Regio- and enantio-selective allylic alkylation catalysed by a chiral monophosphine-palladium complex

Article abstract of DOI:10.1039/a700045f

Allylic alkylation of racemic 1-arylprop-2-enyl acetates [ArCH(OAc)CH=CH₂] with the sodium enolate of dimethyl methylmalonate in the presence of a palladium catalyst coordinated with (R)-2-diphenylphosphino-2′-methoxy-1,1′-binaphthyl [(R)-MeO-MOP] proceeds with high branch selectivity (90%) to give chiral products [ArC*H-(Nu)CH=CH₂] of up to 87% ee.

Full text of DOI:10.1039/a700045f

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Regio- and enantio-selective allylic alkylation catalysed by a chiral
monophosphine–palladium complex
Tamio Hayashi,* Motoi Kawatsura and Yasuhiro Uozumi
Department of Chemistry, Faculty of Science, Kyoto University, Sakyo, Kyoto 606-01, Japan
Allylic alkylation of racemic 1-arylprop-2-enyl acetates
[ArCH(OAc)CHNCH2] with the sodium enolate of dimethyl
methylmalonate in the presence of a palladium catalyst
coordinated with (R)-2-diphenylphosphino-2A-methoxy-
1,1A-binaphthyl [(R)-MeO-MOP] proceeds with high branch
selectivity (90%) to give chiral products [ArC*H-
(Nu)CHNCH2] of up to 87% ee.
[PdCl(p-C3H5)]2 and 1,2-bis(diphenylphosphino)ethane (dppe)
gave linear isomer (E)-3a with 93% regioselectivity (entry 1).
The linear selectivity (79–85% regioselectivity) was also
observed in the reaction with a palladium catalyst coordinated
with triphenylphosphine (entries 2 and 3). It is noteworthy that
the reaction catalysed by palladium–PPh3 requires 2 equiv. of
triphenylphosphine (to Pd) for the allylic substitution to proceed
smoothly. With 1 equiv. of triphenylphosphine, the reaction
stops at about 60% conversion. The opposite regioselectivity
was observed in the same substitution reaction of 1a by use of
MeO-MOP as a ligand, which gave branch isomer 2a with 79%
regioselectivity at 220 °C (entries 4 and 5). With the
palladium–MeO–MOP catalyst, the ratio of phosphine to
palladium did not affect either the catalytic activity or the
regioselectivity. Higher regioselectivity in forming the branch
isomer was observed in the reaction of 1-arylprop-2-enyl
Palladium-catalysed allylic substitution reactions including
catalytic asymmetric reactions have attracted considerable
attention owing to their synthetic utility and mechanistic
interest.1 One of the major problems in developing catalytic
asymmetric allylic substitutions is undesirable regiochemistry
which limits the substitution patterns of allylic substrates. As a
typical example, the substitution with soft carbon nucleophiles
that proceeds through p-allylpalladium intermediates contain-
ing one substituent at the C-1 position produces the linear
