Allenylboronic Acid

[83816-41-5]  · C3H5BO2  · Allenylboronic Acid  · (MW 83.88)

(propargylating reagent for carbonyl groups; chiral allenylboronic ester as a reagent for enantioselective alkylation;1 1,3-asymmetric induction in propargylation of b-hydroxy ketones2)

Physical Data: mp 150 °C (dec).

Solubility: sol ether, alcohol.

Form Supplied in: white solid; widely available.

Analysis of Reagent Purity: 1H NMR (CDCl3-Me2SO-d6) d 4.48 (d, J = 5.8 Hz, 1H), 4.51 (d, J = 7.2 Hz, 1H), 4.83 (dd, J = 5.8 and 7.2 Hz, 1H), 6.52 (br s, 2H).

Preparative Method: from Propargylmagnesium Bromide and Trimethyl Borate.1

Handling, Storage, and Precautions: allenylboronic acid can be stored at -20 °C under argon. In air, it catches fire within several minutes. It should only be used in a fume hood.

Allenylboronic Acid.1

Treatment of propargylmagnesium bromide with trimethyl borate followed by acidic workup gives, after recrystallization from hexane-ether, a single crystalline boronic acid in 40-60% yield (eq 1).3 As far as can be described, a single compound results from this preparation.

Allenylboronic acid is an ambident nucleophile and its reactions with carbonyl compounds can be envisioned to occur either at the a or g position. Treatment of cyclohexanecarbaldehyde with allenylboronic acid in toluene containing 4 equiv. of pentanol and molecular sieves produces exclusively the homopropargylic alcohol (1) in 40% yield. This result suggests that the reaction proceeds through the cyclic transition state (2).

Chiral Allenylboronic Esters.1

Condensations of aldehydes with chiral allenylboronic esters provide b-alkynic alcohols with an exceptionally high degree of enantioselectivity (eq 2). The reagents prepared using bulky tartrate esters like 2,4-dimethyl-3-pentyl as the chiral auxiliary are more enantioselective than reagents prepared from ethyl or isopropyl esters of tartaric acid. These results have been rationalized by the transition state shown in structure (4), in which the ester alkoxy group exerts a screening influence on the prochiral carbonyl compound such that RŽ is positioned as far away from CO2R as possible.

Condensation with aromatic aldehydes appears to be considerably less efficient than the reaction with saturated aldehydes. In addition, only low yields (<50%) of the homopropargylic alcohol are obtained by the reaction with a variety of unsaturated aldehydes with this reagent, indicating that the use of saturated aldehyde is crucial to the success of the asymmetric propargylation reaction. Additional results are summarized in Table 1. This method has been applied to the synthesis of (-)-ipsenol, as summarized in eq 3.1b,4

1,3-Asymmetric Induction.2

The reaction of allenylboronic acid with carbonyl compounds is slow relative to the reaction of allenylboronic esters.1 However, the reaction of allenylboronic acid (1.2 equiv.) with b-hydroxy ketones in anhydrous ether at rt in the presence of molecular sieves (5Å for 20 h), followed by treatment with basic Hydrogen Peroxide, yields the threo diol (10) with excellent levels of 1,3-asymmetric induction (>99%, eq 4). Additional results are summarized in eqs 5-7. The yields in all cases are >90%. The reaction of propargylmagnesium bromide with (9) in ether affords a mixture of the threo and erythro diols, in agreement with related nonselective processes.5

The very high levels of stereoselectivity observed in these reactions strongly suggest the existence of the covalently bonded organometallic (11) as a reactive intermediate (eq 8). Indeed, treatment of a mixture of cyclohexanone and s-phenethyl alcohol with allenylboronic acid gave none of the expected homopropargylic alcohol under the above reaction conditions. Furthermore, treatment of a mixture of the ketone (9; R = cyclohexyl) and 2-hexanone with allenylboronic acid produced the diol (10) as a sole product.

Treatment of threo diols (10) with Ruthenium(III) Chloride-Sodium Periodate6 gave the corresponding lactones in excellent yield (eqs 5-7).

The use of this method for the preparation of a diastereomer of the b-hydroxy-d-lactone substituent of the HMG CoA reductase inhibitor mevinolin7,8 is summarized in eq 9. Unfortunately, however, the product has the (4S,6R) configuration rather than the most active (4R,6R) configuration.7


1. (a) Haruta, R.; Ishiguro, M.; Ikeda, N.; Yamamoto, H. JACS 1982, 104, 7667. (b) Ikeda, N.; Arai, I.; Yamamoto, H. JACS 1986, 108, 483. Synthetic applications using chiral allenylboronic ester, see: (c) Tius, M. A.; Trehan, S. JOC 1986, 51, 765. (d) Fryhle, C. B.; Williard, P. G.; Rybak, C. M. TL 1992, 33, 2327.
2. Ikeda, N.; Omori, K.; Yamamoto, H. TL 1986, 27, 1175.
3. Favre, E.; Gaudemer, M. CR(C) 1966, 262, 1332.
4. Silverstein, R. M.; Rodin, J. O.; Wood, D. L. Science 1966, 154, 509.
5. For studies of propargyl Grignard reagent with 4-t-butyl-2-methoxycyclohexanone, see: Guillerm-Dron, D.; Capmau, M. L.; Chodkiewicz, W. BSF(2) 1973, 1417.
6. Carlsen, H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. JOC 1981, 46, 3936. Ruthenium dioxide-periodate procedure is also effective for this oxidation: Corey, E. J.; Boaz, N. W. TL 1984, 25, 3059.
7. (a) Lee, T.; Holtz, W. J.; Smith, R. L. JOC 1982, 47, 4750. (b) Ferres, H.; Hatton, I. K.; Jennings, L. J. A.; Tyrrell, A. W. R.; Williams, D. J. TL 1983, 24, 3769.
8. (a) Prugh, J. D.; Rooney, C. S.; Deana, A. A.; Ramjit, H. G. TL 1985, 26, 2947. (b) Sletzinger, M.; Verhoeven, T. R.; Volante, R. P.; McNamara, J. M.; Corley, E. G.; Liu, T. M. H. TL 1985, 26, 2951 and references cited therein.

Kazuaki Ishihara & Hisashi Yamamoto

Nagoya University, Japan



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