Tei et al.
TABLE 1. Isola ted Yield s a n d Dia ster eom er F r a ction s of 2 a n d Differ en tia l Activa tion P a r a m eter sa a t 20 °C
fractionc
substrate
isolated yieldb
(11aS)-2
(11aR)-2
k11aS/k11aR
∆∆Gq(kJ mol-1
)
∆∆Hq(kJ mol-1
)
∆∆Sq(J T-1mol-1
)
1a
1b
1c
1d
1e
98%
95%
65%
55%
28%
>0.998
0.960
0.81
0.976
0.5
<0.002
0.040
0.19
0.024
0.5
>500
24
4.2
41
>-15
-7.8
-3.8
-9.1
0
-5.2 ( 0.8
-5.8 ( 0.3
0.5 ( 0.8
0
8.3 ( 2.8
-7.8 ( 1.2
32.0 ( 2.8
0
1
a
b
Calculated from 8 to 12 determinations. See Table S1 (Supporting Information) for individual data. Obtained on a preparative
scale. c Determined from reactions on an analytical scale.
the chiral source on the reaction rates kR and kS in order
to elucidate the stereocontrol mechanism of the PD
tether.
intramolecular enantiotopos (or enantioface in this case)
should be well differentiated, in addition to the regio-
control of the addition sites on the phenoxy ring.
The stereochemically pure substrate 1a was prepared
in three steps through the Mitsunobu reaction of (2R,4R)-
2,4-pentanediol (PD) with phenol (99% yield) followed by
introduction of a diazo acetate ester (82% for two steps),
and the other substrates 1b-e in optically pure form
were prepared according to the same method (21-83%
for 3-5 steps).8 The reaction of the substrates 1a -e was
carried out in dichloromethane by the addition of cata-
lytic amounts of Rh2(OAc)4 (30-120 min at rt). No olefinic
proton other than those of the expected cycloheptatrienes
Resu lts a n d Discu ssion
Selectivity of P D-Teth er ed a n d Rela ted Rea c-
tion s. To analyze the stereocontrol mechanism of the PD-
tethered reactions, we chose a reaction between a phenyl
group and a rhodium carbenoid.2f,6 The role of the methyl
groups in the PD tether as a chiral source was clarified
by comparing the reactions of different tethered sub-
strates 1a -e. The carbenoid generated by the treatment
of 1 with a proper metal catalyst was expected to add to
the phenyl ring to give norcaradiene, which is im-
mediately converted to the chiral cycloheptatriene.7 To
obtain a stereochemically pure product 2, closely placed
1
2a -e was detected in the product mixture by H NMR.
The stereochemistries of the major products were as-
signed as 11aS on the basis of NOE experiments. To
avoid the fragility of the 7-carboxycycloheptatriene units,
diastereomer ratios of 2a -d were determined after the
reduction of the reaction mixture to the diols with LiAlH4.
It was judged that this conversion does not affect the
stereochemical purity of 2 at the 11a-position from the
observation that no deuterium was incorporated into the
diol in the presence of D2O. The determined diastereomer
ratios of 2a -d do not depend on the reaction time; thus,
the present system must consist of kinetically controlled
parallel processes of the addition step, and the product
ratio, (11aS)-2/(11aR)-2, is equal to the intrinsic selectiv-
ity, k11aS/k11aR. The results are given in Table 1.
(2) (a) Sugimura, T.; Futagawa, T.; Tai, A. Tetrahedron Lett. 1988,
29, 5775-5778. Sugimura, T.; Futagawa, T.; Yoshikawa, M.; Tai, A.
Tetrahedron Lett. 1989, 30, 3807-3810. Sugimura, T.; Yoshikawa, M.;
Futagawa, T.; Tai, A. Tetrahedron 1990, 46, 5955-5966. Sugimura,
T.; Yoshikawa, M.; Mizuguchi, M.; Tai, A. Chem. Lett. 1999, 831-832.
Sugimura, T.; Futagawa, T.; Yoshikawa, M.; Katagiri, T.; Miyashige,
R.; Mizuguchi, M.; Nagano, S.; Sugimori, S.; Tai, A.; Tei, T.; Okuyama,
T. Tetrahedron 2001, 57, 7495-7499. (b) Underiner, T. L.; Paquette,
L. A. J . Org. Chem. 1992, 57, 5438-5446. Sugimura, T.; Nishiyama,
N.; Tai, A. Tetrahedron: Asymmetry 1993, 4, 43-44. Sugimura, T.;
Iguchi, H.; Tsuchida, R.; Tai, A.; Nishiyama, N.; Hakushi, T. Tetra-
hedron: Asymmetry 1998, 9, 1007-1013. (c) Sugimura, T.; Nishiyama,
N.; Tai, A.; Hakushi, T. Tetrahedron: Asymmetry 1994, 5, 1163-1166.
(d) Sugimura, T.; Yamada, H.; Inoue, S.; Tai, A. Tetrahedron: Asym-
metry 1997, 8, 649-655. Sugimura, T.; Inoue, S.; Tai, A. Tetrahedron
Lett. 1998, 39, 6487-6490. (e) Mori, A.; Sugimura, T.; Tai, A.
