Oxazaborolidines as catalysts for

The use of chiral oxazaborolidines as catalysts for the enantioselective addition of alkynylboranes to aldehydes took place in a manner analogous to the asymmetric reduction of ketones with boranes mediated by proline-derived oxazaborolidines (Equation (127)).587 Addition of alkynylboranes to A-aziridinylimines provided a convenient method to prepare allenes from carbonyl compounds (Equation (128)).5... 

For aryl ketones the Corey-Bakshi-Shibata (CBS) reduction using oxazaborolidines as catalysts for the boron hydride mediated hydrogenation is particularly useful, with maximum selectivities up to 99 % ee (see Scheme 4) [34]. The excellent review by Corey et al. [35] also shows clearly the power for chemo- and enantioselective reduction of purely aliphatic a,//-enones and -ynones only on the carbonyl group. In the re-... 

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... 

Although it is known that in some cases the lithium salts of chiral amino alcohols are even better catalysts than the chiral ligands themselves, the use of metals other than lithium has rarely been investigated. The oxazaborolidines A and B and the aluminum analog C have been used as catalysts for the enantioselective addition of diethylzinc to benzaldehyde35 (Table 32). 

Corey et al. [24] have used this oxazaborolidine as an effective catalyst for an efficient synthesis of cassiol and gibberellic acid. Similar high diastereo- (exo endo = 99 1) and enantioselectivity (96 4) was observed in the cycloaddition reaction of furan with 2-bro-moacrolein using oxazaborolidine as catalyst. 

The use of oxazaborolidine reagents as catalysts for the asymmetric reduction of ketones in the presence of a borane reducing agent was first... 

Other S/N ligands have been investigated in the enantioselective catalytic reduction of ketones with borane. Thus, Mehler and Martens have reported the synthesis of sulfur-containing ligands based on the L-methionine skeleton and their subsequent application as new chiral catalysts for the borane reduction of ketones." The in situ formed chiral oxazaborolidine catalyst has been used in the reduction of aryl ketones, providing the corresponding alcohols in nearly quantitative yields and high enantioselectivities of up to 99% ee, as shown in Scheme 10.60. 

Oxazaborolidine catalysts behave like an enzyme in the sense of binding with both ketone and borane, bringing them close enough to undergo reaction and releasing the product after the reaction. Thus these compounds are referred to as chemzymes by Corey.78 The oxazaborolidines listed in Figure 6-6 are representative catalysts for the asymmetric reduction of ketones to secondary alcohols. 

Enantioselective reduction of ketones.1 The ability of diborane in combination with the vic-amino alcohol (S)-2-amino-3-methyl-l,l-diphenyl-l-butanol (12, 31) to effect enantioselective reduction of alkyl aryl ketones involves formation of an intermediate chiral oxazaborolidine, which can be isolated and used as a catalyst for enantioselective borane reductions (equation I). 

Futatsugi and Yamamoto have demonstrated that the combination of a chiral oxazaborolidine 12 and SnCl4 leads to an extremely active Lewis acid-assisted chiral Lewis acid (LLA) as a promising catalyst for enantioselective Diels-Alder reactions (Scheme 12.10). The enantioselectivity can be preserved even in the presence of a large amount of achiral Lewis acid activator (SnCl4), which implicates the generation of highly reactive species. Only 0.5... 

If 2-camphanyloxyacrylonitrile (15 R = C8H 02C00) is taken for cycloaddition, diastereoisomeric cycloadducts can be separated, and the basic system, 7-oxabicyclo-[2.2.1]hept-5-en-2-one 17, can be obtained in optically pure form [36]. Another way of obtaining enantiomeric ketones is based on crystallization of a brucine complex obtained from the corresponding cyanohydrines (see Sec. III). Ketone 17 can be converted [e.g., by cis-hydroxylation (—>18), protection of the diol system, and Baeyer-Villiger oxidation] to lactone 19, the opening of which leads to furanuronic acid 20. A new development in this field is based in cycloaddition between furan and 2-chloro- or 2-bromoacrolein in the presence of 5 mol% chiral oxazaborolidine 21 as catalyst [37],... 

The characteristic feature of the aforementioned oxazaborolidine catalyst system consists of a-sulfonamide carboxylic acid ligand for boron reagent, where the five-membered ring system seems to be the major structural feature for the active catalyst. Accordingly, tartaric acid-derived chiral (acyloxy)borane (CAB) complexes can also catalyze the asymmetric Diels-Alder reaction of a,P-unsaturated aldehydes with a high level of asymmetric induction [10] (Eq. 8A.4). Similarly, a chiral tartrate-derived dioxaborolidine has been introduced as a catalyst for enantioselective Diels-Alder reaction of 2-bromoacrolein [11] (Eq. 8A.5). 

The asymmetric catalytic aldol reaction of silyl allenolates ICH=C=CR2OSiMe3 with aldehydes R CHO has been achieved by Li et al. by using N-C3F7CO oxazaborolidine as the catalyst [43], The fluoroacyl group of the catalyst was found to be crucial for control of enantioselectivity. The reaction provides the first enantioselective approach to / -halo Baylis-Hillman-type adducts. 

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... 

