Enantioselective palladium catalyzed allylic substitution with chiral thioether derivatives of ferrocenyl-oxazoline and the role of planar chirality in this reaction

Article abstract of DOI:10.1039/a808267g

A series of chiral thioether dervatives of ferrocenyl-oxazolines, prepared with diastereoselectivities > 95:5, have been shown to be highly efficient catalysts for a palladium catalyzed allylic substitution reaction, with enantioselectivity of 81-98% ee,

Full text of DOI:10.1039/a808267g

Enantioselective palladium catalyzed allylic substitution with chiral thioether
derivatives of ferrocenyl-oxazoline and the role of planar chirality in this
reaction
Shu-Li You, Yong-Gui Zhou, Xue-Long Hou and Li-Xin Dai*
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, China. E-mail: dailx@pub.sioc.ac.cn
Received (in Cambridge, UK) 26th October, 1998 Accepted 12th November 1998
A series of chiral thioether dervatives of ferrocenyl-oxazo-
lines, prepared with diastereoselectivities > 95:5, have been
shown to be highly efficient catalysts for a palladium
catalyzed allylic substitution reaction, with enantioselectiv-
ity of 81–98% ee, and the role of planar chirality in these
ligands was also discussed.
give the pure products. The diastereoselectivities of 3 and 5
determined by 300 MHz 1H NMR were > 95:5.
To assay the effectiveness of ligands and other factors in
palladium catalyzed alylic substitution, we chose the usual test
reaction, the reaction of 1,3-diphenylprop-2-enyl acetate with
the nucleophile derived from dimethyl malonate. Conditions A
[NaCH(CO2Me)2, THF, r.t.] or B [CH2(CO2Me)2, BSA,
LiOAc, DCM, r.t.] were used in the reaction (Scheme 2).
In the past few years, palladium catalyzed allylic substitutions1
have been used extensively in asymmetric carbon–carbon bond
formation to provide chemo-, regio-, diastereo-, and enantio-
selectivity.2 A variety of chiral ligands have been studied. In
addition to the widely used phosphine or phosphite ligands,
sulfur–nitrogen ligands have recently been proved to be
successful.3 For example, Williams explored thioether of
phenyloxazoline ligands for the palladium catalyzed allylic
substitution,13a,b good to excellent enantioselectivities were
obtained. Other groups also showed the high enantioselectivity
obtained with this type of N,S-bidentate ligand. Recently,
planar chiral bidentate ligands have been successfully applied in
many asymmetric reactions. The work of Fu and coworkers
showed that the single planar chiral bidentate ligands were
highly efficient catalysts for several asymmetric reactions.4 In
conjunction with our group’s interest on asymmetric sulfonium
ylide reaction5 and transfer hydrogenation with planar chiral
ferrocene derivatives6 as ligands, we disclose a preliminary
result of our studies on the synthesis of chiral thioether
derivatives of ferrocenyl-oxazoline and application in palla-
dium catalyzed allylic substitution. The role of planar chirality
in this reaction was also studied.
Scheme
2 Condition A: NaCH(CO2Me)2, THF, r.t. Condition B;
CH2(CO2Me)2, BSA [N,O-Bis(trimethyl)acetamide], LiOAc, CH2Cl2, r.t.
First, we investigated the effect of different salts on reaction
yields and enantioselectivies under condition B with the catalyst
3
derived from 3c and [Pd(h -C3H5)Cl]2. The results are summa-
rized in Table 1, and it was found that ee values did not change
in the presence of the salts listed in Table 1 (88.1–89.9%), but
that the reaction time varied significantly (3–48 h). In view of
the reaction time, yield and ee value, the lithium acetate (Table
1, entry 4) was used throughout this work.
Using the above conditions, a variety of ligands and
conditions in the palladium catalyzed asymmetric allylic
substitutions are summarized in Table 2. The sense of
enantioinduction was determined by HPLC and confirmed by
specific rotation of the product methyl-2-carbomethoxy-
3,5-diphenylpent-4-enolate10 and was found to be S in all cases.
Comparing conditions A and B, we obtained higher enantiose-
lectivities with the latter, which is consistent with most
literature reports.1,2 From entries 1–6 we found that ligands 3b
and 3c are superior to 3a. The chiral thioether of ferrocenyl-
oxazolines derived from different amino alcohols show differ-
ent effectiveness for enantioselectivities. The results showed
that R = t-Bu (entries 9,10) is superior to R = i-Pr (entries 3,4)
or Bn (entries 7,8). Entry 11 showed that the palladium complex
with ligand 4 could mediate the allylic substitution reaction
Recently, Ahn et al. have reported an efficient diastereo-
selective synthesis of chiral oxazolinylferrocene compounds.7
According to Ahn’s method and our own experience, a series of
chiral thioether derivatives of ferrocenyl-oxazoline were syn-
thesized as follows: oxazolinylferrocene 2 was treated with n-
BuLi and equimolar amount of TMEDA in Et2O at 278 °C for
2 h (Scheme 1), the resulting mixture quenched with electro-
philes (Me3SiCl, PhSO2SR' or R'SSR'), then usual work-up to
Table 1 Asymmetric palladium catalyzed allylic substitution with different
salts under condition Ba
Entry
Salt
t/h
Yield (%)b Ee (%)c
1
2
3
4
5
None
5
48
48
3
98
96
85
98
98
88.4 (S)
88.1 (S)
88.2 (S)
89.9 (S)
89.4 (S)
KOAc
NaOAc
LiOAc
Cs2CO3
5
3
a Reaction conditions: 2 mol% [Pd(h –C3H5)Cl]2, 6 mol% 3c, 3 mol% salt,
b
300 mol% CH2(CO2Me)2, 300 mol% BSA. Isolated yield based on the
Scheme 1 Reagents and conditions: a, See refs. 7–9; b, (1) n-BuLi,
TMEDA, Et2O 278 °C, 2 h; (2) PhSO2SMe or R'SSR' 67–91%; c, (1) n-
BuLi, TMEDA, Et2O, 278 °C, 2 h; (2) TMSCl 93%; d, (1) n-BuLi, Et2O,
278 °C, 2 h; (2) PhSSPh 70%; e, TBAF, THF, reflux, 6 h 88%.
c
1,3-diphenylprop-2-enyl acetate. Determined by HPLC (chiralcel OJ
d
column).
Absolute configuration of product was assigned through
comparison of the sign of specific rotations with the literature data.10
Chem. Commun., 1998, 2765–2766
2765

