(R*,R*)-a-(2,6-Diisopropoxybenzoyloxy)-5-oxo-1,3,2-dioxaborolane-4-acetic Acid1

(R,R)

[131703-55-4]  · C17H21BO9  · (R*,R*)-a-(2,6-Diisopropoxybenzoyloxy)-5-oxo-1,3,2-dioxaborolane-4-acetic Acid  · (MW 380.16) (S,S)

[131703-56-5]

(chiral Lewis acid catalyst for Diels-Alder,1,2 aldol-type,3 allylation,4 and hetero Diels-Alder5 reactions)

Solubility: sol dichloromethane, propionitrile, THF.

Form Supplied in: the acyloxyborane.THF complex is available as a 0.1-0.2 M solution in dichloromethane or propionitrile.

Analysis of Reagent Purity: 1H NMR (CD2Cl2, -95 °C, 500 MHz) d 1.07-1.13 (m, 6H, 2CH3), 1.24 (br, 6H, 2CH3), 4.50 (br, 2H, 2(CH3)2CH), 4.70-4.92 (m, 1H, CHCO2B), 5.45-5.72 (m, 1H, CHCO2H), 6.48 (br, 2H, 2m-H), 7.21 (br, 1H, p-H).

Preparative Methods: to a solution of (R,R)- or (S,S)-mono-(2,6-diisopropoxybenzoyl)tartaric acid (74 mg, 0.2 mmol) in dry dichloromethane or propionitrile (1 mL) is added BH3.THF (0.189 mL of 1.06 M solution in THF, 0.2 mmol) at 0 °C under an argon atmosphere. The reaction mixture is stirred for 1 h at 0 °C to produce the chiral acyloxyborane. Only 2 equiv of hydrogen gas should evolve under these reaction conditions (0 °C). See also Furuta.1

Handling, Storage, and Precautions: the acyloxyborane solution should be flushed with Ar and stored tightly sealed (to preclude contact with oxygen and moisture) below 0 °C. Use in a fume hood.

Acyloxyborane as an Activating Device for Carboxylic Acids.2a

The reduction of carboxylic acids by borane is an important procedure in organic synthesis. The remarkable reactivity of borane towards carboxylic acids over esters is characteristic of this reagent. Such selectivity is rarely seen with other hydride reagents.

The rapid reaction between carboxylic acids and borane is related to the electrophilicity of the latter. The carbonyl group of the initially formed acyloxyborane intermediate, which is essentially a mixed anhydride, is activated by the Lewis acidity of the trivalent boron atom. Addition of 1/3 equiv of the Borane-Tetrahydrofuran complex to acrylic acid in dichloromethane followed by addition of a diene at low temperature results in the formation of Diels-Alder adducts in good yield (eq 1). Further, the reaction is successful even with a catalytic amount of borane.

Asymmetric Diels-Alder Reaction of Unsaturated Carboxylic Acids.2a

A chiral acyloxyborane (CAB) complex (1) prepared from mono(2,6-dimethoxybenzoyl)tartaric acid and 1 equiv of borane is an excellent catalyst for the Diels-Alder reaction of a,b-unsaturated carboxylic acids and dienes. In the CAB-catalyzed Diels-Alder reaction, adducts are formed in a highly diastereo- and enantioselective manner under mild reaction conditions (eq 2). The reaction is catalytic: 10 mol % of catalyst is sufficient for efficient conversion, and the chiral auxiliary can be recovered and reused.

Asymmetric Diels-Alder Reaction of Unsaturated Aldehydes.1,2b-e

The boron atom of acyloxyborane is activated by the electron-withdrawing acyloxy groups, and consequently acyloxyborane derivatives are sufficiently Lewis acidic to catalyze certain reactions. Thus, asymmetric Diels-Alder reactions of a,b-enals with dienes using (1) as a Lewis acid catalyst have been developed. For example, the reaction of cyclopentadiene and methacrolein gives the adduct in 85% yield (endo:exo = 11:89) and 96% ee (major exo isomer) (eq 3). Some additional examples are listed in Figure 1. The a-substituent on the dienophile increases the enantioselectivity, while b-substitution dramatically decreases the selectivity. In the case of a substrate having substituents in both a- and b-positions, high enantioselectivity is observed; thus the a-substituent effect overcomes that of the b-substituent.

The intramolecular Diels-Alder reaction of 2-methyl-(E,E)-2,7,9-decatrienal with CAB catalysis proceeds with high diastereo- and enantioselectivities.2c

Asymmetric Aldol-Type Reaction.3

CAB complex (2) is an excellent catalyst for the Mukaiyama condensation of simple achiral enol silyl ethers of ketones with various aldehydes. The CAB-catalyzed aldol process allows the formation of adducts in a highly diastereo- and enantioselective manner (up to 96% ee) under mild reaction conditions (eqs 4 and 5). The reactions are catalytic: 20 mol % of catalyst is sufficient for efficient conversion, and the chiral auxiliary can be recovered and reused.

Almost perfect asymmetric induction is achieved in the syn adducts, reaching 96% ee, although a slight reduction in both the enantio- and diastereoselectivities is observed in the reactions with saturated aldehydes. It is noteworthy that, regardless of the stereochemistry of the starting enol silyl ethers, the CAB-catalyzed reaction is highly selective for syn adducts. The high syn selectivity and the independence of selectivity on the stereochemistry of silyl ethers in the CAB-catalyzed reactions are fully consistent with Noyori's Trimethylsilyl Trifluoromethanesulfonate-catalyzed aldol reactions of acetals,6 and thus may reflect the acyclic extended transition state mechanism postulated in the latter reactions (Figure 2). Judging from the product configurations, the CAB catalyst (from natural tartaric acid) should effectively cover the si-face of carbonyl following its coordination and the selective approach of nucleophiles from the re-face should result.

