CBS reduction of ketones

In this chapter, the total synthesis of (+)-laurenyne (1) published by Boeckman et al. in 2002 will be described. Starting from a readily available chiral diol, two of the stereogenic centers are constructed via selective CBS-reduction of ketones. 

Noyori s synthesis of menthol by Rh+-catalysed [1,3]H shifts Corey s CBS Reduction of Ketones A synthesis of the H1 blocker cetirizine Part II - Asymmetric Formation of C-C Bonds Organic Catalysis... 

Epothilone 85 possesses antimitotic properties similar to those of paclitaxel and could therefore have utility in the treatment of cancer. A key intermediate in the synthesis of this natural product is 86, a C 2-C2i subunit of 8S.34 One approach to this compound employed the CBS reduction of ketone 87 to generate 88, an alcohol related to 86. 

CBS Reduction of Ketones (PPG-Sipsy with Caiiery Lonza). Hydride reduction with a proline-derived catalyst (CBS reaction) was applied by Lonza to make 50 kg of an intermediate for Josiphos ligands (79,80). 

The preparation of 22, starting material for a diastereoselective Evans auxiliary-promoted aldol reaction (see Section 11.3.2) and key intermediate in the synthesis of [ C]Sch 58235 (40). is an additional example of the compatibility of CBS reductions with a broad variety of substituents. Alcohol 22 was isolated after CBS reduction of ketone 2S with BH3 Me2S in the presence of 0.3 equivalents of ( )-2fia in nearly quantitative yield and >99% e.e. l... 

Catalytic Enantioselective Reduction of Ketones. An even more efficient approach to enantioselective reduction is to use a chiral catalyst. One of the most developed is the oxazaborolidine 18, which is derived from the amino acid proline.148 The enantiomer is also available. These catalysts are called the CBS-oxazaborolidines. 

Scheme 5.6. Enantioselective Reduction of Ketones Using CBS-Oxazaborolidine... 

Table 11.1 Asymmetric reduction of ketones catalysed by (S)-Me-CBS[T (results...

Scheme 11.1 also summarizes other impressive examples of the performance of the CBS method [1-8]. Several excellent reviews on the CBS method have appeared recently [1, 2], and no detailed discussion of the development of the process or substrate scope shall be presented in this review. Please note, however, that the oxazaborolidine-catalyzed borane reduction of ketones is a prime example of bi-functional catalysis [2, 9] - as shown in Scheme 11.2, the current mechanistic picture involves simultaneous binding of both the ketone and the borane to the Lewis-acidic (boron) and Lewis-basic (nitrogen) sites of the catalyst A. In the resulting ternary complex B, the reaction partners are synergistically activated toward hydride transfer. 

The enantioselective reduction of ketones using borane and a chiral oxazaborolidine as catalyst (CBS Catalyst). Usually, MeCBS... 

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). 

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. 

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 reduction of ketones by borane catalyzed by chiral oxazaborolidines such as (136), derived from the enantiomeric amino alcohols, has been applied to the synthesis of several drug candidates (127). This system is known as the CBS (Corey, Bakshi, Shibata) reduction (153), and Corey himself has applied it to the synthesis of pharmaceutical compounds (154). A further example is provided by the synthesis of MK-499 (137), a... 

CBS reduction of a-chloro ketone commercial production PPG-Sipsy (Callery) [18]... 

The (S)-diphenylprolinol-derived oxazabotohdine with an ethanediolated boron atom is a new catalyst for the as3fmmetric reduction of ketones with BH3 SMe2- 1,3-Cyclo-alkanediones undergo CBS-reduction to provide (3if)-hydroxycycloalkanones. Based on this method a very short synthesis of chiral estrone methyl ether is completed. ... 

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... 

Interactive asymmetric reduction of ketone with CBS catalyst... 

In order to prepare polymer-supported CBS catalyst, monomeric precursors 59, 60 or 61 or bromides 62 and 63 have been synthesized (Scheme 28). The oxazaborolidine could be formed in situ or not before performing the hydride reduction of ketones. 

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

CBS Reduction of a Cyclic Ketone (Carbogen/Amcis). A production process for the reduction of a cyclic ketone on a 2- t/year scale is preferentially... 

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... 

Figure 5. CBS reduction of THP-protected a-hydroxy ketones using...

Figure 7. CBS reduction of a-sulfonoxy ketones to valuable terminal epoxides with excellent ee...

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