Ephedrine-borane1

[126874-38-2]  · C10H14BNO  · Ephedrine-borane  · (MW 175.04)

(chiral Lewis acid catalyst for carbonyl additions, reductions, and hydroborations1)

Alternate Name: (4S,5R)-3,4-dimethyl-5-phenyl-1,3,2-oxazaborolidine.

Physical Data: 2,4 colorless liquid, bp 110-112 °C/20 mmHg, 45 °C (bath)/0.1 mmHg; [a]20D = -108° (c 1.0 CHCl3). For the corresponding reagent prepared from pseudoephedrine (1S,2S), [a]20D = +59° (c 1.0 CHCl3). Spectral data:2a,3,4 1H NMR selected data d (CDCl3) 3.68 (m), 5.58 (d, J = 8.5 Hz); 1H NMR d (C6D6) 0.43 (d, J = 6.6 Hz), 2.50 (s), 3.28 (m), 5.41 (d, J = 8.6 Hz); 11B NMR d +29 ppm (d, J = 147 Hz); 13C NMR d (C6D6) 15.42, 30.25, 59.62, 83.58, 126.59, 127.32, 128.13, 140.02; IRB-H 2562 cm-1. For the corresponding reagent from pseudoephedrine (1S,2S): 1H NMR selected data d (CDCl3) 3.30 (m), 4.90 (d, J =  7.0 Hz).

Solubility: sol THF.

Form Supplied in: not commercially available.

Preparative Methods: 2 a solution of (1R,2S)-(-)-ephedrine (8.25 g, 50 mmol) in anhydrous THF (50 ml) was treated with Borane-Dimethyl Sulfide complex (50 mmol, 5 mL of 10 M solution). The reaction mixture was stirred at 25 °C for 1 h, at which time one equivalent of hydrogen had evolved. The volatiles were removed in vacuo to furnish a white solid, 11B NMR (d ~8 ppm). The solid was gradually heated to 100 °C and maintained at that temperature until the second equivalent of hydrogen had evolved. The product was distilled under reduced pressure to provide the pure oxazaborolidine (86%). An alternative procedure is available.3

Handling, Storage, and Precautions: the reagent is sensitive to moisture and should be handled under a dry, inert atmosphere.

Enantioselective Addition of Diethylzinc to Aldehydes.

The reagent catalyzes the enantioselective addition of Diethylzinc to aldehydes (eq 1).2

Enantioselective Alkene Hydroboration.

Substituted styrene derivatives undergo rhodium-catalyzed hydroboration in the presence of a catalytic amount of the title reagent. However, optimal regio- as well as enantioselection is attained by using the corresponding reagent derived from pseudoephedrine (eq 2).4

If the N-isopropyl analog of the borane reagent is used in conjunction with bis(4-methoxystyrene)rhodium chloride dimer as catalyst, the corresponding (E)-vinylborane and 4-methoxyethylbenzene are obtained in equal proportions (eq 3).5

Enantioselective Carbonyl Reduction.

The title reagent reacts with borane through N->B coordination. This complexation enhances the Lewis acidity at the ring boron atom, thereby triggering dimerization of the adduct via hydride bridging.6 This complex is capable of reducing acetophenone with good enantioselectivity (eq 4). The proposed reactive complex features anti coordination of acetophenone to the ring boron atom and syn to the coordinated BH3.7

Several other 1,3,2-oxazaborolidines have been successfully used as chiral catalysts or reagents in borane-promoted reduction of ketones,8 imines and oxime ethers,9 and lactones10 as well as in aldol condensations,11 Diels-Alder cycloadditions,12 and allylmetal additions to aldehydes.13

Related Reagents.

a,a-Diphenyl-2-pyrrolidinemethanol; Norephedrine-Borane; Tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborole.


1. (a) Nishizawa, M.; Noyori, R. COS 1991, 8, Chapter 1.7. (b) Midland, M. Asymmetric Synthesis; Academic: New York, 1983; Vol. 2. (c) Midland, M. CRV 1989, 89, 1553. (d) Seyden-Penne, J. Reductions by the Alumino- and Borohydrides in Organic Synthesis; VCH: New York, 1991. (e) Wallbaum, S.; Martens, J. TA 1992, 3, 1475.
2. (a) Joshi, N. N.; Srebnik, M.; Brown, H. C. TL 1989, 30, 5551. (b) Soai, K.; Niwa, S. CRV 1992, 92, 833.
3. Tlahuext, H.; Contreras, R. TA 1992, 3, 727.
4. (a) Brown, J. M.; Lloyd-Jones, G. TA 1990, 1, 869. See also: (b) Burgess, K.; Van der Donk, W.; Ohlmeyer, M. J. TA 1991, 2, 613.
5. Brown, J. M.; Lloyd-Jones, G. C. CC 1992, 710.
6. Tlahuext, H.; Contreras, R. TA 1992, 3, 1145.
7. Berenguer, R.; Garcia, J.; Gonzàlez, M.; Vilarrasa, J. TA 1993, 4, 13.
8. (a) Corey, E. J.; Link, J. O. TL 1992, 33, 4141. (b) Martens, J; Dauelsberg, Ch.; Behnen, W.; Wallbaum, S. TA 1992, 3, 347. (c) Rao, A. V. R.; Gurjar, M. K.; Kaiwar, V. TA 1992, 3, 859. (d) Lohray, B. B.; Bhushan, V. AG 1992, 104, 740. (e) Jones, T. K.; Mohan, J. J.; Xavier, L. C.; Blacklock, T. J.; Mathre, D. J.; Sohar, P.; Turner Jones, E. T.; Reamer, R. A.; Roberts, R. A.; Roberts, F. E.; Grabowski, E. J. JOC 1991, 56, 763. (f) Mathre, D. J.; Jones, T. K.; Xavier, L. C.; Blacklock, T. J.; Reamer, R. A.; Mohan, J. J.; Turner Jones, E. T.; Hogsteen, K.; Baum, M. W.; Grabowski, E. J. JOC 1991, 56, 751. (g) De Ninno, M. P.; Perner, R. J.; Lijewski, L. TL 1990, 31, 7415. (h) Rao, A. V. R.; Gurjar, M. K.; Sharma, P. A.; Kaiwar, V. TL 1990, 31, 2341. (i) Corey, E. J.; Link, J. O. TL 1989, 30, 6275. (j) Corey, E. J.; Chen, C.-P.; Reichard, G. A. TL 1989, 30, 5547. (k) Youn, I. K.; Lee, S. W.; Pak, C. S. TL 1988, 29, 4453. (l) Corey, E. J. PAC 1990, 62, 1209. (m) Corey, E. J.; Bakshi, R. K.; Shibata, S.; Chen, C.-P.; Singh, V. K. JACS 1987, 109, 7925. (n) Corey, E. J.; Link, J. O. JACS 1992, 114, 1906. (o) Stingl, K.; Martens, J.; Wallbaum, S. TA 1992, 3, 223. (p) Wallbaum, S.; Martens, J. TA 1991, 2, 1093. Behnen, W.; Dauelsberg, Ch.; Wallbaum, S.; Martens, J. SC 1992, 22, 2143. (q) Corey, E. J.; Yi, K. Y.; Matsuda, S. P. T. TL1992, 33, 2319. (r) Jones, D. K.; Liotta, D. C. JOC 1993, 58, 799. (s) Corey, E. J.; Shibata, S.; Bakshi, R. K. JOC 1988, 53, 2861. (t) Corey, E. J.; Bakshi, R. K. TL 1990, 31, 611. (u) DeNinno, M. P.; Perner, R. J.; Morton, H. E.; DiDomenico, S., Jr. JOC 1992 , 57, 7115. (v) Tanaka, K.; Matsui, J; Suzuki, H. CC 1991, 1311. (w) Corey, E. J.; Bakshi, R. K.; Shibata, S. JACS 1987, 109, 5551.
9. (a) Cho, B. T.; Chun, Y. S. TA 1992, 3, 337. (b) Itsuno, S.; Sakurai, Y.; Ito, K.; Hirao, A.; Nakahama, S. BCJ 1987, 60, 395.
10. Bringmann, G.; Hartung, T. AG(E) 1992, 31, 761.
11. (a) Parmee, E. R.; Tempkin, O.; Masamune, S. JACS 1991, 113, 9365. (b) Kiyooka, S.; Kaneko, Y.; Kume, K. TL 1992, 33, 4927.
12. (a) Corey, E. J.; Loh, T.-P. JACS 1991, 113, 8966. (b) Takasu, M.; Yamamoto, H. SL 1990, 194. (c) Sartor, D.; Saffrich, J.; Helmchen, G.; Richards, C. J.; Lambert, H. TA 1991, 2, 639. (d) Sartor, D.; Saffrich, J.; Helmchen, G. SL 1990, 197. (e) Kagan, H. B.; Riant, O. CRV 1992, 92, 1007.
13. Reetz, M. T.; Zierke, T. CI(L) 1988, 663.

Giovanni Poli

Università di Firenze, Italy



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