Tetrahedron: Asymmetry 1997, 8, 661-664. (f) Sugimura, T.; Nagano,
S.; Tai, A. Chem. Lett. 1998, 45-46. (g) Yamaguchi, K.; Sugimura, T.;
Nishida, F.; Tai, A. Tetrahedron Lett. 1998, 39, 4521-4524. (h) Fujita,
M.; Matsushima, H.; Sugimura, T.; Tai, A.; Okuyama, T. J . Am. Chem.
Soc. 2001, 123, 2946-2957. (i) Sugimura, T.; Tei, T.; Mori, A.;
Okuyama, T.; Tai, A. J . Am. Chem. Soc. 2000, 122, 2128-2129.
(3) For examples of the reactions using other bifunctional chiral
auxiliaries as tethers, see: (a) Green, B. S.; Rabinsohn, Y.; Rejto, M.
J . Chem. Soc., Chem. Commun. 1975, 313-314. (b) Ukaji, Y.; Sada,
K.; Inomata, K. Chem. Lett. 1993, 1227-1230. (c) Lipshutz, B. L.; Liu,
Z.; Kayser, F. Tetrahedron Lett. 1994, 35, 5567-5570. (d) Lipshutz,
B. H.; Kayser, F.; Liu, Z. Angew. Chem., Int. Ed. Engl. 1994, 33, 1842-
1844. (e) Koide, N.; Hattori, T.; Miyano, S. Tetrahedron: Asymmetry
1994, 5, 1899-1994. (f) Lipshutz, B. H.; J ames, B.; Vance, S.; Carrico,
I. Tetrahedron Lett. 1997, 38, 753-756. (g) Faure, S.; Blanc, S. P. L.;
Pica, O.; Pete, J . P. Tetrahedron Lett. 1997, 38, 1045-1048. (h) Spring,
D. R.; Krishnan, S.; Schreiber, S. L. J . Am. Chem. Soc. 2000, 122,
5656-5657.
The stereoselectivity of the reaction of the PD-tethered
substrate 1a is very high, and the de (diastereomeric
excess) of 2a produced is over 99.6%. On the other hand,
the reaction of 1b, a diastereomer of 1a , gives a lower de
of 92.0% of 2b, which should be the result of the
mismatching of the two methyl groups in stereocontrol
on the basis of the results with the monomethylated
substrates; both 1c and 1d give the (11aS)-rich 2 (62%
de of 2c and 95.2% de of 2d 9). The higher selectivity
exhibited by 1d compared to 1c, as well as the same
stereodirection of the chiral tethers of 1a and 1b,
indicates that the addition is stereocontrolled mainly by
the methyl group on the ester side, and the other methyl
on the phenoxy side enhances the stereocontrol in 1a but
diminishes it in 1b.
(4) (a) Sugimura, T.; Futagawa, T.; Tai, A. Chem. Lett. 1990, 2291-
2294. Sugimura, T.; Futagawa, T.; Tai, A. Chem. Lett. 1990, 2295-
2298. (b) Sugimura, T.; Koguro, K.; Tai, A. Tetrahedron Lett. 1993,
34, 509-512. Sugimura, T.; Tai, A.; Koguro, K. Tetrahedron 1994, 50,
11647-11658.
(5) For a preliminary report, see: Sugimura, T.; Hagiya, K.; Sato,
Y.; Tei, T.; Tai, A.; Okuyama, T. Org. Lett. 2001, 3, 37-40.
(6) For related studies, see: (a) Sugimura, T.; Nagano, S.; Kohno,
H.; Fujita, M.; Tai, A. Chem. Lett. 1999, 179-180. (b) Sugimura, T.;
Kohno, H.; Nagano, S.; Nishida, F.; Tai, A. Chem. Lett. 1999, 1143-
1144. (c) Sugimura, T.; Nishida, F.; Tei, T.; Morisawa, A.; Tai, A.;
Okuyama, T. Chem. Commun. 2001, 2180-2181. (d) Sugimura, T.;
Kagawa, M.; Hagiya, K.; Okuyama, T. Chem. Lett. 2002, 260-261.
(7) (a) Davies, H. M. L. In Comprehensive Organic Synthesis; Trost,
B. M. Ed.: Pergamon: Oxford, 1991; Vol. 4, pp 1031-1067. (b) Maas,
G. Topics in Current Chemistry; Springer-Verlag: Berlin, 1987; Vol.
137, pp 75-253. (c) Doyle, M. P.; Mckervey, M. A.; Ye, T. Modern
Catalytic Methods for Organic Synthesis with Diazo Compounds;
Wiley: New York, 1997.
(8) The stereochemistry of the substrate 1b in the preliminary report
(ref 5) should be corrected.
(9) The de of 2d was refined from reported values5 by repeated
experiments.
6594 J . Org. Chem., Vol. 67, No. 19, 2002