Kinetics and mechanisms of the reactions of π-allylpalladium complexes with nucleophiles

Article abstract of DOI:10.1002/(SICI)1521-3773(19990201)38:3<343::AID-ANIE343>3.0.CO;2-X

Which nucleophiles are capable of attacking the allyl ligand of the Pd- stabilized allyl cation 1? This question is answered by the electrophilicity parameter of 1 which is derived from kinetic investigations.

Full text of DOI:10.1002/(SICI)1521-3773(19990201)38:3<343::AID-ANIE343>3.0.CO;2-X

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[2] H. Bock, S. Mohmand, T. Hirabayashi, G. Maier, H. P. Reisenauer,
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[3] J. M. Williams, J. R. Ferraro, R. J. Thorn, K. D. Carlson, U. Geiser,
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(Including Fullerenes): Synthesis, Structure, Properties, and Theory,
Prentice-Hall, New Jersey, 1992, pp. 11 ± 64.
Kinetics and Mechanisms of the
Reactions of p-Allylpalladium Complexes
with Nucleophiles**
Oliver Kuhn and Herbert Mayr*
[4] G. Märkl, R. Hennig, K. M. Raab, Chem. Commun. 1996, 2057 ± 2058.
[5] H. Kurata, T. Tanaka, T. Sauchi, T. Kawase, M. Oda, Chem. Lett. 1997,
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Dedicated to Professor Wolfgang Steglich
on the occasion of his 65th birthday
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2681.
Palladium(0)-catalyzed allylations of nucleophiles proceed
under mild conditions, often with high regio- and stereo-
selectivity.[1] Detailed mechanistic investigations revealed that
these reactions generally involve the intermediacy of cationic
allylpalladium complexes which have been isolated and
characterized by X-ray crystallography.[2] In the course of
our program to quanitify the reactivities of cationic electro-
philes[3] we have now turned to palladium-stabilized allyl
cations. Herein we report on the kinetics of the reactions of
the allylpalladium complexes 1a and 1b with noncharged
nucleophiles, and we demonstrate how to employ the electro-
philicity parameters derived therefrom for analyzing the
reactivities of these cationic complexes.
[7] M. Yoshifuji, I. Shima, N. Inamoto, K. Hirotsu, T. Higuchi, J. Am.
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[8] E. Fluck, G. Heckmann in Phosphorus-31 NMR Spectroscopy in
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York, 1987, pp. 61 ± 113.
[9] R. Appel in Multiple Bonds and Low Coordination in Phosphorus
Chemistry (Eds.: M. Regitz, O. Scherer), Thieme, Stuttgart, 1990,
pp. 157 ± 219.
[10] J. Zhou, A. Rieker, J. Chem. Soc. Perkin Trans. 2 1997, 931 ± 938.
[11] G. G. Aleksandrov, Y. T. Struchkov, D. I. Kalinin, M. G. Neigant, Zh.
Strukt. Khim. 1973, 14, 852 ± 858; R. West, J. A. Jorgenson, K. L.
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[12] J. Q. Chambers in The Chemistry of the Quinoid Compounds, Part 2
(Ed.: S. Patai), Wiley, London, 1974, pp. 737 ± 791; J. Q. Chambers in
The Chemistry of the Quinoid Compounds, Vol. 2, Part 2 (Eds.: S.
Patai, Z. Rappoport), Wiley, Chichester, 1988, pp. 719 ± 758.
[13] M. Geoffroy, A. Jouaiti, G. Terron, M. Cattani-Lorente, Y. Ellinger, J.
Phys. Chem. 1992, 96, 8241 ± 8245.
The allylpalladium complexes 1a, b[4] were synthesized
from 2[5] using known procedures[6, 7] (Scheme 1). The reaction
products 4a ± f were obtained from the nucleophiles 3a ± f and
[14] J. R. Morton, K. F. Preston, J. Magn. Reson. 1978, 30, 577 ± 582.
Â
[15] M. Culcasi, G. Gronchi, J. Escudie, C. Couret, L. Pujol, P. Tordo, J.
Am. Chem. Soc. 1986, 108, 3130 ± 3132; A. J. Bard, A. H. Cowley, J. E.
Kilduff, J. K. Leland, N. C. Norman, M. Pakulski, G. A. Heath, J.
Chem. Soc. Dalton Trans. 1987, 249 ± 251; S. Shah, S. C. Burdette, S.
Swavey, F. L. Urbach, J. D. Protasiewicz, Organometallics 1997, 16,
3395 ± 3400.
