Oxazaborolidine functionalized ketones

In summary, this chapter shows that organoboron-based asymmetric reducing agents, such as K Glucoride (1), K Xylide (2), Alpine-borane (3), Dip-Chloride (4) and oxazaborolidine-catalyzed boranes are highly effective for the reduction of a variety of a-functionalized ketones. We have established a convenient and simple procedure for the preparation of terminal 1,2-diols, a-hydroxy acetals and epoxides with very high optical purity via oxazaborolidine-catalyzed borane reduction using /V-phenylamine-borane complexes as the hydride source. 

Chiral oxazaborolidine catalysts were applied in various enantioselective transformations including reduction of highly functionalized ketones/ oximes or imines/ Diels-Alder reactions/ cycloadditions/ Michael additions, and other reactions. These catalysts are surprisingly small molecules compared to the practically efficient chiral phosphoric acids, cinchona alkaloids, or (thio)ureas hence, their effectiveness in asymmetric catalysis demonstrates that huge substituents or extensive hydrogen bond networks are not absolutely essential for successful as5unmetric organocatalysis. 

Ketones [60], P-functionalized ketones [61] [62] and meso cylic imide [63] have been enantioselectively reduced using polymer-supported ehiral sulfonamides in presence of boranes (NaBH /MesSiCl or BH3.SMe2), leading in situ to the corresponding oxazaborolidine polymer-supported chiral sulphonamide 70 (Scheme 32). 

A review describing the major advances in the field of asymmetric reduction of achiral ketones using borohydrides, exemplified by oxazaborolidines and /9-chlorodiisopino- camphenylborane, has appeared. Use of sodium borohydride in combination with chiral Lewis acids has been discussed.298 The usefulness of sodium triacetoxyboro-hydride in the reductive amination of aldehydes and ketones has been reviewed. The wide scope of the reagent, its diverse and numerous applications, and high tolerance for many functional groups have been discussed.299 The preparation, properties, and synthetic application of lithium aminoborohydrides (LABs) have been reviewed. 

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. 

S) -2-Hydroxy methylindoline (l)1 reacts with borane dimethyl sulfide to form the oxazaborolidine 2, which functions as a catalyst for reduction of ketones by... 

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]. 

Asymmetric reduction of or y-functionalized alkyl aryl ketones provides a wide variety of chiral amino alcohols. Commercial -chloropropiophenone is reduced with borane-tetrahydrofuran adduct catalyzed by oxazaborolidine 45 to provide the chlorohydrin in over 99 % yield with 94 % ee. The resulting alcohol is a key intermediate for synthesis of the R form of fluoxetine (Prozac ), a serotonin-uptake inhibitor [53]. Using hydrogenation processes the functionalized amino ketones are converted directly into the respective products [8, 43e],... 

Price, M. D., Sui, J. K., Kurth, M. J., Schore, N. E. Oxazaborolidines as Functional Monomers Ketone Reduction Using Polymer-Supported Corey, Bakshi, and Shibata Catalysts. J. Org. Chem. 2002, 67, 8086-8089. 

The enantioselective reduction of ketones has become a key reaction not only for the production of chiral alcohols, but for the production of fimctionalized compounds in general, thanks to the versatility of the hydroxyl fimctionality. The oxazaborolidine-catalyzed borane reduction of ketones [2] has become an important reaction due to the fact that the stereochemistry of the alcohols can be predicted and because of the wide substrate acceptance of this catalytic system (it works with aromatic as well as with aliphatic ketones). Among all the known oxazaboroUdine catalysts, the proline-based one is very interesting not only because it is one of the most selective catalysts, but also because another related reagent, the 4-hydroproline, is commercially available and possesses a functional group which could be used for the linkage to a polymer. 

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). 

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