Corey’s oxazaborolidine catalysts

Deprotonation with n-butyllithium and addition of aldehyde 148 generated alcohol 149 as a 2 l-diastereomeric mixture. Again the stereochemistry at the newly created center was corrected by an oxidation reduction sequence via ketone 151. This time the chiral reduction had to be performed with using Corey s oxazaborolidine catalysts (19). In this way both the (31 )- and (3S)-diastereomer of alcohol were available. LAH-reduction of (3S)-149 led to the -alkene 150 which was eventually oxidized to aldehyde 154 after protection-deprotection via 152 and 153. Addition of the potassium salt of pyrone 131 gave 155 as a 4 l-epimeric mixture. Removal of the PMB protective group led to selective destruction of the minor diastereomer, so that a 95 5-mixture in favor of the desired stereoisomer 156 was obtained (Scheme 26). 

Ketone reductions. Corey s oxazaborolidine continues to be a popular catalyst for borane reduction. A cheap borane source for the reduction is LiH-BF3-OEt2. " There are also modifications, for example, using aluminum(III) ethoxide, and the sulfonamide derivative 85. ... 

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. 

Although the lipase resolution results looked promising, direct enantioselective 1,2-reduction of the enone would be much more efficient if appropriate conditions could be found. It was known that Corey s oxazaborolidine (CBS) catalyst would reduce 2-bromo-cyclopent-2-enone with high enantioselectivity (34) due to the large bromine atom being located alpha to the ketone. It was uncertain if 22 would reduce with enantioselectivity since the iodine atom was one atom further removed from the ketone. After an extensive effort at this reduction, our best conditions gave a 90% yield of enantioenriched 24 (3 1 S R) using 5 mol % (R) 5-methyl CBS catalyst.(i5)... 

Addition of triethylamine to the oxazaborolidine reaction system can significantly increase the enantioselectivity, especially in dialkyl ketone reductions.79 In 1987, Corey et al.80 reported that the diphenyl derivatives of 79a afford excellent enantioselectivity (>95%) in the asymmetric catalytic reduction of various ketones. This oxazaborolidine-type catalyst was named the CBS system based on the authors names (Corey, Bakshi, and Shibata). Soon after, Corey s group81 reported that another fi-methyl oxazaborolidine 79b (Fig. 6-6) was easier to prepare and to handle. The enantioselectivity of the 79b-catalyzed reaction is comparable with that of the reaction mediated by 79a (Scheme 6-36).81 The -naphthyl derivative 82 also affords high enantioselectivity.78 As a general procedure, oxazaborolidine catalysts may be used in 5-10 mol%... 

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]. 

Ac = Acetyl acac = Acetylacetonate bda = Benzylidene-acetone BINOL = l,l -bi-2-naphthol Bn = Benzyl brsm = Yield based on recovered starting material Bu = Bntyl CAN = Ceric anunonium nitrate CBS = Corey/Bakshi/Shibata catalyst [(+) or (—)-(S)-2-methyl-oxazaborolidine] COD = Cyclo-l,5-octadiene COT = Cyclooctatetraene Cp = Cyclopentadienyl Cp = Penta-methylcyclopentadienyl Cy = Cyclohexyl DCC = Dicy-clohexylcarbodiimde DMF = Ai,A-dimethylformainide DMPU = l,3-dunethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidin-one DMSO = Dimethylsnlfoxide dppe = Diphenylphosp-hinoethane dr = Diastereomer ratio dppm = Diphenylphos-phinomethane E = Electrophile ee = Enantiomeric excess EHMO = Extended htickel molecular orbital Et =... 

Scheme 6.51. Asymmetric cycloaddition of 2-bromoacrolein and cyclopenta-diene using Corey s indenyl oxazaborolidine catalyst [215,216]...

E. J. Corey, C. J. Helal, Angew. Chem. 1998, 110, 2092 Angew. Chem. Int. Ed. 1998, 37, 1986 (Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts A New Paradigm for Enantioselective Catalysis and a Powerful New Synthetic Method.), S. Itsuno, in Organic Reactions , Ed. L. A. Paquette, John Wiley Sons, New York, 1998, Vol. 52, pp. 395-576 (Enantioselective Reduction of Ketones). 