[16] M. Geoffroy, E. A. C. Lucken, C. Mazeline, Mol. Phys. 1974, 28, 839 ±
845; B. Cetinkaya, A. Hudson, M. F. Lappert, H. Goldwhite, J. Chem.
Ç
Soc. Chem. Commun. 1982, 609 ± 610.
[17] A. Altomare, M. C. Burla, M. Camalli, M. Cascarano, C. Giacovazzo,
A. Guagliardi, G. Polidori, J. Appl. Crystallogr. 1994, 27, 435.
[18] P. T. Beuskens, G. Admiraal, G. Beuskens, W. P. Bosman, R. de Geld-
er, R. Israel, J. M. M. Smits, The DIRDIF-94 program system,
Technical Report of the Crystallography Laboratory, University of
Nijmegen, The Netherlands, 1994.
[19] Crystal Structure Analysis Package, Molecular Structure Corporation,
1985 and 1992.
Scheme 1. Synthesis of the complexes 1a-BF4 and 1b-BF4 from 2.
the allyl complexes 1a and 1b, either by employing stoichio-
metric quantities of the allylpalladium tetrafluoroborates 1a-
BF4 or 1b-BF4 or by generating 1a and 1b in situ in the
presence of the nucleophiles
3 from [Pd(PPh3)4] or
[Pd2(dba)3 ´ CHCl3]/P(OPh)3 (10 mol%) and 3-phenylallyl
acetate, as specified in Table 1 (Scheme 2; dba ˆ dibenzyli-
deneacetone).
To determine the reaction kinetics, the allyl complexes 1a-
BF4 and 1b-BF4 were prepared and combined with 10 ± 50
equivalents of the nucleophiles 3a ± f, and the decay of the
[*] Prof. Dr. H. Mayr, Dr. O. Kuhn
Institut für Organische Chemie der Universität
Karlstrasse 23, D-80333 München (Germany)
Fax: (‡49)89-5902-254
E-mail: hmy@cup.uni-muenchen.de
[**] We thank C. Schlierf for experimental contributions as well as the
Deutsche Forschungsgemeinschaft and the Fonds der Chemischen
Industrie for financial support.
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Table 1. Products and rate constants (208C, CH2Cl2) of the reactions of 1a and 1b
with the nucleophiles 3a ± f.
Nucleophile
Product
Yield Pd
k
1
[%]
complex
[Lmol 1 s
]
(number of
experiments)
61[a]
67[a]
1a-BF4
4.49 Æ 0.30 (3)
1a-BF4
1a-PF6
1a-BF4
1a-BF4
7.53 Æ 0.18 (4)
7.03 Æ 0.40 (2)
7.30
[h]
[i]
Figure 1. UV spectra during the reaction of the complex 1a-BF4 with
diethylamine 3b (CH2Cl2, 208C).
6.49
average value
7.25 Æ 0.42 (8)
80[b]
61[a]
1b-BF4
2410 Æ 735[c] (6)
1a-BF4
1a-PF6
29.9 Æ 1.2 (6)
36.8
average value 30.9 Æ 2.8 (7)
93[b]
1b-BF4
5227 Æ 970[d] (6)
0.35 Æ 0.03[f] (4)
70[e]
69[b]
1a-BF4
1b-BF4
52[b]
1b-BF4
1b-BF4
4.49 Æ 0.23 (3)
17.5 Æ 2.1 (4)
55[g]
Scheme 3. Proposed mechanism of the synthesis of 4a ± d, which proceeds
via 1a, b.
[a] Reaction of 3-phenylallyl acetate with 3 in the presence of [Pd(PPh3)4]
(10 mol%). [b] Dropwise addition of 3-phenylallyl acetate and 3 to a solution of
[Pd2(dba)3 ´ CHCl3] (10 mol%) and P(OPh)3. [c] Calculated from DH=ˆ (32.74 Æ
view of the stereoselectivities of the reactions of related
allylpalladium complexes with amines[11] and silylated ketene
acetals.[12] Identical rates for the disappearance of the
reactants and the appearance of 4d were found when the
reaction of 1b-BF4 with 3d was monitored by 1H NMR
spectroscopy, in accord with the mechanism in Scheme 3. The
rate constant determined from NMR spectra in CDCl3 is 35%
smaller than that determined from UV spectra in CH2Cl2,[13]
corroborating the internal consistency of these kinetic data.
