Palladium-catalyzed electrophilic substitution via monoallylpalladium intermediates

Article abstract of DOI:10.1002/anie.200351477

Nucleophilic rather than electrophilic reactivity is ascribed to the allyl moiety in (η¹-allyl) palladium complexes such as 1, which are generated catalytically from allylstannanes and a palladium pincer complex and react smoothly with aldehydes.

Full text of DOI:10.1002/anie.200351477

Communications
Pd-Catalyzed Allylation
Palladium-Catalyzed Electrophilic Substitution
via Monoallylpalladium Intermediates
Niclas Solin, Johan Kjellgren, and Kµlmµn J. Szabó*
Scheme 1. Pincer complexes used as catalysts.
Allylpalladium chemistry is one of the most successful areas
in transition-metal catalysis. In the most common application
of these complexes an allylpalladium intermediate is gener-
Scheme 1) are employed in palladium-catalyzed electrophilic
substitution of allylstannanes 4a–c [Eq. (2)].
[
1]
ated which subsequently reacts with nucleophiles. The
recent extension of the synthetic scope of these
compounds to reactions with electrophilic sub-
[
2,3]
strates has attracted much attention.
It was
shown that in order for the allyl moiety to have
nucleophilic reactivity bisallylpalladium inter-
[
2a,3a]
mediates must be generated [Eq. (1)].
How-
ever,the diverse reactivity of the bisallylpalladium
The reactions were performed with 4a–c and various
aldehydes 5 and imine 6 in the presence of catalytic amounts
of 1–3 to obtain homoallylic alcohols 7 and amines 8,
[
4c]
[5a,c]
respectively (Table 1). Complexes 1a and 2a
showed
high catalytic activity and very high stability under the
reaction conditions. Although the reactions could be per-
formed in many different solvents,the best results were
obtained in DMF (for 1a) and THF (for 2a). Activated
aldehydes 5b–e reacted faster and usually with a higher yield
than benzaldehyde (5a) itself (entries 1–9). The reactions
proceed under neutral reaction conditions without added
base or Lewis-acid catalyst,and therefore,many function-
intermediates imposes considerable synthetic limitations on
the reaction. Controlling the regioselectivity is difficult when
the two allylic moieties bear different substituents [cf.
alities,such as NO 2,F,CN,and CH
3CO are tolerated
(entries 3–9). Cinnamylstannane 4b readily undergoes palla-
dium-catalyzed allylic substitution providing exclusively the
branched allylic products 7g, 7h,and 8b with high diaster-
eoselectivity (entries 13–15,17). The corresponding reaction
with crotylstannane 4c also gives the branched allylic isomer
7i,albeit without stereoselectivity (entry 16). The N-Pd-N
[
3b,c]
Eq. (1)].
A further problem is that bisallylpalladium
complexes may undergo allyl–allyl (Stille) coupling prior to
[
2d]
the reaction with electrophiles. Because of these limitations
it would be desirable to conduct the catalytic transformations
with monoallylpalladium intermediates. This is a challenging
task,since it is well known that monoallylpalladium com-
[
4a]
type complex 3 was also tested in these reactions (entry 15);
however,it showed lower catalytic activity than 1a and 2a.
We attempted to increase the catalytic activity of 1a and 2a
by replacing the chloride ligand with acetate (1b) and with
tetrafluoroborate (1c and 2b). These complexes displayed a
very high initial catalytic activity even at room temperature;
however,within a couple of hours these catalysts were
completely deactivated. Nevertheless,complexes 1b and 1c
were stable enough to achieve full conversion of 4a with
activated aldehyde 5e (entries 7 and 8) at moderate temper-
ature.
[
1]
plexes react with nucleophiles. Nevertheless,our previous
mechanistic studies showed that the electrophilic attack on a
1
bisallylpalladium complex proceeds through the h -coordi-
[
3a–b]
3
nated allyl moiety,
while the other, h -coordinated allyl
group acts as a strong p-donor spectator ligand [cf. Eq. (1)].
1
This model suggests that the catalytic generation of an (h -
allyl)palladium intermediate coordinated to an electron-
donating spectator ligand provides nucleophilic reactivity to
the allyl moiety. We have now found that this type of
[
4]
reactivity occurs when so-called pincer complexes (1–3,
Transition-metal pincer complexes are widely used in
organometallic chemistry and catalysis. Complex 2 is known
[
4]
to readily undergo transmetalation with organometallic
[
*] Prof. Dr. K. J. Szabó, N. Solin, J. Kjellgren
Deparment of Organic Chemistry
Stockholm University
SE-10691 Stockholm (Sweden)
Fax : (+46)8-154-908
[5b,c]
[5b]
reagents.
For example,Cotter and co-workers
have
shown that 2-furylstannane undergoes tin-to-palladium trans-
metalation with the triflate salt of 2. It is reasonable to assume
that the first step in the above reaction [Eq. (2)] is also
transmetalation of the allylstannane 4 with the pincer
E-mail: kalman@organ.su.se
3
656
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/anie.200351477
Angew. Chem. Int. Ed. 2003, 42, 3656 –3658

