Palladium(0)-catalyzed allylic aminations: kinetics and mechanism of the reaction of secondary amines with cationic [(η3-allyl)PdL 2]+ complexes

Article abstract of DOI:10.1021/om060686p

The mechanism of the reaction of secondary amines (piperidine, morpholine) with the cationic complexes [(η³-PhCHCHCHR)PdL₂] ⁺BF₄^- (R = Ph, L = PPh₃ or L ₂ = dppb; R = H, L₂ = dppb) has been investigated in DMF. The reaction, which affords the tertiary allylic amine, is irreversible when L is a monodentate ligand such as PPh₃, whereas the reaction is reversible when L₂ is a bidentate ligand such as dppb. In all cases, piperidine is more reactive than morpholine. The rate and equilibrium constants have been determined in DMF. These results can be combined with our previous results on the mechanism of the reversible formation of cationic [(nη³-PhCHCHCHPh)PdL₂]⁺AcO_- by reacting Pd⁰L₂ complexes with (E)-PhCH=CHCH(Ph)OAc. Fully established catalytic cycles are now proposed for the Pd-catalyzed allylic amination of (E)-PhCH=CHCH(Ph)OAc by piperidine and morpholine. The amine and AcO^z- are in competition in their reaction with the cationic complexes [(η³-PhCHCHCHPh)PdL₂]⁺. The nucleophilic attack of the amine may be faster than the attack of AcO ^- and thus limited by the ionization step in which [(η³-PhCHCHCHPh)PdL₂]⁺ is formed, this ionization step being turnover limiting for the catalytic cycle.

Full text of DOI:10.1021/om060686p

Organometallics 2007, 26, 1875-1880
1875
Palladium(0)-Catalyzed Allylic Aminations: Kinetics and
Mechanism of the Reaction of Secondary Amines with Cationic
[(η3-allyl)PdL2]+ Complexes†
Christian Amatore,* Emilie Ge´nin, Anny Jutand,* and Laure Mensah
De´partement de Chimie, Ecole Normale Supe´rieure, UMR CNRS-ENS-UPMC 8640, 24, Rue Lhomond.
F-75231 Paris Cedex 5, France
ReceiVed July 31, 2006
The mechanism of the reaction of secondary amines (piperidine, morpholine) with the cationic complexes
-
[(η3-PhCHCHCHR)PdL2]+BF4 (R ) Ph, L ) PPh3 or L2 ) dppb; R ) H, L2 ) dppb) has been
investigated in DMF. The reaction, which affords the tertiary allylic amine, is irreversible when L is a
monodentate ligand such as PPh3, whereas the reaction is reversible when L2 is a bidentate ligand such
as dppb. In all cases, piperidine is more reactive than morpholine. The rate and equilibrium constants
have been determined in DMF. These results can be combined with our previous results on the mechanism
of the reversible formation of cationic [(η3-PhCHCHCHPh)PdL2]+AcO- by reacting Pd0L2 complexes
with (E)-PhCHdCHCH(Ph)OAc. Fully established catalytic cycles are now proposed for the Pd-catalyzed
allylic amination of (E)-PhCHdCHCH(Ph)OAc by piperidine and morpholine. The amine and AcO- are
in competition in their reaction with the cationic complexes [(η3-PhCHCHCHPh)PdL2]+. The nucleophilic
attack of the amine may be faster than the attack of AcO- and thus limited by the ionization step in
which [(η3-PhCHCHCHPh)PdL2]+ is formed, this ionization step being turnover limiting for the catalytic
cycle.
Scheme 1
Introduction
The mechanism of the palladium-catalyzed nucleophilic
allylic substitutions has been extensively studied (Scheme 1).1-3
Kinetic data on the first steps of the catalytic cycles, i.e., the
oxidative addition of Pd0L2 (L ) monodentate phosphines or
L2 ) bisphosphine) with allylic acetates2 or carbonates,3 are
now available and the cationic complexes (η3-allyl)PdL2
+
formed in the oxidative addition have been well characterized.2,3
* To whom correspondence should be addressed. Fax: (+33)-0-4432-
3325. E-mail: Anny.Jutand@ens.fr (A.J.); christian.amatore@ens.fr (C.A.).
† This work is dedicated to our friend, the late Professor Marcial Moreno-
Man˜as.
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Yamamoto, A.; Ito, Y.; Nishioha, E.; Miura, H.; Yanagi, K. J. Am. Chem.
Soc. 1989, 111, 6301. (e) Godleski, S. A. In ComprehensiVe Organic
Synthesis; Trost, B. M., Pflemming, I., Semmelhack, M. F., Eds.; Perga-
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Kinetic data on the further step, i.e., nucleophilic attack on (η3-
allyl)PdL2+ complexes, are more scarce. Uguagliati et al.4 and
Crociani et al.5 have investigated the reaction of secondary
amines with cationic [(η3-CH2CHCH2)Pd(N,N)]+ and [(η3-CH2-
CHCH2)Pd(P,N)]+, respectively. In both cases, the secondary
amines were found to attack in parallel the η3-allyl ligand in an
(2) (a) Amatore, C.; Jutand, A.; Meyer, G.; Mottier, L. Chem. Eur. J.
