Sin gle Rou te to Ch ir a l syn - a n d
a n ti-2-Am in o-1,2-d ip h en yleth a n ols via a
New Ster eod iver gen t Op en in g of
tr a n s-1,2-Dip h en yloxir a n e
Paolo Lupattelli,* Carlo Bonini,* Leonilde Caruso, and
Augusto Gambacorta†
F IGURE 1.
Dipartimento di Chimica, Universita` degli Studi della
Basilicata, via Nazario Sauro 85, 85100 Potenza, Italy
aminohydroxylation on trans-stilbene10 gave a modest
yield and ee. To date, the most straightforward synthesis
of these optically active compounds employed the Sharp-
less AD of trans-stilbene to the corresponding syn-1,2-
diphenylethanediol, followed by nucleophilic amination
of the corresponding cyclic sulfate with inversion11 or
retention of configuration.12 Although the AD and sub-
sequent elaborations to syn or anti diols allow the
preparation of 1 and 2 from the same chiral precursor,
the synthetic sequence to the syn compound 112 appears
to be complicated by the several steps to deprotect the
intermediate 2-benzyloxazilidinone.
lupattelli@unibas.it
Received J anuary 30, 2003
Abstr a ct: Oxiranyl ring opening of trans-stilbene oxide
gave rise to anti- or syn-2-bromo-1,2-diphenylethanols, using
either MgBr2‚Et2O or MgBr2‚Et2O, NaBr, and KBr with
Amberlyst 15, respectively. Starting from optically pure
(R,R)-trans-stilbene oxide, (1R,2R)- and (1R,2S)-2-amino-1,2-
diphenylethanols were obtained in high yield and ee.
On the other hand, despite its easy availability in the
optically active form,13 the 1,2-diphenyl epoxide 3 has
never been utilized as a starting chiral synthon for the
obtaining compounds 1 and 2, despite the developed
methodologies for stereocontrol in the ring opening of the
oxirane ring.
Herein we present a simple and straightforward syn-
thesis of both 1 and 2 starting from the same chiral
compound 3 and employing a new stereodivergent open-
ing of the oxirane ring.
Due to our experience in the regio and stereoselective
opening of three-membered heterocyclic rings such as
epoxides and aziridines with metal halides,2c,14 we envis-
aged a possible route to the synthesis of 1 and 2 (Scheme
1).
The success of the synthesis in affording both diaster-
eoisomers would depend mainly on a diastereoselective
and divergent opening of the oxirane ring, which would
be followed by standard nitrogen substitution, already
utilized for the preparation of 1,2 amino-alcohol sub-
units.15 Our study and other studies have mainly re-
vealed that the oxirane opening by metal halides cleanly
follows the SN2 replacing mechanism with inversion of
configuration. Only more recently, in the case of special
â-Amino alcohol subunits, since their discovery in
many biologically active compounds, especially as R-amino-
â-hydroxy or R-hydroxy-â-amino acids,1 have attracted
the attention of synthetic chemists, and several ap-
proaches to the synthesis of these units have now been
developed.2 Among this class of compounds, the 2-amino-
1,2-diphenylethanols, with both syn and anti relative
configurations (compounds 1 and 2, respectively, in
Figure 1), have recently received great attention due to
their use, in optically active forms, as chiral auxiliaries
in asymmetric synthesis,3 chiral stationary phases for
HPLC,4 and chiral ligands in asymmetric catalysis.5
Due to their important use, they are now commercially
available, although expensive.6 Several syntheses of both
antipodes and diastereomeric couples have been reported
such as the early resolution7 of benzoin derivatives, which
was recently performed via biocatalysis.7b More recent
approaches employed the asymmetric reduction of 1,2-
diaryl-2-benzyloxyiminoethanones8 or the asymmetric
enolate oxidation of deoxybenzoin.9 Direct asymmetric
* Correspondingauthor.Phone: ++390971202369.Fax: ++39097120-
2223.