isomer rather than the branch isomer.1 It follows that the
reaction cannot be extended to asymmetric synthesis because
the linear isomer lacks the chiral carbon centre. The regio-
selectivity in forming the branch isomer is usually very low
except when methyl is the substituent.2 Here we report that the
(E = CO2Me)
NaCMeE2
Ar
Ar
Ar
CMeE2
+
*
[PdCl(π-C3H5)]2
(2 mol% Pd)
L (P/Pd = 2 or 1)
OAc
DL-1a–c
CMeE2
use
of
2-diphenylphosphino-2A-methoxy-1,1A-binaphthyl
(S)-2a–c
3a–c
(MeO-MOP),3 which is a sterically bulky chiral mono-
phosphine ligand, for the allylic alkylation of 1-arylprop-2-enyl
acetates 1 reversed the regiochemistry to give branch isomers 2
with high selectivity and up to 87% ee in this new allylic
alkylation system.
a Ar = Ph
b Ar =
c Ar =
OMe
MeO
The results obtained for the allylic substitution of racemic
1-arylprop-2-enyl acetates dl -1 in the presence of palladium–
phosphine complexes (Scheme 1) are summarized in Table 1.
The reaction of dl -1-phenylprop-2-enyl acetate 1a with the
sodium salt of dimethyl methylmalonate in THF at 220 °C in
the presence of 2 mol% of palladium catalyst generated from
PPh2
OMe
OMe
Scheme 1
(R)-MeO-MOP
Table 1 Regio- and enantio-selective allylic alkylation of acetate 1 catalysed by palladium–phosphine complexesa
Conditions
Ee (%)
of 2
Allyl
ester
Ligand
(ratio P:Pd)
Yield (%)b
Ratioc
Entry
T/°C
t/h
2 and 3
2:3
(config.)
1
2
3
4
5
6
7
8
9
10
11
12
13
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1c
dppe (2:1)
PPh3 (2:1)
PPh3 (1:1)
(R)-MeO-MOP (2:1)
(R)-MeO-MOP (1:1)
(R)-MeO-MOP (1:1)
dppe (2:1)
PPh3 (2:1)
PPh3 (1:1)
(R)-MeO-MOP (2:1)
(R)-MeO-MOP (1:1)
(R)-MeO-MOP (1:1)
(R)-MeO-MOP (1:1)
220
220
220
220
220
230
220
220
220
220
220
230
230
4
4
24
6
6
6
2
6
24
2
2
92
99
63
99
99
97
96
97
58
97
99
96
99
7:93
15:85
21:79
79:21
79:21
82:18
27:73
30:70
28:72
86:14
85:15
90:10
89:11
—
—
—
68d
68d
86d,e
—
—
—
76f (S)
76f (S)
87f (S)e
85g,e
2
2
a All reactions were carried out in THF under nitrogen: THF (1.0 ml), allylic acetate (0.20 mmol), NaCMe(CO2Me)2 (0.40 mmol), [PdCl(p-C3H5)]2 (0.002
b
c
mmol) and phosphine ligand. Isolated yield by silica gel column chromatography. The ratio was determined by 1H NMR analysis of the products.
d Determined by GLC analysis with CP Cyclodex b236M after demethoxycarbonylation of one of the two methoxycarbonyl groups. e Specific rotations of
2a (entry 6), 2b (entry 12) and 2c (entry 13) were [a]2D0 +46.4, +50.3 and +45.0 (c 1.1–1.8, CHCl3), respectively. Determined by HPLC analysis with
f
Chiralpak AD (hexane–propan-2-ol = 9:1). g Determined by HPLC analysis with Chiralcel OD-H (hexane–propan-2-ol = 9:1).
Chem. Commun., 1997
561