1999, 5, 466. (b) Amatore, C.; Gamez, S.; Jutand, A.; Chem. Eur. J. 2001,
7, 1273. (c) Amatore, C.; Gamez, S.; Jutand, A.; Meyer, G.; Mottier, L.
Electrochim. Acta 2001, 46, 3237. (d) Agenet, N.; Amatore, C.; Gamez,
S.; Ge´rardin, H.; Jutand, A.; Meyer, G.; Orthwein, C. ARKIVOC 2002, 92
(http://www.arkat-usa.org/). (e) Amatore, C.; Bahsoun, A. A.; Jutand, A.;
Mensah, L.; Meyer, G.; Ricard, L. Organometallics 2005, 24, 1569-1577.
(f) Amatore, C.; Jutand, A.: Mensah, L.; Fiaud, J.-C.; Legros, J.-Y. Eur. J.
Org. Chem. 2006, 1185-1192.
(3) Amatore, C.; Gamez, S.; Jutand, A.; Meyer, G.; Moreno-Man˜as, M.;
Morral, L.; Pleixats, R. Chem. Eur. J. 2000, 6, 3372-3376.
(4) Canovese, L.; Visenti, F.; Uguagliati, P. Crociani, B.; Di Bianca, F.
Inorg. Chim. Acta 1995, 235, 45-50.
(5) (a) Crociani, B.; Antonaroli, S.; Bandoli, G.; Canovese, L.; Visenti,
F.; Chessa, G.; Niero, A.; Uguagliati, P. Organometallics 1999, 18, 1137-
1147. (b) Crociani, B.; Antonaroli, S.; Canovese, L.; Visentin, F.; Uguagliati,
P. Inorg. Chim. Acta 2001, 315(2), 172-182.
10.1021/om060686p CCC: $37.00 © 2007 American Chemical Society
Publication on Web 03/09/2007

1876 Organometallics, Vol. 26, No. 8, 2007
Amatore et al.
irreversible reaction and the PdII center by reversible coordina-
tion. Canovese et al. have investigated the reaction of secondary
amines with cationic [(η3-CH2CHCH2)Pd]+ ligated by terdentate
S-N-S, N-S-N, N-N-N, and P-N-N ligands, and a parallel attack
was also observed.6 As far as monophosphine ligands are
concerned, secondary amines were found to only attack the allyl
ligand. Kuhn and Mayr have determined the rate constant of
the irreversible reaction of secondary amines (piperidine,
morpholine) with [(η3-PhCHCHCH2)Pd(PPh3)2]+ in CH2Cl2.7
Jutand et al. have determined the rate constant of the irreversible
reaction of morpholine with [(η3-CH2CHCH2)Pd(PAr3)2]+ (Ar
) 4-Cl-C6H4, 4-Me-C6H4) in DMF.8 The latter reactions were
found to be faster than those of the neutral complexes (η1-CH2d
CHCH2)PdCl(PAr3)2 generated upon addition of chloride ions
to the cationic complexes [(η3-CH2CHCH2)Pd(PAr3)2]+.8,9
The mechanism of the reaction of (E)-PhCHdCHCH(Ph)-
OAc (an allylic acetate specifically designed by Trost et al. to
test the effect of chiral ligands on the enantioselectivity of Pd-
catalyzed nucleophilic allylic substitutions)10 with Pd0L2 (L )
PPh3, L2 ) dppb )1,4-bis(diphenylphosphino)butane) has been
fully established in our group,2e and the cationic complexes [(η3-
PhCHCHCHPh)PdL2]+ (L ) PPh3, L2 ) dppb) formed in these
reactions have been fully characterized.2e
-
Figure 1. Reaction of [(η3-PhCHCHCHPh)Pd(PPh3)2]+BF4
(1a+BF4-) with morpholine in DMF at 10 °C, as monitored by
UV spectroscopy in a 1 mm cell: (a) 1a+BF4-, C0 ) 1 mM; (b)
1a+BF4- + morpholine (2 equiv); (c) Pd0(dba)(PPh3)2 formed after
addition of dba (2 equiv) to (b).
We report herein the mechanism of the reaction of secondary
amines (morpholine, piperidine) with cationic complexes [(η3-
PhCHCHCHPh)PdL2]+ (L ) PPh3, L2 ) dppb). PPh3 and dppb
were selected as representative of monodentate and bidentate
ligands, respectively. The kinetics of the successive steps of
palladium-catalyzed allylic aminations,11 i.e., oxidative addition
leading to the cationic complex2e followed by its nucleophilic
attack by the amine reported in the present work, can now be
compared with each other to define the rate-determining step
of the catalytic cycle.
Figure 2. Kinetics of the reaction of morpholine (5.99 mM) with
-
[(η3-PhC3H3Ph)Pd(PPh3)2]+BF4 (C0 ) 1 mM) in DMF at 10 °C,
as monitored by UV spectroscopy at 345 nm, performed in a 1
mm cell:14 plot of ln[(n - 2 + 2x)/nx] versus time (see eq 2).