Table 2 Asymmetric palladium catalyzed allylic substitution with different
ligands
Table 3 Asymmetric palladium catalyzed allylic substitution with 3 and 9
Conditionb t/h Yield (%) Ee (%)c
Entry Ligand
Reaction
condition t/h
Entry Ligand
Yield (%)a Ee (%)b
1
2
3
4
5
6
9aa
3b
A'
A
B'
B
B'
B
36
2
36
3
96
12
91
98
96
98
92
98
78
84.0
90
89.4
96
98.0
1
2
3
4
5
6
7
8
9
3a
3a
3b
3b
3c
3c
3d
3d
3e
3e
4
A
B
A
B
A
B
A
B
A
B
B
B
1
3
2
3
2
3
2
5
98
98
98
98
98
98
98
98
98
98
98
98
73.9 (S)
81.9 (S)
84.0 (S)
89.4(S)
83.9 (S)
89.9 (S)
81.1 (S)
87.8 (S)
95.6(S)
98.0 (S)
75.3 (S)
90.4 (S)
9aa
3b
9ba
3e
O
a
N
R
b
3
9a: R = i-Pr; 9b: R = t-Bu. Condition A': [Pd(h -
SPh
12
10
3
C3H5)Cl]2 (2.5 mol%), 9 (10 mol%), NaCH(CO2Me)2, THF, 20 °C.
Condition B': [Pd(h -C3H5)Cl]2 (2.5 mol%), 9 (10 mol%), KOAc (3 mol%),
BSA, CH2(CO2Me)2,CH2Cl2, 20 °C. Absolute configuration of product
3
10
11
12
c
5
3
was S for all cases.
a Isolated yield based on the 1,3-diphenylprop-2-enyl acetate. b Determined
c
by HPLC (chiralcel OJ column). Absolute configuration of product was
assigned through comparison of the sign of specific rotations with the
literautre data.10
5 achieved only a little higher ee than ligand 3b (90.4% entry 12
vs. 89.4% entry 4 in Table 2); the planar chirality matched the
central chirality in 5 for the oxazoline ring whereas they are
mismatched in ligand 3. The ee obtained with ligand 8 was low
but did have an influence in this asymmetric allylic substitution
reaction. Furthermore, it is noteworthy to compare the reaction
rate of the reaction catalyzed by 3 with the counterpart of the
thioether of phenyloxazoline 9 (Table 3). For all the reactions
catalyzed by 9, the rates are much slower than those of the
ferrocene derivatives.12
smoothly, while the bulkier trimethylsilyl group may decrease
the enantioselectivity of the product.
Compared with the palladium complexes of chiral thioethers
of phenyloxazoline ligands reported by Williams,3a the palla-
dium complexes with chiral thioethers of ferrocenyl–oxazolines
are more efficient. The allylic substitution reaction catalyzed by
the latter under our conditions is much faster and gives almost
quantitative yields.
In order to investigate the effect of planar chirality on the
absolute configuration and enantioselectivity of this reaction,
diastereoisomer 5 was also synthesized, and subjected to
palladium catalyzed allylic substitution. Under essentially
similar conditions (condition B), a similar enantioselectivity
(89.4% in entry 4 vs. 90.4% in entry 12, Table 2) and the same
absolute configuration was obtained. It seems that the absolute
configuration is governed mainly by the central chirality of the
oxazoline ring. (It seems that planar chirality plays a much less
important role in palladium catalyzed allylic substitution.) This
phenomenon was also found in our previous work on ruthe-
