyl alcohols137. Asymmetric amplification has also been studied in the asymmetric addition of dialkylzincs to carbonyl compounds. 

Organozinc compounds add to conjugated systems. The use of chiral ligands is effective for conjugate addition of diaUcylzinc compounds to a,p-unsaturated ketones, esters, and so on, including conjugated lactones." Many dialkyl-zinc compounds can be used, including vinylzinc compounds.Dialkylzinc... 

Katritzky and Harris reported in 1992 the use of diethylzinc for the chiral amino alcohol-mediated enantioselective addition to the C=N bond in these compounds (Scheme 12) [34]. These substrates act as masked activated N-acylimines. Of the large variety of Hgands available for the catalytic asymmetric reactions of dialkylzinc reagents,the sterically constrained P-dialkylamino alcohol, (-)-N,N-dibutylnorephedrine (DBNE) 18, prepared by alkylation of commercially available norephedrine, was selected for this study. Some preliminary experiments conducted with the use of -(aminobenzyl)benzotriazoles gave the ethylated product, but with no enantioselectivity. Diethylzinc (Et2Zn) was found to react even in the absence of a chiral promoter. The behavior of the less reactive N-(amidobenzyl)benzotriazoles 19a-g was then investigated. 

These points will be further illustrated in three specific cases (1) reductions of carbonyl compounds by chiral oxazaborolidines-borane complexes ( 2.3), (2) reactions of carbonyl compounds with dialkylzinc reagents in the presence of chiral ligands ( 2.5.4), and (3) dihydroxylation of olefins by OSO4 in the presence of cinchona alkaloids ( 2.9). 

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