345 nm in DMF (Figure 1).2e It totally disappeared only after
addition of 2 equiv of morpholine, attesting to a facile reaction
between the nucleophile and 1a+. The final value of the
absorbance was similar, whatever the amount of added mor-
pholine (n g 2 equiv), evidencing that the overall reaction was
irreversible.
The absorption band of Pd0(dba)(PPh3)2 at λmax 400 nm2e
appeared after addition of dba (2 equiv). This indicates that the
reaction of morpholine with 1a+ produced the stable Pd0
complex 2m,12 whose reaction with dba generated Pd0(dba)-
(PPh3)2 and the final substitution product 3m (Scheme 2). The
latter was characterized by comparison with an authentic sample
synthesized by reacting morpholine with PhCHdCHCH(Ph)-
OAc in the presence of Pd0(PPh3)4 (10%) in dichloromethane
(vide infra).
Results and Discussion
Rate and Mechanism of the Reaction of Amines (Mor-
pholine, Piperidine) with the Cationic Complex [(η3-
PhCHCHCHPh)Pd(PPh3)2]+BF4- in DMF. (a) Reaction with
Morpholine. The reaction of Pd0(PPh3)2 with (E)-PhCHd
CHCH(Ph)OAc gives the complex [(η3-PhC3H3Ph)Pd(PPh3)2]+-
AcO- in a reversible reaction.2e Consequently, the latter complex
could not be isolated with AcO- as the counteranion. The
reaction with morpholine was thus investigated on the isolated
stable complex [(η3-PhC3H3Ph)Pd(PPh3)2]+BF4- (1a+BF4-).2e
The reaction was followed by UV spectroscopy. As previously
reported, the complex 1a+ exhibits an absorption band at λmax
(6) Canovese, L.; Visenti, F.; Chessa, G.; Niero, A.; Uguagliati, P. Inorg.
Chim. Acta 1999, 293, 44-52.
(7) Kuhn, O.; Mayr, H. Angew. Chem., Int. Ed. 1999, 38, 343-346.
(8) Cantat, T.; Ge´nin, E.; Giroud, C.; Meyer, G.; Jutand, A. J. Organomet.
Chem. 2003, 687, 365-376.
The UV spectrum in Figure 1 (curve b) recorded after reaction
of morpholine with 1a+, in the absence of dba, exhibited a new
absorption band at λmax 315 nm. This band characterized the
Pd(0) complex 2m. Indeed, the UV spectrum of Pd0(PPh3)4 (1
mM in DMF) exhibited an absorption band at λmax 323 nm.
After addition of an authentic sample of the substitution product
3m (10 mM), a new band was observed at λmax 317 nm, attesting
to a complexation of Pd0(PPh3)2 to 3m, as in the Pd(0) complex
(9) Cantat, T.; Agenet, N.; Jutand, A.; Pleixats, R., Moreno-Man˜as, M.
Eur. J. Org. Chem. 2005, 4277-4286.
(10) Trost, B. M.; Murphy, D. J. Organometallics 1985, 4, 1143-1145.
(11) For palladium-catalyzed aminations of allylic acetates or carbonates,
see ref 1n,u,w and: (a) Trost, B. M.; Keinan, E. J. Am. Chem. Soc. 1978,
100, 7779-7781. (b) Trost, B. M.; Keinan, E. J. Org. Chem. 1979, 44,
3451-3457. (c) Hayashi, T.; Kishi, K.; Yamamoto, A.; Ito, Y. Tetrahedron
Lett. 1990, 31, 1743-1746. (d) Ba¨ckvall, J.-E.; Granberg, K. L.; Heumann,
A. Isr. J. Chem. 1991, 31, 17-24. (e) Granberg, K. L.; Ba¨ckvall, J.-E. J.
Am. Chem. Soc. 1992, 114, 6858-6863. (f) Trost, B. M.; Krische, M. J.;
Radinov, R.; Zanoni, G. J. Am. Chem. Soc. 1996, 118, 6297-6298. (g)
Moreno-Man˜as, M.: Morral, L.; Pleixats, R. J. Org. Chem. 1998, 63, 6160-
6166. (h) Muchow, G.; Brunet, J. M.; Maffei, M.; Pardigon, O.; Buono, G.
Tetrahedron 1998, 54, 10435-10448. (i) Watson, I. D. G.; Styler, S. A.;
Yudin, A. K. J. Am. Chem. Soc. 2004, 126, 5086-5087. (j) Piechaczyk,
O.; Thoumazer, C.; Jean, Y.; Le Floch, P. J. Am. Chem. Soc. 2006, 128,
14306-14317.
-
2m.8,12 The reaction of morpholine (0.02 mmol) with 1a+BF4
1
(0.01 mmol) in acetone-d6 (0.5 mL) was followed by H and
31P NMR spectroscopy. The substitution product 3m was
1
detected on the first recorded H spectrum without the signals
(12) For coordination of Pd0 to the CdC bond of the final substitution
product see ref 8 and: Steinhagen, H.; Reggelin, M.; Helmchen, G. Angew.
Chem., Int. Ed. 1997, 36, 2108-2110.

