Itsuno-Corey reduction

Complex B can be isolated, characterized and stored. The B atom of the complex B of the Corey-Itsuno reduction (Figure 10.26) is a Lewis acid. Unlike heterocycle A, its boron atom does not possess a neighboring lone pair of electrons and is adjacent to an atom with a formal positive charge. Therefore, the empty orbital is available for binding a carbonyl group to form the ternary complex. 

The N atom of the ketone-associated heterocycle B of the Corey-Itsuno reduction (Figure 8.21) is a Lewis base Other than in the ketone-free heterocycle A, its lone electron pair is not shared with the boron atom because the latter has already acquired a valence electron octet. Therefore, the electron pair is available for binding a molecule of the Lewis acid BH3, whereby the ternary complex C is produced. 

In a direct comparison of the reduction of acetophenone to highly enantio-en-riched (R)-phenylethanol (94% e.e.) by heterogenized (S)-diphenyloxazaborolidine (Corey-Itsuno catalyst) or to enantiomerically pure (S)-phenylethanol (> 99% e.e.) by Candida parapsilosis carbonyl reductase (CPCR), the superior solubility of acetophenone in THF (0.25 m) versus water (0.04 m) leads to a vastly superior space-time yield of 290 g (L d) 1 in THF with the Corey-Itsuno catalyst in comparison with 27 g (L d) 1 in water with CPCR (Rissom, 1999). Conversely, the turnover frequencies (tofs) of 0.3 min-1 (Corey-Itsuno catalyst) versus 2.3 x 104 min-1 (CPCR) portend the difference in total turnover number (TTNs) of 2.4 x 108 versus 560. 

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. 

In other reports, /i-cyclodcxtrins have been used to induce asymmetry in borohydride reduction of ketones,166 a diastereoselective reduction has been controlled167 by a real lyltricarbonyl iron lactone tether , a phosphinamide has been combined with a dioxaborolidine unit as an activated, directed catalyst for ketone reduction,168 reductive amination using benzylamine-cyanoborohydride converts 3-hydroxy ketones into syn-1,3-amino alcohols,169 l-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)propan-l-one has been reduced diastereoselectively,170 and production of chiral alcohols via (i) Itsuno-Corey and Brown procedures171 and (ii) lithium aluminium hydride modified by chiral nucleophiles172 has been reviewed. 

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... 

Apart from these techniques, the most interesting method recently described is the Itsuno-Corey reduction. This catalytic reaction is general, is highly predictable, and can rapidly be scaled up. 

Building on the excellent work of Itsuno,9 10 who first described the use of oxazaborolidine as a chiral ligand, and of Kraatz,11 Corey was the first to report the enantioselective reduction of ketones to chiral secondary alcohols in the presence of an oxazaborolidine in substoichiometric amounts.12 13 This general method was named the CBS method (Scheme 16.1). 

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. 

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]. 

Enantioselective Ketone Reduction. After the pioneering work of Itsuno et al., Corey s group isolated the 1,3,2-oxazaborolidine derived from chiral a,a-diphenyl-2-pyrrolidinemethanol (2) and applied it (and also other related B-alkyl compounds) to the stereoselective reduction of ketones with borane-tetrahydrofuran, borane-dimethyl sulfide (BMS) or catecholborane.It was named the CBS method (after Corey, Bakshi, and Shibata). Since then, the CBS method has become a standard and has been extensively used, specially for aromatic and a,p-unsaturated ketones, not only in academic laboratories but also in industrial processes. ... 

Prolinol or diphenylprolinol were found by Corey et al. [87] and Itsuno et al. [88] to catalyze the enantioselective diborane reduction of many ketones. Corey et al. developed this new route greatly, often called CBS reduction (from the names of the authors of Ref. [87]). An oxazaborolidine which is either formed in situ or can be preformed, is the actual catalyst. A mechanistic picture has been proposed [87]. 

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 first attempt to use a chiral ligand to modify borane was Kagan s attempt at enantioselective reduction of acetophenone using amphetamine-borane and desoxy-ephedrine-borane in 1969 [18]. However, both reagents afforded 1-phenyl ethanol in <5% ee. The most successful borane-derived reagents are oxazaborolidines, introduced by Hirao in 1981, developed by Itsuno, and further developed by Corey several years later (reviews [19,20]). Figure 7.2 illustrates several of the Hirao-Itsuno and Corey oxazaborolidines that have been evaluated to date. All of these examples are derived from amino acids by reduction or Grignard addition. Hirao... 

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