A R T I C L E S
Yoshida et al.
Table 6. Diastereoselective Reactions Using Unsymmetrical
Scheme 9. Proposed Transition States for the Diastereoselective
Cascade Reaction
Substrates with p-Methoxyphenola
generation of the chiral cyclic carbonate (R)-3ga in 31% yield
with a 62% ee (Table 7, entry 1).15,16 Superior results are ob-
tained by employing dioxane as solvent (entry 2) and when 4
Å MS is used as an additive (entry 3). Yields are dramatically
improved by carrying out the reaction under a CO2 atmosphere
(75% yield with 71% ee, entry 4), but the % ee decreases slightly
when the reaction is run under 5 atm of CO2 (entry 5). The use
of (S)-TolBINAP (17)17 in place of (S)-BINAP results in the
formation of (R)-3ga in 88% yield with a 67% ee (entry 6).
Reactions using other chiral phosphine ligands (e.g., 18,18 19,19
20,20 and 2121) do not result in the production of the cyclic
carbonate (entries 7-10).
We next evaluated the scope of the (S)-BINAP-promoted
asymmetric reaction by using various propargylic carbonates.
Treatment of the five-to-eight-membered ring substrates
1a-1d with phenol 2a leads to production of the cyclic car-
bonates (R)-3aa-3da in moderate yields and enantiomeric puri-
a Reactions were carried out in the presence of 5 mol % Pd2(dba)3‚CHCl3,
20 mol % dppe, and 1.1 equiv of p-methoxyphenol in dioxane for 4-24 h
at 50 °C in a sealed tube. b Ar ) p-methoxyphenyl. c The stereochemistry
of the trans-product was determined by 1H-NOESY. d The stereochemistry
of the products were tentatively assigned by analogy with the 1H NMR
spectrum of the other product.
propargylic carbonates were examined next. The substrate 1o,
having a â-phenylcyclohexyl group, reacts with phenol 2a to
form 3oa as a single diastereomer in 58% yield (Table 6, entry
1). The yield of 3oa increases to 92% when reaction of 1o and
2a is conducted under a CO2 atmosphere (entry 2). The
menthone-derived substrate 1p is also stereoselectively con-
verted to trans-carbonate 3pa (entries 3 and 4). On the other
hand, reactions of the estrone- and camphor-derived propargylic
carbonates, 1q and 1r, afford predominantly epoxides 5qa and
5ra instead of the corresponding cyclic carbonates (entries 5
and 7). The cyclic carbonate 3qa was produced together with
epoxide 5qa from reaction of 1q under a CO2 atmosphere, but
no cyclic carbonate was generated from 1r under these reaction
conditions (entry 8). In these cases, it appears that steric
crowding of the hydroxyl groups prevents refixation of CO2.
The high diastereoselectivities observed in these reactions are
likely the result of steric factors which influence the relative
energies of the competing transition states for cyclization of
the interconverting, isomeric π-allylpalladium intermediates, A
and B (Scheme 9). Equilibration between A and B occurs by
π-σ-π isomerization.13 It is expected that the transition state
for cyclization A, forming the trans-product, would be of lower
energy because of the absence of the A1,3-strain that is present
in the transition state derived from B.
Enantioselective Formation of Cyclic Carbonates. Al-
though a large number of asymmetric reactions of allylic com-
pounds with nucleophiles are known, only a few asymmetric
palladium-catalyzed nucleophilic substitution reactions of pro-
pargylic substrates have been reported.10e In the reaction de-
scribed above, a new asymmetric center is formed by cyclization
of the π-allylpalladium intermediate. We anticipated that the
absolute configuration of the newly formed stereogenic center
could be controlled by using chiral palladium catalysts.14 Indeed,
reaction of 1g with 2a in the presence of 5 mol % Pd2(dba)3‚
CHCl3 and 20 mol % (S)-BINAP (16) in THF leads to
(13) (a) Cuvigny, T.; Julia, M.; Rolande, C. J. Organomet. Chem. 1985, 285,
395. (b) Akermark, B.; Krakenberger, B.; Hanson, S.; Vitagliano, A.
Organometallics 1987, 6, 620. (c) Akermark, B.; Zetterberg, K.; Hansson,
S.; Krakenberger, B.; Vitagliano, A. J. Organomet. Chem. 1987, 335, 133.
(d) Åkermark, B.; Hansson, S.; Vigagliano, A. J. Am. Chem. Soc. 1990,
112, 4587. (e) Sjo¨gren, M.; Hansson, S.; Norrby, P.-O.; Åkermark, B.;
Cucciolito, M. E.; Vitagliano, A. Organometallics 1992, 11, 3954. (f)
Sjo¨gren, M. P. T.; Hansson, S.; Åkermark, B.; Vitagliano, A. Organome-
tallics 1994, 13, 1963.
(14) Examples about palladium-catalyzed asymmetric intramolecular cyclizations
via π-allylpalladium speacies, see: (a) Yamamoto, K.; Tsuji, J. Tetrahedron
Lett. 1982, 23, 3089. (b) Geneˆt, J. P.; Grisoni, S. Tetrahedron Lett. 1989,
29, 4543. (c) Takemoto, T.; Nishikimi, M.; Sodeoka, M.; Shibasaki, M.
Tetrahedron Lett. 1992, 33, 3531. (d) Koch, G.; Pfaltz, A. Tetrahedron:
Asymmetry 1996, 7, 2213. (e) Trost, B. M.; Krische, M. J.; Radinov, R.;
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J. M. J. Org. Chem. 1995, 60, 482. (g) Zenner, J. M.; Larock, R. C. J.
Org. Chem. 1999, 64, 7312.
(15) (a) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi,
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H. Acc. Chem. Res. 1990, 23, 345.
(16) For reports of enantioselective reactions via π-allylpalladium intermediate
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4, 1113. (b) Yamaguchi, M.; Shima, T.; Yamagishi, T.; Hida, M.
Tetrahedron Lett. 1990, 31, 5049. (c) Yamaguchi, M.; Shima, T.;
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Kuwano, R.; Ito, Y. J. Am. Chem. Soc. 1999, 121, 3236. (e) Kuwano, R.;
Nishino, R.; Ito, Y. Org. Lett. 1999, 1, 837. (f) Braun, M.; Laicher, F.;
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(17) (a) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi, H.;
Kaketomi, T.; Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51, 629. (b)
Larksarp, C.; Alper, H. J. Am. Chem. Soc. 1997, 119, 3709.
(18) Yoshizaki, H.; Satoh, H.; Sato, Y.; Nukui, S.; Shibasaki, M.; Mori, M. J.
Org. Chem. 1995, 60, 2016.
(19) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J. Am. Chem. Soc. 1992,
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(20) (a) Muller, D.; Umbricht, G.; Weber, B.; Pfaltz, A. HelV. Chim. Acta 1991,
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4878 J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003