Pd0-Catalyzed Allylic Aminations
Scheme 2
Organometallics, Vol. 26, No. 8, 2007 1877
Table 1. Rate or Equilibrium Constants for the Reaction of
Morpholine and Piperidine with Cationic (η3-allyl)PdL2
+
Complexes in DMF (see Schemes 3 and 6 for the Definition
of k and K)
Scheme 3
(Figure 2),14 confirming a first-order reaction for 1a+. The value
of k was determined from the slope of the straight line. Similar
values of k were obtained regardless of the concentration of
morpholine investigated here (n ) 5.99, k ) 23.4 M-1 s-1; n
) 7, k ) 21.8 M-1 s-1; n ) 8.2, k ) 24.4 M-1 s-1; n ) 9.45,
k ) 25 M-1 s-1), attesting also to a first-order reaction for the
morpholine, in agreement with eq 2 and the mechanism
proposed in Scheme 3: i.e., nucleophilic attack of the morpho-
line onto the allyl ligand of 1a+ is the rate-determining step (k
) 23 ( 1 M-1 s-1; Table 1), followed by the faster deproto-
nation of 4m by a second morpholine.
of 1a+BF4- 2e attesting to a fast reaction. Two broad multiplets
,
centered at 6.70 and 7.01 ppm were assigned to the two vinylic
protons of complex 2m.13 When the same reaction was
performed in CD2Cl2, two similar broad multiplets were
observed at 6.65 and 6.96 ppm, associated with two broad 31P
NMR signals at 30.74 and 28.66 ppm of same magnitude,
characteristic of two nonmagnetically equivalent PPh3 groups.
They were assigned to complex 2m.
Jutand et al.8 have established that the reaction of morpholine
with [(η3-CH2CHCH2)Pd(PAr3)2]+BF4- proceeds via two suc-
cessive irreversible steps. The first one, the nucleophilic attack
of the amine at the allyl ligand, is rate-determining. By
(b) Reaction with Piperidine. The reaction of piperidine with
1a+BF4 gave the allylic piperidine 3p, as established by H
NMR spectroscopy. The reaction was followed by UV spec-
troscopy at 10 °C, as was done for morpholine. This reaction
was considerably faster than the reaction with morpholine, in
agreement with their respective pKA values (11.12 vs 8.21).15
Though the behavior was similar to the previous case, the rate
constant k could not be determined, due to lack of accuracy
(Table 1).
-
1
-
similarity, the mechanism of the reaction of 1a+BF4 with
morpholine is proposed in Scheme 3. Note that the fate of the
Pd(0) complex 2m (equilibrium with 3m) does not interfere in
the kinetics of the overall reaction, which is limited by the rate
of the first step (vide infra).
The reaction was too fast to be followed by UV spectroscopy
at room temperature. Its kinetics was thus investigated at
10 °C with a low excess of morpholine (n < 10 equiv). The
decrease of the absorbance Dt of 1a+ at 345 nm was recorded
versus time after addition of morpholine. The kinetic law of
the mechanism proposed in Scheme 3 is given in eqs 1 and 2,
taking into account the variation of the morpholine concentration
during the reaction (C0 ) initial concentration of 1a+BF4-, n
) initial number of equivalents of morpholine, x ) [1a+]t/[1a+]0
) (Dt - D∞)/D0 - D∞) with Dt being the absorbance of 1a+ at
t, D∞ the final absorbance at infinite time, and D0 the initial
absorbance of 1a+).
Rate and Mechanism of the Reaction of Amines (Mor-
pholine, Piperidine) with the Cationic Complex [(η3-
PhCHCHCHPh)Pd(dppb)]+BF4- in DMF. (a) Reaction with
Morpholine. As previously reported, the reaction of (E)-PhCHd
CHCH(Ph)OAc with Pd0(dppb) gives the complex [(η3-PhC3H3-
Ph)Pd(dppb)]+AcO- in a reversible reaction.2e The latter
complex could not be isolated with AcO- as the counteranion.
The reaction with morpholine was thus investigated on the
-
-
isolated stable BF4 salt, [(η3-PhC3H3Ph)Pd(dppb)]+BF4
(1b+BF4-).2e The latter exhibits an absorption band at λmax 352
nm in DMF.2e The decrease of the absorbance of 1b+BF4- (C0
) 1 mM) at 352 nm in the presence of morpholine (50 equiv)
was recorded with time at 25 °C. The absorbance decreased
and stabilized with time but did not reach its expected final
value. Furthermore, it decreased again and stabilized after further
dx/dt ) -kC0(n - 2 + 2x)x
(1)
(2)
ln[(n - 2 + 2x)/nx] ) kC0(n - 2)t
The plot of ln[(n - 2 + 2x)/nx] against time was linear
(14) The reaction of morpholine (5.99 mM) with [(η3-PhC3H3Ph)Pd-
-
(13) (a) The main signal detected in the 31P NMR spectrum was that of
triphenylphosphine oxide at 24.94 ppm, together with a minor signal at
35.46 ppm characteristic of O2Pd(PPh3)2.13b Both were formed by a side
reaction of oxygen and the residual water of the solvent with Pd0(PPh3)2
released from the Pd(0) complex 2m. (b) Adamo, C.; Amatore, C.; Ciofini,
I.; Jutand, A.; Lakmini, H. J. Am. Chem. Soc. 2006, 128, 6829.
