Oxazaborolidines Diels-Alder reaction

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

In the same area, a (5)-tryptophan-derived oxazaborolidine including a p-tolylsulfonylamide function has been used by Corey et al. to catalyse the enantioselective Diels-Alder reaction between 2-bromoacrolein and cyclo-pentadiene to form the corresponding chiral product with an unprecedented high (> 99% ee) enantioselectivity (Scheme 5.27)." This highly efficient methodology was extended to various 2-substituted acroleins and dienes such as isoprene and furan. In addition, it was applied to develop a highly efficient total synthesis of the potent antiulcer substance, cassiol, as depicted in Scheme 5.21... 

Acyloxyboron complexes and oxazaborolidines have been shown to catalyse Diels-Alder reactions featuring aldehydes as one component for example, the complex (51) allows the coupling of cyclopentadiene and a-bromoacrolein in high yield to give a product of high optical purity (Scheme 46)[132]. The immobilized catalyst system of this genre, recently introduced by Itsuno, is... 

Corey, E. J. Shibata, T. Lee, T. W. Asymmetric Diels-Alder Reactions Catalyzed by a Triflic Acid Activated Chiral Oxazaborolidine. J. Am. Chem. Soc. 2002,124,3808-3809. 

Chiral 1,2,3-oxazaborolidines simply obtained from a-amino acid derived sulfonamides and borane were first applied in Diels-Alder reactions by Taliasu and Yamamoto228, and Helmchen and colleagues229. Yamamoto prepared catalysts from a-aminobutyric acid derived arylsulfonamides and found that the enantioselectivity of the reaction between... 

Later, Corey reported that the bulky superacid triflylimide (Tf2NH) protonates chiral oxazaborolidines to form superactive, stable, chiral acids 11a and 11b, which are highly effective catalysts for a wide variety of enantioselective Diels-Alder reactions that were beyond the reach of synthetic chemists (Scheme... 

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... 

The chiral oxazaborolidines introduced in Section 2.1.3.5 as enantioselective aldol addition catalysts have also been found to be useful in Diels-Alder reactions. The tryptophan-derived catalyst A, for example, can achieve 99% enantioselectivity in the Diels-Alder reaction between 5-benzyloxymethyl-l,3-cyclopentadiene and 2-bromopro-penal. The adduct is an important intermediate in the synthesis of prostaglandins.64... 

Yamamoto had earlier reported that Lewis acid activation of valine-derived oxazaborolidine 60 yielded a highly reactive and moisture-tolerant LLA catalyst 61 for the Diels-Alder reaction (Scheme 5.76) [145]. In later studies, activation of 60 with the super Bronsted acid, C,sF5CHTf2, was found to produce the even more reactive catalytic species BLA 62. During studies toward an enantioselective route to Platensimycin [146], BLA 62 was found to catalyze the Diels-Alder reaction between various monosubstituted dienes and ethyl acrylate to afford adducts... 

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). 

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... 

Starting with quinone 180, which was obtained by methylation of hydroxyqui-none 169, the oxazaborolidine-catalyzed intermolecular Diels-Alder reaction with butadiene was conducted at —50°C in toluene. Within 48 hours, 99% of the starting material was converted into adduct 171 in 99% optical purity (Scheme 18). 

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. ... 

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... 

Enantioselective Diels-Alder Reactions Using Oxazaborolidine Catalysis O... 

A tryptophan-derived oxazaborolidine has been shown to be an effective catalyst for aldehyde-based Diels-Alder reactions. Complex 10, prepared from a-methyl tryptophan and BuB(OH)2 with removal of water, effects the cycloaddi-... 

The utility of such cycloadditions has been demonstrated by the elaboration of the cycloadducts to complex natural products [60]. For example, the adduct derived from a cyclopentadiene having a 2-bromoallyl sidechain has been converted to an intermediate employed in a previous (racemic) synthesis of gibberel-lic acid. As illustrated in Scheme 12, an exceptionally efficient synthesis of cassi-ol is realized by the successful execution of a rather difficult endo-selective Diels-Alder reaction using a slightly modified oxazaborolidine (11). The high catalyst loading is balanced by the fact that all the carbons and the quaternary center of the natural product are introduced in a single step. 

Asymmetric Diels—Alder reactions.6 The oxazaborolidine la, prepared by reaction of N-tosyl-(S)-tryptophan with BuB(OH)2 in toluenc-THF (2 1) with removal of HjO, is a highly effective catalyst for cnantioselective Dicls-Aldcr reactions. The same reaction but with BH3"THF at 23° provides lb. 

Scheme 6. Asymmetric Diels-Alder reaction catalysed by oxazaborolidine 20.

A ligand having C2-symmetry is not a necessity and a variety of catalysts are known that promote highly enantioselective Diels-Alder reactions. For example, the oxazaborolidine 148 is a good catalyst for the cycloaddition of cyclopentadi-ene and 2-bromoacrolein (3.104). The cycloaddition reaction is highly diastereo-and enantioselective in favour of the exo-aldehyde. However, the enantioselectiv-ity is poor with this catalyst when the dienophile lacks a substituent (for example bromine) in the 2-position. A solution to this problem is the use of the protonated oxazaborolidine 149, which promotes highly selective cycloaddition of cyclopen-tadiene with a range of dienophiles, such as ethyl vinyl ketone or ethyl acrylate (3.105). Asymmetric cycloaddition of a,p-unsaturated aldehydes or ketones with various dienes can alternatively be achieved in the presence of a chiral secondary amine as a catalyst. 

Cationic Lewis acids show improved acidity and hence activity. For instance, even at —94°C, relatively unreactive dienes such as butadiene (8.29) react with bromoacrolein (8.05) with excellent yields and good selectivities in the presence of the oxazaborinane (8.30). The Lewis acidity of oxazoborolidines can also be enhanced by protonation using strong Bronsted acids. The triflate salt (8.32) generated by protonation of the corresponding oxazaborolidine with triflic acid shows high activity and wide scope catalysing the Diels-Alder reaction of acyclic... 

Corey et al. have shown the asymmetric Diels-Alder reactions catalyzed by a triflic acid activated chiral oxazaborolidine (eq 45). Triflic acid has also been found to be an efficient catalyst (1 mol %) for the hetero-Diels-Alder reaction between aromatic aldehydes and unactivated dienes. ... 

The Diels-Alder reaction was performed with cyclopentadiene and methacroleine (Scheme 56) in presence of 15 mol% of the oxazaborolidine and oxazaborolidinone catalysts derived respectively from supported aminoalcohols and from V-sulfonylamino acid polymers. The oxazaborolidine and oxazaborolidinone catalysts were formed in situ by action of BH3, BH2Br, BHBr2 or BBrs. The diastereoselectivity was excellent in favour of the exo adduct and yields from 65 to 99%. It is noteworthy that higher loading of chiral catalyst site in the polymer, lower exo selectivity and enantioselectivity. The diastereoselection depended not only on the nature of the supported ligand, the crosslinker but also on the borane and the solvent. Results are summarized in Table 6. 

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