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acetates 1b and 1c which contain methoxy group(s) on the
aromatic ring (entries 10–13). At the reaction temperature of
230 °C, 1-(4-methoxyphenyl)prop-2-enyl acetate 1b gave
branch isomer 2b with 90% regioselectivity (entry 12). The
enantiomeric purity of 2b determined by a chiral stationary
phase column (Chiralpak AD) was 87% ee and its absolute
configuration was assigned to be (+)-(S) by correlation with
addition of 1 to bis(phosphine)palladium(0) will undergo
nucleophilic attack on the less hindered end of the p-allyl,
namely, C-3 position of p-(1-aryl)allyl group (Scheme 3). It
gives the thermodynamically more stable product 3 where the
double bond is conjugated with aromatic ring. On the other
hand, the reaction with MeO-MOP ligand should proceed via
neutral [p-(1-aryl)allyl](acetato)(phosphine)palladium(ii) inter-
mediate 7 because the steric bulkiness of the MOP ligand does
not allow the palladium to form a cationic bis(phosphine)
complex which is analogous to 6.
The p-allylpalladium complex 7b (Ar = 4-MeOC6H4) was
prepared by mixing the [p-(1-aryl)allyl](acetato)palladium(ii)
dimer with 1 equiv. (to Pd) of (R)-MeO-MOP and it was
characterized by 31P and 1H NMR spectra. In CDCl3 at 250 °C
the complex exists as a mixture of isomers in a ratio of 9:1.†
The main isomer has substituted carbon (C-1) of the p-allyl
trans to the phosphorus atom of MeO-MOP and the un-
substituted carbon (C-3) cis to phosphorus, which is determined
by a large coupling constant (J = 8.2 Hz) between C-1 proton
and phosphorus and no couplings between C-3 protons and
phosphorus. Our structural studies of related PdCl(p-allyl)-
(MeO-MOP) complexes6 also showed that the unsubstituted
p-allyl carbon adopts the cis position to phosphorus. The
nucleophile attacks the C-1 carbon which is more weakly
bonded to palladium due to a stronger trans influence of
phosphine ligand to give branch product preferentially. The
stoichiometric reaction of p-allylpalladium complex 7b with
the sodium enolate of dimethyl methylmalonate in THF at
220 °C gave (S)-2b of 90% ee with 88% regioselectivity, which
is in good agreement with the catalytic reactions in terms of both
regio- and enantio-selectivity.
known
(R)-(2)-4-(4-methoxylphenyl)tetrahydro-2H-pyran-
2-one4 4 by way of (R)-(+)-dimethyl (1-arylprop-2-enyl)malo-
nate 5 (Scheme 2). Here again the palladium catalyst containing
dppe or triphenylphosphine gave linear isomer 3b preferentially
(entries 7–9). The reaction of allylic acetate 1c in the presence
of MeO-MOP at 230 °C also gave the corresponding alkylation
product 2c of 85% ee with high branch selectivity (entry 13).
Thus, chiral monodentate phosphine ligand, MeO-MOP, is
playing a key role on the high branch selectivity in the catalytic
allylic alkylation of 1-arylprop-2-enyl acetates. This type of
asymmetric alkylation is considered to be difficult with
chelating bisphosphine ligands so far used mostly for the
asymmetric allylic alkylation which proceeds by way of
palladium intermediates containing 1,3-disubstituted p-allyl
moieties such as 1,3-diphenyl.1,5
The preferential formation of linear isomers in the allylic
alkylation of 1 catalysed by palladium–dppe or palladium–PPh3
is as expected because cationic [p-(1-aryl)allyl]bis-
(phosphine)palladium(ii) intermediate 6 formed by oxidative
Ar
Ar
Ar
i
ii, iii, iv
O
CMeE2
Ar = 4-MeOC6H4, E = CO2Me
(S)-(+)-2b (R)-(+)-5
CHE2
O
We thank the Ministry of Education, Japan, for a Grant-in-
Aid for Scientific Research for partial financial support of this
work.
(R)-(–)-4
Scheme 2 Reagents and conditions: i, (R)-(+)-5 {[a]2D0 + 15.9 (c 1.0,
CHCl3)}, MeI, NaOMe, MeOH, reflux, 86% {[a]2D0 + 40.7 (c 1.7, CHCl3)};
ii, LiCl, Me2SO, H2O 120 °C, 79%, iii, BH3·THF, 77%; iv, p-TsOH,
benzene, 96% {[a]2D0 26.2 (c 1.0, CHCl3)}
Footnote
† Selected NMR data for the major isomer of 7b: 1H NMR (CDCl3 at
250 °C) d 1.51 (s, 3 H), 1.56 (d, J = 11.6 Hz, 1 H, anti-H on C-3), 2.66 (d,
J = 6.3 Hz, 1 H, syn-H on C-3), 3.03 (s, 3 H), 3.28 (m, 1 H, H on C-2), 3.89
(s, 3 H), 5.41 (dd, JH–H = 13.5 Hz, JH–P = 8.2 Hz, 1 H, H on C-1),
6.87–8.10 (m, 26 H). 31P NMR (CDCl3 at 250 °C) d 23.2 (s). 31P NMR for
minor isomer of 7b: d 24.8 (s).
Nu
2
+
2
Ar
Ar
1
1
References
3
3
–OAc
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Pd
Pd
R3P
PR3
AcO
L*
6 2PR3 = 2PPh3 or dppe
7 L* = (R)-MeO-MOP
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2
2
Ar
Ar
1
1
3
3
Pd
Pd
AcO
L*
AcO
L*
(1S,2S)-7b
(1R,2R)-7b
L* = (R)-MeO-MOP
Ar =
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Ar
*
OMe
CMeE2
(S)-2b
Scheme 3
Received, 2nd January 1996; Com. 7/00045F
562
Chem. Commun., 1997