Aldehydes diphenylzinc addition

Compared to the well-developed organozinc addition to aldehydes, the related addition to ketones has been far less studied. However, the first catalytic addition of diaUcylzinc to ketones has been achieved few years ago using camphorsulfonamide alcohols ligands and Ti(0-(-Pr)4 salt (equation 66). In the same year, it was also discovered that 15 mol % of (-l-)-DAIB catalyze the diphenylzinc addition to ketones to generate chiral (see Chiral) tertiary alcohols with up to 91% e.e. (equation 67). 

In 2002, Ha and coworkers [72a] reported the preparation of binaphthyl-based amino alcohols (Figure 7.9, C) and their application in the asymmetric diphenylzinc additions to aldehydes. The corresponding diarylmethanol derivatives were obtained with very high enantioselectivities (92—98% ee) and in excellent yields (95—98%). Curiously, aliphatic aldehydes were tested as well, but poorer enantioselectivities were obtained (66—68% ee). 

In the reported enantioselective additions of dialkylzincs and diphenylzinc to aldehydes, a great variety of structurally different ligands with different kinds of chirality have been used. A very detailed account of major developments in this area up to the year of 2001 can be found in a review of L. Pu and H.-B. Yu.2 0 The majority of... 

Our first results in this field were published in 1999 [13], when we reported that ferrocene 9 was capable of catalyzing the enantioselective addition of diphe-nylzinc to aromatic aldehydes, affording diaryl methanols with good to high enantioselectivities. For example, from the reaction between p-chlorobenzaldehyde 37a and diphenylzinc 7 in the presence of 5 mol% ferrocene 9 (at 0 °C), product 27a was obtained with 82% ee (Scheme 2.1.2.6). 

A chiral Hg-BINOL derivative catalyses an efficient direct enantioselective addition of diphenylzinc to both aromatic and aliphatic aldehydes, with particularly good results for straight-chain cases.229 Aggregation phenomena in solution have been studied by NMR spectroscopy. 

A binol derivative (23) has allowed high enantioselectivities in the reaction of diphenylzinc with both aliphatic and aromatic aldehydes.105 Unlike other catalysts developed for the addition of diphenylzinc, the use of (23) avoids the need for additive and gives excellent results at room temperature. 

Pyrrolidinylmethanols derived from (S)-proline have been employed in the zinc-catalysed addition of arylboronic acids to aromatic aldehydes, giving ees up to 98%.242 An arylzinc species is generated via a boron-zinc exchange, avoiding the need for expensive diphenylzinc. 

DFT calculations have been used to probe the mechanism of enantioselective addition of diphenylzinc to aldehydes, and in particular the enhanced selectivity which accompanies addition of diethylzinc to the system.245... 

With regard to diorganozincs other than primary dialkylzincs, various diorganozincs such as divinylzinc (> 96% ee, addition to benzaldehyde),4 difurylzinc (72% ee, addition to benzaldehyde),5 diphenylzinc (78-82% ee, addition to various aldehydes),6 and diisopropylzinc (93% ee, addition to benzaldehyde)7 have been utilized in the chiral (3-aminoalcohol catalysed reactions. Alkenyl(alkyl)zincs4b,c and alkynyl(alkyl)zincs8 afford the corresponding chiral allylic and propargyl alcohols. 

Chiral benzylic alcohols. The addition of diphenylzinc to aldehydes is rendered enantioselectively by 3,3 bis(2,5-dihexyloxyphenyl)-l,l -bi-2-naphthol. 

Scheme 7.44 Asymmetric addition of diphenylzinc to various aldehydes in the presence of 5 mol% of ferrocene chiral ligand, as described by Bolm and Muniz [68].

In 2004, Pericas and coworkers [75] reported another effective catalyst for the enantioselective phenyl addition to aldehydes. 2-Piperidino-l,2,2-triphenylethanol along with a mixture of diethylzinc and diphenylzinc (ratio 2 1) provided the corresponding addition products with overall very good enantioselectivities (up to 99% ee) (Scheme 7.46) and yields (also up to 99%). A study of the temperature/ ee relationship between 0 and 25 °C revealed that the maximum enantioselectivity was achieved at 10 °C with only 1.5 mol% catalyst (Scheme 7.46). 

Readily available chiral amines related to the Betti base [phenyl(2-hydroxy-l-naphthyl)methanamine] catalyse enantioselective addition of diethylzinc to aldehydes in moderate to excellent ee Observed enantioselectivities in addition of diethylzinc to aldehydes catalysed by a series of (5)-proline-derived pyrrolidines have been explained in terms of steric effects. New 2,5-diazabicyclo[2.2.1]heptanes have been applied to enantioselective addition of diethylzinc to benzaldehyde. (S)-2-(3-Methyl-2-pyridyl)-3,5-di-r-butylphenol (76) has been used as an enantioselective catalyst of diethylzinc addition to benzaldehydes. Reaction in toluene shows a significant variation in % ee with temperature, including observation of an inversion temperature with maximum ee. This value varies with the nature of the para-substituent in the aldehyde, and the overall behaviour may be due to a shift in the rate-determining step of the reaction. Other reports of zinc reagents include enantioselective addition of diethylzinc to aldehydes addition of diphenylzinc to aldehydes using a chiral ferrocene-based hydroxyoxazoline catalyst in up to 96% ee and 3-exo-morpholinoisoborneol has been proposed as a more convenient and efficient enantioselective catalyst of alkylzincs than Noyori s original 3-exo-dimethylamino catalyst. ... 

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