Noyori s reagent

In cases where Noyori s reagent (see p. 102f.) and other enantioselective reducing agents are not successful, (+)- or (—)-chlorodiisopinocampheylborane (Ipc BCl) may help. This reagent reduces prochiral aryl and tert-alkyl ketones with exceptionally high enantiomeric excesses (J. Chandrasekharan, 1985 H.C. Brown, 1986). The initially formed boron moiety is usually removed hy precipitation with diethanolamine. Ipc2BCl has, for example, been applied to synthesize polymer-supported chiral epoxides with 90% e.e. from Merrifield resins (T. Antonsson, 1989). 

Application of Noyori s reagent to the synthesis of prostaglandin intermediates was highly successful (80). The iodovinyl ketone 57a was reduced to the (S)-carbinol 58a in a 95% synthetic yield and a 97% optical yield with (5)-56 (OR = OEt). The analogous bromovinyl ketone 57b gave the corresponding (S)-carbinol in 96% synthetic and optical yield (eq. [21]). These intermediates... 

Asymmetric reduction of 25-24-oxosteroids. Reduction of the unsaturated 24-oxosteroid 2 with LiAlH, and the (R)-( + )-isomer of Noyori s reagent (1) gives a mixture of the two diols 3 and 4 in the ratio 95 5. The stereoselectivity is reversed by use of (SM )-l. This reaction was used to prepare optically pure (24R)- and (24S)-24-hydroxycholcstcrol and the epimeric pairs of 24,25-dihydroxycholesterol and 25,26-dihydroxycholcsterol.2... 

The complex of the biphenanthryl diol (4) with LAH has been prepared and its reduction properties have been examined. This reagent gives excellent enantioselectivity in the reduction of aromatic ketones. For example, acetophenone is reduced in 75% yield with 97% ee. As with Noyori s reagent, reductions with the (S)-reagent give (5)-alcohols and aliphatic ketones are reduced with low enantioselectivity. Both enantiomers of this auxiliary can be readily prepared and can also be recovered for reuse at the end of the reduction. 

Recently, the preparation of the chiral biphenyl (6) and its use as a modifying agent with LAH has been reported." A complex of LAH-(6)-EtOH (1 1 1) at —78°C gives the best enantiose-lectivities in the reduction of prochiral ketones. Similar to Noyori s reagent, use of the LAH complex with (S)-(6) leads to the (S)-alcohol. Enantioselectivity is usually high for aromatic ketones (acetophenone 97% ee, 93% yield). This reagent reduces 2-octanone in higher enantioselectivity (76% ee) than 3-heptanone (36% ee). 

Asymmetric reduction of ketones. A reagent 2, prepared by reaction of LiAlH4 with 1 and C2H5OH (1 equiv. each) in THF at 20°, effects asymmetric reduction of dialkyl ketones or alkyl aryl ketones in 53-93% yield and 60-97% ee. The enantioselectivity is generally greater than that obtained with Noyori s reagent BINAL-H (9,169-170), particularly in reduction of dialkyl ketones in which the alkyl groups have similar steric effects. 

In 1998, two other examples of chiral ligands that enabled the asymmetric addition of organozinc reagents to ketones were reported by two groups independently. Thus, Dosa and Fu employed the nonsulfur-containing Noyori s DAIB " ligand in the asymmetric addition of ZnPh2 to ketones with... 

Based on Noyori s finding that f -monosubstituted sulfonamide and cop-per(I) catalyze the addition of diorganozinc reagents to cycloalkenone [63], the effect of the chiral sulfonamide 27 (Scheme 14) was examined by Sewald it was found that catalytic amounts of both sulfonamide and copper(I) are necessarily to effect the reaction,but the ee was at the most 32% [64]. 

Scheme 7.1. Preparation of Noyori s BINAL-H reagents [12). The aluminum complexes shown are postulated structures that may represent time averages of several equilibrating species.

On the other hand, it was possible to cleave the biaryl lactones with chiral hydride transfer reagents, such as Noyori s BINAL-H, or borane THF in the presence of Corey-Bakshi-Shibata (CBS) reagent, furnishing the corresponding alcohols in excellent yields and enantioselectivities, as shown in Scheme 5.11. 

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. ... 

Inspired by Cozzi s studies on the imine Reformatsky reaction [164] and guided by Noyori s investigation of reactive zinc species [165], the authors propose an oxygen-initiated radical mechanism for the formation of the Reformatsky reagent and a catalytic cycle that is included in a modified version in Scheme 5.87. First, it is assumed that the reaction of dimethyl zinc with oxygen produces - via the peroxide MeOOZnMe - a-methyl radical that enters the first catalytic cycle A. 

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