Lewis base-catalyzed addition of triethylaluminum to epoxides

Article abstract of DOI:10.1016/S0040-4039(00)00332-4

Lewis bases like phosphines, arsines, and antimonies catalyze the nucleophilic addition of triethylaluminum to epoxides very efficiently. They are proposed to coordinate to triethylaluminum with formation of monomeric and more reactive triethylaluminum Le

Full text of DOI:10.1016/S0040-4039(00)00332-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3043–3046
Lewis base-catalyzed addition of triethylaluminum to epoxides
Christoph Schneider ∗ and Jörg Brauner
Institut für Organische Chemie der Georg-August-Universität, Tammannstr.2, D-37077 Göttingen, Germany
Received 18 January 2000; accepted 21 February 2000
Abstract
Lewis bases like phosphines, arsines, and antimonies catalyze the nucleophilic addition of triethylaluminum to
epoxides very efficiently. They are proposed to coordinate to triethylaluminum with formation of monomeric and
more reactive triethylaluminum Lewis base adducts. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: Lewis bases; epoxides; triethylaluminum; catalysis.
Recently, substantial research efforts have been devoted to desymmetrization reactions of meso
epoxides giving rise to functionalized, optically active alcohols as valuable fine chemicals for organic
synthesis.1 In particular, several highly efficient methods for the catalytic, enantioselective opening of
meso epoxides by hetero nucleophiles have emerged most of which have a chiral Lewis acid in common
which activates the epoxide towards the nucleophile and differentiates the enantiotopic carbon atoms of
the epoxide. As a noteworthy exception Denmark et al. achieved a Lewis base-catalyzed addition of SiCl4
to epoxides to deliver enantiomerically enriched chlorohydrins by way of reagent rather than substrate
activation.2 In contrast, the catalyzed addition of carbon nucleophiles towards epoxides has received less
attention presumably reflecting the difficulty to prepare an organometallic reagent which is sufficiently
reactive towards the epoxide and compatible with the metal catalyst at the same time.3 We speculated
that this problem could be overcome by employing an organometallic reagent which is activated by a
Lewis base in close analogy to the amine-catalyzed addition of dialkylzinc reagents to aldehydes.4
In this letter we wish to report our results on Lewis base-catalyzed ring opening reactions of epoxides
by triethylaluminum. Cyclohexene oxide (1) as well as cis-2-butene oxide (2) were readily opened by
triethylaluminum in high yields at ambient temperature with only 5 mol% of the Lewis base employed
(Scheme 1 and Table 1).5 Phosphines as well as arsines and antimonies were identified as suitable
catalysts. Whereas the uncatalyzed addition of triethylaluminum to cyclohexene oxide did not proceed
at all at rt,6 trans-2-ethyl cyclohexanol (3) was obtained in 99% yield after 24 h at rt with 5 mol% of
either triphenylphosphine or tris(dimethylamino)phosphine. Likewise, the addition of triethylaluminum
to cis-2-butene oxide (2) catalyzed by 5 mol% of triphenylphosphine gave trans-3-methyl-2-pentanol (4)
in 82% yield again with no background reaction being observed.
∗
Corresponding author. Fax: 0049-551-399660; e-mail: cschnei1@gwdg.de (C. Schneider)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00332-4
tetl 16612

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Scheme 1.
Table 1
Lewis base-catalyzed addition of triethylaluminum to epoxides (Scheme 1)
Just one equivalent of the aluminum reagent was sufficient for a complete reaction although the
addition was accelerated when two equivalents were used. Tributylphosphine, triphenylarsine, and
triphenylantimony could also be used as catalysts giving comparable results in the case of cyclohexene
oxide (1) and inferior results with cis-2-butene oxide (2). Amines (NEt3, TMEDA) turned out to be
totally ineffective as catalysts. The choice of the solvent was crucial to the success of the reaction. Only
non-coordinating solvents like toluene and hexane were suitable whereas in particular etheral solvents
significantly slowed down the reaction due to coordination to the Lewis acidic aluminum reagent thereby
attenuating its reactivity. The catalyzed reaction could not be extended to terminal epoxides because they
were sufficiently reactive to take part in an uncatalyzed process even at low temperatures.
In order to shed light on the catalytic activity of the Lewis base 27Al and 31P NMR spectra were
recorded with solutions of triethylaluminum and tris(dimethylamino)phosphine each alone and after
mixing both compounds.7 In the 27Al NMR spectrum a significant downfield shift from δ=155 ppm to
δ=165 ppm (relative to external AlCl3) was observed when going from triethylaluminum to a 1:1 mixture
of triethylaluminum and tris(dimethylamino)phosphine. In the 31P NMR spectrum a corresponding
upfield shift from δ=123 ppm to δ=97 ppm was noted (relative to external H3PO4). These results clearly
support a coordination of the phosphine to the aluminum reagent which may result in the breakage of
the triethylaluminum dimer and formation of a monomeric triethylaluminum–phosphine adduct which
apparently releases the ethyl group more easily and is thus more reactive than the triethylaluminum dimer.
A quite similar coordination of phosphines to silicon was recently noted in the phosphine-catalyzed
addition of trimethylsilyl cyanide8 and silyl ketene acetals9 to aldehydes.
The phosphine-catalyzed rate acceleration was also observed in the reaction of triethylaluminum with
other electrophiles. The typically fast reaction of triethylaluminum with benzaldehyde10 in toluene at

