Oxazaborolidines aldol reaction

Of the catalysts that are based on boron, the Masamune oxazaborolidines (44) are typical, being able to promote aldol reactions of the type described in Scheme 42[124]. 

Kiyooka et al. have shown that the asymmetric aldol reaction of ketene silyl acetals is promoted by 20 mol % of oxazaborolidine catalyst derived from (5)-valine with enantioselectivity employing nitromethane as the solvent [47]. 

The mechanism A very detailed mechanistic study of this phosphoramide-catalyzed asymmetric aldol reaction was conducted by the Denmark group (see also Section 6.2.1.2) [59, 60], Mechanistically, the chiral phosphoramide base seems to coordinate temporarily with the silicon atom of the trichlorosilyl enolates, in contrast with previously used chiral Lewis acids, e.g. oxazaborolidines, which interact with the aldehyde. It has been suggested that the hexacoordinate silicate species of type I is involved in stereoselection (Scheme 6.15). Thus, this cationic, diphosphoramide silyl enolate complex reacts through a chair-like transition structure. 

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. 

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... 

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. ... 

Other approaches to the bryostatins have also used enantio- or diastereoselective aldol reactions. An interesting iterative strategy for the synthesis of the Cj-Cg polyacetate region 134 has been disclosed where each aldol addition proceeds with excellent stereocontrol (99 1) under the catalytic influence of oxazaborolidine 135 (Scheme 9-42) [60J. Finally, a moderately selective, auxiliary controlled, acetate aldol reaction has been used for the introduction of the C3 stereocenter of the bryostatins giving adduct 136 (84% d.s) [61]. 

The synthesis of another Ci-Ce ketone 210 used an asymmetric Mukaiyama aldol reaction catalyzed by oxazaborolidine 135 (Scheme 9-58) [78]. This concise synthesis is reminiscent of an earlier approach to the bryostatins (see Scheme 9-42) and can also be compared with the chromium-mediated addition of a-bromoimide 211 to simple aldehyde 212 to give 213, which proceeded with excellent stereo-control (>99 1) [76]. 

Kiyooka et al. have reported that stoichiometric use of chiral oxazaborolidines (e.g. (S)-47), derived from sulfonamides of a-amino acids and borane, is highly effective in enantioselective aldol reactions of ketene TMS acetals such as 48 and 49 (Scheme 10.39) [117]. The use of TMS enolate 49 achieves highly enantioselective synthesis of dithiolane aldols, which can be readily converted into acetate aldols without epimerization. The chiral borane 47-promoted aldol reaction proceeds with high levels of reagent-control (Scheme 10.40) [118] - the absolute configuration of a newly formed stereogenic center depends on that of the promoter used and not that of the substrate. 

Enantioselective aldol reactions.-1 The tryptophan-derived oxazaborolidine 1 can also effect enantioselective Mukaiyama-aldol reactions of aldehydes with trimethyl-->ilyl ethers. 

Aldolization and related reactions. Tartaric acid-derived acyloxyborane complexes are shown to be useful catalysts for asymmetric aldol reactions. (5)-4-Isopropyl-3-tosyl-l,3,2-oxazaborolidin-5-one is an excellent cataly.st, not only for the aldolization " between a silyl enol ether and an aldehyde it also reduces the products to afford syn-l,3-diols. ... 

Scheme 9. Enantioselective aldol reaction catalyzed by oxazaborolidine.

The reaction can be applied to silyl enol esters as well. Good asymmetric induction can be achieved in the Mukaiyama aldol reaction. The reaction of silyl enol thioether 246 and nonanal, for example, gave 247 in 60% yield and in 93% ee when the (/ )-BINOL-titanium catalyst shown was used. In this work, the reaction was also done in supercritical fluoroform and in supercritical carbon dioxide. A similar reaction was reported using catalysts closely related to 244 and dichloromethane as the solvent.Chiral oxazaborolidine catalysts have also been shown to be effective for enantioselective Mukaiyama aldol reactions. 

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... 

Oxazaborolidines have also been used as catalysts in atrop enantioselective ring-opening (49), asymmetric addition of diethylzinc to aldehydes (50), asymmetric Diels-Alder reactions (57, 52), aldol reactions (55), Rh catalyzed hydroboration (54), etc. 

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). 

Intrigued by results obtained with the catalyst 79, Corey et al. developed amino-acid-based oxazaborolidines (e.g., 85). Evans et al. proposed tin (II)- and copper (Il)-bisoxazoline-catalyzed aldol reactions (catalysts 86,... 

Masamune examined the use of Ca-alkylated a-amino acids for the generation of optically active oxazaborolidines 249 which were used as Lewis acid catalysts (Scheme 4.30) [125, 126]. The expectation in these studies was that the additional rigidity proffered by the unnatural amino acid scaffold would lead to improved selectivities. Several excellent catalysts for asymmetric Mukaiyama aldol reactions with a broad range of aldehydes were identified, both for acetate aldol reactions [125] and for the addition of isobutyrate-derived silyl enol ethers [126], as shown for the case of catalyst 249. 

Corey examined and documented another class of amino-acid-derived N-sulfonamide oxazaborolidines, characterized by their convenient synthesis, for the catalytic asymmetric Mukaiyama aldol reaction. Oxazaborolidine 256, for example, can be assembled from the condensation of L-N-tosyl-tryp-tophan and n-butylboronic acid. It was shown to be an effective catalyst for the Mukaiyama addition of enoxysilanes with a variety of aldehydes (Equation 25) [127]. 

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. 

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... 

Corey, E. J., Cywin, C. L., Roper, T. D. Enantioselective Mukaiyama-aldol and aldol-dihydropyrone annulation reactions catalyzed by a tryptophan-derived oxazaborolidine. Tetrahedron Lett. 1992, 33, 6907-6910. 

During the last decade, use of oxazaborolidines and dioxaborolidines in enantioselective catalysis has gained importance. [1, 2] One of the earliest examples of oxazaborolidines as an enantioselective catalyst in the reduction of ketones/ketoxime ethers to secondary alco-hols/amines was reported by Itsuno et al. [3] in which (5 )-valinol was used as a chiral ligand. Since then, a number of other oxazaborolidines and dioxaborolidines have been investigated as enantioselective catalysts in a number of organic transformations viz a) reduction of ketones to alcohols, b) addition of dialkyl zinc to aldehydes, c) asymmetric allylation of aldehydes, d) Diels-Alder cycloaddition reactions, e) Mukaiyama Michael type of aldol condensations, f) cyclopropana-tion reaction of olefins. 

Thus, a,a-disubstituted A(-arylsulfonylgly-cines were used for the preparation of the oxazaborolidine 32 which resulted in catalytic asymmetric aldol processes providing fi-hydroxy esters of > 97 % ee from a-unbran-ched aldehydes (R-CH2CHO) and 84-96% ee with a-branched aldehydes (R2CHCHO). The reaction proceeds smoothly in propioni-trile at -78 °C if the aldehyde is added slowly over 3.5 h affording high yields (68-89 %) of the adduct. 

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