In previous work we have shown that the reactions of
cationic metal p complexes[14] with noncharged nucleophiles
follow the same linear free enthalpy relationship [Eq. (1);
1
1
2.05) kJmol and DS=ˆ ( 68.35 Æ 9.49) Jmol 1 K (six experiments in the range
1
between 72 and 318C). [d] Calculated from DH=ˆ (26.18 Æ 1.53) kJmol and
1
DS=ˆ ( 84.29 Æ 6.99) Jmol 1 K (six experiments in the range between 72 and
308C). [e] Reaction of 3d with stoichiometric amounts of 1a-BF4. [f] The 1H NMR
spectroscopic investigation in CDCl3 yielded k ˆ 0.2 Lmol 1s 1. [g] Reaction of 3 f
with stoichiometric amounts of 1b-BF4. [h] Under addition of 3 equivalents of
tolane. [i] Under addition of 5 equivalents of fumaronitrile.
Scheme 2. Palladium-catalyzed synthesis of 4a ± f.
lgk ˆ s(E ‡ N)
(1)
absorbance at 350 nm (1a) or 330 nm (1b) was determined by
using an immersion probe and fiber optics.[8] The pseudo first-
order rate constants were found to depend linearly on the
concentrations of the nucleophiles, indicating a second-order
rate law. The observation of isosbestic points (Figure 1) rules
out the appearance of long-lived intermediates.
Neither the replacement of BF4 by PF6 nor the addition of
tolane or fumaronitrile (additives for trapping PdL2 frag-
ments[9]) affected the reaction rates noticeably (Table 1).
In accord with these findings we suggest the mechanism
outlined in Scheme 3.[10] While the initial attack of the
nucleophiles at the metal centers of 1a and 1b cannot be
excluded by the kinetic data, the direct nucleophilic attack at
the allyl ligand, as depicted in Scheme 3, is highly probable in
E ˆ electrophilicity parameter, N ˆ nucleophilicity parame-
ter, s ˆ nucleophile-specific slope parameter] as the corre-
sponding reactions of ordinary carbocations.[3] It seemed
probable, therefore, that the rate constants summarized in
Table 1 could be reproduced by Equation (1). However, since
reliable reactivity parameters for the amines 3a ± c are not
available at present, only the E parameter of 1b can be
determined by substituting the lg k value and the N and s
parameters of 3d ± f into Equation (1).
In spite of its relatively large error limit, the electrophilicity
parameter E(1b) ˆ 10.1 Æ 0.8 (Table 2) provides a semi-
quantitative characterization of the electrophilic reactivity of
1b, since the E value is based on reactions with nucleophiles
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Table 2. Determination of the electrophilicity parameter
allylpalladium complex 1b.
E for the
This is exemplified by the fact that the reaction of 1a with
allyltributylstannane, which does not follow clear-cut second-
order kinetics, is approximately 104 times faster than pre-
dicted by Equation (1). The NMR
spectroscopic monitoring of this reac-
tion showed the formation of the bisall-
yl complex 6,[17] indicating the attack of
Nucleophile
N
s
lgk[a]
0.45
0.65
1.24
E
3d
3e
3 f
9.49[b]
11.7[b]
10.5[c]
0.93[b]
0.93[b]
1
10.0
11.0
9.3
[a] From Table 1 of this work. [b] Ref. 15. [c] H. Mayr, A. R. Ofial, K.-H.
Müller, N. Hering, unpublished results.
allylstannane at the palladium center,
in accord with literature reports.[18]
Equation (1) and Figure 2, therefore,
allow one to predict that only nucleo-
philes with N > 6 ± 7 may attack directly at the allylic ligand of
1a and 1b. If reactions with weaker nucleophiles take place,
they must proceed by initial attack at the metal center, which
has consequences for the regio- and stereoselectivities.
of large structural variety (Table 2). The relative reactivities
of the complexes 1a and 1b towards diethylamine and pi-
peridine (Table 1) yield E(1a) ꢀ 12.5. Because of the higher
electron-donating ability of P(Ph)3 compared to P(OPh)3, 1a is
two orders of magnitude less electrophilic than 1b.
The E parameters thus derived now allow one to compare
the reactivities of 1a and 1b with those of other electrophiles.
As shown in Figure 2, the palladium complexes 1a and 1b are
Received: August 7, 1998 [Z12264IE]
German version: Angew. Chem. 1999, 111, 356 ± 358
Keywords: allyl complexes
´ carbocations ´ kinetics ´
palladium ´ reaction mechanisms
[1] a) B. M. Trost, T. R. Verhoeven in Comprehensive Organometallic
Chemistry, Vol. 8 (Eds.: G. Wilkinson, F. G. A. Stone, E. W. Abel),
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hensive Organic Synthesis, Vol. 4 (Eds.: B. M. Trost, I. Fleming, M. F.