(PPh3)2]+BF4 was fast. The UV measurements were performed after the
cell was shaken by hand just after addition of morpholine to the cationic
complex. This requires some time during which the absorbance could not
be measured. This is why the first part of the kinetics is missing.
(15) Weast, R. C., Ed. Handbook of Chemistry and Physics, 52nd ed.;
CRC Press: Cleveland, OH, 1971-1972, p D-177.

1878 Organometallics, Vol. 26, No. 8, 2007
Amatore et al.
Scheme 4
Figure 3. Reaction of morpholine (n is the total number of
equivalentsofaddedmorpholine)with[(η3-PhCHCHCHPh)Pd(dppb)]+-
Scheme 5
-
BF4 (C0 ) 1 mM) in DMF at 25 °C, as monitored by UV
spectroscopy at 352 nm, performed in a 1 mm cell.
Scheme 6
Figure 4. Determination of the K value of the equilibrium observed
-
in the reaction of [(η3-PhC3H3Ph)Pd(dppb)]+BF4 (1b+BF4-; 1
mM) with morpholine (n equiv) in DMF at 25 °C, as monitored
by UV spectroscopy at 352 nm, performed in a 1 mm cell. (1 -
x)3/x ) K(n - 2 + 2x)2.
addition of morpholine (Figure 3).16 This establishes that the
reaction of morpholine with 1b+ was reversible.17
The reaction was also followed by 1H and 31P NMR
performed on a solution of 1b+BF4- in CDCl3 after addition of
morpholine (2 equiv). The final substitution product, 3m, was
1
(b) Reaction with Piperidine. The reaction of piperidine with
observed on the H NMR spectrum together with protonated
1b+BF4 was followed by UV spectroscopy and H and 31P
NMR, as for morpholine. The reaction was also reversible
(Scheme 5). The equilibrium constant K was determined by UV
spectroscopy (Table 1; see also Figure S1 in the Supporting
Information).
-
1
morpholine (δ 2.9 (m, 4H), 3.7 (m, 4H), and 4.9 (s, 2H) ppm).
The protonated 3m was not observed. The 31P NMR spectrum
exhibited the singlet of unreacted 1b+ at 22.89 ppm and a singlet
at 21.28 ppm but did not exhibit any doublets which would
characterize a complex involving a Pd0(dppb) moiety ligated
to the CdC bond of the final compound 3m or an intermediate
product. This confirms that 1b+ and morpholine remained at
equilibrium with the final product 3m, the protonated morpho-
line and Pd0(dppb) (21.28 ppm) (Scheme 4).
The equilibrium constant K ) (1 - x)3/[x(n - 2 + 2x)2]equil
(x ) [1a+]equil/[1a+]0 ) (Dequil - D∞)/D0 - D∞), with Dequil
being the absorbance of 1b+ in the presence of n equiv of
morpholine when the equilibrium was reached, D∞ the final
absorbance when the reaction was made fully irreversible, and
D0 the initial absorbance of 1b+) was determined by UV
spectroscopy. The plot of (1 - x)3/x versus (n - 2 + 2x)2 was
linear, so that the value of K was determined from the slope of
the straight line (Figure 4, Table 1).
Comparative Reactivities of Morpholine and Piperidine
with Cationic Complexes [(η3-allyl)PdL2]+ and Relevance
to the Mechanism of Pd-Catalyzed Allylic Aminations
(Monophosphine versus Bisphosphine). The reaction of mor-
pholine and piperidine with complex 1a+, i.e., when the PdII
was ligated by 2 PPh3, was irreversible and piperidine was found
to be more reactive than morpholine (see k in Table 1). The
same reactions with 1b+, i.e., when the PdII was ligated by the
bidentate dppb ligand, were reversible, and the equilibrium lies
more toward the final products when using piperidine rather
than morpholine (see K in Table 1). These results are in
agreement with the higher basicity and thus higher reactivity
of piperidine.15
The fact that the reaction was irreversible when using a
monodentate phosphine and reversible when using a bidentate
bisphosphine seems to be a general feature. Indeed, as previously
reported the reaction was found to be irreversible when reacting
morpholine with [(η3-CH2CHCH2)Pd(PAr3)2]+ (Ar ) 4-Cl-
C6H4, 4-Me-C6H4)8 or with [(η3-PhCHCHCH2)Pd(PPh3)2]+.7
However, the reaction of morpholine with [(η3-PhCHCHCH2)-
Pd(dppb)]+ (1c+) investigated in the present work was found
(16) After a while, the solution turned pink and an absorption band at
λmax 520 nm was observed, attesting to the formation of degradation
products, e.g. PdI clusters, as was proposed by: Tromp, M., Sietsma, J. R.
A.; van Bokhoven, J. A, van Strijdonck, G. P. F.; van Haaren, R. J.; van
der Eerden, A. M. J.; van Leeuwen, P. W. N. M.; Koningsberg, D. C. Chem.
Commun. 2002, 128-129.
(17) For the reversibility of nucleophilic attack of cationic (η3-allyl)-
palladium(II) complexes by secondary amines, see ref 1w.