nium-catalyzed asymmetric transfer hydrogenation with ferro-
cene derived catalysts.6
In order to further clarify the role of the planar chirality in this
reaction, we may remove the central chirality on the oxazoline
ring. For this purpose, the single planar chiral thioether of
ferrocenyl-oxazoline (8) was designed and synthesized11
(Scheme 3). Ligand 8 was subjected to palladium catalyzed
allylic substitution under essential similar conditions as above
(condition B) but only 8.5% ee was obtained and the absolute
configuration is R. This result can explain why diastereosiomer
Financial support from the National Foundation of China
(29790127) and Chinese Academy of Sciences is gratefully
acknowledged.
Notes and references
1 Reviews: C. G. Frost, J. Howarth and J. M. J. Williams, Tetrahedron:
Asymmetry, 1992, 3, 1089; B. M. Trost and D. L. Van Vranken, Chem.
Rev., 1996, 96, 395; G. Consiglio and R. M. Waymouth, Chem. Rev.,
1989, 89, 257; S. A. Godleski, in Comprehensive Organic Synthesis, ed.
B. H. Trost, Pergamon Press, Oxford, 1991, vol. 4, p. 585.
2 Recent examples: B. M. Trost and R. C. Bunt, Angew. Chem. Int. Ed.
Engl, 1996, 35, 99; B. M. Trost and F. D. Toste, J. Am. Chem. Soc.,
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63, 1339.
3 (a) G. J. Dawson, C. G. Frost, C. J. Martin and J. M. J. Williams,
Tetrahedron Lett., 1993, 34, 7793; (b) J. V. Allen, J. F. Bower and
J. M. J. Williams, Tetrahedron Asymmetry, 1994, 5, 1895; (c) J. V.
Allen, S. J. Coote, G. J. Dawson, C. G. Frost, C. J. Martin and J. M. J.
Williams, J. Chem. Soc., Perkin Trans. 1, 1994, 2065; (d) K. Boog-
wick, P. S. Pregosin and G. Trabesinger, Organometallics, 1998, 17,
3254 (e) B. Koning, A. Meetsma and R. M. Kellogg, J. Org. Chem.,
1998, 63, 5533, and references therein.
4 J. C. Ruble, J. Tweddell and G. C. Fu, J. Org. Chem., 1998, 63, 2794;
S. Qiao and G. C. Fu, J. Org. Chem., 1998, 63, 4168.
5 A. H. Li, L. X. Dai, X. L. Hou, Y. Z. Huang and F. W. Li, J. Org. Chem.,
1996, 61, 489; A. H. Li, Y. G. Zhou, L. X. Dai, X. L. Hou, L. J. Xia and
L. Lin, Angew. Chem., Int. Ed. Engl., 1997, 36, 1317.
6 X.-D. Du, L.-X. Dai, X.-L. Hou, L.-J. Xia and M.-H. Tang, Chin.
J. Chem., 1998, 16, 90.
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1996, 61, 4937.
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Whitman, J. Am. Chem. Soc., 1957, 79, 3416.
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12 We also noticed a similar rate enhancing effect in the asymmetric
transfer hydrogenation of ketones catalyzed by ruthenium complexes
with phosphinoferrocenyloxozolines (ref. 6).
Scheme 3 Reagents and conditions: a, (1) TFA, H2O, Na2SO4, THF; (2)
Ac2O, Py, CH2Cl2, 88%; b, (1) 2.5 M NaOH (aq), THF, 55 °C (2) H3O+,
85%; c, (1) (ClCO)2, NH2(CH2)2OH, Et3N, CH2Cl2, (2) TsCl, Et3N,
DMAP, CH2Cl2, 63%.
Communication 8/08267G
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Chem. Commun., 1998, 2765–2766