In reactions with polymer-bound catalysts, a mass-transfer limitation often results in slowing down the rate of the reaction. To avoid this disadvantage, homogenous organic-soluble polymers have been utilized as catalyst supports. Oxazaborolidine 5, supported on linear polystyrene, was used as a soluble immobilized catalyst for the hydroboration of aromatic ketones in THF to afford chiral alcohols with an ee of up to 99% [40]. The catalyst was separated from the products with a nanofiltration membrane and then was used repeatedly. The total turnover number of the catalyst reached as high as 560. An intramolecularly cross-linked polymer molecule (microgel) was also applicable as a soluble support [41]. 

R) -1 on a preparative scale. Variation of several reaction parameters such as catalyst loading, solvent, temperature, and addition order, have led to the development of an optimized procedure for this reduction. To achieve a selectivity of >90% ee, the reaction requires the use of 10 mol% of the oxazaborolidine catalyst, which is easily prepared in two steps from natural proline4 or in one step from commercially available... 

D. The use of chiral oxazaborolidines as enantioselective catalysts for the reduction of prochiral ketones, imines, and oximes, the reduction of 2-pyranones to afford chiral biaryls, the addition of diethylzinc to aldehydes, the asymmetric hydroboration, the Diels-Alder reaction, and the aldol reaction has recently been reviewed.15b d The yield and enantioselectivity of reductions using stoichiometric or catalytic amounts of the oxazaborolidine-borane complex are equal to or greater than those obtained using the free oxazaborolidine.13 The above procedure demonstrates the catalytic use of the oxazaborolidine-borane complex for the enantioselective reduction of 1-indanone. The enantiomeric purity of the crude product is 97.8%. A... 

Asymmetric Borane Reduction. The reaction of ATBH with trimethylboroxine by refluxing in toluene affords the chiral B-methyl oxazaborolidine in high yield (eq 2) This oxaz-aborolidine can serve as an efficient catalyst for the asymmetric borane reduction ofprochiral ketones (eq 3). The corresponding chiral secondary alcohols are obtained in high yields with good enantioselectivities. 

In addition to these simple examples, oxazaborolidines derived from dipheny Iprolinol have been used as enantioselective catalysts for the preparation of prostaglandins, PAF antagonists, a key intermediate of ginkgolide B, a key intermediate of forskolin, ... 

Enantioselective Reduction of Imines and Ketoxime O-Ethers. In addition to the reduction of prochiral ketones, chiral oxazaborolidines have been employed as enantioselective reagents and catalysts for the reduction of imines (eq 11) and ketoxime O-ethers (eq 12) - to give chiral amines. It is interesting to note that the enantioselectivity for the reduction of ketoxime O-ethers is opposite that of ketones and imines. For more information, see 2-Amino-3-methyl-l,l-diphenyl-I-butanol. 

Other Applications. Chiral oxazaborolidines derived from ephedrine have also been used in asymmetric hydroborations, and as reagents to determine the enantiomeric purity of secondary alcohols. Chiral l,3,2-oxazaborolidin-5-ones derived from amino acids have been used as asymmetric catalysts for the Diels-Alder reaction,and the aldol reaction. ... 

Oxazaborolidines have been found to be a unique catalyst for asymmetric borane reduction of ketones and imines [35,36]. Coordination of BH3 to the nitrogen atom of 24 serves to activate BH3 as a hydride donor and to increase the Lewis acidity of the boron atom (Eq. 9). The Lewis acidity of the boron atom in the oxazaborolidine plays an important role in the reduction. Several types of polymer-supported oxazaborolidine have been reported and are considered to be polymer-supported boron-based Lewis acids. 

The same reaction has also been catalyzed by chiral oxazaborolidinones derived from amino acids and boranes. They proved to be efficient catalysts for enantioselec-tive Diels-Alder reaction [91,92]. The polymer-supported chiral oxazaborolidinones 75 were reported to be efficient catalysts [93]. These polymer-supported chiral oxaza-borolidinone ligands were prepared both by chemical modification and by the copolymerization shown in Sch. 5 [94]. The polymer-supported chiral ligands were then reacted with borane to give the oxazaborolidines which were used as catalysts in Diels-Alder reaction of cyclopentadiene with methacrolein. 

In most Diels-Alder reactions, no catalyst is needed, but Lewis acids are effective catalysts in many cases, particularly those in which Z in the dienophile is a C=0 or C=N group. A Lewis acid catalyst usually increases both the regioselec-tivity of the reaction (in the sense given above) and the extent of endo addition, °° and, in the case of enantioselective reactions, the extent of enantioselectivity. It has been shown that InCla is an effective catalyst for aqueous Diels-Alder reactions,which is suitable for ionic Diels-Alder reactions, and there are other Lewis acid catalysts that are effective in water. °° Brpnsted acids have also been used to accelerate the rate of the Diels-Alder reaction.Lanthanum triflate [La(OTf)3] has been reported as a reusable catalyst ° ° and Me3SiNTf2 has been used as a green Lewis acid catalyst. ° Cationic Diels-Alder catalysts have been developed, particularly oxazaborolidine catalysts. ° Some Diels-Alder reactions can also be catalyzed by the addition of a stable cation radical, for... 

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