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0°C could be slowed down significantly at −78°C so that only 15% of 1-phenyl-1-propanol (5) were
obtained after 3 h. In the presence of 5 mol% of tris(dimethylamino)phosphine, however, a 94% yield of
the addition product 5 was obtained after 3 h at −78°C (Scheme 2 and Table 2). Tributylphosphine and
triethyl phosphite gave equally good results. Here, amines also displayed catalytic activity although the
rate acceleration was not as pronounced as in the case of the phosphines.
Scheme 2.
Table 2
Lewis base-catalyzed addition of triethylaluminum to benzaldehyde (Scheme 2)
In conclusion, we have demonstrated that a range of P-, As-, and Sb-containing Lewis bases very
efficiently catalyze the addition of triethylaluminum to epoxides and aldehydes through coordination
to the aluminum reagent and presumably formation of monomeric Lewis base-aluminum adducts. This
protocol clearly holds potential for asymmetric catalysis when chiral, enantiomerically pure Lewis bases
are employed in the indicated reactions.
Acknowledgements
This work was supported by the Fonds der Chemischen Industrie. We would like to thank Professor
Tietze for constant support and encouragement.
References
1. Reviews: (a) Hodgson, D. M.; Gibbs, A. R.; Lee, G. P. Tetrahedron 1996, 52, 14361; (b) Jacobsen, E. N.; Wu, M. H. In
Comprehensive Asymmetric Catalysis; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds.; Springer: Berlin–Heidelberg–New
York, 1999, 3, 1309.
2. Denmark, S. E.; Barsanti, P. A.; Wong, K. T.; Stavenger, R. A. J. Org. Chem. 1998, 63, 2428.
3. For notable exceptions, see: (a) Hayashi, M.; Tamura, M.; Oguni, N. Synlett 1992, 663; (b) Cole, B. M.; Shimizu, K. D.;
Krueger, C. A.; Harrity, J. P. A.; Snapper, M. L.; Hoveyda, A. H. Angew. Chem., Int. Ed. Engl. 1996, 35, 1668; (c) Oguni,
N.; Miyagi, Y.; Itoh, K. Tetrahedron Lett. 1998, 39, 9023; (d) Ooi, T.; Kagoshima, N.; Ichigawa, H.; Maruoka, K. J. Am.
Chem. Soc. 1999, 121, 3328; using stoichiometric amounts of activating agents, see: (e) Mizuno, M.; Kanai, M.; Iida, A.;
Tomioka, K. Tetrahedron: Asymmetry 1996, 7, 2483; (f) Alexakis, A.; Vrancken, E.; Mangeney, P. Synlett 1998, 1165; (g)
Abe, N.; Hanawa, H.; Maruoka, K.; Sasaki, M.; Miyashita, M. Tetrahedron Lett. 1999, 40, 5369.

3046
4. (a) Kitamura, M.; Suga, S.; Kawai, K.; Noyori, R. J. Am. Chem. Soc. 1986, 108, 6071; (b) Soai, K.; Watanabe, M.; Koyano,
M. Bull. Chem. Soc. Jpn. 1989, 62, 2124.
5. Typical experimental procedure: to a solution of 0.10 ml (1.00 mmol) cyclohexene oxide (1) in 2 ml dry toluene was added
9 µl (0.05 mmol) tris(dimethylamino)phosphine and subsequently 1.00 ml (1.00 mmol) 1 M Et3Al-solution in hexane. The
mixture was stirred for 24 h at rt, quenched with 2 ml 1 M HCl and extracted with ether. The combined organic extracts
were dried over MgSO4 and evaporated in vacuo. The yields given in Table 1 were determined by GC against n-decane as
internal standard. For preparative purposes the crude product was purified by chromatography over silica gel (ether:pentane
1:1) to yield 116 mg (91%) of trans-2-ethyl-1-cyclohexanol (3). The structure of the products 3–5 was determined by NMR,
IR, UV, MS in comparison to the published data, for compound 3 see: (a) Bryan Jones, J.; Takemura, T. Can. J. Chem. 1982,
60, 2950; for compound 4 see: (b) Berrada, S.; Desert, S.; Metzner, P. Tetrahedron 1988, 44, 3575; for compound 5 see: (c)
Guijarro, D.; Guillena, G.; Mancheno, B.; Yus, M. Tetrahedron 1994, 50, 3427.
6. Pfaltz, A.; Mattenberger, A. Angew. Chem. 1982, 94, 79; Angew. Chem., Int. Ed. Engl. 1982, 21, 71 and references cited
therein.
7. For 27Al and 31P NMR studies, see: (a) Benn, R.; Rufinska, A.; Lehmkul, H.; Janssen, E.; Krüger, C. Angew. Chem. 1983,
95, 808; Angew. Chem., Int. Ed. Engl. 1983, 22, 779; (b) Barron, A. R. J. Chem. Soc., Dalton Trans. 1988, 3047.
8. Kobayashi, S.; Tsuchiya, Y.; Mukaiyama, T. Chem. Lett. 1991, 537.
9. Matsukawa, S.; Okano, N.; Imamoto, T. Tetrahedron Lett. 2000, 41, 103.
10. For catalytic enantioselective addition reactions of trialkylaluminums to aldehydes, see: (a) Chan, A. S. C.; Zhang, F.-Y.;
Yip, C.-W. J. Am. Chem. Soc. 1997, 119, 4080; (b) Pagenkopf, B. L.; Carreira, E. M. Tetrahedron Lett. 1998, 39, 9593.