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D. L. Van Vranken, Chem. Rev. 1996, 96, 395 ± 422; d) P. von Matt,
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1995, 78, 265 ± 284; e) J. Sprinz, M. Kiefer, G. Helmchen, M. Reggelin,
G. Huttner, O. Walter, L. Zsolnai, Tetrahedron Lett. 1994, 35, 1523 ±
1526; f) A. Stolle, J. Ollivier, P. P. Piras, J. Salaün, A. de Meijere, J. Am.
Chem. Soc. 1992, 114, 4051 ± 4067.
[2] a) P. S. Manchand, H. S. Wong, J. F. Blount, J. Org. Chem. 1978, 43,
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Chem. 1987, 333, 403 ± 414.
[3] a) H. Mayr, M. Patz, Angew. Chem. 1994, 106, 990 ± 1010; Angew.
Chem. Int. Ed. Engl. 1994, 33, 938 ± 957; b) H. Mayr, O. Kuhn, M. F.
Gotta, M. Patz, J. Phys. Org. Chem. 1998, 11, 642 ± 654.
[4] Physical properties: O. Kuhn, Dissertation, Universität München,
1998.
[5] P. R. Auburn, P. B. Mackenzie, B. Bosnich, J. Am. Chem. Soc. 1985,
107, 2033 ± 2046.
[6] R. R. Schrock, J. A. Osborn, J. Am. Chem. Soc. 1971, 93, 3089 ± 3091.
[7] B. Škermark, B. Krakenberger, S. Hansson, A. Vitagliano, Organo-
metallics 1987, 6, 620 ± 628.
[8] H. Mayr, R. Schneider, C. Schade, J. Bartl, R. Bederke, J. Am. Chem.
Soc. 1990, 112, 4446 ± 4454.
[9] a) B. Crociani, S. Antonaroli, F. Di Bianca, L. Canovese, F. Visentin, P.
Uguagliati, J. Chem. Soc. Dalton Trans. 1994, 1145 ± 1151; b) P. B.
Mackenzie, J. Whelan, B. Bosnich, J. Am. Chem. Soc. 1985, 107, 2046 ±
2054.
[10] In contrast, the first step of the aminations of allylpalladium
complexes containing stronger donor ligands (chloride, amines) is
reversible, and the deprotonation of the allylammonium ions (e.g. 5)
becomes rate-determining, resulting in a second-order dependence of
the rates on amine concentration: A. Vitagliano, B. Škermark, J.
Organomet. Chem. 1988, 349, C22 ± C26.
[11] A ratio of 93:7 to 86:14 for trans:cis attack was observed for the
additions of secondary amines to (4-methoxy-1,2,3-h3-cyclohexenyl)-
palladium tetrafluoroborates: J.-E. Bäckvall, R. E. Nordberg, K.
Zetterberg, B. Škermark, Organometallics 1983, 2, 1625 ± 1629.
[12] C. Carfagna, L. Mariani, A. Musco, G. Sallese, R. Santi, J. Org. Chem.
1991, 56, 3924 ± 3927.
Figure 2. Combination of the electrophilicity and the nucleophilicity scale.
considerably weaker electrophiles than dicobalt-coordinated
propargyl cations,[14c] the tropylium ion,[3a] or iminium ions.[16]
By using the respective electrophilicities as criteria, 1b
corresponds to the tricarbonylironcycloheptadienylium
ion,[14a] while 1a corresponds to the N-methylquinolinium ion.
The approximation s ꢀ 1, which holds for most nucleo-
philes, implies the rule of thumb that electrophiles and
nucleophiles which are located on an equal level in Figure 2
(N ‡ E ˆ 5) will combine slowly at room temperature,
whereas electrophiles will not react with nucleophiles which
are located above them.[3] The applicability of this rule to
reactions of allylpalladium complexes is limited, however:
Because of the ambident electrophilic character of 1, reac-
tions with nucleophiles may either occur at the allyl ligand or
at the metal center. The latter reaction is not covered by
Equation (1).
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[13] The solvent dependence of the reactions of cationic electrophiles with
neutral nucleophiles was shown in Table 1 of ref. [3a].
[14] a) Tricarbonyldienyliron cations: H. Mayr, K.-H. Müller, D. Rau,
Angew. Chem. 1993, 105, 1732 ± 1734; Angew. Chem. Int. Ed. Engl.
1993, 32, 1630 ± 1632; b) ferrocenylmethylium ions: H. Mayr, D. Rau,
Chem. Ber. 1994, 127, 2493 ± 2498; c) hexacarbonylpropargyldicobalt
cations: O. Kuhn, D. Rau, H. Mayr, J. Am. Chem. