Norephedrine-Borane1

(+)

[154145-14-9]  · C9H15B2NO  · Norephedrine-Borane  · (MW 174.87) (-)

[161512-50-1]

(chirally modified hydride reagent1)

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

Physical Data: the title reagent has never been isolated; the structure shown above has been assigned on the basis of related studies2 and by analogy to other well-characterized 1,3,2-oxazaborolidines.3

Solubility: THF.

Preparative Method: a 1M THF solution of BH3 (3.0 mmol) was added to a THF solution of (-)-norephedrine (1.5 mmol) at -30 °C and the resulting mixture was warmed to 20 °C; the thus-formed chiral hydride reagent was used in situ for enantioselective reductions.

Handling, Storage, and Precautions: moisture sensitive; handle under a dry, inert atmosphere.

Enantioselective Reductions.

This chiral hydride reagent reduces aromatic ketones to the corresponding alcohols with high enantioselectivity (eq 1).4

Anti and syn ketoxime ethers are also reduced by this reagent to the corresponding amines in up to 92% ee. The absolute configuration of the resulting amine is dependent on the geometry of the starting oxime ethers: anti oximes give (S) configurated amines whereas syn oximes afford the (R) antipodes (eqs 2 and 3); see Table 1.4,5

Similar results can be obtained if the borane is substituted for the system Sodium Borohydride/Aluminum Chloride.6

On the basis of experimental3b as well as theoretical7 studies on similar systems, the mechanism of carbonyl reduction is expected to involve:

  • 1)In situ formation of the 1,3,2-oxazaborolidine from borane and the 1,2-amino alcohol with 2 equiv of H2 uptake;
  • 2)coordination between the N atom of the oxazaborolidine and a second equivalent of borane;
  • 3)coordination at the heterocyclic B atom by the oxygen of the solvent and then by that of the carbonyl compound;
  • 4)hydride transfer from the NBH3- unit to the substrate via a six-membered transition state.

    Although these reactions are expected to be catalytic in oxazaborolidine, the reported examples use the chiral ligand in stoichiometric amounts.

    Related Reagents.

    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. Itsuno, S.; Hirao, A.; Nakahama, S.; Yamazaki, N. JCS(P1) 1983, 1673.
    3. (a) Joshi, N. N.; Srebnik, M.; Brown, H. C. TL 1989, 30, 5551. (b) Corey, E. J.; Bakshi, R. K.; Shibata, S. JACS 1987, 109, 5551. (b) Corey, E. J.; Azimioara, M.; Sarshar, S. TL 1992, 33, 3429.
    4. Didier, E.; Loubinoux, B.; Ramos Tombo, G. M.; Rihs, G. T 1991, 47, 4941. (b) Komeyoshi, Y.; Suzukamo, T.; Hamada, K.; Nishioka, T. Jpn. Patent 62 10 024 [87 10 024] (CA 1987, 106, 175 410t).
    5. (a) Sakito, Y.; Yoneyoshi, Y.; Suzukamo, G. TL 1988, 29, 223. (b) Sakito, Y; Suzukamo, G.; Yoneyoshi, Y. Eur. Pat. Appl. 237 305 (CA 1988, 108, 150 040a).
    6. Konya, N.; Suzukamo, K.; Komeyoshi, Y. Jpn. Patent 02 311 446 [90 311 446] (CA 1991, 114, 228 361b).
    7. Nevalainen, V. TA 1992, 3, 1441.

    Giovanni Poli

    Università di Firenze, Italy



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