A practical method for synthesis of terminal 1,2-diols in high enantiomeric excess via oxazaborolidine-catalyzed asymmetric reduction

Article abstract of DOI:10.1016/S0957-4166(99)00184-6

Asymmetric borane reduction of α-hydroxy ketones protected with a tetrahydropyranyl (THP) group catalyzed by Corey's CBS reagent using N- phenylamine-borane complexes as the hydride source provided the corresponding terminal 1,2-diols with a very high enantiomeric excess.

Full text of DOI:10.1016/S0957-4166(99)00184-6

Pergamon
Tetrahedron: Asymmetry 10 (1999) 1843–1846
A practical method for synthesis of terminal 1,2-diols in high
enantiomeric excess via oxazaborolidine-catalyzed asymmetric
reduction †
Byung Tae Cho ∗ and Yu Sung Chun
Department of Chemistry, Hallym University, Chunchon, Kangwondo 200-702, South Korea
Received 14 April 1999; accepted 6 May 1999
Abstract
Asymmetric borane reduction of α-hydroxy ketones protected with a tetrahydropyranyl (THP) group catalyzed
by Corey’s CBS reagent using N-phenylamine–boranecomplexes as the hydride source provided the corresponding
terminal 1,2-diols with a very high enantiomeric excess. © 1999 Elsevier Science Ltd. All rights reserved.
Enantiomerically pure terminal 1,2-diols are important synthetic intermediates.1 A number of
synthetic methods for these compounds have been extensively investigated.2 Foremost among these
methods is the catalytic asymmetric dihydroxylation of olefins.2a Another potentially powerful route
into optically active 1,2-diols is the asymmetric reduction of α-hydroxy ketones.3 Very recently
we reported oxazaborolidine-catalyzed asymmetric reduction of α-triorganosiloxy ketones using
borane–tetrahydrofuran(BH3–THF) as a reductant to give optically active 1,2-diols.3a Although this
proves to be a convenient and simple procedure to provide terminal 1,2-diols with enantiomeric excesses
(ees) approaching 100%, for most aromatic analogues, this method is not free from certain disadvantages
for large scale applications, owing to the low concentration and stability of the BH3–THF reagent. Also,
this method afforded somewhat lower enantioselectivity for unhindered aliphatic analogues compared
with those obtained from aromatic analogues. Recently, the wide applicability of amine–borane
complexes as reducing agents has been progressively studied, since the amine–borane adducts offer
the advantages of being soluble in most common solvents at high concentration and low sensitivity
to moisture and air.4 In fact, highly enantioselective oxazaborolidine-catalyzed borane reduction of
prochiral ketones using the N,N-diethylaniline–borane complex (DEANB) as a reductant has been
reported.4a In order to develop a practical method useful for the large-scale synthesis of optically active
1,2-diols, we studied the oxazaborolidine-catalyzed asymmetric reduction of protected α-hydroxy
ketones 2 using amine–borane complexes as the hydride source.
∗
†
Corresponding author. E-mail: btcho@sun.hallym.ac.kr
Catalytic enantioselective reactions. Part 17.
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00184-6

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Initially, we selected the tetrahydropyranyl (THP) group as a protecting group for the hydroxy group
because of its ease of introduction, the low cost of dihydropyran, its general stability to most nonacidic
reagents, and its ease of removal. The tetrahydropyranylation of 2 was carried out by treating 2 with
excess 3,4-dihydro-2H-pyran (DHP) in the presence of a catalytic amount of p-toluenesulfonic acid in
dichloromethane at room temperature. We started our study by comparing the asymmetric reduction
of 2-(tetrahydro-2H-pyran-2-yloxy)-1-phenylethanone 3a catalyzed by Corey’s CBS reagent 15 using
commercially available N-phenylamine–borane reagents, namely, N,N-diethylaniline–borane 6, N-ethyl-
N-isopropyl-aniline–borane 7 and N-phenylmorpholine–borane 8. The reduction was carried out by
adding 3a over 1 h to a solution of 1.0 equiv. of each amine–borane adduct in the presence of 10 mol%
of 1 in THF at 25°C (Scheme 1).6 As shown in Table 1, all the reactions were complete within 10
min to provide 2-(tetrahydro-2H-pyran-2-yloxy)-1-phenylethanol 4a in 91–95% yields, which was easily
converted to 1-phenyl-1,2-ethanediol 5a by the usual work-up procedure in almost quantitative yields.
The enantiomeric excess of 5a determined by HPLC analysis using a chiral column revealed 100% ee
in all the cases using the amine–borane adducts 6–8 (entries 1–3). Encouraged by these results, the
same procedure was applied to other aromatic analogues such as 3b–e having p-tolyl, p-chlorophenyl,
p-methoxyphenyl and 2-naphthyl groups, respectively. Again, we obtained the corresponding product
1,2-diols with very high enantiomeric excesses (entries 4–12). For aliphatic analogues 3f–i bearing ethyl,
isopropyl, cyclohexyl, and tert-butyl groups, respectively, we also obtained the product diols with high
enantioselectivities, such as 85–88% ee for 3f, 90–91% ee for 3g, 97% ee for 3h and 97% ee for 3i
(entries 13–21). Such high enantioselectivities for both aromatic and aliphatic analogues revealed that
the present procedure was superior to our previous report3a for synthesis of optically active 1,2-diols
via oxazaborolidine-catalyzed asymmetric reduction. Among the amine–borane complexes 6–8 used,
structural effects of the amine on their asymmetric inductions were not observed. We assume that the
reduction would be initiated by 1–BH3 formed by coordination of oxazaborolidine 1 with free BH3
liberated from dissociation of the amine–borane reagents,11 resulting in a catalytic process by 1,5 based
on a very slow reduction with the borane adducts themselves under the same reaction conditions.
Scheme 1.

