A convenient resolution of long-chain alkyl epoxides with Jacobsen's salen(Co)III(OAc) catalysts

Article abstract of DOI:10.1016/S0957-4166(98)00175-X

Non-racemic terminal long-chain alkyl epoxides are prepared from racemic epoxides and 1 mol% (R,R)- and (S,S)-salen(Co)III catalysts following a modified procedure for kinetic resolution. The ee's for all epoxides (C-10, C-12, C-14, C-16, C-18, C-20) exceed 95% and the chemical yields range from 85% to 95%.

Full text of DOI:10.1016/S0957-4166(98)00175-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 1843–1846
A convenient resolution of long-chain alkyl epoxides with
Jacobsen’s salen(Co)III(OAc) catalysts†
Prashant S. Savle, Marika J. Lamoreaux,‡ John F. Berry‡ and Richard D. Gandour ∗
Department of Chemistry, Virginia Tech, Blacksburg, VA 24061-0212, USA
Received 17 April 1998; accepted 20 April 1998
Abstract
Non-racemic terminal long-chain alkyl epoxides are prepared from racemic epoxides and 1 mol% (R,R)- and
(S,S)-salen(Co)III catalysts following a modified procedure for kinetic resolution. The ee’s for all epoxides (C-10,
C-12, C-14, C-16, C-18, C-20) exceed 95% and the chemical yields range from 85% to 95%. © 1998 Elsevier
Science Ltd. All rights reserved.
Our interest1 in designing mimetics of molecules that comprise biomembranes has led us to prepare
non-racemic long-chain 2-alkyloxiranes. Many pioneering methods focus on converting long-chain
alkenes2–4 and long-chain alkyl chirons5–10 into non-racemic epoxides; other methods use enzymatic
resolution11 to isolate non-racemic epoxides and precursors to epoxides. In our hands, such methods12
have limitations with long-chain (>C-10) compounds. To date, large-scale syntheses of non-racemic
long-chain 2-alkyloxiranes have required multiple steps. The recent, hydrolytic kinetic resolution of 2-
hexyloxirane with a chiral salen(Co)III catalyst13 has prompted us to evaluate this procedure for resolving
long-chain 2-alkyloxiranes.
Non-racemic long-chain 2-alkyloxiranes are used in syntheses for natural products, e.g., (R)-14,15
and (S)-4-dodecanolide,16 (R)- and (S)-5-dodecanolide,17–19 (R)-20 and (S)-8-hydroxydecanoic acid,21
(2R,2S0)-1-O-(20-hydroxyhexadecyl)glycerol,22 and 6-alkyl-δ-lactones,23 and non-natural products, e.g.,
chiral stationary phase,24 liquid crystals,25 chirons,26,27 and chiral dopants.28 Because of this usage, we
report herein the success of Jacobsens’s chiral salen(Co)III catalysts in resolving six even-numbered
homologues. With 2-octyl-, 2-decyl-, 2-dodecyl-, 2-tetradecyl-, 2-hexadecyl-, and 2-octadecyloxirane,29
we find >95% ee for both enantiomers and excellent chemical yields (Table 1). We have not fully
optimized these resolutions, but we present these results to inform the chemical community of a
convenient resolution of these compounds (Scheme 1).
∗
†
‡
Corresponding author. E-mail: gandour@vt.edu
Keywords: asymmetric reactions; epoxides; resolution; enantiomeric purity.
Undergraduate research participant.
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00175-X

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P. S. Savle et al. / Tetrahedron: Asymmetry 9 (1998) 1843–1846
Table 1
Comparison of chiroptical properties
Scheme 1.
To decrease reaction times, we slightly modified the reported13 procedure by increasing the amount of
catalyst30 from 0.2 to 1.0 mol% and using ethyl ether31 as a solvent. With 2.0 mol% catalyst, we detected
the formation of alkene, which likely resulted from (Co)II-catalyzed deoxygenation of the epoxide.32 We
recovered the non-racemic epoxide and isolated the non-racemic diol in certain cases.33 This procedure
gave modest % ee’s, however, in an attempted resolution of 2-eicosyloxirane (C-22 epoxide).
We determined the % ee of the Mosher’s ester of 2, which formed in the reaction of (R)- and (S)-
1 with N-benzylmethylamine (Scheme 2). We used this amine because it: (a) favors attack on terminal
epoxy carbon, (b) imparts UV activity in the products, and (c) produces a norbenzalkonium spermicidal34
analogue. In all cases, signals in 1H and 19F NMR spectra for the opposite enantiomer were absent.35
Scheme 2.

P. S. Savle et al. / Tetrahedron: Asymmetry 9 (1998) 1843–1846
1845
In summary, the kinetic resolution of long-chain 2-alkyloxiranes proceeds smoothly with Jacobsen’s
salen(Co)III catalysts to give excellent chemical yields and high % ee’s. Many groups will find these
chirons valuable in the synthesis of natural products, biomimetic molecules, chiral lipids, and surfactants.
Acknowledgements
We thank Dr. John Schwab for suggesting this procedure and Professor Eric N. Jacobsen and Mr. Scott
E. Schaus of Harvard University for helpful discussions. We also thank Atochem of North America for
their generous gift of C-10 to C-18 epoxides.
References
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31. A typical procedure was: To a mixture of (R,R)- or (S,S)-salen(Co)II (0.17 mmol) in toluene (1 mL), acetic acid (0.34
mmol) was added and the mixture was stirred, open, in air for 1 h. The solvent was removed and the dark brown residue
was dried under a high vacuum. The residue was diluted with Et2O (5 mL), the epoxide (17 mmol) was added, followed by
water (8.5 mmol). The dark red–brown mixture was stirred for 3 days at rt. The reaction mixture was concentrated. 2-Octyl-
, 2-decyl, (for both bp 80–85 EC/5 mmHg) and 2-dodecyloxiranes (bp 135–140 EC/3 mmHg) were distilled directly from
the reaction mixture using Kugelrhor distillation (see Ref. 33). 2-Tetradecyl, 2-hexadecyl, and 2-octadecyloxirane were
isolated by column chromatography. The column was eluted with hexanes (300 mL) and then with 5% EtOAc/hexanes
(v/v) (300 mL), when epoxide eluted. The diol was eluted by 50% EtOAc/hexanes (v/v), crude yield <20%, contaminated
with the catalyst. All epoxides gave satisfactory 1H and 13C NMR spectra. (R)- and (S)-2-Tetradecyl-, -2-hexadecyl-, and
-2-octadecyloxiranes were isolated as low melting waxy solids, mp <36 EC.
32. Dowd, P; Kang, K. J. Chem. Soc., Chem. Commun. 1974, 384–385.
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tetradecanediol using the reported13 procedure in >80% yields; we presume that the enantiomers of 1,2-decane- and
-dodecanediol can also be isolated in this manner. The high-boiling 1,2-hexadecane, -octadecane, and -eicosanediols are
contaminated with the catalyst after chromatography.31
34. Levin, R. J. Pharmcol. Toxicol. 1997, 81, 219–225.
1
35. Key H NMR (400 MHz) data for (R,R)-3: 2.19 (s, 3H, N–Me), 3.61 (q, JHF=1.2 Hz, 3H, OMe), 5.35–5.42 (m, 1H,
CHOMTPA), 19F NMR (377 MHz) −72.21. Data for (R,S)-3: 2.15 (s, 3H, N–Me), 3.54 (q, JHF=1.2 Hz, 3H, OMe),
5.27–5.34 (m, 1H, CHOMTPA), 19F NMR −72.67.
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