Itsuno-Corey asymmetric reduction

The past fifteen years witnessed the development of oxazaborolidines as catalysts for various organic reactions (44). The Itsuno-Corey asymmetric reduction is a prominent example (Figure 12) (45, 46). This chemistry led... 

Reiff EA, Nair SK, Reddy BSN, Inagaki J, Henri JT, Greiner JF, Georg GI. Practical syntheses of the C12-C21 epothilone subunit via catalytic asymmetric reductions Itsuno-Corey oxazaborolidine reduction and asymmetric Noyori hydrogenation. Tetrahedron Lett. 2004 45(30) 5845-5847. 

Boranes have opened the door to asymmetric reduction of carbonyl compounds. The first attempt at modifying borane with a chiral ligand was reported by Fiaud and Kagan,75 who used amphetamine borane and desoxyephedrine borane to reduce acetophenone. The ee of the 1-phenyl ethanol obtained was quite low (<5%). A more successful borane-derived reagent, oxazaborolidine, was introduced by Hirao et al.76 in 1981 and was further improved by Itsuno and Corey.77 Today, this system can provide high stereoselectivity in the asymmetric reduction of carbonyl compounds, including alkyl ketones. 

The use of oxazaborolidines as asymmetric reduction catalysts257 and the enantioselectivity of diphcnyloxazaborolidinc reduction of ketones have been reviewed.258 Large-scale practical enantioselective reduction of prochiral ketones has been reviewed with particular emphasis on the Itsuno-Corey oxazaborolidinc and Brown s 5-chlorodiisopinocampheylborane (Ipc2BCl) as reagents.259 Brown himself has also reviewed the use of Ipc2BCl.260 Indolinoalkylboranes in the form of dimers have been confirmed by 11B NMR as the products of the reduction of trifluoroacetylindoles by diborane.261... 

The organocatalytic enantioselective reduction of C=C, C=0, and C=N double bonds is a relatively young area for which many new and exciting developments can be expected in the near future. Hantzsch esters are useful organic hydrides, and a recent review has summarized the results obtained to date in organocataly-sis [27]. The case of silicon hydrides is convenient for imine or ketone reductions, as a chiral base can act as an organic catalyst. The asymmetric reductions of ketones catalyzed by oxazaborolidines and pioneered by Itsuno [28] and Corey [29] could not be included in this chapter. 

Since the first asymmetric reduction of ketones with chiral borohydrides by Itsuno et al. [ 1 ], a number of studies on the asymmetric reduction of ketones with chiral borane reagents have been demonstrated [2]. Corey s oxazaborolidines are some of the most successful reagents [3 ]. The effect of fluorine substituents was examined in the asymmetric reduction of acetophenone with LiBH4 by the use of chiral boronates (73) obtained from substituted phenyl boronic acid and tartaric acid [4]. Likewise, 3-nitro, fluorine, and trifluoromethyl groups on the 3- or 4-position provided enhanced stereoselection (Scheme 5.20). 

The great utility of this asymmetric reduction system is a result of the detailed and systematic analysis of its mechanism by the Corey group at Harvard and others.16 6- 7 Using the Itsuno conditions as a starting point, the Corey laboratories obtained pure (after sublimation) oxazaborolidine 10 from the reaction of amino alcohol 9 with two equivalents of BH3-THF... 

Asymmetric reduction ofketimmes found to achieve high enaniioselectix of Itsuno, prepared from BH.t and (S derived from (S)-valine, (12,31). is the Like Corey s oxazaborolidines derised amounts. The highest enantioselectiv aromatic ketones (as high as 88% ce of N-r-butylimines of aryl ketones (8<> dialkyl ketones with 1 results in ( -... 

Asymmetric reduction of ketimines to sec-aminesf Of the various hydride reagents found to achieve high enantioselective reduction of ketones, the oxazaborolidine 1 of Itsuno, prepared from BH3 and (S)-(—)-2-amino-3-methyl-I,l-diphenylbutane-l-ol, derived from (S)-valine, (12,31), is the most effective in terms of asymmetric induction. Like Corey s oxazaborolidines derived from (S)-proline, 1 can also be used in catalytic amounts. The highest enantioselectivities obtain in reduction of N-phenylimines of aromatic ketones (as high as 88% ee). The enantioselectivities are lower in the case of N-t-butylimines of aryl ketones (80% ee). Reduction of N-phenylimines of prochiral dialkyl ketones with 1 results in 10-25% ees. 

The Itsuno-Corey oxazaborolidine-H3B THF reduction, the CBS process, is the method of choice for obtaining high level of asymmetric induction (>95% ee) in the reduction of ketones (9-7/). We have shown that the CBS... 

See also Itsuno, S, Ito, K, HIrao, A, Nakahama, S, Asymmetric Reduction of Aliphatic Ketones with the Reagent Prepared from (S)-(-)-2-Amino-3-methyl-1,1-dlphenylbutan-1-ol and Borane" J. Org. Chem. 1984,49,555-557. Fora review see Corey, E. J. Helal, C. J. Angew. Chem. Int. Ed. 1998, 37, 1986-2012,... 

The pioneering work from Itsuno group [11-14] on stoichiometric 1,2-aminoalcohol-borane complex-mediated borane reduction of ketones led to the discovery of well-defined oxazaborolidine catalyzed asymmetric reduction by Corey and coworkers [15-18]. Known as Corey-Bakshi-Shibata reaction, or CBS reduction, this reaction has become a standard method for making chiral secondary alcohols for complex molecule synthesis [19]. The generally accepted mechanism of this reaction is shown in Fig. 2. Coordination of the electrophilic reductant BH3 to the nitrogen atom of... 

Borane is one of the most common agents for reducing C=0 and C=N bonds and its applications for the enantioselective reduction of ketones and imines have been extensively studied in past decades [77]. Among such agents, the Corey-Bakshi-Shibata (CBS) catalyst, a chiral oxazaborolidine complex, which was discovered by Itsuno in 1981 [78] and further developed by Corey in 1987 [79], was widely considered as the most successful catalytic system. Several excellent reviews are already available [77a, 80]. In this chapter, we only give limited coverage of the organocatalytic asymmetric reduction of ketones by catalytic systems other than chiral oxazaborolidines. 

Fig. 10.26. Catalytic asymmetric carbonyl group reduction according to Corey and Itsuno.

The pioneering studies by Itsuno [1] and Corey [2] on the development of the asymmetric hydroboration of ketones using oxazaborolidines have made it possible to easily obtain chiral secondary alcohols with excellent optical purity [3]. Scheme 1 shows examples of Corey s (Corey-Bakshi-Shibata) CBS reduction. When oxazaborolidines 1 were used as catalysts (usually 0.01-0.1 equiv), a wide variety of ketones were reduced by borane reagents with consistently high enan-tioselectivity [2]. The sense of enantioselection was predictable. Many important biologically active compounds and functional materials have been synthesized using this versatile reaction [2-4]. 

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