A catalytic asymmetric aldol-type reaction of ketene silyl acetals with achiral aldehydes also proceeds with the CAB catalyst (2), which can furnish syn-b-hydroxy esters with high enantioselectivity (eq 6).

This reaction is sensitive to the substituents of the starting ketene acetals. The use of ketene silyl acetals from phenyl esters leads to good diastereo- and enantioselectivities with excellent chemical yields.

Analogous with the previous results of enol silyl ethers of ketones, nonsubstituted ketene silyl acetals are found to exhibit lower levels of stereoregulation, while the propionate-derived ketene silyl acetals display a high level of asymmetric induction. The reactions with aliphatic aldehydes, however, resulted in a slight reduction in optical and chemical yields. With phenyl ester-derived ketene silyl acetals, syn adducts predominate, but the selectivities are moderate in most cases in comparison with the reactions of ketone-derived silyl enol ethers. Exceptions are a,b-unsaturated aldehydes, which revealed excellent diastereo- and enantioselectivities. The observed syn selectivity and re-face attack of nucleophiles on the carbonyl carbon of aldehydes are consistent with the aforementioned aldol reactions of ketone-derived enol silyl ethers.

Asymmetric Allylation (Sakurai-Hosomi Allylation).4

Condensation of achiral aldehydes with allylsilanes promoted by CAB catalyst (2) (20 mol %) at -78 °C in propionitrile produces homoallylic alcohols with excellent enantioselectivity (eq 7).

Alkyl substitution at the alkene of the allylsilanes increases the reactivity, permitting lower reaction temperature and improved asymmetric induction. g-Alkylated allylsilanes exhibit excellent diastereo- and enantioselectivities, affording syn homoallylic alcohols with high enantiomeric purity. The syn selectivity of these reactions is independent of the allylsilane stereochemistry. Thus regardless of the geometry of the starting allylsilane, the predominant isomer in this reaction has syn configuration. The observed preference for relative and absolute configurations for the adduct alcohols derived from reaction catalyzed by the (2R,3R)-ligand-borane reagent can be rationalized on the basis of an extended transition state model similar to that for the CAB-catalyzed aldol reaction (see Figure 2).

Allystannanes are more nucleophilic than allylsilanes. Addition of achiral allylstannanes to achiral aldehydes in the presence of (1) (20 mol %) and Trifluoroacetic Anhydride (40 mol %) also affords homoallylic alcohols with high diastereo- and enantioselectivities (eq 8).

Asymmetric Hetero Diels-Alder Reaction.5

In contrast to the CAB catalyst (2; R = H) which is stable and both air and moisture sensitive, the B-alkylated CAB catalyst (3; R = Ph or alkyl) is stable and can be stored in a closed container at rt. A solution of the CAB (3; R = Ph) catalyzes Diels-Alder, aldol, and Sakurai-Hosomi reactions. Although the asymmetric inductions achieved by these complexes are slightly less efficient than that of the corresponding hydride-type catalyst, the CAB catalyst (3; R = Ph) is shown to be an excellent system for hetero Diels-Alder reactions.

The B-alkylated CAB catalyst (3) is easily prepared in situ by mixing a 1:1 molar ratio of tartaric acid derivative and phenylboronic acid in dry propionitrile at room temperature for 0.5 h. The hetero Diels-Alder reaction of aldehydes with Danishefsky dienes is promoted by 20 mol % of this catalyst solution at -78 °C for several hours to produce dihydropyranone derivatives of high optical purity (eq 9).


1. Furuta, K.; Gao, Q.; Yamamoto, H. OS 1995, 72, 86.
2. (a) Furuta, K.; Miwa, Y.; Iwanaga, K.; Yamamoto, H. JACS 1988, 110, 6254. (b) Furuta, K.; Shimizu, S.; Miwa, Y.; Yamamoto, H. JOC 1989, 54, 1481. (c) Furuta, K.; Kanematsu, A.; Yamamoto, H. TL 1989, 30, 7231. (d) Ishihara, K.; Gao, Q.; Yamamoto, H. JOC 1993, 58, 6917. (e) Ishihara, K.; Gao, Q.; Yamamoto, H. JACS 1993, 115, 10412.
3. (a) Furuta, K.; Maruyama, T.; Yamamoto, H. JACS 1991, 113, 1041. (b) Furuta, K.; Maruyama, T.; Yamamoto, H. SL 1991, 439. (c) Ishihara, K.; Maruyama, T.; Mouri, M.; Gao, Q.; Furuta, K.; Yamamoto, H. BCJ 1993, 66, 3483.
4. (a) Furuta, K.; Mouri, M.; Yamamoto, H. SL 1991, 561. (b) Marshall, J. A.; Tang, Y. SL 1992, 653. (c) Ishihara, K.; Mouri, M.; Gao, Q.; Maruyama, T.; Furuta, K.; Yamamoto, H. JACS 1993, 115, 11490.
5. (a) Gao, Q.; Maruyama, T.; Mouri, M.; Yamamoto, H. JOC 1992, 57, 1951. (b) Gao, Q.; Ishihara, K.; Maruyama, T.; Mouri, M.; Yamamoto, H. T 1994, 50, 979.
6. Noyori, R.; Murata, S.; Suzuki, M. T 1981, 37, 3899.

Kazuaki Ishihara & Hisashi Yamamoto

Nagoya University, Japan



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