Pd0-Catalyzed Allylic Aminations
Organometallics, Vol. 26, No. 8, 2007 1879
Scheme 7. Mechanism of the Pd-Catalyzed Allylic
Amination When L Is a Monophosphine
Scheme 8. Mechanism of the Pd-Catalyzed Allylic
Amination When P,P Is the Bisphosphine dppb
to be reversible (Scheme 6 and Table 1; see also Figure S2 in
the Supporting information). This suggests that the nucleophilic
attack of the amine at the allyl ligand of cationic complexes
ligated by a P,P ligand is reversible (eq 1 in Scheme 6). The
reverse reaction is an oxidative addition (viz. an activation of a
C-N bond), which is indeed expected to be faster with
Pd0(dppb) than with Pd0(PPh3)2 because (i) Pd0(dppb) is
intrinsically more nucleophilic and consequently more reactive
than Pd0(PPh3)2 and (ii) the bite angle of dppb is smaller than
the P-Pd-P angle for PPh3, favoring of the oxidative addition.
Relevance to the Catalytic Cycle of Allylic Aminations
(Monophosphine versus Bisphosphine). The present work on
the mechanism of nucleophilic attack of secondary amines on
[(η3-PhC3H3Ph)PdL2]+ complexes can be connected to our
previous work on the mechanism of formation of such com-
plexes by reacting PhCHdCHCH(OAc)Ph with the related
Pd0L2 complexes.2e
The mechanism of the Pd-catalyzed allylic amination when
the palladium is ligated by two monophosphine ligands is
presented in Scheme 7. We must now take into account the
fact that acetate ions are released in catalytic reactions and can
play the role of a base for the deprotonation of the ammonium
salt in (η2-PhCHdCHCH(NHR2+)Ph)Pd0(PPh3)2 if the second-
ary amine is not used in excess.
The rate of the reaction of morpholine or piperidine with 1a+
investigated in this work (rate constant k) can be compared to
the rate of formation of 1a+AcO- in the oxidative addition of
(E)-PhCHdCHCH(Ph)OAc to Pd0(PPh3)2 generated from Pd0-
(dba)2 + 2PPh3 in DMF (Scheme 7).2e The complexation step
performed from Pd0(dba)(PPh3)2 was found to be irreversible
as soon as [PhCHdCHCH(Ph)OAc] > 30 mM (kobs > 0.135
s-1).2e The slowest step of the overall reaction was the ionization
of the intermediate Pd0 complex (η2-PhCHdCHCH(Ph)OAc)-
Pd0(PPh3)2 to 1a+AcO- (Scheme 7). The latter reaction was
reversible with k2 ) 5 × 10-3 s-1 and k-2 ≈ 60 M-1 s-1 in
DMF at 25 °C. In a catalytic reaction, the secondary amine will
therefore be in competition with the acetate ions in their reaction
with the cationic complex 1a+ (Scheme 7). If k[R2NH] >
k-2[AcO-], the overall fast irreversible nucleophilic attack of
the amine in the catalytic reaction will be limited by the
ionization step (rate constant k2), which will be the rate-limiting
step of the catalytic cycle. Considering the attack of the
morpholine with k ) 23 M-1 s-1 at 10 °C (Table 1), k can be
estimated to be ca. 90 M-1 s-1 at 25 °C, assuming an average
activation enthalpy. In a catalytic reaction involving 2 equiv of
morpholine per PhCHdCHCH(Ph)OAc, one has k[morpholine]
> k-2[AcO-] up to a 75% conversion. The nucleophilic attack
of morpholine on 1a+ will be faster than the attack of AcO-
and thus will be limited by the ionization step (rate constant
k2). This is in contradiction with the postulated mechanism of
the palladium-catalyzed nucleophilic substitution, which sup-
poses that the nucleophilic attack on cationic (η3-allyl)palladium-
(II) complexes is slower than the fast overall oxidative addition.1
The mechanism of the Pd-catalyzed allylic amination when
the palladium is ligated by a bisphosphine ligand is presented
in Scheme 8. It takes into account the role of acetate ions
released in the course of the catalytic reaction, which can
compete with the amine in the reversible deprotonation of the
free ammonium PhCHdCHCH(NHR2+)Ph.
The oxidative addition was found to be reversible when the
catalytic precursor is Pd0(dba)2 associated with dppb (1 equiv)
(Scheme 8).2e Consequently, all steps of the catalytic cycle are
reversible (Scheme 8). The overall equilibrium which releases
the final substitution product PhCHdCHCH(NHR2)Ph after the
ionization step might be made irreversible under the conditions
of catalytic reactions upon depleting the free ammonium PhCHd
CHCH(NHR2+)Ph by using a base which is stronger than
acetate, piperidine, or morpholine but which is not nucleophilic
and cannot attack the allyl ligand or the PdII center.18
The complexation step performed from Pd0(dba)(dppb) was
found to be irreversible as soon as [PhCHdCHCH(Ph)OAc] >
10 mM (kobs > 5.3 × 10-3 s-1).2e The reversible ionization step
lies more toward the cationic complex 1b+ in comparison to
the same step involving PPh3 with k′2 ) 3 × 10-4 s-1 and k′-2
< 3 × 10-7 M-1 s-1 in DMF at 25 °C.2e However, the slowest
step of the overall reaction of Pd0(dba)(dppb) and PhCHd
CHCH(Ph)OAc is still the ionization of the intermediate (η2-
PhCHdCHCH(Ph)OAc)Pd0(dppb) to 1b+AcO- (Scheme 8).2e
Considering the reversible nucleophilic attack of morpholine
onto complex 1b+ in Scheme 6, with the equilibrium constant
K ) 3 × 10-6 (Table 1), one can calculate that 18 000 equiv of
morpholine would be required to make the equilibrium in
Scheme 6 (R ) Ph) fully shifted toward its right-hand side.
