COREY Enantioselective Borane Reduction

COREY Oxidizing reagents for alcohols 78 COREY Enantioselective borane reduction 77 COREY Homologatne epaxidation 78 COREY - KIM Oxidizing reagent 79 COREY-WINTERAlkenesynthesis 80 CORNFORTH Rearrangement 81 Crafts 131... 

COREY Enalioselaclive borane reduction Enantioselective reduction ol ketones by borane or catecholborane catalyzed by oxazaborolldine 3... 

Corey, E. J., Bakshi, R. K., Shibata, S. Highly enantioselective borane reduction of ketones catalyzed by chiral oxazaborolidines. 

The structurally more rigid (S)-prolinol-based amino alcohol was introduced early in the study of borane reductions [18]. Sterically more hindered ox-azaborolidines 4 (Fig. 1) based on (S)-(-)-diphenylhydroxymethylpyrrolidine have been prepared by Corey [23,25]. These catalysts have been widely used for the borane reduction of various kinds of ketones. After these successful results had appeared for asymmetric ketone reduction, several oxazaborohdines (Fig. 1) were prepared. Many of them were successfully used in the reduction of aromatic ketones. Selected results of enantioselective borane reduction using various oxazaborohdines are shown in Scheme 4. The table to this scheme shows only the data obtained from the reduction of acetophenone as a representative aromatic ketone. In most cases, high enantioselectivity is obtained in the nearly quantitative yield. 

The CBS (Corey-Bakshi-Shibata) reagent is a chiral catalyst derived from proline. Also known as Corey s oxazaborohdine, it is used in enantioselective borane reduction of ketones, asymmetric Diels-Alder reactions and [3 + 2] cycloadditions. 

Corey originally used borane-THF as a stoichiometric reducing agent [2, 5]. The use of more robust borane sources, borane-N,N-diethylaniline [6, 7] and borane-N-ethyl-N-isopropylaniline [8, 9], rendered the CBS reduction easier to handle without sacrificing enantioselectivity. Borane-THF prepared in situ from NaBH4 and (CHalaSiCl in THF [10] was also shown to be useful for this type of reduction [11]. 

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. ... 

The Corey-Bakshi-Shibata reduction (CBS reduction) is a highly enantioselective method for arylketones, diaryl ketones, and dialkylketones. In addition, cyclic a,p-unsaturated ketones, acyclic a,p-unsaturated ketones, and a,p-ynones are reduced enantioselectively in a 1,2-fashion. The high enantioselective nature of this reduction relies on the chiral oxazaborolidine catalyst, shown in the reaction scheme, in the presence of borane or a dialkylborane. Reviews (a) Singh, V. K. Synthesis 1992, 605-617. (b) Deloux, L. Srebnik M. Chem. Rev. 1993,93,163-1. (c) Corey, E. J. Helal, C. J. Angew. Chem. Int. Ed. 1998, 37. 1986-2012. 

The term CBS-reduction refers to the enantioselective, oxazaborolidine-catalyzed borane reduction for a review, see Corey EJ, Helal C (1998) Angew Chem 110 2093 Angew Chem Int Ed Engl 37 1986... 

The second stereochemical problem, enantioselective reduction of the keto-group in the w-side-chain, was solved by Corey already in 1987. The reduction was successful with borane-THF in presence of 10 mole% of the (H)-prolme-derived (H)-oxazaborolidine (Corey-Bakshi-Shibata reduction). If the enone was reduced in presence of the corresponding (S)-oxazaborolidine, the inverse product distribution resulted. Obviously, the other stereocentres in the educt have no impact on the stereochemical course of the reduction at C-15. 

There have been significant discoveries of methods that enable the enantioselective addition of an alkyne to an aldehyde or a ketone [182]. The resulting chiral propargyl alcohols are amenable to a wide variety of subsequent structural modifications and function as useful, versatile chemical building blocks. In 1994, Corey reported the enantioselective addition reactions of boryl acetylides such as 292, prepared from the corresponding stannyl acetylenes (e.g., 291) in the presence of the oxazaborolidine 293 as the chiral catalyst (Scheme 2.36) [183]. Both aliphatic and aromatic aldehydes were demonstrated to participate in these addition reactions, which proceeded in high yields and with impressive enantioselectivity. The proposed transition state model 295 is believed to involve dual activation both of the nucleophile (acetylide) and of the electrophile (aldehyde). The model bears a resemblance to the constructs previously proposed for alkylzinc addition reactions (Noyori, 153) and borane reductions (Corey. 188). 

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]. 

In 1987, Corey and co-workers proved that highly enantioselective reduction of ketones could be achieved by using stoichiometric borane in the presence of catalytic amounts of the oxazaborolidine 28a11 (Scheme 4.3j). Compound 28a, synthesized by heating (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine at reflux in THF with 3 equivalents of BH3 THF, shows excellent catalytic activity for the asymmetric reduction of acetophenone and other ketones. The B -methylated analog 28b was later synthesized to improve the air and moisture sensitivity associated with 28a. The third analog, 28c, with a 2-naphthyl substituent on the oxazaborolidine ring, has proven to be the best to afford the alcohol 29 with superb levels of enantioselectivity. 

Enantioselective reduction of ketones by boranes and an enantiomeric catalyst oxazaboro-lidine (the CBS catalyst) is known as the Corey, Bakshi and Shibata method . Both enantiomers of 2-methyl-CBS-oxazaborolidine (6.52 and 6.53) are used for the reduction of prochiral ketones, imines and oximes to produce chiral alcohols, amines and amino alcohols in excellent yields and enantiomeric excesses. 

Corey demonstrated that oxazaborolidine (6) can be used cat-alytically (2.5-100 mol %) with excess borane (60-200 mol %) for the enantioselective reduction of prochiral ketones (eq 3 Table 1). ... 

E.J. Corey and co-workers synthesized the cdc25A protein phosphatase inhibitor dysidiolide enantioselectively. In the last phase of the total synthesis, the secondary alcohol functionality of the side-chain was established with a highly diastereoselective oxazaborolidine-catalyzed reduction using borane-dimethylsulfide complex in the presence of the (S)-6-methyl CBS catalyst. Finally, a photochemical oxidation generated the y-hydroxybutenolide functionality. This total synthesis confirmed the absolute stereochemistry of dysidiolide. 

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... 

The Corey-Bakshi-Shibata (CBS) reduction1 employs the use of borane in conjunction with a chiral oxazaborolidine catalyst to conduct enantioselective reductions of ketones. 

Corey et al. [4] have investigated enantioselective reduction of ketones with THF-BHa and (5 )-diphenyl prolinol-borane adduct as catalyst. They further introduced modification of oxazaborolidines in which R = CH3, n-butyl as catalyst 1 and used along with other boranes as reducing agents (Scheme 1). The catalysts 1 are known as CBS catalysts and... 

CBS (Corey, Bakshi, and Shtbata) Catalyst Itsuno [67] paved the way for the discovery of oxazaborolidines as chiral catalysts for the borane-mediated enantioselective reduction of a wide variety of achiral ketones, the so-called CBS reduction. Scheme 2.139 summarizes some of these results and the proposed transition state [68], These data show that the CBS reduction process results in exceUent enanti-oselectivities and leads to a product whose absolute configuration can be predicted from the relative effective steric bulk of the two carbonyl appendages. It is noteworthy that the oxazaborolidine catalyst behaves like an enzyme in the sense that it binds with both ketone and borane and brings... 

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. 

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