Enantiomerically pure boron-based Lewis acids have also been used successfully in catalytic aldol reactions. Corey s catalyst (7.10a) provides good enantioselectivity with ketone-derived silyl enol ethers, including compound (7.11). Other oxazaborolidine complexes (7.13) derived from a,a-disubstituted a-amino acids give particularly high enantioselectivity, especially with the disubstituted ketene... 

One of the most effective classes of asymmetric Diels-Alder catalysts is the family of chiral oxazaborolidines originally developed by Corey. In a recent example from Corey s lab, combining cyclopentadiene (42) with quinone 43 in the presence of catalyst 44 fiimishes cycloadduct 45 in 99% yield and 99% Yamamoto used a similar catalyst for enantioselective Diels-Alder reactions of a,p-unsaturated acetylenic ketones, and Paddon-Row and Houk reported a computational investigation into the reactivity of oxazaborolidine catalysts. 

Since our group (22) and Hehnchen s (23) independently announced a new class of chiral acyloxyboranes derive from iV-sulfonylamino acids and borane THF, chiral 1,3 -oxazaborolidines, their utility as chiral Lewis acid catalysts in enantioselective synthesis has been convincingly demonstrated (2(5). In particular, Corey s tryptophan-derived chiral oxazaborolidines 10a and 10b are highly effective for not only Mukaiyama aldol reactions (24) but also Diels-Alder reactions (25). More than 20 mol% of 10b is required for the former reaction, however. Actually, the reaction of the trimethylsilyl enol ether derived from cyclopentanone with benzaldehyde afforded the aldoI products in only 71% yield even in the presence of 40 mol%of 10b (24). We recently succeed in renewing 10b as a new and extremely active catalyst lOd using arylboron dichlorides as Lewis acid components (2(5). 

Fig. 3 Application of strong Brpnsted acid-activated oxazaborolidine catalysts, and Corey s pretransition state assembly models...

A series of chiral boron catalysts prepared from, e.g., N-sulfonyl a-amino acids has also been developed and used in a variety of cycloaddition reactions [18]. Corey et al. have applied the chiral (S)-tryptophan-derived oxazaborolidine-boron catalyst 11 and used it for the conversion of, e.g., benzaldehyde la to the cycloaddition product 3a by reaction with Danishefsky s diene 2a [18h]. This reaction la affords mainly the Mukaiyama aldol product 10, which, after isolation, was converted to 3a by treatment with TFA (Scheme 4.11). It was observed that no cycloaddition product was produced in the initial step, providing evidence for the two-step process. 

As an example of non-enzymatic catalyst using oxazaborolidines [10], Corey and his associates have described an efficient synthesis of (-i-)-l(S),5(R),8(S)-8-phenyl-2-azabicyclo[3.3.0]octan-8-ol (2.) and its enantiomer. The B-methyloxazaborolidine derivatives (3) of these amino alcohols are excellent catalysts -or chemzymes- for the enantioselective reduction of a variety of achiral ketones to chiral secondary alcohols [11]. 

The CBS-catalyst [(S)-2-methyl-CBS-oxazaborolidine] (S)-5 (1.0 M in toluene) (The CBS catalyst is named after Corey, Bakshi, and Shibata) and the borane-THF complex (1.0 M in THF) were obtained from Aldrich Chemical Co., Inc. and used as received. THF was distilled from potassium directly before use. 

The use of oxazaborohdines as asymmetric reduction catalysts and the enantioselectivity of diphenyloxazaborohdine reduction of ketones have been reviewed. Large-scale practical enantioselective reduction of prochiral ketones has been reviewed with particular emphasis on the Itsimo-Corey oxazaborolidine and Brown s 5-chlorodiisopinocampheylborane (Tpc2BCl) as reagents. Brown himself has also reviewed the use of Ipc2BCl. Indohnoalkylboranes in the form of dimers have been confirmed by B NMR as the products of the reduction of trifluoroacetylindoles by diborane. ... 

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. 

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