Such reaction would, however, be too fast to allow the
calculation of the forward rate constant (kf) of the overall
(18) It is also expected that any other ligand of the Pd0(dppb) moiety,
as dba in catalytic reactions, will interfere in the equilibrium which releases
the Pd0(dppb) complex by formation of Pd0(dba)(dppb) (Scheme 8).

1880 Organometallics, Vol. 26, No. 8, 2007
Amatore et al.
6.08 (sext, 1H, JHH ) 12 Hz, JHH ) 12 Hz, JHH ) 7 Hz), 6.8-7.5
(m, 25H); 31P NMR (101.6 MHz, acetone-d6, H3PO4): δ 19.26 (d,
1P, JPP ) 54 Hz), 25.50 (d, 1P, JPP ) 54 Hz). 31P NMR (101.6
MHz, CDCl3, H3PO4): δ 17.12 (d, 1P, JPP ) 54 Hz), 23.07 (d, 1P,
JPP ) 54 Hz). FAB-MS (MB 001): m/z 649 [M]+, 532 [M -
PhC3H4]+.
equilibrium. The forward rate constant kf was thus estimated
from the initial slope of the curve obtained in Figure 3, after
addition of morpholine to complex 1b+ (at t ) 1670 s in Figure
3). This gives: kf ≈ 0.1 M-2 s-1 (DMF, 25 °C). In catalytic
reactions involving 2 equiv of morpholine/equiv of PhCHd
CHCH(Ph)OAc (initial concentration C0), one has kf[morpho-
line]2 . k′-2[AcO-], as soon as C0 > 10-4 M. Consequently,
the nucleophilic attack of morpholine on 1b+ is always faster
than the attack of AcO- in the usual catalytic reactions and
thus may be limited by the slow ionization step. This effect
will be amplified for the more reactive piperidine.
-
General Procedure for the Reaction of 1a+BF4-, 1b+BF4
,
and 1c+BF4- with Morpholine or Piperidine, As Monitored by
UV Spectroscopy. A 300 µL aliquot was transferred under argon
to a UV cell thermostated at 10 °C (1 mm length) from a mother
solution of 5 mL of DMF containing 4.5 mg (5 µmol, 1 mM) of
1a+BF4-. UV measurements were performed (Figure 1a). These
were followed by addition of 2 equiv of morpholine from a mother
solution. UV measurements were again performed (Figure 1b). Two
equivalents of dba (10 µL from a mother solution containing 28
mg (0.12 mmol) of dba in 2 mL of DMF) was then added, and the
UV measurements were performed (Figure 1c). In other experi-
ments, the kinetics of the reaction was followed by recording the
Conclusion
The reaction of amines (piperidine, morpholine) with cationic
complexes [(η3-PhCHCHCHPh)PdL2]+ (L ) PPh3, L2 ) dppb)
has been investigated in DMF. It proceeds via the attack at the
allyl ligand. This reaction is irreversible when L ) PPh3,
whereas it is reversible when considering the bidentate ligand
dppb. In both cases, piperidine is more reactive than morpholine.
These results can be connected to our previous work on the
mechanism and kinetics of the reaction of (E)-PhCHdCHCH-
(Ph)OAc with Pd0L2 (L ) PPh3, L2 ) dppb),2e which gives the
cationic complexes [(η3-PhCHCHCHPh)PdL2]+. Entire catalytic
cycles are now proposed for the Pd-catalyzed allylic amination
of (E)-PhCHdCHCH(Ph)OAc by piperidine or morpholine,
where the mechanisms of all steps have been established,
including characterization of all active intermediate Pd(0) or
Pd(II) complexes and their reactivities as well (Schemes 7 and
8). It appears that the nucleophilic attack of piperidine and
morpholine on [(η3-PhCHCHCHPh)PdL2]+ is in competition
with the nucleophilic attack of acetate ions generated in the
ionization step. The nucleophilic attack of the amine might thus
be limited by the slow ionization step in which the cationic
complex [(η3-PhCHCHCHPh)PdL2]+ is formed, the ionization
being turnover limiting for the catalytic cycle in the usual
catalytic reactions.
-
absorbance of 1a+BF4 at 345 nm with time after addition of a
known amount of morpholine (or piperidine) immediately after
shaking the cell by hand (Figure 2).
Similar experiments were performed for the reaction of 1b+BF4
-
(mother solution of 5 mL of DMF containing 4.1 mg (5 µmol, 1
mM) of 1b+BF4-) with morpholine and piperidine. The absorbance
-
of 1b+BF4 at 352 nm was recorded with time after successive
addition of known amounts of morpholine (Figure 3) or piperidine.
