August 1998
SYNLETT
931
Thus we developed several new preparative routes to the optically pure
cyclopenta[b]benzofurans (-)-1 and (-)-2 by the combination of
Mitsunobu reaction and palladium catalyzed etherification with the
optically active monoacetate (+)-3 and phenol derivatives. Those routes
via 5 or 8 are almost the same in synthetic efficiency. It is also evaluated
that the last route starting from the meso-compound 12 can compete
with the above processes with the optically pure starting compound.
Acknowledgment. This work was financially supported by the
Ministry of Education, Science and Culture, Japan (No. 09555285).
References and Notes
(1) a) Ohno, K.; Nishiyama, H.; Nagase, H.; Matsumoto, K.;
Ishikawa, M. Tetrahedron Lett. 1990, 31, 4489. b) Nagase, H.;
Matsumoto, K.; Yoshihara, H.; Tajima, A.; Ohno, K. Tetrahedron
Lett. 1990, 31, 4493. c) Nishiyama, H.; Isaka, K.; Itoh, K.; Ohno,
K.; Nagase, H.; Matsumoto, K.; Yoshihara, H. J. Org. Chem.
1992, 57, 407. d) Nishiyama, H.; Sakata, N.; Motoyama, Y.;
Wakita, H.; Nagase, H. Synlett 1997, 1147.
As a short step transformation, we examined a direct introduction of
2,4,6-tribromophenol to the cis-cyclopentenol (-)-7 by Mitsunobu
reaction to produce the corresponding trans-ether 10 (92% yield), which
1c
could be readily cyclized by a metal-halogen exchange reaction with
Grignard reagent and subsequent treatment with CuI (5 mol%) to afford
11
(-)-2 in 68% yield.
(2) a) Larock, R. C.; Lee, N. H. J. Org. Chem. 1991, 56, 6253.
b) Yoshida, Y.; Sato, Y.; Okamoto, S.; Sato, F. J. Chem. Soc.,
Chem. Commun. 1995, 811.
(3) (+)-3 is available from Fluka (00850); >99% ee.
(4) For Mitsunobu reaction with phenol derivatives; see, Paquette, L.
A. (editor-in-chief) "Encyclopedia of Reagents for Organic
Synthesis"; John Wiley & Sons, New York: 1995, Vol. 8, p. 5382.
25
1
(5) 4: m.p. 78 °C; [α]
+153° (c 1.25, CHCl ); H NMR (270 MHz,
3
D
CDCl ) δ 1.62 (d, J = 5.4 Hz, 1H), 2.20 (ddd, 1H), 2.36 (ddd, 1H),
3
5.13 (bs, 1H), 5.50 (bm, 1H), 6.18 (s, 2H), 6.85-7.0 (m, 3H), 7.23-
1
7.36 (m, 2H) ppm.; EA (CH). 5: white solids; H NMR (270
MHz, CDCl ) δ 2.15 (dt, 1H), 3.08 (dt, 1H), 5.23 (bm, 2H), 6.30
3
(s, 2H), 6.80-7.0 (m, 4H), 7.2-7.35 (m, 4H), 7.55 (d, 1H) ppm.
Finally, we adopted an enantioselective catalytic reaction developed by
Trost with a chiral bidentate phosphine 11 and Pd (dba) (CHCl ) (dba =
(6) a) Goux, C.; Lhoste, P.; Sinou, D. Synlett 1992, 725. As a review,
b) Tsuji, J. Palladium Reagents and Catalysis, Innovations in
Organic Synthesis; John Wiley & Sons: Chichester, 1995; p. 61 or
p. 290. c) Trost, B. M. Acc. Chem. Res. 1996, 29, 355.
2
3
3
12
dibenzylidenacetone) (Scheme 4).
The cis-1,4-diacetoxy-2-
cyclopentene 12 was treated with phenol (1.2 eq) and diazabi-
cycloundecene (DBU, 1.2 eq) at 0~20 °C for 2 h in the presence of 11
and the palladium complex (3 mol% of Pd to 12). The catalytic
25
1
(7) 7: oil; [α]
-11.1° (c 0.90, CHCl ); H NMR (270 MHz, CDCl )
3 3
D
procedure
produced
the
(1R,4S)-cis-1-acetoxy-4-phenoxy-2-
δ 1.80 (dt, J = 9.3, 3.5x2 Hz, 1H), 2.90 (dt, J = 9.3, 7.0x2 Hz, 1H),
13
cyclopentene 13, in 60% yield with >99.5% ee, which can be utilized
as a precursor of (-)-7.
4.75 (m, 1H), 5.18 (m, 1H), 6.18 (s, 2H), 6.90-7.0 (m, 3H), 7.32
1
(m, 2H) ppm. 8: white solids; H NMR (270 MHz, CDCl ) δ 2.4-
3
2.6 (m, 2H), 5.57 (m, 2H), 6.35 (s, 2H), 6.8-7.0 (m, 4H), 7.2-7.37
25
(m, 4H), 7.58 (d, 1H) ppm. 9: oil; [α]
-50.8° (c 1.28, CHCl );
3
D
1
H NMR (270 MHz, CDCl ) δ 1.71 (d, J = 9.8 Hz, 1H), 1.90 (dt,
3
1H), 2.83 (m, 1H), 4.72 (m, 1H), 5.14 (m, 1H), 6.20 (m, 2H), 6.85
(t, 1H), 6.96 (d, 1H), 7.25 (t, 1H), 7.55 (d, 1H) ppm.
(8) (-)-1: oil; for spectroscopic data, see ref 1c and 1d; optical purity
(chiral GC analysis, Astec Chiraldex GT-A), >99%.
(9) (-)-2: white solids; m.p. 113 °C; for spectroscopic data, see ref 1c;
optical purity (chiral LC analysis, Daicel Chiralcel-OJ), >99%;
25
[α]
-147° (c 1.0, CHCl ).
3
D
(10) Nagase, H.; Matsumoto, K.; Nishiyama, H. J. Synth. Org. Chem.
Jpn. 1996, 54, 1055; see, scheme 10 and 11. And ref 1b.
1
(11) 10: white solids; H NMR (270 MHz, CDCl ) δ 2.38 (ddd, 1H),
3
2.75 (ddd, 1H), 5.57 (m, 1H), 5.63 (m, 1H), 6.30 (m, 2H), 6.9-7.0
(m, 3H), 7.30 (d, 1H), 7.68 (s, 2H) ppm.
(12) a) Trost, B. M.; Patterson, D. E. J. Org. Chem. 1998, 63, 1339 and
references therein. b) Trost, B. M.; Breit, B.; Peukert, S.;
Zambrano, J.; Ziller, J. W. Angew. Chem., Int. Ed. Engl. 1995, 34,
2396.