Role of planar chirality of S,N- and P,N-ferrocene ligands in palladium-catalyzed allylic substitutions

Article abstract of DOI:10.1021/jo016330z

Palladium-catalyzed asymmetric allylic substitutions using thioether and phosphino derivatives of ferrocenyloxazoline as ligands have been investigated with a focus on studying the role of planar chirality. In allylic alkylation, up to 98% ee and 95% ee were achieved with S,N- and P,N-ligands, respectively. In allylic amination, 97% ee was realized with P,N-ligands in the presence of TBAF. Several palladium allylic complexes were characterized by X-ray diffraction and/or solution NMR. Thioether derivatives of ferrocenyloxazolines with only planar chirality showed lower enantioselectivity in the allylic alkylation except 5c because of the formation of a new chirality on sulfur atom during the coordination of sulfur with palladium. On the other hand, in the planar chiral P,N-ligands without central chirality, (Sp)-11a-c there was no such disturbance and comparatively higher enantioselectivity in both palladium-catalyzed allylic alkylation and amination was provided.

Full text of DOI:10.1021/jo016330z

Role of P la n a r Ch ir a lity of S,N- a n d P ,N-F er r ocen e Liga n d s in
P a lla d iu m -Ca ta lyzed Allylic Su bstitu tion s
Shu-Li You,† Xue-Long Hou,*,† Li-Xin Dai,*,† Yi-Hua Yu,‡ and Wei Xia‡
State Key Laboratory of Organometallic Chemistry, and Laboratory of Analytical Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
xlhou@pub.sioc.ac.cn; dailx@pub.sioc.ac.cn
Received November 29, 2001
Palladium-catalyzed asymmetric allylic substitutions using thioether and phosphino derivatives
of ferrocenyloxazoline as ligands have been investigated with a focus on studying the role of planar
chirality. In allylic alkylation, up to 98% ee and 95% ee were achieved with S,N- and P,N-ligands,
respectively. In allylic amination, 97% ee was realized with P,N-ligands in the presence of TBAF.
Several palladium allylic complexes were characterized by X-ray diffraction and/or solution NMR.
Thioether derivatives of ferrocenyloxazolines with only planar chirality showed lower enantiose-
lectivity in the allylic alkylation except 5c because of the formation of a new chirality on sulfur
atom during the coordination of sulfur with palladium. On the other hand, in the planar chiral
P,N-ligands without central chirality, (Sp)-11a -c there was no such disturbance and comparatively
higher enantioselectivity in both palladium-catalyzed allylic alkylation and amination was provided.
In tr od u ction
and application of planar chiral ferrocene ligands culmi-
nated recently in two industrial asymmetric hydrogena-
tion processes.11 Although many excellent results were
derived from planar chiral ferrocene ligands,12 the un-
derstanding of the role of planar chirality is overlooked.
Some examples showed that the planar chirality had
significant effect on the enantioselectivity,13 while in
other examples it was not so apparent.14 Kumada and
Hayashi’s results showed that the planar chirality was
a decisive factor for exerting control over enantiomer
excess and absolute configuration in the cross-coupling
reaction catalyzed by (R,Sp)-PPFA, (R,Rp)-PPFA, and
(Sp)-PPFA 1 with only planar chirality, respectively.15
Bolm et al. found that on removal of the central chirality
in hydroxyoxazolinyl ligand 2 the enantioselectivity in
the diethylzinc addition reaction dropped significantly.16
Chirotechnology is one of the most interesting and
challenging technologies of recent years.1 Great efforts
have been made toward the establishment of asymmetric
catalytic industrial processes. Therein, design and syn-
thesis of chiral ligands are always the key point.2
Ferrocene-containing3 ligands are among the most in-
teresting ligands because of their stability, easy introduc-
tion of planar chirality,4-9 inherent special electronic and
stereoproperties of the ferrocene skeleton. It is notewor-
thy that most ferrocene ligands contain planar chirality
and/or central chirality (even axial chirality10). Synthesis
† State Key Laboratory of Organometallic Chemistry.
‡ Laboratory of Analytical Chemistry.
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Eliel, E., Wilen, S. H., Eds.; Wiley: New York, 1988; Vol. 18, p 129.
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R., Ed.; Springer: Berlin, 1989; p 115. (c) Ojima, I., Ed. Catalytic
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Deng, W.-P.; Hou, X.-L.; Dai, L.-X. Tetrahedron: Asymmetry 1999, 10,
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10.1021/jo016330z CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/21/2002
4684
J . Org. Chem. 2002, 67, 4684-4695

Palladium-Catalyzed Allylic Substitutions
F IGURE 1. Structures of ligands 1-5.
F IGURE 2. Structures of ligands 6-8.
Recently, the work of Fu and co-workers on the single
planar chiral ferrocene ligand 3 revealed that it is a
highly efficient catalyst for asymmetric reactions.17 For
this reason, there is an urgent need to study the role of
planar chirality in ferrocene systems for the purpose of
new, efficient ligand design. In the course of studying the
role of planar chirality,18 we found that planar chirality
dominated the enantiomer excess and absolute configu-
ration in the palladium-catalyzed Heck reaction and
allylic substitution reaction catalyzed by planar chiral
1,1′-P,N-2′-substituted ferrocene ligands 4.19,20 We also
found that S,N-ligands 5a and 5b with only planar
chirality showed very low enantioselectivity while the
ligands with central and planar chiralities 6 gave the
product with high ee (Figure 1).21 Further studies showed
that a new chiral center on the sulfur atom was formed
during the coordination of 5a and 5b with metal, and
two diastereomeric complexes were formed so that they
gave the lower enantioselectivity. To reveal the role of
planar chirality in 1,2-disubstituted ferrocenes and to
avoid the formation of a new chiral center on a coordi-
nated atom, P,N-ligands with or without central chirality
were synthesized and tested. In this paper, we report the
results of these studies in detail. With the aid of X-ray
crystallographic and NMR studies, the role of planar
chirality in 1, 2-disubstituted ferrocene ligands is dis-
cussed.
trol in the asymmetric catalysis sometimes.23 However,
two kinds of chirality in the above two pairs of ligands,
6a vs 7a and 6b vs 7b, most likely may be matched or
mismatched in reactions. To show the role of planar
chirality more clearly, ligands (Sp)-5a , -5b, and -5c
having a similar backbone but only planar chirality were
synthesized. Ligand (Sp)-5a was synthesized in good
yields from ligand (S,Sp)-6a and ethylamino alcohol in
our previous paper,21 and ligands (Sp)-5b and (Sp)-5c
were synthesized by using corresponding amino alcohol
and similar method. Geminal R-disubstituted 8 was
synthesized according to the literature procedure (Figure
2).24
Also, ligands (S,Sp)-9, (S,Rp)-10, and (Sp)-11a -c were
chosen to study the role of planar chirality in palladium-
catalyzed allylic substitution reaction with P,N-ligands.
Ligand (S,Sp)-9 and (S,Rp)-10 were prepared according
(17) (a) Ruble, J . C.; Latham, H. A.; Fu, G. C. J . Am. Chem. Soc,
1997, 119, 1492. (b) Fu, G. C. Acc. Chem. Res. 2000, 33, 412.
(18) (a) You, S.-L.; Hou, X.-L.; Dai, L.-X.; Cao, B.-X. J . Sun, Chem.
Commun. 2000, 1933. (b) You, S.-L.; Hou, X.-L.; Dai, L.-X.; Zhu, X.-Z.
Org. Lett. 2001, 3, 149. (c) You, S.-L.; Hou, X.-L.; Dai, L.-X. Tetrahe-
dron: Asymmetry 2000, 11, 1495. (d) Du, X.-D.; Dai, L.-X.; Hou, X.-L.;
Xia, L.-J .; Tang, M.-H. Chin. J . Chem. 1998, 16, 90. (e) Dai, L.-X.; Hou,
X.-L.; Deng, W.-P.; You, S.-L.; Zhou, Y.-G. Pure Appl. Chem. 1999, 71,
1401. (f) Zhou, X.-T.; Lin, Y.-R.; Dai, L.-X.; Sun, J .; Xia, L.-J .; Tang,
M.-H. J . Org. Chem. 1999, 64, 1331. (g) You, S.-L.; Zhu, X.-Z.; Hou,
X.-L.; Dai, L.-X. Hua Xue Xue Bao 2001, 59, 1667.
(19) (a) Deng, W.-P.; Hou, X.-L.; Dai, L.-X.; Yu, Y.-H.; Xia, W. Chem.
Commun. 2000, 285. (b) Deng, W.-P.; Hou, X.-L.; Dai, L.-X.; Dong, X.-
W. Chem. Commun. 2000, 1483. (c) Deng, W.-P.; You, Shu-Li; Hou,
X.-L.; Dai, L.-X.; Yu, Y.-H.; Xia, W. J . Am. Chem. Soc. 2001, 123, 6518.
(20) For reviews of asymmetric allylic substitution reactions: (a)
Consiglio, G.; Waymouth, R. M. Chem. Rev. 1989, 89, 257. (b) Frost,
C. G.; Howarth, J .; Williams, J . M. J . Tetrahedron: Asymmetry 1992,
3, 1089. (c) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96,
395. (d) Hayashi, T. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.;
VCH Publishers: New York, 1993. (e) Pfaltz, A.; Lautens, M. in ref 2,
Vol. 2, p 833.
(21) You, S.-L.; Zhou, Y.-G.; Hou, X.-L.; Dai, L.-X. Chem. Commun.
1998, 2765.
(22) Ahn, K. H.; Cho, C.-W.; Beak, H.-H.; Park, J .; Lee, S. J . Org.
Chem. 1996, 61, 4937.
(23) (a) Evans, D. A.; Faul, M. M.; Bilodeau, M. T.; Anderson, B. A.;
Barnes, D. M. J . Am. Chem. Soc. 1993, 115, 5328. (b) Kanemasa, S.;
Oderaotoshi, Y.; Tanaka, J .; Wada, E. J . Am. Chem. Soc. 1998, 120,
12355. (c) Andrus, M. B.; Asgari, D.; Sclafani, J . A. J . Org. Chem. 1997,
62, 9365.
Resu lts a n d Discu ssion s
Syn th esis of Liga n d s. Ligands (S,Sp)-6a -e were
prepared in high diastereoselectivity from ferrocene and
chiral amino alcohols by using known procedures.21,22 For
the purpose of studying the relative asymmetric inductive
effect between planar chirality and central chirality, the
ligands (S,Rp)-7a and (S,Rp)-7b with only a different
configuration of planar chirality compared to (S,Sp)-6a
and (S,Sp)-6b were also prepared. In addition, ligand
(R,Rp)-6f with phenyl as substituent on the oxazoline
ring was also prepared with high diastereoselectivity as
a phenyl group on the oxazoline showed good stereocon-
(24) O’Donnell, M. J .; Polt, R. L. J . Org. Chem. 1982, 47, 2663.
J . Org. Chem, Vol. 67, No. 14, 2002 4685

You et al.
SCHEME 1a
a
Condition and reagent: (a) (1) TFA, H2O, Na2SO4, THF; (2) Ac2O, Pyr, DCM 63%; (b) MeONa, THF/MeOH, 55 °C 94%; (c) Na,
NH2(CH2)2OH, 100 °C 92%; (d) Et3N, MsCl, DCM 85%; (e) (1) (ClCO)2, NH2CR2CH2OH, Et3N, DCM; (2) PPh3, CCl4, Et3N, CH3CN; (f) (1)
n-BuLi; (2) Ph2PCl.
TABLE 1. Asym m etr ic P a lla d iu m -Ca ta lyzed Allylic
instead of potassium acetate, was used as the additive
in palladium-catalyzed allylic alkylation with S,N-
ligands,26 which accelerated the reaction and improved
the enantioselectivity a little.21 Using the above condi-
tions, the palladium-catalyzed asymmetric allylic alky-
lation with S,N-ligands was carried out (eq 1), and the
Alk yla tion s w ith P la n a r Ch ir a l S,N-Liga n d sa
entry
ligand
time (h) yieldb (%) eec (%) configurationd
1
2
3
4
5
6
7
8
9
(S,Sp)-6a
(S,Sp)-6b
(S,Sp)-6c
(S,Sp)-6d
(S,Sp)-6e
(R,Rp)-6f
(S,Rp)-7a
(S,Rp)-7b
(Sp)-5a
3
10
3
3
5
1
3
1
98
98
98
98
98
98
98
98
90
92
98
89.4
98.0
81.9
89.9
87.8
89.1
90.4
89.8
8.3
S
S
S
S
S
R
S
S
R
R
S
48
48
5
10
11
(Sp)-5b
(Sp)-5c
12.5
71.8
results are summarized in Table 1. The sense of enantio
induction was determined by HPLC and specific rotation
of the reaction product, methyl 2-carbomethoxy-3,5-
diphenylpent-4-enoate.27 Ligands 6b-f show high cata-
lytic efficiency and high to excellent enantioselectivities
(81.9-98.0% ee). Ligand 6d with a p-methylphenylthio
group provides almost equal enantioselectivity given by
ligand 6a with a phenylthio group (entry 4 vs entry 1 in
Table 1). It seems that ligands with an arylthio group
give higher enantioselectivity than ligand 6c with a
methylthio group does (entry 3 in Table 1). The results
also indicate that the ligand with R1 ) t-Bu (entry 2 in
Table 1) is superior to R1 ) i-Pr (entry 1 in Table 1), Bn
(entry 5 in Table 1), or Ph (entry 6 in Table 1).
To disclose the role of planar chirality, ligands (S,Rp)-
7a , (S,Rp)-7b, and (Sp)-5a -c are tested in this reaction
under the above conditions. We noticed that products are
always in the S configuration, no matter if the planar
chirality of the ligand is S (6a ,b) or R (7a ,b). That is,
the absolute configuration of the product in this reaction
a
b
See the Experimental Section. Isolated yield based on 12.
c Determined by chiral HPLC (Chiracel OD column). Absolute
d
configuration of product was assigned through comparison of the
sign of specific rotations with the literature data.27
F IGURE 3. Structures of ligands 9-11.
to the reported methods.22 (Sp)-11a -c were also synthe-
sized from (S,Sp)-9 or (Sp)-2-iodine-1-(4,4-dibenzylox-
azolinyl)ferrocene (Scheme 1, Figure 3).
Asym m etr ic Alk yla tion . The allylic substitutions of
rac-1,3-diphenylprop-2-enyl acetate with dimethyl mal-
onate or benzylamine as nucleophile were used in this
paper as the model reaction because the mechanism of
these reactions is fairly understood and the efficiency of
the ligands can be quickly deciphered.25 Lithium acetate,
(26) Selected S,N-ligands in Pd-catalyzed allylic substitutions: (a)
Wu, X.-W.; Hou, X.-L.; Dai, L.-X.; Cao, B.-X. J . Sun, Chem. Commun.
2000, 1195. (b) Dawson, G. J .; Frost, C. G.; Martin, C. J .; Williams, J .
M. J .; Coote, S. J . Tetrahedron Lett. 1993, 34, 7793. (c) Allen, J . V.;
Bower, J . F.; Williams, J . M. J . Tetrahedron: Asymmetry 1994, 5, 1895.
(d) Koning, B.; Meetsma, A.; Kellogg, R. M. J . Org. Chem. 1998, 63,
5533. (e) Adams, H.; Anderson, J . C.; Cubbon, R.; J ames, D. S.;
Mathias, J . P. J . Org. Chem. 1999, 64, 8256. (f) Imai, Y.; Zhang, W.;
Kida, T.; Nakatsuji, Y.; Ikeda, I. Synlett 1999, 1319.
(25) (a) Allen, J . V.; Coote, S. J .; Dawson, G. J .; Frost, G. C.;
Williams, J . M. J . J . Chem. Soc., Perkin Trans. 1 1994, 2065. (b) Matt,
P. V.; Loiseleur, O.; Koch, G.; Pfaltz, A.; Lefeber, C.; Feucht, T.;
Helmchen, G. Tetrahedron: Asymmetry 1994, 5, 573.
(27) Wimmer, P.; Widhalm, M. Tetrahedron: Asymmetry 1995, 6,
657.
4686 J . Org. Chem., Vol. 67, No. 14, 2002

Palladium-Catalyzed Allylic Substitutions
TABLE 2. Asym m etr ic P a lla d iu m -Ca ta lyzed Allylic
TABLE 3. Asym m etr ic P a lla d iu m -Ca ta lyzed Allylic
Alk yla tion s w ith P la n a r Ch ir a l P ,N-Liga n d sa
Am in a tion s w ith P la n a r Ch ir a l P ,N-liga n d sa
entry
ligand
time (h) yieldb (%) ee (%)c configurationd
T
TBAF yieldb eec
entry
ligand
(°C) (equiv)
(%)
(%) configurationd
1
2
3
4
5
(S,Sp)-9
(S,Rp)-10
(Sp)-11a
(Sp)-11b
(Sp)-11c
12
48
3
48
4
96
94
98
90
96
92.3
94.6
76.6
54.0
5.9
S
S
R
R
S
1
2
3
4
5
6
7
8
9
(S,Sp)-9
(S,Rp)-10
(S,Rp)-10
(S,Rp)-10
(S,Rp)-10
(S,Sp)-9
(Sp)-11a
(Sp)-11b
(Sp)-11c
40 none
40 none
95
67
96
96
90
83
96
95
71
47.7
86.1
95.8
97.2
96.6
91.3
73.7
60.3
52.7
R
R
R
R
R
R
S
40
50
50
50
50
50
50
2
2
4
2
2
2
2
a
b
See the Experimental Section. Isolated yield based on 12.
c Determined by chiral HPLC (Chiracel OD column). Absolute
d
configuration of product was assigned through comparison of the
S
S
sign of specific rotations with the literature data.27
a
b
See the Experimental Section. Isolated yield based on 12.
is governed by the central chirality. This conclusion is
further supported as follows: (1) when the central
chirality of ligand 6f is R, the configuration of the product
is also changed to R (entry 6 in Table 1); (2) the very low
ee values from ligands 5a ,b with only planar chirality
(entries 9 and 10, 8.3% and 12.5%, respectively) also
indicate the smaller influence of planar chirality on
asymmetric induction. Based on these results, we might
conclude that the planar chirality has little effect on the
enantioselectivity in our preliminary communication.21
On further comparison of the results in entries 2 and 8
of Table 1, (S,Sp)-6b is apparently a matched one and
(S,Rp)-7b is not. Thus, the effect of planar chirality
should not be overlooked. However, a jump of ee values
was observed by using ligand (Sp)-5c with two benzyl
groups as substituent (71.8% ee in entry 11, Table 1). In
addition, the absolute configuration was S, while that for
ligands (Sp)-5a and (Sp)-5b was R ,although three
ligands have the same S configuration of planar chirality.
On careful examination of the structure of the ligands,
we reasoned that a new chirality on the sulfur atom was
produced when ligands 5 coordinated with palladium,
which disturbed the asymmetric induction. In the ligands
with central chirality, a substituent on the oxazoline ring
would exert a definite asymmetric induction during the
coordination and direct the phenyl group on sulfur in the
opposite position due to the steric effect. In the ligands
without central chirality, there will be almost no dias-
tereoselectivity in the coordinating process and the
chirality on the S-atom will be easily racemized, causing
the very low ee value of the product. To exclude this
disturbance, the diphenylphosphinoferrocenyloxazolines
were chosen as ligands and the same reaction was carried
out (eq 2). The reaction conditions were almost the same
c Determined by chiral HPLC (Chiracel OD column). Absolute
d
configuration of product was assigned through comparison of the
sign of specific rotations with the literature data.30
corresponding S,N-ligands (Sp)-5a and 5b (entries 3 and
4, Table 2 vs entries 9 and 10, Table 1). For these ligands,
it seemed that enantioselectivity was higher when the
groups on the oxazolines became less steric (entries 3 and
4 in Table 2). It was interesting that an unexpected low
ee value was observed by using ligand (Sp)-11c with two
benzyl groups (entry 5 in Table 2). (Sp)-11a gave the
product with highest ee up to 76.6% in the R configura-
tion, which indicated also that (S,Rp)-10 should have one
pair of matched chiralities.
Planar chiral P,N-ligands were also subjected in asym-
metric palladium-catalyzed allylic amination reaction29
(eq 2), and the results are listed in Table 3.
The allylic amination reaction was performed at 40 °C
in THF. The enantioselectivity of product obtained from
(S,Rp)-10 was higher than that from (S,Sp)-9 (entry 1
vs 2, Table 3). The reaction was completed very quickly,
and the enantioselectivity was improved greatly when 2
equiv of TBAF was added as additive (entry 3 vs 2, Table
3).31 In addition, the enantioselectivity was improved by
increasing the temperature to 50 °C but affected little
by increasing the amount of TBAF to 4 equiv (entries 4
and 5 in Table 3). At the same time, product with higher
enantioselectivity could be achieved also from (S,Sp)-9
when 2 equiv of TBAF was added (entry 6 vs 1, Table 3).
Ligands with only planar chirality showed good enanti-
oselectivity in the optimized allylic amination similar to
that in the allylic alkylation reaction. The same conclu-
sion as for the allylic alkylation reaction could be drawn
that enantioselectivity was higher when the groups on
the oxazolines was smaller (entries 7-9 in Table 3). (Sp)-
11a gave the product with highest 73.7% ee in S
configuration, which indicated also that (S,Rp)-10 should
contain one pair of matched chiralities. For P,N-ligands
in these two reactions, it is evident that the planar
chirality plays an important role in asymmetric induction
and the matching of central and planar chiralities may
offer excellent enantioselectivity. The very low ee values
for 5a and 5b are a special case due to the formation of
a new chiral center on S atom.
as above, but KOAc was used as the additive and 8 mol
% ligand was used. The results are summarized in Table
2. Ligand (S,Rp)-10 was found to be better than (S,Sp)-9
and gave a higher enantioselectivity (94.6% ee in entry
2 vs 92.3% ee in entry 1, Table 2).28 The product obtained
with both ligands is in the S configuration despite their
different planar chirality. It was noteworthy that the
ligands (Sp)-11a ,b with only planar chirality provided
good ee, which is far better than that by using the
(29) Malone, Y. M.; Guiry, P. J . J . Organomet. Chem. 2000, 603,
110.
(30) Hayashi, T.; Yamamoto, A.; Ito, Y.; Nishioka, E.; Miura, H.;
Yanagi, K. J . Am. Chem. Soc. 1989, 111, 6301.
(31) Burckhardt, U.; Baumann, M.; Togni,A. Tetrahedron: Asym-
metry 1997, 8, 155.
(28) Ahn, K. H.; Cho, C.-W.; Park, J .; Lee,S. Tetrahedron: Asymmetry
1997, 8, 1179.
J . Org. Chem, Vol. 67, No. 14, 2002 4687

You et al.
X-r a y Cr ysta llogr a p h ic Stu d y of th e In ter m ed ia te
Com p lex: S,N-Liga n d s a n d P ,N-Liga n d s. To inves-
tigate the relative inductive effect of planar chirality and
central chirality and the role of planar chirality through
studying the mechanism in this reaction,32,33 palladium
allylic complexes 15-20 were prepared (eq 3).
Crystals of complexes 15, 17, 19, and 20 were obtained
by slow evaporation from the proper organic solvents. The
crystals were stable for several months in air without
any additional precautions. The crystal structure of 15
was found to be the allylic intermediate 15A with M-type
(endo-syn-syn). (Nomenclature note: the endo-isomer is
defined as the isomer in which the central allyl proton
points to the ferrocene core.) The phenyl group on the
sulfur is trans to tert-butyl group on the oxazoline ring
due to the steric effect. In line with the structural
evidence for nitrogen-phosphorus or nitrogen-sulfur
ligands, we found that the two palladium-terminal allylic
carbon bond distances are slightly different from each
other, with the bond trans to sulfur longer than the bond
trans to nitrogen. The actual bond distances for Pd-C30
and Pd-C32 are 2.21 and 2.15 Å, respectively.
The crystal of complex 17 was given as a dark red
crystal containing one EtOAc molecule from hexane/CH2-
Cl2/EtOAc. Consistent with 15, the crystal structure of
17 was found to be the M type (endo-syn-syn) allylic
intermediate 17A. In addition, the bond trans to sulfur
is longer than that trans to nitrogen in the crystal
structure; the actual bond distances are 2.26 and 2.18
Å, respectively. The data show that the sulfur atom is a
better π-acceptor than the oxazoline nitrogen atom. The
phenylthio group was also trans to the nonsubstituted
Cp ring, and the most interesting thing is that the two
benzyl groups mount across the 1,3-diphenyl allylic
moiety. The plane of phenyl in one of the benzyl groups
was almost perpendicular with the plane of the allylic
moiety (the angle is 86°). The plane of allylic moiety was
almost parallel with the skeleton of the ferrocene (the
angle between plane C(40)-C(41)-C(42) and Cp ring is
70°). The two geminal benzyl groups on the oxazoline ring
have a significant effect on the conformation of the allylic
intermediate 17A. This is the reason for the rather high
ee value of allylic alkylation reaction by using ligand 5c,
even there is still a new chiral center on the S atom (entry
11 in Table 1).
F IGURE 4. Sections of the NOESY spectrum of complex 15
showing the cross-peaks due to the interactions of the t-Bu
protons with H32, with H26 (or 30), and with H34 (or 37),
respectively. The arrows show the NOEs (400 MHz, mixing
time 0.7 s, 273 K, CD2Cl2). Though the NOE between the t-Bu
protons and H32 is weak, it can be easily found when the
mixing time changes to 1.0 or 1.3 s (see also the text).
that, the bonds of Pd-P and Pd-N in 20 were shorter
than that in 19. From these data, we can see that the
π-allyl moiety is closer to the ferrocene backbone in 20
than that in 19.
NMR Stu d y of th e In ter m ed ia te Com p lexes. The
1HNMR spectrum of the complex 15 at the same tem-
perature of the reaction (25 °C) in CD2Cl2 showed that
there was a mixture of two conformers in a ratio of 3.1:1
and their conformations were assigned by a combination
of COSY, 13C-1H correlation, and two-dimensional NOE
1
experiments. The HNMR manifested only the syn,syn
arrangement of the allylic unit, as evidenced by the
coupling constants between the allyl protons H(31),
H(32), and H(33) of ∼12 Hz and no apparent NOE
between H(31) [or H(33)] and H(32) in the 2D NOESY
spectrum. The major structure was deduced to be in the
M conformation in solution, which is the same as the
solid-state conformation of 15A (Figure 4). To confirm
this conclusion, two important evidences were provided
in the relevant NOE experiment. First, we found that
H(32) showed NOE relevant with the protons of tert-butyl
in the major structure. Though the NOE was weak, it
was distinct in the 2D NOESY spectra with different
exchange times such as 0.7, 1.0, and 1.3 s (Figure 4). The
shortest distance between them is 3.10 Å in the X-ray
structure, which was responsible to the weak NOE here.34
Second, the doublet peak at 7.63 ppm was deduced to be
H(26) and H(30) in the major component, for it had NOE
with H(31) and H(32). Similarly, the doublet peak at 6.81
ppm was deduced to be H(34) and H(37) in the major
intermediate, for it had NOE with H(32) and H(33). At
the same time, both of them had NOE with a tert-butyl
group in the major component, which indicated that the
major intermediate was M type (endo-syn-syn).
The crystal structure of 19 was found to be 19B (exo-
syn-syn). That of 20 was found to be exo-syn-syn also.
Comparing these two complexes, the 94.5° angle of
P-Pd-N in 20 is larger than that in 19; in addition to
From the results listed in Table 1, we found that 6b
showed a better stereocontrol over that of 7b, which has
the same central chirality but opposite planar chirality.
Palladium allylic complex 16 was investigated in order
to give a proper explanation. The solution NMR of 16 was
(32) (a) Steinhagen, H.; Reggelin, M.; Helmchen,G. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 2108. (b) Sprinz, J .; Kiefer, M.; Helmchen, G.;
Reggelin, M.; Huttner, G.; Walter, O.; Zsolnai, L. Tetrahedron Lett.
1994, 35, 1523. (c) Togni, A.; Burckhardt, U.; Gramlich, V.; Pregosin,
P. S.; Salzmann, R. J . Am. Chem. Soc. 1996, 118, 1031. (d) Selvakumar,
K.; Valentini, M.; Wo¨rle, M.; Pregosin, P. S.; Albinati, A. Organome-
tallics 1999, 18, 1207.
(33) Boog-wick, K.; Pregosin, P. S.; Trabesinger, G. Organometallics
1998, 17, 3254.
(34) Pregosin, P. S.; Valentini, M. Enantiomer 1999, 4, 529.
4688 J . Org. Chem., Vol. 67, No. 14, 2002

Palladium-Catalyzed Allylic Substitutions
F IGURE 6. Equilibrium of complexes 15 and 16.
TABLE 4. Selected NMR Da ta for P a lla d iu m Allylic
Com p lexes 15 a n d 16
1H NMR (ppm)
H2
13C NMR (ppm)
C2
F IGURE 5. Sections of the NOESY spectrum of complex 16
(A, endo-syn-syn isomer; B, exo-syn-syn isomer). H4 indicates
the unsubstituted cp ring protons. The arrows show the NOEs
(400 MHz, mixing time 1.0 s, 273 K, CD2Cl2) (see also text).
H1
H3
C1
C3
15A
15B
16B
16A
5.58
5.07
5.67
5.21
6.34
6.32
6.77
6.83
3.85
4.81
5.06
4.97
94.2
86.5
92.2
86.8
108.6
107.0
105.5
107.0
76.5
83.8
75.3
81.9
studied in detail though a suitable X-ray structure of 16
was not obtained. CD2Cl2 was also chosen as the solvent.
1
The H NMR spectrum of the complex at 25 °C showed
It was reported that there was a correlation between
the downfield shifts in the 13C NMR and relative positive
charge of the carbon nuclear.36 With such a correlation,
the 13C NMR was used for predicting the reactivity of
carbon termini of the palladium allylic complexes.37 For
15 there are two isomers, 15A and 15B, in a ratio of 3.1:1
(Figure 6). Chemical shifts for terminal carbons of allyl
are δ ) 94.2 (allylic carbon trans to S, C1) and 76.5 (trans
to N, C3) for 15A (∆δ ) 17.7) and δ ) 86.5 (allyl carbon
trans to S, C1) and 83.8 (trans to N, C3) for 15B (∆δ )
2.7). It means that C1 of both 15A and 15B is more
sensitive than C3 for nucleophilic attack. We can also
reason that 15A is more reactive than 15B by comparison
of their 13C chemical shifts of C1 (Table 4). Because
nucleophilic attack at diastereomer 15A is more favored,
the product will be given in S configuration. It is
consistent with our experimental results. For 16, there
are also two conformers, 16A and 16B, in a ratio of 2.2:1
(Figure 6). Terminal allyl carbon chemical shifts are δ )
86.8 (allyl carbon trans to S) and 81.9 (trans to N) for
16A (∆δ ) 4.9) and δ ) 92.2 (allyl carbon trans to S)
and 75.3 (trans to N) for 16B (∆δ ) 16.9), suggesting that
16B is the more reactive conformer (Table 4). Although
16A occupies a higher population and is a favorable
diastereomer during the thermodynamic equilibrium, it
that it was a mixture of two conformers in a ratio of 2.2:
1, and their conformations were assigned by a combina-
tion of COSY, 13C-1H correlation, and dimensional NOE
1
experiments. The HNMR manifested only the syn,syn
arrangement of the allylic unit. Consistent with 15, the
results revealed that the M-type allylic moiety (endo-syn-
syn) was the major conformer (Figure 5).
Some evidence supports our conclusion. First, the
nonsubstituted Cp ring [H(4)] showed NOE with H(2) in
the major component. Second, the H(1) (doublet peak at
5.67 ppm) showed NOE relevant with a nonsubstituted
Cp ring [H(4)] in the minor component. Third, a multiple
peak at 7.81 ppm was deduced to be H(5) or H(6) for it
showed NOE relevant with H(1) and H(2) in the major
component. A multiple peak at 7.69 ppm was deduced to
be H(7) or H(8) for it showed NOE relevant with H(2)
and H(3) in the major component. At the same time, both
of them showed NOE relevant with the nonsubstituted
Cp ring [H(4)]. As a result, the major component is the
M type (endo-syn-syn). We are surprised by this result,
for the product should have an R configuration when the
two components reacted with nucleophile at the same
rate, and it is in contrast with our experimental results.
Again, an identical alkylation reaction was performed
with 2 mol % intermediate 16 as the catalyst and the
product was isolated in 90% ee and 98% yield with S
configuration, showing that 16 is actually the intermedi-
ate. One reasonable explanation is two conformers may
have different reactivity with the nucleophile.35
(36) (a) Åkermark, B.; Krakenberger, B.; Hansson, S.; Vitagliano,A.
Organometallics 1987, 6, 620. (b) Åkermark, B.; Zetterberg, K.;
Hansson, S.; Krakenberger, B.; Vitagliano, A. J . Organomet. Chem.
1987, 335, 133. (c) Macsa´r, i I.; Szabo´, K. J . Organometallics 1999, 18,
701. (d) Malet, R.; Moreno-Man˜as, M.; Parella, T.; Pleixats, R.
Organometallics 1995, 14, 2463.
(37) (a) Macsa´ri, I.; Hupe, E.; Szabo´,K. J . J . Org. Chem. 1999, 64,
9547. (b) Aranyos, A.; Szabo´, K. J .; Castan˜o, A. M.; Ba¨ckvall, J .-E.
Organometallics 1997, 16, 1058. (c) Moreno-Man˜as, M.; Pajuelo, F.;
Parella, T.; Pleixats, R. Organometallics 1997, 16, 205.
(35) (a) Auburn, P. R.; Mackenzie, P. B.; Bosnich, B. J . Am. Chem.
Soc. 1985, 107, 2033. (b) Mackenzie, P. B.; Whelan, J .; Bosnish, B. J .
Am. Chem. Soc. 1985, 107, 2033.
J . Org. Chem, Vol. 67, No. 14, 2002 4689

You et al.
TABLE 5. Selected NMR Da ta for P a lla d iu m Allylic
com p lexes 18 a n d 19
1H NMR (ppm)
H2
13C NMR (ppm)
C2
H1
H3
C1
C3
18A
18B
19A
19B
5.84
6.14
5.21
5.69
6.47
6.41
6.89
6.69
3.44
5.07
3.89
4.57
104.4
109.6
94.0
111.3
111.1
108.8
132.9
69.9
74.4
78.0
66.3
103.7
F IGURE 7. Proposed mechanism in palladium-catalyzed
allylic substitution reaction with planar chiral ligands 5a and
5c.
is a less reactive species. The S product was obtained by
kinetic control.
Palladium allylic complex 17 synthesized from ligand
(Sp)-5c was studied also. The allylic moiety was M type
(endo-syn-syn) in the X-ray structure. Unfortunately, the
1H NMR gave all wide and broad peaks. The allylic
protons were difficult to assign. We think that it may be
caused by the fast equilibrium between the two isomers
of complex 17. In the ligands without central chirality,
the phenyl group on the sulfur will become more flexible.
For all the palladium allyl complexes with planar chiral
S,N-ligands, there would exist four intermediates caused
by the chirality of sulfur and the conformation of the allyl.
However, only two major intermediates were discussed
since the other two were less stable as steric reason
caused by phenyl group on sulfur and the phenyl group
of the allyl when they were on the same direction (Figure
7). With the ligands (Sp)-5a , 21A (endo-syn-syn) and 21B
(exo-syn-syn) represented the two major components, in
which a chiral center on sulfur was formed. The product
was given in low ee value because the difference was
small between 21A and 21B. The situation was changed
greatly in complex 17. For the two benzyl groups mounted
across the diphenyl allyl moiety, component 17A (endo-
syn-syn) was more stable than 17B (exo-syn-syn). As a
result, the product could be given in high ee with S
configuration by using (Sp)-5c as ligand. It also explained
the difference between the ee values provided by P,N-
ligands 11 and S,N-ligands 5a and 5b. Higher ee values
were obtained for P,N-ligands 11 because no new chiral
center was formed on the phosphorus atom during the
coordination of them with palladium. NMR spectra of
complexes derived from P,N-ligands 18-20 have also
been studied. On the basis of the NMR data of the
complexes, it is difficult to assign the conformation of the
intermediates. All the complexes except 19 reached
equilibrium between the two conformers as soon as they
dissolved in the solvent. It took 9 h to reach equilibrium
for complex 19, and only one conformer was observed
immediately after dissolution of the complex. Because the
X-ray structure of complex 19 was determined as 19A
(endo-syn-syn), we elucidated that it was the major
component in the solution. For complex 18, the ratio of
F IGURE 8. Equilibrium of complexes 18 and 19.
the two conformers is 8.8:1. Terminal 13C allyl chemical
shifts are δ ) 104.4 (allyl carbon trans to P) and 69.9
(trans to N) for the major component (∆δ ) 34.5) and δ
) 109.6 (allyl carbon trans to P) and 75.3 (trans to N)
for the minor one (∆δ ) 35.2), suggesting that the minor
conformer was the more reactive species (Table 5). When
the product was given in high ee in the S configuration,
the minor component was probably 18A (endo-syn-syn).
For 19 there are two isomers, 19A and 19B, in a ratio of
1:7.1 (Figure 8). Terminal 13C allyl chemical shifts are δ
) 94.0 (allyl carbon trans to P) and 78.0 (trans to N) for
19A (∆δ ) 26.0) and δ ) 103.7 (allyl carbon trans to P)
and 66.3 (trans to N) for 19B (∆δ ) 37.4) (Table 5). Again,
13C chemical shifts of C1 for 18 and 19 showed that both
18B and 19B were more reactive species compared with
that of 18A and 19A (Table 5). The fact that the major
component 19B is the more reactive one suggested that
19 should be a better catalyst than complex 18, giving
high enantioselectivity.
P,N-ligands with only planar chirality (Sp)-11a -c
showed moderate enantioselectivity in both allylic alky-
lation and amination reaction. (Sp)-11a with two H-
atoms on the oxazoline gave highest enantioselectivity.
For complex 20 there are two isomers in a ratio of 2.8:1.
Terminal 13C allyl chemical shifts are δ ) 100.7 (allyl
carbon trans to P) and 71.1 (trans to N) for the major
component (∆δ ) 29.6) and δ ) 96.3 (allyl carbon trans
to P) and 75.5 (trans to N) for the minor one (∆δ ) 20.8),
suggesting that the major component has a higher
reactivity. When the product of the allylic alkylation was
in theR configuration, the major component was assigned
as W type (exo-syn-syn) which is just the same as the
structure of the X-ray.
4690 J . Org. Chem., Vol. 67, No. 14, 2002

Palladium-Catalyzed Allylic Substitutions
1
0.26 in CHCl3); H NMR δ 7.07-7.19 (m, 5H), 4.88 (m, 1H),
Con clu sion
4.39-4.40 (m, 2H), 4.28 (s, 5H), 4.27-4.30 (m, 1H), 3.93-4.02
(m, 2H), 1.79 (m, 1H), 0.93 (d, J ) 6.8 Hz, 3H), 0.83 (d, J )
6.8 Hz, 3H); MS (EI) m/z 405 (M+, 27), 361 (5), 263 (14), 121
(10); IR (KBr, cm-1) 2964 (w), 1658 (s), 1480 (m), 1147 (m),
981 (m). Anal. Calcd for C22H23FeNOS: C, 65.19; H, 5.72; N,
3.46. Found: C, 65.18; H, 5.62; N, 3.46.
High enantioselectivity was obtained in palladium-
catalyzed allylic alkylation and amination reactions by
thioether and phosphino derivatives of ferrocenyloxazo-
lines with central and planar chiralities. The importance
of planar chirality in 1,2-disubstituted ferrocene systems
was showed both in alkylation and amination reactions.19
Newly formed central chirality on sulfur atom of ligands
5a and 5b during the complexation with palladium might
be the reason for their poor enantiocontrol. Compara-
tively higher enantioselectivities were obtained for P,N-
ligands (Sp)-11 with only planar chirality, since there was
no such disturbance. The matching of planar and central
chiralities is essential for excellent asymmetric induction
and the absolute configuration of the product are mainly
governed by the central chirality.
(S,Sp)-2-(p-Meth ylph en ylth io)-1-(4-isopr opyloxazolin yl)-
fer r ocen e (S,Sp)-6d . Similar procedures as for 6c (except for
being quenched with TolSSTol) give 6d in 76% yield (1 mmol
scale) as an orange solid: mp 69-70 °C; [R]20 ) -60 (c )
D
0.35 in CHCl3); 1H NMR δ 7.16 (d, J ) 8.1 Hz, 2H), 7.03 (d, J
) 8.4 Hz, 2H), 4.82-4.84 (m, 1H), 4.31-4.35 (m, 3H), 4.25 (s,
5H), 3.97-4.03 (m, 2H), 1.81 (m, 1H), 0.95 (d, J ) 6.8 Hz, 3H),
0.86 (d, J ) 6.8 Hz, 3H); MS (EI) m/z 419 (M+, 100), 375 (4),
263 (16), 177 (10), 121 (16); IR (KBr, cm-1) 2960 (w), 1659 (s),
1492 (m), 1147 (w), 977 (m). Anal. Calcd for C23H25FeNOS:
C, 65.87; H, 6.01; N, 3.34. Found: C, 66.03; H, 5.95; N, 3.15.
(S ,S p )-2-(P h e n y lt h i o )-1-(4-b e n z y lo x a z o li n y l)fe r -
r ocen e (S,Sp)-6e. Similar procedures as for 6c (except for
being quenched with PhSSPh) give 6e in 76% yield (1 mmol
scale) as a red oil: [R]20D ) +119 (c ) 1.13 in CHCl3); 1H NMR
δ 7.18-7.30 (m, 10H), 4.89 (m, 1H), 4.38-4.47 (m, 3H), 4.25
(s, 5H), 4.22-4.33 (m, 1H), 3.94-4.00 (m, 1H), 3.18 (dd, J )
4.6, 13.7 Hz, 1H), 2.61 (dd, J ) 8.9, 13.7 Hz, 1H); MS (EI) m/z
453 (M+, 100), 361 (24), 319 (20), 253 (27), 121 (39), 91 (50);
IR (KBr, cm-1) 3084 (w), 2924 (m), 1657 (s), 1478 (m), 1142
(m), 983 (s); HRMS calcd for C26H23FeNOS 453.0849, found
453.0816.
Exp er im en ta l Section
Gen er a l Meth od s. The commercially available reagents
were used as received without further purification. Chiral
amino alcohols were synthesized from the amino acids follow-
ing a standard procedure.38 PhSO2Me, PhSSPh, TolSSTol,39
[Pd(C3H5)Cl]2,40 [Pd(η3-PhCHCHCHPh)Cl]2,29 8b, 9b, 10b, 17,
18,22 11,24 23, and 24a 16a were prepared by using literature
procedures.
All reactions were performed under an atmosphere of either
argon or nitrogen using oven-dried glassware. Solvents were
treated prior to use according to the standard methods.
Melting points are uncorrected. 1H NMR spectra were recorded
in CDCl3 at room temperature. Chemical shifts are given in
parts per million relative to TMS as an internal standard.
Optical rotations were measured using a polarimeter with a
thermally jacketed 10 cm cell at 25 °C (concentration c given
as g/100 mL). IR spectra were measured in cm-1 Ee values
were determined by chiral HPLC on Chiracel OD and OJ
columns.
(S ,S p )-2-(P h e n y lt h io )-1-(4-p h e n y lo x a zo lin y l)fe r -
r ocen e (S,Sp)-6f. Similar procedures as for 6c (except for
being quenched with PhSSPh) give 6f in 57% yield (1 mmol
scale) as an orange solid: mp 72-73 °C; [R]20 ) -83 (c )
D
1
0.31 in CHCl3); H NMR δ 7.14-7.29 (m, 10H), 5.21 (dd, J )
8.2, 9.7 Hz, 1H), 4.96 (dd, J ) 1.5, 2.7 Hz, 1H), 4.70 (dd, J )
8.5, 9.9 Hz, 1H), 4.44-4.48 (m, 2H), 4.33 (s, 5H), 3.18 (t, J )
8.3 Hz, 1H); MS (EI) m/z 439 (M+, 100), 297 (20), 269 (31),
177 (38), 121 (56); IR (KBr, cm-1) 3081 (w), 2897 (w), 1653 (s),
1580 (m), 1477 (m), 1139 (m), 992 (s). Anal. Calcd for C25H21
-
FeNOS: C, 68.39; H, 4.78; N, 3.19. Found: C, 68.27; H, 4.99;
N, 3.17.
(S ,S p )-2-(Me t h ylt h io)-1-(4-isop r op yloxa zolin yl)fe r -
r ocen e (S,Sp)-6c. To a solution of [4-(S)-isopropyl-2-oxazoli-
nyl]ferrocene (311 mg, 1 mmol) in dry ether (15 mL) was added
TMEDA (0.2 mL, 1.3 mmol) at 25 °C. The resulting mixture
was cooled to -78 °C, and n-BuLi (0.8 mL, 1.6M in hexane,
1.3 mmol) was added dropwise and stirred for 2 h at this
temperature. The mixture was treated with PhSO2SMe (282
mg, 1.5 mmol) and stirred for another 1 h at rt. The reaction
mixture was diluted with Et2O and quenched with saturated
aqueous NaHCO3 solution. The organic layer was extracted
twice with Et2O. The combined organic layer was dried over
Na2SO4 and concentrated in vacuo to give the crude product,
which was purified by column chromatography (EtOAc/
petroleum ether ) 1/10) to give 6c (274 mg, 80%) as an orange
(S,Rp)-2-(p h e n ylt h io)-1-(4-isop r op yloxa zolin yl)fe r -
r ocen e 7a . To a solution of 2-(S,Sp)-(trimethylsilyl)-1-(4-
isopropyloxazolinyl)ferrocene (369 mg, 1 mmol) in dry ether
(15 mL) at 25 °C was added n-BuLi (0.8 mL, 1.6M in hexane).
The reaction mixture was stirred at the same temperature for
1 h before treatment with PhSSPh (327 mg, 1.5 mmol). After
usual workup and column chromatography (EtOAc/petroleum
ether ) 1/10), (S)-2-(Rp)-(phenylthio)-5-(Sp)-(trimethylsilyl)-
1-(4-isopropyloxazolinyl)ferrocene was given (334 mg, 76%) as
an orange solid: mp 93-94 °C; [R]20 ) -16 (c ) 0.20 in
D
CHCl3); 1H NMR δ 7.07-7.26 (m, 5H), 4.52 (d, J ) 2.5 Hz,
1H), 4.31 (d, J ) 2.5 Hz, 1H), 4.27 (s, 5H), 4.19-4.25 (m, 1H),
3.86-4.02 (m, 1H), 1.71 (m, 1H), 0.96 (d, J ) 6.7 Hz, 3H), 0.80
(d, J ) 6.7 Hz, 3H), 0.31 (s, 9H); MS (EI) m/z (rel intensity)
477 (M+, 100), 462 (47), 375 (17), 121 (11), 73 (13); IR (KBr,
cm-1) 2956 (m), 1651 (m), 1477 (m), 1168 (m), 992 (m). Anal.
Calcd for C25H31FeNOSSi: C, 62.88; H, 6.54; N, 2.93. Found:
C, 63.10; H, 6.62; N, 2.69.
solid: mp 83-84 °C; [R]20 ) -280 (c ) 0.21 in CHCl3); 1H
D
NMR δ 4.72 (dd, J ) 1.6, 2.6 Hz, 1H), 4.40 (dd, J ) 1.6, 2.4
Hz, 1H), 4.26-4.33 (m, 2H), 4.19 (s, 5H), 4.01-4.14 (m, 2H),
2.40 (s, 3H), 1.88 (m, 1H), 1.03 (d, J ) 6.8 Hz, 3H), 0.97 (d, J
) 6.8 Hz, 3H); MS (EI) m/z 343 (M+, 100), 328 (38), 300 (10),
242 (18), 190 (21), 121 (29); IR (KBr, cm-1) 2959 (w), 1660 (s),
1361 (w), 1147 (m), 977 (m). Anal. Calcd for C17H21FeNOS:
C, 59.48; H, 6.17; N, 4.08. Found: C, 59.44; H, 6.07; N, 3.88.
(S ,S p )-2-(P h e n ylt h io)-1-(4-isop r op yloxa zolin yl)fe r -
r ocen e (S,Sp)-6a . Similar procedures as for 6c (except for
being quenched with PhSSPh) give 6a in 93% yield (1 mmol
To a solution of (trimethylsilyl)-1-(4-isopropyloxazolinyl)-
ferrocene (477 mg, 1 mmol) in THF (5 mL) at 25 °C was added
tetrabutylammonium fluoride (5 mL, 1M in THF). The result-
ing reaction mixture was refluxed for 3 h. After usual workup
and column chromatography (EtOAc/petroleum ether ) 1/10),
scale) as an orange solid: mp 78-79 °C; [R]20 ) +69 (c )
D
title compound 7a was afforded (356 mg, 88%) as a red oil:
1
[R]20 ) - 252 (c ) 0.45 in CHCl3); H NMR δ 7.04-7.26 (m,
D
(38) Mckennon, M. J .; Meyers, A. I.; Drauz, K.; Schwarm, M. J . Org.
Chem. 1993, 58, 3568.
(39) (a) Hayashi, S.; Furukawa, M.; Yamamoto, J .; Niigata, K. Chem.
Pharm. Bull. 1967, 15, 1188. (b) Mikolajczyk, M.; Drabowicz, Synthesis
1980, 32.
5H), 4.94 (br, 1H), 4.47 (m, 1H), 4.44 (m, 1H), 4.29 (s, 5H),
4.19 (m, 1H), 4.08 (m, 1H), 3.98 (m, 1H), 1.75 (m, 1H), 0.88 (d,
J ) 6.8 Hz, 3H), 0.84 (d, J ) 6.8 Hz, 3H); MS (EI) m/z (rel
intensity) 405 (M+, 27), 253 (10), 177 (11), 121 (12); IR (KBr,
cm-1) 2958 (m), 1659 (s), 1479 (m), 1143 (w), 1002 (w), 983
(40) Dent, W. T.; Wilkinson, A. I. J . Chem. Soc. 1964, 1585.
J . Org. Chem, Vol. 67, No. 14, 2002 4691

You et al.
(m). Anal. Calcd for C22H23FeNOS: C, 65.19; H, 5.72; N, 3.46.
Found: C, 65.38; H, 5.63; N, 3.30.
perature over 7 h. The solution was washed with cold 3 N HCl
(3 ω 5 mL) and saturated NaHCO3 (5 mL). The organic layer
was dried, and the solvent was removed. The crude product
was purified by column chromatography (EtOAc/petroleum
ether ) 1/3) to afford (S,Sp)-[2′-(N-acetyl)amino-3′-methylbu-
tyl]-2-(phenylthio)ferrocene-1-carboxylate (82 mg, 88%) as a
yellow solid: mp 102-103 °C; [R]20D ) +37 (c ) 0.31 in CHCl3);
1H NMR δ 7.22 (d, J ) 7.7 Hz, 2H), 7.05-7.13 (m, 3H), 5.30
(br, 1H), 5.11 (m, 1H), 4.56-4.58 (m, 2H), 4.46 (dd, J ) 2.9,
11.4 Hz, 1H), 4.30 (s, 5H), 4.01 (dd, J ) 2.9, 11.4 Hz, 1H),
3.90 (m, 1H), 2.10 (m, 1H), 1.60 (s, 3H), 1.03 (d, J ) 6.7 Hz,
3H), 0.94 (d, J ) 6.71 Hz, 3H); MS (EI) m/z 465 (M+, 17), 338
(100), 292 (9), 200 (18), 171 (13); IR (KBr, cm-1) 3304 (m), 3084
(w), 2960 (w), 1726 (s), 1644 (s), 1479 (m), 1154 (m), 1004 (m).
Anal. Calcd for C24H27FeNOS: C, 61.94; H, 5.85; N, 3.01.
Found: C, 61.76; H, 5.88; N, 2.84.
1-P h en yl-2-a m in o-2-ben zylp r op a n ol 8. (1) N-[1-(Meth -
oxycar bon yl)-1-ben zyl-2-ph en yleth yl]ben zoph en on e Im i-
n e. A solution of KHMDS (8 mL, 1 M in THF, 8 mmol) was
added to the methyl 1-[N-(diphenylmethylene)]phenylalanate
(2.3 g, 6.7 mmol) in THF (35 mL) at -78 °C to give a red
solution that was allowed to stir for 1 h. BnBr (1.1 mL, 9 mmol)
was added, and the reaction mixture was allowed to warm to
rt and stir for 3 h. The resulting yellow solution was poured
into water (30 mL) and extracted with EtOAc (3 × 30 mL).
The combined organic extracts were washed with brine (30
mL), dried (Na2SO4), and filtered. The filtrate was concen-
trated to give the crude product, which was recrystallized from
EtOAc to give pure product (3.1 g, 72% yield) as a white solid:
mp 144-145 °C; 1H NMR δ 7.56-7.58 (m, 2H), 7.19-7.38 (m,
16H), 6.62-6.64 (m, 2H), 3.32 (dd, J ) 14.0, 19.9 Hz, 4H), 3.05
(s, 3H); MS (EI) m/z 434 (M+1, 5), 342 (100), 251 (35), 165
(52), 91 (50), 77 (6); IR (KBr, cm-1) 3055 (w), 2926 (w), 1730
(s), 1641 (m), 1494 (m), 1215 (m), 1087 (m), 698 (s). Anal. Calcd
for C30H27NO2: C, 83.21; H, 6.24; N, 3.23. Found: C, 82.95;
H, 6.11; N, 3.06.
(2) Met h yl (1-P h en yl-2-a m in o-2-b en zyl)p r op a n oa t e.
Hydrochloric acid (20 mL, 1 M, 20 mmol) was added dropwise
to a solution of benzophenone imine prepared in a previous
experiment (5.6 g, 12.9 mmol) in Et2O/CH2Cl2 (50 mL/10 mL)
at 0 °C, and the two-phase mixture was allowed to stir at rt
overnight. The aqueous layer was removed and washed with
CH2Cl2 (2 ω 15 mL). The combined organic layers were
extracted with 2 M hydrochloric acid (2 × 15 mL), and the
aqueous layers were combined and concentrated to give a solid
mass, which was dissolved in a saturated aqueous solution of
NaHCO3 (50 mL) and stirred for 30 min. The resulting
suspension was extracted with CH2Cl2 (4 × 20 mL). The
organic phase was combined, dried (Na2SO4), and filtered. The
filtrate was concentrated to give propanoate (2.3 g, 66% yield)
as a white solid: mp 72-73 °C; 1H NMR δ 7.16-7.31 (m, 10H),
3.66 (s, 3H), 3.37 (d, J ) 13.1 Hz, 2H), 2.85 (d, J ) 13.1 Hz,
2H), 1.55 (br, 2H); MS (EI) m/z 270 (M + 1, 7), 178 (100), 118
(69), 91 (96); IR (KBr, cm-1) 3381 (w), 3028 (w), 2931 (w), 1737
(s), 1494 (m), 1209 (m), 1177 (s), 1083 (s). Anal. Calcd for
(2) (Sp)-2-(P h en ylth io)-1-fer r ocen eca r boxylic Acid . A
solution of carboxylate obtained in the last step (70 mg, 0.15
mmol) in THF (4 mL) and water (3.5 mL) was treated with
aqueous 2.5 N NaOH solution (0.39 mL, 0.97 mmol) and heated
at 55 °C for 8 h. The mixture was cooled, and the THF was
removed in vacuo. The aqueous layer was extracted with
CHCl3 (2 × 10 mL), cooled in an ice bath, acidified (pH ∼1)
with 3 N HCl, and extracted with CH2Cl2 (2 × 10 mL). The
CH2Cl2 extract was dried (Na2SO4) and evaporated in vacuo.
The crude product was purified by column chromatography
(EtOAc/petroleum ether ) 1/2) to afford ferrocene carboxylic
acid (43 mg, 87%) as an orange crystalline solid: mp 115-
1
116 °C; [R]20 ) + 68 (c ) 0.29 in CHCl3); H NMR δ 7.14-
D
7.28 (m, 5H), 5.13 (dd, J ) 1.6, 2.7 Hz, 1H), 4.65 (dd, J ) 1.5,
2.5 Hz, 1H), 4.61 (dd, J ) 2.62.7 Hz, 1H), 4.30 (s, 5H); MS
(EI) m/z 338 (M+, 23), 258 (44), 200 (45), 171 (39), 121 (9); IR
(KBr, cm-1) 3150-2700 (s), 1739 (m), 1681 (s), 1457 (w), 1265
(m); HRMS calcd for C17H14FeNO2S 338.0064, found 338.0056.
(Sp)-2-(P h en ylth io)-1-(4, 4-d im eth yl)fer r ocen yloxa zo-
lin e 5b: A solution of (Sp)-ferrocene carboxylic acid (338 mg,
1 mmol) in 8 mL CH2Cl2 under argon was treated at ambient
temperature by dropwise addition of oxalyl chloride (0.17 mL,
2 mmol) via syringe. After about 0.5h, all gas evolution had
ceased, and the solvent was directly removed into a trap. After
drying for 2 h, the red solid was dissolved in 4 mL CH2Cl2
under argon, and the resulting solution was transferred via
cannula to a second Schlenk tube, which contained a solution
of 2-amino-2-methylpropanol (107 mg, 1.2 mmol) and triethy-
lamine (0.24 mL, 1.6 mmol) in 8 mL CH2Cl2. The resulting
mixture was allowed to stir at rt overnight and then quenched
with 20 mL of distilled water. The organic phase was sepa-
rated, and the aqueous phase was extracted twice with 10 mL
CH2Cl2. After the combined organic phases were dried over
Na2SO4, the solvent was removed in vacuo. The crude product
was purified by column chromatography (EtOAc/Petroleum
ether ) 1/1) to afford the corresponding amide (342 mg, 84%)
C
17H19NO2: C, 75.90; H, 7.06; N, 5.20. Found: C, 75.75; H,
7.13; N, 5.03.
(3) 1-P h en yl-2-a m in o-2-ben zylp r op a n ol 8. A solution of
propanoate obtained from the last procedure (1.88 g, 7 mmol)
in Et2O (30 mL) was added to a solution of lithium aluminum
hydride (1.33 g, 35 mmol) in Et2O (15 mL) at such a rate as to
maintain gentle reflux. The reaction mixture was then stirred
at rt overnight, cooled to 0 °C, and quenched by cautious
addition of water (1.6 mL), followed by 15% aqueous NaOH
solution (1.6 mL) and finally water (4.8 mL). The mixture was
allowed to stir for 2 h and filtered, and the salts were washed
with Et2O. The Et2O fractions were combined, dried (Na2SO4),
and concentrated to give aminopropanol 8 (1.5 g, 89%) as a
white solid: mp 134-135 °C; 1H NMR δ 7.13-7.25 (m, 10H),
3.19 (s, 2H), 2.73 (dd, J ) 13.3, 19.5 Hz, 4H), 2.08 (br, 3H);
MS (EI) m/z 242 (M+1, 2), 210 (32), 150 (100), 91 (88); IR (KBr,
cm-1) 3341 (w), 3155 (s), 1577 (s), 1167 (m), 1064 (s). Anal.
Calcd for C16H19NO: C, 79.73; H, 7.88; N, 5.81. Found: C,
79.38; H, 7.88; N, 5.56.
(Sp)-2-(P h en ylth io)-1-(4, 4-d im eth yl)fer r ocen yloxa zo-
lin e (Sp)-5b. 1) (S,Sp)-[2′-(N-Acetyl)a m in o-3′-m eth ylbu -
tyl]-2-(p h en ylth io)fer r ocen e-1-ca r boxyla te. A solution of
6a (81 mg, 0.2 mmol) in THF (22 mL) was treated with
powdered Na2SO4 (1.48 g, 10 mmol), water (0.2 mL, 11 mmol),
and trifluoroacetic acid (0.08 mL, 1 mmol). The suspension was
stirred for 12 h, and anhydrous Na2SO4 (0.4 g, 2.8 mmol) was
added. Filtration and concentration at <30 °C afforded the
unstable ammonium salt, which was dissolved in CH2Cl2 (4
mL), cooled in an ice bath, and treated sequentially with acetic
anhydride (0.7 mL, 7 mmol) and pyridine (1.1 mL, 14 mmol).
The reaction mixture was allowed to warm to ambient tem-
20
as an orange solid: mp 123-124 °C; [R]D ) + 60.2 (c ) 0.31
1
in CHCl3); H NMR δ 7.95 (s, 1H), 7.02-7.27 (m, 5H), 5.18-
5.19 (m, 1H), 4.60-4.61 (m, 1H), 4.56-4.58 (m, 1H), 4.31 (s,
5H), 4.01 (br, 1H), 3.55 (dd, J ) 12.0, 19.5 Hz, 2H), 1.31 (s,
3H), 1.09 (s, 3H); MS (EI) m/z 409 (M+, 30), 408 (M-1, 100),
321 (48), 292 (19), 195 (13), 121 (14); IR (KBr, cm-1) 3299 (s),
2966 (w), 1627 (s), 1545 (s), 1476 (m), 1077 (m), 1026 (m). Anal.
Calcd for C21H23FeNO2S: C, 61.62; H, 5.66; N, 3.42. Found:
C, 61.47; H, 5.51; N, 3.28. To a solution of the above amide
(345 mg, 0.6 mmol) in 5 mL of CH2Cl2 were added TsCl (191
mg, 1 mmol), triethylamine (0.14 mL, 1 mmol), and a catalytic
amount of DMAP. Then the reaction mixture was allowed to
stir at rt overnight. After complete conversion of the amide,
the reaction was quenched with 20 mL of distilled water. The
organic phase was separated, and the aqueous phase was
extracted twice with 10 mL CH2Cl2. After the combined organic
phases were dried over Na2SO4, the solvent was removed in
vacuo. The crude product was purified by column chromatog-
raphy (EtOAc/Petroleum ether ) 1/10) to afford the title
compound (217 mg, 92%) as an orange solid: mp 105-106 °C;
4692 J . Org. Chem., Vol. 67, No. 14, 2002

Palladium-Catalyzed Allylic Substitutions
1
[R]20 ) +340 (c ) 0.36 in CHCl3); H NMR δ 7.09-7.19 (m,
was neutralized with methanolic acetic acid, and the solvent
was removed by evaporation in vacuo. The residue was
dissolved in dichloromethane, and the resulting solution was
washed with water and then with brine and dried over MgSO4.
After removal of the solvent, the residue was purified by
column chromatography with ethyl acetate/petroleum (1:20)
as an eluent to afford 2-(diphenylphosphino)-1-ferrocenecar-
boxylate as an orange solid (402 mg, 94%): mp 206-207 °C;
D
5H), 4.97 (m, 1H), 4.43-4.44 (m, 2H), 4.29 (s, 5H), 4.07 (d, J
) 8.0 Hz, 1H), 3.86 (d, J ) 8.0 Hz, 1H), 1.31 (s, 3H), 1.28 (s,
3H); MS (EI) m/z 391 (M+, 34), 319 (32), 249 (12), 177 (13),
121 (32); IR (KBr, cm-1) 2959 (w), 1636 (s), 1581 (m), 1481
(m), 1284 (m), 1122 (s), 1059 (m). Anal. Calcd for C21H21
FeNOS: C, 64.46; H, 5.41; N, 3.58. Found: C, 64.50; H, 5.21;
N, 3.46.
-
[R]20 ) -251.0° (c ) 0.33 in CHCl3); 1H NMR δ 7.48-7.50
D
(Sp)-2-(P h en ylth io)-1-fer r ocen yloxa zolin e 5a . Following
the procedure of synthesis 5b as above by using corresponding
amino alcohol give 5a (63% yield for over two steps) as an
orange solid: mp 136-137 °C; [R]20D ) +36 (c ) 0.23 in CHCl3);
1H NMR δ 7.10-7.23 (m, 5H), 4.91 (m, 1H), 4.42-4.46 (m, 2H),
4.29 (s, 5H), 4.25-4.36 (m, 2H), 3.87-3.95 (m, 2H); MS (EI)
(m, 2H), 7.36-7.38 (m, 3H), 7.20-7.25 (m, 5H), 5.05 (m, 1H),
4.44 (t, J ) 2.5 Hz, 1H), 4.22 (s, 5H), 3.72 (m, 1H), 3.69 (s,
3H); 31P NMR (161.92 MHz, CDCl3) δ -16.36. MS m/z 428 (M+,
100), 413 (36), 385 (71), 275 (6), 229 (8); IR (KBr) 3065 (w),
2950 (w), 1707 (s), 1447 (m), 1254 (s), 1162 (s), 746 (m). Anal.
Calcd for C24H21O2PFe: C, 67.35; H, 4.91. Found: C, 67.37;
H, 4.85.
m/z 363 (M+, 25), 222 (13), 177 (19), 121 (13); IR (KBr, cm-1
)
2964 (w), 1658 (s), 1479 (m), 1142 (m), 987 (s); HRMS calcd
for C19H17FeNOS 363.0383, found 363.0380.
(3) (Sp)-1-[N-(2′-Hydr oxyeth yl)am ido]-2-(diph en ylph os-
p h in o)fer r ocen e. A mixture of 2-(diphenylphosphino)-1-
ferrocenecarboxylate (86 mg, 0.2 mmol), 2 mL of 2-aminoet-
hanol, and a small amount of sodium was heated at 100 °C
for 1 h. The mixture was diluted with dichloromethane and
neutralized with acetic acid. The neutralized solution was
washed with water and then with brine and dried over Na2-
SO4. After removal of the solvent, the residue was purified by
column chromatography with ethyl acetate/petroleum (1:2) as
an eluent to afford compound (Sp)-1-[N-(2′-hydroxyethyl)-
amido]-2-(diphenylphosphino)ferrocene as a yellow solid (97
(Sp)-2-(P h en ylth io)-1-(4, 4-diben zyloxazolin yl)fer r ocen e
5c. The corresponding amide was synthesized following a
procedure similar to that for the synthesis of 5b (1 mmol scale)
by using amino alcohol 8. The crude amide was dissolved in
20 mL of acetonitrile. To this solution were added PPh3 (1.57
g, 6 mmol), Et3N (0.65 mL, 5 mmol), and CCl4 (1.45 mL, 15
mmol), and the mixture was stirred overnight. The deep red
solution was worked up with 100 mL of distilled water. This
mixture was extracted with hexane until the organic layer
showed no orange color. The combined organic phases were
dried over Na2SO4, and the solvent was removed in vacuo. The
crude product was purified by column chromatography (EtOAc/
petroleum ether ) 1/10) to afford the title compound (341 mg,
mg, 92%): mp 73-75 °C; [R]20 ) -223.2 (c ) 0.65 in CHCl3);
D
1H NMR δ 7.15-7.58 (m, 11H), 5.15-5.16 (m, 1H), 4.48 (t, J
) 2.6 Hz, 1H), 4.14 (s, 5H), 3.83 (m, 1H), 3.63-3.68 (m, 2H),
3.48-3.51 (m, 2H), 2.79 (br, 1H); 31P NMR (161.92 MHz,
CDCl3) δ -20.07; MS m/z 457 (M+, 25), 392 (100), 374 (39),
361 (21), 201 (15), 121 (4); IR (KBr) 3318 (s), 2924 (w), 1628
(s), 1533 (s), 1433 (m), 1273 (m), 1068 (m); HRMS calcd for
62%) as an orange solid: mp 115-116 °C; [R]20 ) +186 (c )
0.48 in CHCl3); H NMR δ 7.05-7.23 (m, 15H), 4.76 (m, 1H),
4.37-4.41 (m, 2H), 4.09 (dd, J ) 8.6, 16.1 Hz, 1H), 3.99 (s,
5H), 3.06 (dd, J ) 13.8, 19.5 Hz, 1H), 2.80 (dd, J ) 13.7, 15.4
Hz, 1H); MS (EI) m/z 543 (M+, 47), 452 (58), 361 (13), 121 (22),
91 (100); IR (KBr, cm-1) 3083 (w), 2919 (w), 1656 (s), 1477
(m), 1026 (s). Anal. Calcd for C33H29FeNOS: C, 72.99; H, 5.34;
N, 2.58. Found: C, 72.90; H, 5.28; N, 2.63.
D
1
C
25H24NO2PFe 457.08934, found 457.08998.
(4) (Sp)-2-(Dip h en ylp h osp h in o)-1-fer r ocen yloxa zolin e
(Sp)-11a . To a solution of (Sp)-1-[N-(2′-hydroxyethyl)amido]-
2-(diphenylphosphino)ferrocene (137 mg, 0.3 mmol) and tri-
ethylamine (0.23 mL, 1.5 mmol) in dichloromethane (3 mL)
was added methanesulfonyl chloride (0.02 mL, 0.3 mmol) at 0
°C. After being stirred at rt for 5 h, the reaction solution was
washed with distilled water (10 mL) and then with brine, dried
over Na2SO4, and concentrated under reduced pressure to
provide a residue that was purified by column chromatography
with ethyl acetate/petroleum (1:5) as an eluent to afford (Sp)-
(Sp)-2-(Diph en ylph osph in o)-1-fer r ocen yloxazolin e 11a.
(1)
(S,Sp )-[2′-(N-Acet yl)a m in o-3′,3′-d im et h ylb u t yl]-2-
(d ip h en ylp h osp h in o)-1-fer r ocen eca r boxyla te. A solution
of (S,Sp)-9 (1.98 g, 4 mmol) in THF (40 mL) was treated with
powdered Na2SO4 (29 g, 60 mmol), water (4 mL, 220 mmol),
and CF3COOH (1.74 mL, 22 mmol), The suspension was
stirred for 3 d, and anhydrous Na2SO4 (8.4 g, 60 mmol) was
added. Filtration and concentration at <30 °C afforded the
unstable ammonium salt, which was dissolved in CH2Cl2 (70
mL), cooled in an ice bath, and treated sequentially with acetic
anhydride (14 mL, 15 mmol) and pyridine (22 mL, 27 mmol).
The reaction mixture was allowed to warm to ambient tem-
perature over 7 h. The solution was washed with cold 3 N HCl
(3 ω 100 mL) and saturated NaHCO3 (100 mL). The organic
layer was dried and condensed. The crude product was purified
by column chromatography (EtOAc/petroleum ether ) 1/3) to
afford [2′-(N-Acetyl)amino-3′,3′-dimethylbutyl]-2-(diphenylphos-
phino)-1-ferrocenecarboxylate (1.40 g, 63%) as a yellow solid:
11a as a yellow solid (112 mg, 85%): mp 177-178 °C; [R]20
D
) -65.0 (c ) 0.45 in CHCl3); 1H NMR δ 7.18-7.52 (m, 10 H),
4.99 (m, 1 H), 4.39 (t, J ) 2.6 Hz, 1 H), 4.29 (dt, J ) 10.2, 8.0
Hz, 1 H), 4.19 (s, 5 H), 4.04 (dd, J ) 9.5, 17.5 Hz, 1 H), 3.75-
3.87 (m, 2 H), 3.68 (m, 1 H); 31P NMR (161.92 MHz, CDCl3) δ
-17.27; MS m/z 439 (M+, 100), 410 (60), 362 (26), 348 (19),
183 (9); IR (KBr) 2877 (w), 1658 (m), 1639 (s), 1432 (m), 1257
(w), 1122 (m), 699 (s). Anal. Calcd for C25H22NOPFe: C, 68.39;
H, 5.01; N, 3.19. Found: C, 68.11; H, 4.98; N, 3.17.
(Sp )-2-(Dip h en ylp h osp h in o)-1-(4,4-d ib en zyloxa zoli-
n yl)fer r ocen e 11c. (1) (Sp)-2-Iod in e-1-(4,4-d iben zylox-
a zolin yl)fer r ocen e. A solution of (Sp)-2-iodine-1-ferrocen-
ecarboxylic acid (356 mg, 1 mmol) in 8 mL of CH2Cl2 under
argon was treated at ambient temperature by dropwise
addition of oxalyl chloride (0.17 mL, 2 mmol) via syringe. After
about 0.5 h, all gas evolution had ceased, and the solvent was
directly removed into a trap. After drying for 2 h, the red solid
was dissolved in 4 mL of CH2Cl2 under argon, and the resulting
solution was transferred via cannula to a second Schlenk tube,
which contained a solution of amino alcohol 8 (289 mg, 1.2
mmol) and Et3N (0.24 mL, 1.6 mmol) in 8 mL of CH2Cl2. The
resulting mixture was allowed to stir at rt overnight and then
quenched with 20 mL of distilled water. The organic phase
was separated, and the aqueous phase was extracted twice
with 10 mL of CH2Cl2. After the combined organic phases were
dried over Na2SO4, the solvent was removed in vacuo. The
crude product was used without purification. The crude amide
mp 188-189 °C dec; [R]20 ) -231 (c ) 0.33 in CHCl3); 1H
D
NMR δ 7.52 (m, 2H), 7.39-7.41 (m, 3H), 7.22-7.24 (m, 3H),
7.14-7.15 (m, 2H), 5.92 (d, J ) 9.4 Hz, 1H), 5.08 (m, 1H), 4.64
(dd, J ) 6.8, 11.5 Hz, 1H), 4.48 (t, J ) 2.6 Hz, 1H), 4.17 (s,
5H), 4.09 (m, 1H), 3.95 (dd, J ) 4.0, 11.5 Hz, 1H), 3.80 (m,
1H), 1.74 (s, 3H), 1.01 (s, 9H); MS (EI) m/z 555 (M+, 100), 490
(14), 414 (73), 369 (51), 213 (26); IR (KBr, cm-1) 3332 (m), 3057
(w), 2966 (m), 1702 (s), 1652 (s), 1434 (m), 1254 (s), 1165 (s),
696 (m). Anal. Calcd for C31H34FeNO3P: C, 67.00; H, 6.13; N,
2.52. Found: C, 66.57; H, 6.23; N, 2.32.
(2) (Sp)-Meth yl 2-(Dip h en ylp h osp h in o)-1-fer r ocen e-
ca r boxyla te. To a solution of 2-(diphenylphosphino)-1-fer-
rocenecarboxylate prepared above (555 mg, 1.0 mmol) in THF
(15 mL) was added a sodium methoxide solution prepared from
sodium metal (1.0 g, 46 mmol) and 50 mL of methanol/THF
(v/v 40:10). After being stirred for 2 h at 55 °C, the mixture
J . Org. Chem, Vol. 67, No. 14, 2002 4693

