Aromatic aldehydes chiral reaction with diethylzinc

Zhang and Chan122 found that Hg-BINOL, (R)- or (S )-134, in which the naphthyl rings in the BINOL were partially hydrogenated,123 can give even better results in the diethylzinc reactions. Using (R)- or (5,)-134 as the chiral ligand, addition of diethylzinc to aromatic aldehydes proceeds smoothly with over 95% ee and, in most cases, quantitative conversion.122... 

Enantioselective addition of R2Zn to aldehydes. Corey and Hannon2 have prepared the diamino benzylic alcohol 1 from (S)-proline and (lS,2R)-( + )-ephed-rine and report that the chelated lithium salt of 1 is an effective catalyst for enantioselective addition of diethylzinc to aromatic aldehydes. Thus benzaldehyde can be converted into (S)-( - )-3 with 95% ee, via an intermediate tridentate lithium complex such as 2 formed from 1. Similar reactions, but catalyzed by diastereomers of 1, show that the chirality of addition of dialkylzincs to aldehydes is controlled by the chirality of the benzylic alcohol center of 1. 

The research on asymmetric organozinc additions to carbonyl compounds started in 1984 when Oguni and Omi obtained 49% e.e. in the reaction of diethylzinc with benzaldehyde catalyzed by (X)-leucinol. Since then, a huge number of chiral (see Chiral) catalysts, mostly derived from amino alcohols, have been developed and the subject has been extensively reviewed. 63.264 jjjg highly enantioselective (see Electrophile) ligand (—)-3-exo-dimethylaminoisobomeol [(-)-DAIB] developed by Noyori and coworkers in 1986 is still used even if its application is mostly limited to aromatic and heteroaromatic aldehydes (equation 62). As shown by previous studies, chiral (see Chiral) ligands have a dual... 

The enantioselective addition of organometallics to aldehydes is a useful approach to optically active secondary alcohols. Diorganozinc reagents add with excellent enantioselectivity to aldehydes in the presence of a chiral catalyst such as 1,2- or 1,3-amino alcohols (see equation 14 and Table 2). In most cases, diethylzinc has been used, but the reaction could be extended to some other dialkylzinc reagents and to divinylzinc. Alkylzinc halides afford secondary alcohols with a substantially lower enantiomeric excess. Many aldehydes are good substrates, "- but the best results are usually obtained with aromatic aldehydes. ... 

Solvent precipitation is widely used with polymers other than poly(ethylene glycol) and polystyrene too. For example, the chiral polymer copolymer catalyst 72 developed by Pu, containing both BINOL and BINAP groups in the polymer main chain, is recovered by precipitation in methanol after its use in a tandem asymmetric reaction where it catalyzes both the asymmetric addition of diethylzinc to an aromatic aldehyde and asymmetric hydrogenation of the aryl methyl ketone (Eq. 26) [109]. 

This latter was employed in the enantioselective addition of diethylzinc to aromatic and aliphatic aldehydes. For example, (S)-l-phenylpropanol was isolated in a yield of 92% and an ee of 96% when the reaction was performed in a 1/1 mixture of toluene and dichloromethane. The presence of dichloromethane proved to be essential for swelling of the polymer and making the catalytic sites accessibles to substrates. With other aromatic aldehydes and cyclohexane carboxaldehyde, the same range of chemical yield and ee was obtained. But with acyclic aliphatic aldehydes the chemical yield and ee dropped significantly. The recyclability of the chiral polymer 160 has been investigated and it was noticed a slightly decrease of the enantioselectivity of 1% per run. 

Liskamp has reported the synthesis and the screening in asymmetric catalysis of a library of polymer-supported peptidosulfonamide [147]. Rt) or (5 -pyrrolydines 222 prepared in six steps from D or Z-tartaric acid were anchored onto Argonaut resin (0.41 mmol/g) to afford the corresponding supported pyrrolidines 223 (Scheme 91). The polymeric peptidosulfonamides 224 and 225 were then synthesized in four steps from the immobilized pyrrolidines 223. The different chiral polymers were tested in the titanium-mediated diethylzinc addition to benzaldehyde,/ -chlorobenzaldehyde, cyclohexanecarboxaldehyde and phenylacetaldehyde. Both yield and ee were very low with all these supported-ligands for the enantioselective reaction with the two aliphatic aldehydes. With aromatic aldehydes, the best results were observed with both leucine-derived supported peptidosulfonamides 224d and 225d. 

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