† Current address: Dipartimento di Ingegneria Meccanica e indus-
triale, Universita` “Roma Tre”, via della Vasca Navale 79, 00146 Roma,
Italy.
(1) (a) The Merck Index, 12th ed.; Chapman & Hill: New York, 1996.
(b) Shaw, G. In Comprehensive Heterocyclic Chemistry II; Katrirzky,
A. R., Rees, C. W., Scriven, E. F. V., Eds. Pergamon: New York, 1996;
Vol. 7, p 397.
(2) For more recent reviews, see: (a) Ager, D. J .; Prakash, I.; Schaad,
R. R. Chem. Rev. 1996, 96, 835. (b) Bergmeier, S. C. Tetrahedron 2000,
56, 2561. (c) Bonini, C.; Righi, G. Tetrahedron 2002, 58, 4981.
(3) Williams, R. M. In Advances in Asymmetric Synthesis; Hassner,
A., Ed.; J AI Press: 1995; Vol. 1, pp 45-94 and references therein.
(4) Yuki, Y.; Saigo, K.; Tachibana, K.; Hasegava, M. Chem. Lett.
1986, 1347.
(5) (a) Hegedus, L. S. Acc. Chem. Res. 1995, 28, 299. (b) Brown, B.;
Hegedus, L. S. J . Org. Chem. 1998, 63, 8012.
(6) Price ranges between 40 and 100 Euros/g in the Aldrich
catalogue, depending on the isomer.
(7) (a) Weijlard, J .; Pfister, K.; Swanezy, E. F.; Robinson, C. A.;
Tishler, M. J . Am. Chem. Soc. 1951, 73, 1216. (b) Aoyagi, Y.; Agata,
N.; Shibata, N.; Horiguchi, M.; Williams, R. M. Tetrahedron Lett. 2000,
41, 10159.
(9) Davis, F. A.; Haque, M. S.; Przeslawski, R. M. J . Org. Chem.
1989, 54, 2021.
(10) Schillingloff, G.; Sharpless, K. B. In Asymmetric Oxidation
Reactions. A Practical Approach in Chemistry; Katsuki, T., Ed.; Oxford
University Press: New York, 2001; Chapter 2, 104.
(11) Chang, H.-T.; Sharpless, K. B. Tetrahedron Lett. 1996, 37, 3219.
(12) Cho, G. Y.; Ko, S. Y. J . Org. Chem. 1999, 64, 8745.
(13) For the preparation of the (R,R)-epoxide see: (a) Tu, Y.; Wang,
Z.-X.; Shi, Y. J . Am. Chem. Chem. 1996, 118, 9806 (73% yield, >95%
ee, from trans-stilbene). (b) Solladie´-Cavallo, A.; Roje, M.; Isarno, T.;
Sunjic, V.; Vinkovic, V. Eur. J . Org. Chem. 2000, 1077 (70% yield, 97%
ee, from benzaldeyde). For the preparation of the (S,S)-epoxide from
trans-stilbene, see: Solladie´-Cavallo, A.; Bouerat, L.; J ierry, L. Eur.
J . Org. Chem. 2001, 4557 (90% yield, 90% ee).
(14) For reviews on metal halide opening of oxiranes and aziridines,
see: (a) Bonini, C.; Righi, G. Synthesis 1994, 225. (b) Righi, G.; Bonini,
C. In Targets in Heterocyclic Systems, Chemistry and Properties;
Attanasi, O. A.; Spinelli, D., Eds.; Italian Society of Chemistry: Roma,
2001; Vol. 4, p 139.
(8) Shimizu, M.; Tsukamoto, K.; Matsutani, T.; Fujisawa, T. Tetra-
hedron 1998, 54, 10265.
(15) For recent application of this route, see: Righi, G.; Ronconi,
S.; Bonini, C. Eur. J . Org. Chem. 2002, 1573 and references therein.
10.1021/jo034133p CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/25/2003
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J . Org. Chem. 2003, 68, 3360-3362