Noyori reagent

Fig. 10.23. Asymmetric carbonyl group reduction with the Noyori reagent Note that the chirality of the reducing agent resides in the ligand but that the aluminum atom is not a stereocenter.

Fig. 8.18. Asymmetric carbonyl group reduction with the Noyori 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). 

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... 

Scheme 10. Noyori synthesis of 6,7-dehydro-3-hydroxytropanes 168 and 169. Reagents i, Fe2(CO)9, C6H6, 50°C ii, 2n-Cu, NH4C1,20°C iii, DIBAH, THF, -78- 20°C.

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... 

Tandem 1,4-addition to cycloalkenones constitutes an extremely versatile and elegant methodology for the synthesis of 2,3-disubstituted cycloalkanones, as is evident from its application in areas such as prostaglandin synthesis. Noyori et al. have reported the use of organozinc reagents in copper-catalyzed tandem additions [64]. The zinc enolate resulting from the catalytic enantioselective 1,4-addition of Et2Zn to cyclohexenone reacts readily with an aldehyde in a subsequent aldol condensation. 

For lists of other reagents that accomplish this convetsion, with references, see Tsunoda Suzuki Noyori Tetrahedron Lett. 1979, 4679 Kotsuki Ushio Yoshimura Ochi J. Org. Chem. 1987,52, 2594 Ref. 508, pp. 463-465. 

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... 

K. Kitamura, R. Noyori, Encyclopedia of Reagents for Organic Synthesis, John Wiley and Sons,... 

Reviews on chiral hydride reagents M. Nishizawa and R. Noyori, Reduction of C=X to CHXH by Chirally Modified Hydride Reagents, in B. M. Trost and I. Fleming, eds., Comprehensive Organic Synthesis, Vol. 8, Chap. 1, p. 159, Per-gamon Press, Oxford, 1991 V. K. Singh, Synthesis, 605 (1992). 

An amino alcohol was found to accelerate the addition reaction of diethlylzinc to aldehyde [8], and then chiral amino alcohols were proved to be efficient chiral catalysts for asymmetric alkylation by using dialkylzinc reagents [9], Oguni reported a remarkable asymmetric amplification in chiral amino alcohol-promoted alkylation (Scheme 9.4). In the presence of (-)-l-piperidino-3,3-dimethyl-2-butanol (5) of 11% ee, benzaldehyde is alkylated enantioselectively to give (/ )-l-phenylpropanol with 82% ee [10]. Asymmetric amplification was also observed by Noyori using partially resolved (2.S )-3-exo-(dimethylamino)isobomeol (6) [11]. 

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