Similarly, UV spectroscopy was performed at 25 °C on 300 µL
-
of a mother solution of 1c+BF4 (7.2 mg, 1 mmol in 10 mL of
DMF) in a 1 mm cell. The UV was performed after addition of
various amounts of morpholine from a mother solution (0.25 mL
of morpholine in 5 mL of DMF).
Procedure for the Reaction of 1a+BF4 with Morpholine or
-
Piperidine, As Monitored by 1H and 31P NMR Experiments. A
3.8 mg amount (5 µmol) of 1a+BF4- was introduced into an NMR
tube containing 0.5 µL of acetone-d6, followed by 1 µL (10 µmol)
of morpholine. The solution turned orange without formation of
1
palladium black. The H and 31P NMR signals2e of 1a+ were not
detected on the first recorded NMR spectra, attesting to a fast
reaction. The substitution product 3m was formed, exhibiting the
same signals as those of an authentic sample. 1H NMR (250 MHz,
acetone-d6, TMS): δ 2.22 (m, 2H), 2.36 (m, 2H), 3.48 (t, J ) 5
Hz, 4H), 3.72 (d, J ) 9 Hz, 1H), 6.24 (dd, J ) 16 Hz, J ) 9 Hz,
1H), 6.53 (d, J ) 16 Hz, 1H), 7.01-7.30 (m, 10 H). MS (CI +
NH3): m/z 280 [M + H]+, 193 [M - C4H8NO] (100%).
Experimental Section
General Considerations. 31P NMR spectra were recorded in
acetone-d6 on a Bruker spectrometer (101 MHz) with H3PO4 as an
1
external reference. H NMR spectra were recorded in acetone-d6
of CDCl3 on a Bruker spectrometer (250 MHz). UV spectra were
recorded on an mc2 Safas Monaco spectrometer. All experiments
were performed under an argon atmosphere.
In another experiment, 3.8 mg (5 µmol) of 1a+BF4 was
-
introduced into an NMR tube containing 0.5 µL of acetone-d6,
followed by 1 µL (10 µmol) of piperidine. The coupling product
3p was formed, exhibiting the same signals as those of an authentic
Chemicals. DMF was distilled from calcium hydride under
vacuum and kept under argon. dba, morpholine, and piperidine were
obtained from commercial sources. [(η3-PhCHCHCHPh)Pd(PPh3)2]+-
1
sample. H NMR (250 MHz, acetone-d6, TMS): δ 1.35 (m, 6H),
2.20 (m, 2H), 2.34 (m, 2H), 3.73 (d, J ) 9 Hz, 1H), 6.25 (dd, J )
16 Hz, J ) 9 Hz, 1H), 6.48 (d, J ) 16 Hz, 1H), 7.01-7.40 (m, 10
H). MS (CI + CH4): m/z 278 [M + H]+, 193 [M - C5H10N]
(100%).
-
-
BF4 and [(η3-PhCHCHCHPh)Pd(dppb)]+BF4 were synthesized
as reported in our previous work.2e
Synthesis of [(η3-PhCHCHCH2)Pd(dppb)]+BF4-. dppb (0.166
g, 0.4 mmol) in 6 mL of acetone was added to a solution of [Pd-
(η3-Ph-CH-CH-CH2)(µ-Cl)]21a (0.102 g, 0.2 mmol) in 4 mL of
acetone. 4 mL of water was then added, followed by NaBF4 (0.322
g, 3.0 mmol) in 8 mM of water. A yellow solid was formed after
25 min. After filtration, the yellow solid was dissolved in dichlo-
romethane and crystallized from petroleum ether. A 127 mg amount
of [(η3-PhCHCHCH2)Pd(dppb)]+BF4- was collected (43% yield).
1H NMR (250 MHz, acetone-d6, TMS): δ 1.76 (m, 4H), 2.6 (m,
4H), 3.15 (dd, 1H, JHH ) 12 Hz, JPH ) 5 Hz), 3.90 (dd, 1H, JHH
) 7 Hz, JPH ) 7 Hz), 5.19 (dd, 1H, JHH ) 12 Hz, JPH ) 5 Hz),
6.45 (sext, 1H, JHH ) 12 Hz, JHH ) 12 Hz, JHH ) 7 Hz), 6.84-
7.71 (m, 25H). 1H NMR (250 MHz, CDCl3, TMS): δ 1.7-2.9 (m,
8H), 3.41 (dd, 1H, JHH ) 12 Hz, JPH ) 5 Hz), 3.68 (dd, 1H, JHH
) 7 Hz, JPH ) 7 Hz), 5.16 (dd, 1H, JHH ) 12 Hz, JPH ) 5 Hz),
Acknowledgment. This work has been supported in part
by the Centre National de la Recherche Scientifique (UMR
CNRS-ENS-UPMC 8640) and the Ministe`re de la Recherche
(Ecole Normale Supe´rieure). We thank Johnson Matthey for a
generous loan of palladium salt.
Supporting Information Available: Figures giving determina-
tions of equilibrium constants for the reactions of piperidine with
1b+BF4- and morpholine with 1c+BF4-. This material is available
free of charge via the Internet at http://pubs.acs.org.
OM060686P