B. T. Cho, Y. S. Chun / Tetrahedron: Asymmetry 10 (1999) 1843–1846
1845
Table 1
Asymmetric reduction of 3 with amine–borane complexes 6–8in the presence of 10 mol% of 1in THF
at 25°Ca
In conclusion, we have developed a practically useful and efficient synthesis of both aliphatic and
aromatic terminal 1,2-diols with very high ee by the asymmetric reduction of α-hydroxy ketones
protected with a THP group catalyzed by Corey’s CBS reagent using N-phenylamine–borane complexes
6–8 as the hydride source. This procedure can be used as an excellent alternative to a facile synthesis of
optically active terminal 1,2-diols.
Acknowledgements
This study was financially supported by the Hallym Academy of Sciences, Hallym University (1999)
and OCRC/KOSEF.

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References
1. (a) Hanessian, H. Total Synthesis of Natural Products: the ‘Chiron’ Approach; Pergamon Press: Oxford, 1983. (b) Seyden-
Penn, J. Chiral Auxiliaries and Ligands in Asymmetric Synthesis; John Wiley: New York, 1995.
2. (a) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483–2457 and references cited therein. (b)
Eisenberg, C.; Knochel, P. J. Org. Chem. 1994, 59, 3760–3761. (c) Wong, C.-H.; Whitesides, G. M. Enzymes in Synthetic
Organic Chemistry; Pergamon Press: Oxford, 1994 and references cited therein.
3. (a) Cho, B. T.; Chun, Y. S. J. Org. Chem. 1998, 63, 5280–5282. (b) Bolm, C.; Felder, M. Tetrahedron Lett. 1993, 34,
6041–6044. (c) Bolm, C.; Seger, A.; Felder, M. Tetrahedron Lett. 1993, 34, 8079–8080. (d) Ramachandran, P. V.; Lu,
Z.-H.; Brown, H. C. Tetrahedron Lett. 1997, 38, 761–764. (e) Burk, M. J.; Feaster, J. E. Tetrahedron Lett. 1992, 33,
2099–2102.
4. (a) Salunkhe, A. M.; Burkhardt, E. R. Tetrahedron Lett. 1997, 38, 1523–1526. (b) Salunkhe, A. M.; Burkhardt, E. R.
Tetrahedron Lett. 1997, 38, 1519–1522. (c) Periasamy, M.; Kanth, J. V. B.; Prasad, B. A. S. Tetrahedron 1994, 50,
6411–6416. (d) Periasamy, M.; Kanth, J. V. B.; Reddy, Ch. K. J. Chem. Soc., Perkin Trans. 1 1995, 427–430. (e) Periasamy,
M.; Kanth, J. V. B. J. Chem. Soc., Chem. Commun. 1990, 1145–1147. (f) Brown, H. C.; Kanth, J. V. B.; Zaidelwicz, M. J.
Org. Chem. 1998, 63, 5154–5163.
5. Corey, E. J.; Bakshi, R. K.; Shibata, S.; Chen, C.-P.; Singh, V. K. J. Am. Chem. Soc. 1987, 109, 7925–7926.
6. We also examined the same reduction of 2 protected with MOM, BOM, 1-ethoxyethyl (EE) and trimethylacetyl (Piv)
groups using N,N-diethylaniline–borane. The reductions produced 5a with somewhat lower enantioselectivity (93–95%
ee) than that for 3a protected with a THP group. The same catalytic asymmetric borane reduction for an unprotected
α-hydroxy ketone 2a provided 5a in only 9% ee.
7. Becker, H.; King, S. B.; Taniguchi, M.; Vanhessche, K. P. M.; Sharpless, K. B. J. Org. Chem. 1995, 60, 3940–3941.
8. Moussou, P.; Archelas, A.; Baratti, J.; Furstoss, R. J. Org. Chem. 1998, 63, 3532–3537.
9. Mori, K.; Saaki, M.; Tamada, S.; Suguro, T.; Masuda, S. Tetrahedron 1979, 35, 1601–1605.
10. Bach, J.; Berenguer, R.; Ferras, J.; Garcia, J.; Meseguer, J.; Vilarrasa, J. Tetrahedron: Asymmetry 1995, 6, 2683–2686.
11. Brown, H. C.; Murray, L. T. Inorg. Chem. 1984, 23, 2746–2753.