Angewandte
Chemie
[
a]
Table 1: Palladium-catalyzed electrophilic substitution reactions [Eq. (2)].
1
[b]
[c]
Entry
Substrates
Cat.
Prod.
Q
R
Solv.
Cond.
Yield [%]
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
4b
4b
5a
5a
5b
5c
5d
5e
5e
5e
5e
5 f
6
1a
2a
1a
1a
1a
1a
1b
1c
2a
2a
1a
2a
2a
2a
3
7a
7a
7b
7c
7d
7e
7e
7e
7e
7 f
8a
8a
7 g
7h
7h
7i
C6H5
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
Ph
Ph
Ph
Me
Ph
DMF
THF
60/22
60/21
60/22
60/17
60/17
60/17
40/2
81
88
77
88
82
82
95
95
95
80
66
69
61
95
85
77
65
4-FC H
DMF
DMF
DMF
DMF
CHCl3
CHCl3
THF
THF
DMF
THF
THF
THF
THF
DMF
THF
6
5
4-CNC H
4-CH COC H
4-NO C H
5
4-NO C H
4-NO C H
4-NO C H
cinnamyl
–
–
C6H5
4-NO C H
4-NO
4-NO C H
–
6
5
3
6
5
2
6
2
6
5
5
5
20/3
2
6
40/21
60/21
60/17
60/21
60/21
60/21
20/64
60/14
60/21
2
6
1
1
1
1
1
1
1
1
6
[
[
[
d]
d]
d]
5a
5e
5e
5e
6
2
6
5
5
5
2
C
6
H
[
e]
[f]
g]
4c
4b
1a
2a
2
6
8b
[
6a]
[
[
a] Catalyst amount: 5 mol%. [b] Temperature [8C]/time [h]. [c] Yield of isolated product. [d] Diastereomer ratio anti/syn =10:1. [e] Z/E ratio=2:1.
f] Diasteromer ratio syn/anti =1:1. [g] Diastereomer ratio syn/anti =12:1.
[
6b]
[6c]
3
complex (1, 2). Because of the strong h -coordination of the
ing via bisallylpalladium intermediates this reaction is
thought to involve monoallylpalladium intermediates. Appli-
cation of this procedure eliminates the side reactions that
occur in bisallylpalladium-catalyzed transformations,thus
extending the synthetic scope of electrophilic reagents in
allylpalladium chemistry.
pincer ligands to palladium only one coordination site is
available for the allyl moiety. Accordingly,an h -allyl complex
is formed,in which the allyl moiety is trans to the strongly
electron-donating phenyl group [Eq. (3)]. This structure lends
nucleophilic character to the allyl moiety,which is similar to
1
Experimental Section
Representative procedure for palladium-catalyzed allylation
of electrophiles: To a mixture of the aldehyde (0.15 mmol)
and 1a (5 mg,0.007 mmol) in DMF (0.5 mL) was added 4a
(59.7 mg,0.18 mmol). This solution was then heated at the
designated temperature for the allotted time (Table 1).
Subsequently,the reaction mixture was quenched by addi-
tion of water and extracted with ether. The collected organic
phases were dried and concentrated to dryness,and then purified by
chromatography with pentane/ethyl acetate as the eluent.
1
that of the h moiety in the bisallylpalladium intermediates
[
1
cf. Eq. (1)]. Subsequently,the h -allyl complex reacts with
electrophiles (5, 6) providing the final product of the reaction
7, 8).
An alternative mechanism may involve Lewis-acid-type
activation of the aldehydes by the pincer complexes.
However, 1c and 2b undergo rapid reaction with 4a even in
Received: March 25,2003 [Z51477]
(
[
4a,5d]
Keywords: aldehydes · allylation · electrophilic substitution ·
.
homogenous catalysis · palladium
the absence of aldehydes. When this reaction was carried out
with 1c and 4a or (allyl)trimethylstannane at À108C in
1
CDCl ,rapid formation of propene was observed by H NMR
3
[
1] J. Tsuji in Palladium Reagents and Catalysis:Innovations in
Organic Synthesis,Wiley,Chichester, 1995.
spectroscopy. This process indicates transmetalation of the
allylstannane with palladium [cf. Eq. (3)] followed by proton-
1
[2] a) H. Nakamura,H. Iwama,Y. Yamamoto, J. Am. Chem. Soc.
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ation of the h -allyl moiety by traces of water present in the
1
1
reaction mixture. The high proton affinity of the h -allyl
moiety is a characteristic feature of bisallylpalladium com-
G. Shim,Y. Yamamoto, J. Am. Chem. Soc. 2001, 123,372; d) H.
Nakamura,M. Bao,Y. Yamamoto, Angew. Chem. 2001, 113,3308;
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[
3d,5e,5f]
plexes.
anism is provided by the high reactivity of sulfonimine 6
Table 1,entries 11,12,and 17),which cannot be activated by
Further evidence for the transmetalation mech-
[
3] a) K. J. Szabó, Chem. Eur. J. 2000, 6,4413; b) N. Solin,S. Narayan,
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Chem. 2003, 68,2934.
(
Lewis-acid catalysts.
In summary,we have found a new procedure for
palladium-catalyzed electrophilic substitution of allylstan-
nanes. In this procedure pincer complexes 1–3 serve as
catalyst sources. In contrast to previous applications proceed-
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4] a) M. Albrecht,G. van Koten, Angew. Chem. 2001, 113,3866;
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Angew. Chem. Int. Ed. 2003, 42, 3656 –3658
www.angewandte.org
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3657

Communications
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[
3
658
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2003, 42, 3656 –3658