You et al.
was dissolved in 20 mL of acetonitrile. To this solution were
added PPh3 (0.78 g, 3 mmol), Et3N (0.32 mL, 2.5 mmol), and
CCl4 (0.72 mL, 7.5 mmol) subsequently, and the mixture was
stirred overnight. The deep red solution was worked up with
100 mL of distilled water. This mixture was extracted with
hexane until the organic layer showed no orange color. The
combined organic phases were dried over Na2SO4, the solvent
was removed in vacuo. The crude product was purified by
column chromatography (EtOAc/petroleum ether ) 1:10) to
(3.1/1), major, δ 7.64 (d, J ) 6.8 Hz, 2 H), 7.23-7.50 (m, 5H),
7.49 (t, J ) 7.3 Hz, 1H), 7.40 (t, J ) 7.9 Hz, 2H), 7.17 (t, J )
7.3 Hz, 1H), 6.97 (t, J ) 7.9 Hz, 2H), 6.81 (d, J ) 7.2 Hz, 2H),
6.34 (dd, J 1 ) 10.6 Hz; J 2 ) 13.1 Hz, 1H), 5.58 (d, J ) 13.1
Hz, 1H), 4.82 (dd, J 1 ) 1.4 Hz; J 2 ) 2.6 Hz, 1H), 4.50 (t, J )
2.7 Hz, 1H), 4.31 (dd, J ) 3.5, 9.4 Hz, 1H), 4.21 (dd, J ) 1.5,
2.6 Hz, 1H), 4.14 (s, 5H), 3.85 (d, J ) 11.9 Hz, 1H), 3.83 (t, J
) 9.4 Hz, 1H), 2.08 (dd, J ) 3.4, 9.4 Hz, 1H), 0.84 (s, 9H);
minor, δ 7.56 (d, J ) 7.1 Hz, 2 H), 7.23-7.50 (m, 5H), 7.35
(dd, J ) 7.2, 9.1 Hz, 2H), 7.25-7.30 (m, 1H), 7.20-7.24 (m,
1H), 7.09 (d, J ) 7.3 Hz, 2H), 7.01 (t, J ) 7.9 Hz, 2H), 6.32
(dd, J ) 11.7, 13.1 Hz, 1H), 5.07 (d, J ) 12.3 Hz, 1H), 4.81 (d,
J ) 11.2 Hz, 1H), 4.75 (m, 1H), 4.48 (t, J ) 2.7 Hz, 1H), 4.28
(m, 1H), 4.24 (dd, J ) 3.2, 10.1 Hz, 1H), 4.02 (s, 5H), 3.51 (t,
J ) 9.3 Hz, 1H), 2.71 (dd, J ) 3.3, 9.3 Hz, 1H), 1.07 (s, 9H);
13C NMR (CD2Cl2, 100 MHz) major isomers, δ 94.2 (allyl trans
to S), 108.6 (central allyl), 76.5 (allyl trans to N); minor
isomers, δ 86.5 (allyl trans to S), 107.0 (central allyl), 83.8 (allyl
trans to N); MS (EI) m/z (rel intensity) 419 (100), 362 (43),
253 (39), 121 (42), 91 (13); IR (KBr, cm-1) 2965 (w), 1627 (s),
1487 (m), 1256 (m), 1172 (m), 1028 (w), 656 (s). Anal. Calcd
for C38H38F6NOSSbFePd: C, 47.80; H, 3.98; N, 1.47; S, 3.36.
Found: C, 47.69; H, 3.88; N, 1.44; S, 3.46.
afford the title compound (415 mg, 73%) as an orange solid:
1
mp 45-46 °C; [R]20 ) + 0.4 (c ) 0.62 in CHCl3); H NMR δ
D
7.19-7.36 (m, 10H), 4.57 (m, 1H), 4.52 (m, 1H), 4.28 (t, J )
2.6 Hz, 1H), 4.15 (s, 5H), 3.90 (s, 5H), 3.17 (t, J ) 13.7 Hz,
1H), 2.91 (d, J ) 5.0 Hz, 1H), 2.86 (d, J ) 4.9 Hz, 1H); MS
(EI) m/z 561 (M+, 28), 470 (39), 342 (100), 209 (8), 91 (82); IR
(KBr, cm-1) 3027 (w), 2916 (m), 1658 (s), 1454 (m), 1107 (m),
987 (m), 701 (s). Anal. Calcd for C27H24FeNOI: C, 57.80; H,
4.28; N, 2.50. Found: C, 57.86; H, 4.36; N, 2.35.
(2) (Sp)-2-(Dip h en ylp h osp h in o)-1-(4,4-d iben zyloxa zoli-
n yl)fer r ocen e 11c. 2-Iodine-1-(4,4-dibenzyloxazolinyl)fer-
rocene (561 mg, 1 mmol) was dissolved in 15 mL of dry diethyl
ether and cooled to -78 °C. n-BuLi (0.7 mL, 1.6 M in n-hexane,
1.1 mmol) was added at this temperature. The resulting
mixture was stirred for 2 h, and chlorodiphenylphosphine (0.22
mL, 1.3 mmol) was added. The reaction mixture was allowed
to warm to rt for 2 h, and the reaction solution was washed
with distilled water (10 mL) and then with brine, dried over
Na2SO4, and concentrated under reduced pressure to provide
a residue that was purified by column chromatography with
ethyl acetate/petroleum (1:10) as an eluent to afford (Sp)-11c
[(S,Rp )-2-(P h en ylt h io)-1-(4-ter t-b u t yloxa zolin yl)fer -
r ocen e]-(η3-tr a n s-1, 3-d ip h en yla llyl)p a lla d iu m Hexa flu o-
r oa n tim on a te 16. Similar procedures as for 15 from (S,Rp)-
7b give complex 16 in 94% yield (0.4 mmol scale) as an orange
1
solid: mp 248 °C dec; [R]20 ) +333 (c ) 0.58 in CHCl3); H
D
NMR (CD2Cl2, 400 MHz) two isomers (2.2/1), major, δ 6.99-
7.82 (m, 14H), 6.83 (t, J ) 11.7 Hz, 1H), 5.21 (d, J ) 11.9 Hz,
1H), 5.06 (dd, J ) 1.5, 2.6 Hz, 1H), 4.97 (d, J ) 11.5 Hz, 1H),
4.80 (m, 2H), 4.45 (s, 5H), 4.20 (dd, J ) 3.1, 12.7 Hz, 1H), 3.57
(t, J ) 9.3 Hz, 1H), 2.68 (dd, J ) 3.1, 9.1 Hz, 1H), 0.61 (s, 9H);
minor, δ 6.99-7.82 (m, 13H), 6.77 (dd, J ) 11.0, 12.9 Hz, 1H),
6.08-6.10 (m, 2H), 5.67 (d, J ) 12.8 Hz, 1H), 5.17 (dd, J )
1.5, 2.8 Hz, 1H), 5.06 (d, J ) 10.7 Hz, 1H), 4.96-4.97 (m, 1H),
4.88 (dd, J ) 2.7, 2.9 Hz, 1H), 4.66 (s, 5H), 4.22 (dd, J ) 3.1,
10.0 Hz, 1H), 3.96 (t, J ) 9.2 Hz, 1H), 2.17 (dd, J ) 3.1, 9.0
Hz, 1H), 0.28 (s, 9H); 13C NMR (CD2Cl2, 100 MHz) major
isomers, δ 86.8 (allyl trans to S), 107.0 (central allyl), 81.9 (allyl
trans to N); minor isomers, δ 92.2 (allyl trans to S), 105.5
(central allyl), 75.3 (allyl trans to N); MS (EI) m/z (rel intensity)
as a yellow solid (192 mg, 31%): mp 150-151 °C; [R]20
)
D
1
-31.0 (c ) 0.42 in CHCl3); H NMR δ 6.93-7.48 (m, 20 H),
4.77 (m, 1H), 4.29 (t, J ) 2.4 Hz, 1H), 4.00 (d, J ) 8.5 Hz,
1H), 3.93 (s, 5H), 3.87 (d, J ) 8.4 Hz, 1H), 3.61 (m, 1H), 2.87
(d, J ) 13.5 Hz, 1H), 2.80 (s, 2H), 2.65 (d, J ) 13.5 Hz, 1H);
31P NMR (161.92 MHz, CDCl3) δ -17.33; MS m/z 619 (M+, 73),
528 (53), 450 (22), 410 (30), 343 (100), 121 (20); IR (KBr) 2911
(w), 1655 (s), 1433 (m), 1126 (m), 986 (m), 699 (s). Anal. Calcd
for C39H34NOPFe: C, 75.67; H, 5.49; N, 2.26. Found: C, 75.48;
H, 5.32; N, 2.12.
(Sp)-2-(Diph en ylph osph in o)-1-(4,4-dim eth yloxazolin yl)-
fer r ocen e 11b . (Sp)-2-Iodine-1-(4,4-methyloxazolinyl)-fer-
rocene (409 mg, 1 mmol) was dissolved in 15 mL of dry diethyl
ether and cooled to -78 °C. n-BuLi (0.7 mL, 1.6 M in n-hexane,
1.1 mmol) was addedat this temperature. The resulting
mixture was stirred for 2 h, and chlorodiphenylphosphine (0.22
mL, 1.3 mmol) was added. The reaction mixture was allowed
to warm to rt for 2 h, and the reaction solution was washed
with distilled water (10 mL) and then with brine, dried over
Na2SO4, and concentrated under reduced pressure to provide
a residue that was purified by column chromatography with
ethyl acetate/petroleum (1:10) as an eluent to afford compound
419 (100), 362 (26), 193 (96), 186 (16), 121 (42); IR (KBr, cm-1
)
2957 (w), 1626 (s), 1486 (m), 1181 (m), 988 (m), 657 (s). Anal.
Calcd for C38H38F6NOSSbFePd: C, 47.80; H, 3.98; N, 1.47; S,
3.36. Found: C, 47.64; H, 4.17; N, 1.30; S, 3.53.
[(Sp )-2-(P h en ylt h io)-1-(4, 4-d ib en zyloxa zolin yl)fer -
r ocen e]-(η3-tr a n s-1, 3-d ip h en yla llyl)p a lla d iu m Hexa flu o-
r oa n tim on a te 17. By using (Sp)-5c and similar procedures
as for 15 give the title compound in 94% yield (0.4 mmol scale)
as a red solid. After slowly crystallized from hexane/dichlo-
romethane/ethyl acetyl ester give 30‚EtOAc as a dark-red
11b as a yellow solid (296 mg, 63%): mp 127-128 °C; [R]20
crystal: mp136-138 °C; [R]20 ) +16.5 (c ) 0.41 in CHCl3);
D
D
) +81.6 (c ) 0.57 in CHCl3); 1H NMR δ 7.21-7.51 (m, 10 H),
5.02 (m, 1H), 4.37 (t, J ) 2.5 Hz, 1H), 4.22 (s, 5H), 3.99 (d, J
) 8.0 Hz, 1H), 3.61 (m, 1H), 3.50 (d, J ) 8.0 Hz,1H), 1.20 (s,
3H), 1.15 (s, 3H); 31P NMR (161.92 MHz, CDCl3) δ -15.73;
MS m/z 467 (M+, 96), 411 (100), 409 (93), 318 (35), 121 (33);
IR (KBr) 2964 (w), 1649 (s), 1434 (m), 1115 (m), 698 (s). Anal.
Calcd for C27H26NOPFe: C, 69.44; H, 5.57; N, 3.00. Found:
C, 69.08; H, 5.66; N, 2.88.
1H NMR (CD2Cl2, 400 MHz) δ 7.19-7.67 (m, 27H), 6.55 (m,
1H), 4.76 (br, 1H), 4.61-4.63 (m, 2H), 4.34 (s, 5H), 4.22 (d, J
) 9.3 Hz, 1H), 4.07 (d, J ) 9.6 Hz, 1H), 4.07 (q, J ) 7.2 Hz,
2H), 3.00 (br, 1H), 2.61 (br, 2H), 2.38 (br, 1H), 1.99 (s, 1H),
1.21 (t, J ) 7.2 Hz, 3H); 13C NMR (CD2Cl2, 100 MHz) major
isomers, δ 171.5, 135.9, 131.4, 131.0, 130.8, 130.7, 129.5, 129.4,
128.1, 106.1, 78.1, 77.8, 74.6, 73.4, 73.2; MS (EI) m/z (rel
intensity) 753 (23), 543 (72), 452 (61), 218 (100), 91 (60); IR
(KBr, cm-1) 3028 (w), 1727 (m), 1612 (s), 1479 (m), 1251 (m),
657 (s). Anal. Calcd for C48H42F6NOSSbFePd‚EtOAc: C, 53.52;
H, 4.29; N, 1.20; S, 2.74. Found: C, 53.27; H, 4.32; N, 1.20; S,
2.81.
[(S,Sp )-2-(P h en ylt h io)-1-(4-ter t-b u t yloxa zolin yl)fer -
r ocen e]-(η3-tr a n s-1,3-d ip h en yla llyl)p a lla d iu m Hexa flu o-
r oa n tim on a te 15. To a solution of 1,3-diphenylallylpalladium
chloride dimmer (134 mg, 0.2 mmol) and 6b (168 mg, 0.4
mmol) in MeOH/CH2Cl2 (v/v 1:1, 10 mL) was added silver
hexafluoroantimonate (137 mg, 0.4 mmol) at rt in the absence
of light. After 2 h, the reaction mixture was filtered through
a 2-cm plug of Celite and washed with MeOH/CH2Cl2 (v/v 1:1).
The filtrate was concentrated in vacuo to give Pd complex 15
[(S,Sp)-2-(Diphenylphosphino)-1-(4-tert-butyloxazolinyl)-
fe r r o c e n e ]-(η3 -t r a n s -1,3-d i p h e n y la lly l)p a lla d i u m
Hexa flu or oa n tim on a te 18. Similar procedures as for 15 give
the title compound in 96% yield (0.4 mmol scale) as an orange
1
solid: mp 256-258 °C; [R]20 ) -186 (c ) 0.48 in CHCl3); H
D
(366 mg, 96%) as a red crystal: mp 238 °C dec; [R]20 ) +63
NMR (CD2Cl2, 400 MHz) two isomers (8.8/ 1), major, δ 6.70-
7.72 (m, 20H), 6.47 (dd, J ) 10.9, 13.5 Hz, 1H), 5.84 (dd, J )
D
(c ) 0.15 in CHCl3); 1H NMR (CD2Cl2, 400 MHz) two isomers
4694 J . Org. Chem., Vol. 67, No. 14, 2002

Palladium-Catalyzed Allylic Substitutions
8.1, 14.0 Hz, 1H), 5.15 (s, 1H), 4.83 (s, 1H), 4.51 (s, 1H), 4.36
(dd, J ) 3.7, 9.2 Hz, 1H), 4.01 (t, J ) 9.4 Hz, 1H), 3.71 (s, 5H),
3.44 (d, J ) 10.3 Hz, 1H), 2.60 (dd, J ) 3.2, 9.3 Hz, 1H), 0.87
(s, 9H); minor, δ 6.70-8.12 (m, 20H), 6.41 (dd, J ) 7.6, 11.9
Hz, 1H), 6.14 (t, J ) 11.9 Hz, 1H), 5.17 (m, 1H), 5.07 (d, J )
7.6 Hz, 1H), 5.05 (s, 1H), 4.74 (m, 1H), 4.33-4.38 (m, 1H), 3.78
(s, 5H), 3.59 (t, J ) 9.3 Hz, 1H), 3.15 (dd, J ) 3.2, 9.3 Hz, 1H),
1.11 (s, 9H); 31P NMR (161.92 MHz, CDCl3) δ 17.1 (major),
20.8 (minor); 13C NMR (CD2Cl2, 100 MHz) major isomers, δ
104.4 (allyl trans to P), 111.3 (central allyl), 69.9 (allyl trans
to N); minor isomers, δ 109.6 (allyl trans to P), 111.1 (central
allyl), 74.4 (allyl trans to N); MS (EI) m/z (rel intensity) 495
(6), 368 (6), 193 (100), 115 (24), 91 (6); IR (KBr, cm-1) 2962
(w), 1619 (s), 1482 (w), 1439 (m), 1175 (m), 1104 (m), 657 (s).
Anal. Calcd for C44H43F6NOPSbFePd: C, 51.27; H, 4.17; N,
1.36. Found: C, 51.23; H, 4.15; N, 1.40.
MS (EI) m/z (rel intensity) 683 (23), 611 (7), 541 (12), 399 (100),
326 (20), 242 (24); IR (KBr, cm-1) 3055 (w), 1629 (s), 1482 (w),
1438 (m), 1309 (w), 1177 (s), 1102 (m), 996 (m), 660 (s). Anal.
Calcd for C40H35F6NOPSbFePd: C, 46.55; H, 3.34; N, 1.32.
Found: C, 46.52; H, 3.56; N, 1.18.
Gen er a l P r oced u r e for th e P a lla d iu m -Ca ta lyzed Al-
lylic Su bstitu tion s of r a c-1,3-Dip h en yl-2-p r op en yl Ac-
eta te. [Pd(η3-C3H5)Cl]2 (3.7 mg, 0.01 mmol) and the proper
ligand (0.03 or 0.04 mmol) were dissolved in dry CH2Cl2 (2
mL), and the mixture was stirred for 30 min at rt under an
atmosphere of argon. To this solution were successively added
rac-1, 3-diphenyl-2-propenyl acetate (126 mg, 0.5 mmol),
dimethylmalonate (0.17 mL, 1.5 mmol), N,O-bis(trimethylsi-
lyl)acetamide (0.37 mL, 1.5 mmol), and lithium acetate or
Potassium acetate (0.015 mmol). The reaction mixture was
stirred at rt and monitored by TLC. After completion, the
reaction mixture was diluted with CH2Cl2 (20 mL) and washed
twice with ice-cold saturated aqueous ammonium chloride. The
organic phase was dried over anhydrous MgSO4 and then
concentrated under reduced pressure. The residue was purified
by preparative TLC (EtOAc/petroleum ether ) 1/15) to give
the pure product. The enantiomeric purities were determined
by HPLC analysis (Chiracel OD column, hexane/2-propanol
(80:20); flow rate ) 0.7 mL/min; tR ) 18.7 min, tS ) 20.4 min).
Gen er a l P r oced u r e for th e P a lla d iu m -Ca ta lyzed Al-
lylic Am in a tion of r a c-1,3-Dip h en yl-2-p r op en yl Aceta te.
[Pd(η3-C3H5)Cl]2 (3.7 mg, 0.01 mmol) and ligand (0.04 mmol)
were dissolved in dry THF (2 mL), and the mixture was stirred
for 30 min at rt under an atmosphere of argon. To this solution
were successively added rac-1,3-diphenyl-2-propenyl acetate
(126 mg, 0.5 mmol), BnNH2 (0.11 mL, 1.0 mmol), and TBAF
(1 M in THF, 1 mL, 1 mmol). The reaction mixture was stirred
at 50 °C and monitored by TLC. After completion, the reaction
mixture was diluted with Et2O (20 mL) and washed twice with
ice-cold saturated aqueous ammonium chloride. The organic
phase was dried over anhydrous MgSO4 and then concentrated
under reduced pressure. The residue was purified by prepara-
tive TLC (EtOAc/petroleum ether ) 1:10) to give the pure
product. The enantiomeric purities were determined by HPLC
analysis (Chiracel OJ column, hexane/2-propanol (87:13); flow
rate ) 0.6 mL/min; tS ) 20.3 min, tR ) 24.3 min).
[(S,Rp)-2-(Diphen ylph osph in o)-1-(4-ter t-bu tyloxazolin yl)-
fe r r o c e n e ]-(η3 -t r a n s -1,3-d i p h e n y la lly l)p a lla d i u m
Hexa flu or oa n tim on a te 19. Similar procedures as for 15 give
the title compound in 98% yield (0.4 mmol scale) as an orange
1
solid: mp 267-269 °C; [R]20 ) +490 (c ) 0.19 in CHCl3); H
D
NMR (CD2Cl2, 400 MHz) two isomers (7.1/1), major, δ 7.04-
7.74 (m, 18H), 6.69 (dd, J ) 10.3, 14.0 Hz, 1H), 6.48 (dd, J )
7.5, 11.7 Hz, 2H), 6.04 (dd, J ) 8.2, 14.0 Hz, 2H), 5.22 (s, 1H),
4.86 (t, J ) 2.5 Hz, 1H), 4.69 (d, J ) 10.3 Hz, 2H), 4.57 (s,
5H), 4.19 (dd, J ) 3.1, 9.4 Hz, 1H), 4.12 (m, 1H), 3.86 (dd, J )
9.2, 9.4 Hz, 1H), 2.21 (dd, J ) 3.1, 9.2 Hz, 1H), 0.31 (s, 9H);
minor, δ 6.98-7.74 (m, 20H), 6.89 (m, 1H), 5.31 (m, 1H), 5.21
(m, 1H), 5.11 (m, 1H), 4.76 (t, J ) 2.6 Hz, 1H), 4.41 (s, 5H),
4.17 (dd, J ) 3.0, 9.3 Hz, 1H), 3.89 (m, 1H), 3.50 (dd, J ) 9.3,
9.2 Hz, 1H), 3.13 (dd, J ) 3.0, 9.2 Hz, 1H), 0.50 (s, 9H); 31P
NMR (161.92 MHz, CDCl3) δ 15.7 (major), 20.1 (minor); 13C
NMR (CD2Cl2, 100 MHz) major isomers, δ 103.7 (allyl trans
to P), 132.9 (central allyl), 66.3 (allyl trans to N); minor
isomers, δ 94.0 (allyl trans to P), 108.8 (central allyl), 78.0 (allyl
trans to N); MS (EI) m/z (rel intensity) 687 (5), 495 (23), 336
(26), 203 (69), 165 (100); IR (KBr, cm-1) 2956 (w), 1622 (s),
1546 (w), 1484 (m), 1435 (m), 1179 (m), 1099 (w), 756 (m), 658
(s). Anal. Calcd for C44H43F6NOPSbFePd: C, 51.27; H, 4.17;
N, 1.36. Found: C, 50.91; H, 4.15; N, 1.33.
[(Sp)-2-(Dip h en ylp h osp h in o)-1-(oxa zolin yl)fer r ocen e]-
(η3-tr a n s-1,3-d ip h en yla llyl)p a lla d iu m H exa flu or oa n t i-
m on a te 20. Similar procedures as for 15 give the title
Ack n ow led gm en t. This research was financially
supported by the Major Basic Research Development
Program (Grant No. G2000077506), National Natural
Science Foundation of China, National Outstanding
Youth Fund, Chinese Academy of Sciences, and Shang-
hai Committee of Science and Technology.
compound in 96% yield (0.4 mmol scale) as an orange solid:
1
mp 266 °C dec; [R]20 ) -494.4 (c ) 0.35 in CHCl3); H NMR
D
(CD2Cl2, 400 MHz) two isomers (2.8/1), major, δ 6.92-7.78 (m,
18H), 6.57 (t, J ) 11.7 Hz, 1H), 6.22 (dd, J ) 8.0, 11.1 Hz,
2H), 5.84 (dd, J ) 8.2, 10.1 Hz, 2H), 5.13 (s, 1H), 4.82 (d, J )
11.1 Hz, 1H), 4.74 (s, 1H), 4.18-4.33 (m, 3H), 4.15 (s, 5H),
3.25 (dd, J ) 10.3, 20.7 Hz, 1H), 2.96 (dd, J ) 10.2, 20.9 Hz,
1H); minor, δ 6.78 (t, J ) 11.1 Hz, 1H, central allylic proton),
5.47 (dd, J ) 10.3, 11.1 Hz, 1H, allylic proton trans to P), 4.69
(d, J ) 11.1 Hz, 1H, allylic proton trans to N); 31P NMR (161.92
MHz, CDCl3) δ 16.9 (major), 17.9 (minor); 13C NMR (CD2Cl2,
100 MHz) major isomers, δ 100.6 (allyl trans to P), 112.1
(central allyl), 71.1 (allyl trans to N); minor isomers, δ 96.3
(allyl trans to P), 111.5 (central allyl), 75.5 (allyl trans to N);
Su p p or tin g In for m a tion Ava ila ble: ORTEP drawings
andX-ray crystallographic files (CIF) of compounds 15, 17, 19,
and 20 and selected bond distances and angles for compound
15, 17, 19, and 20. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O016330Z
J . Org. Chem, Vol. 67, No. 14, 2002 4695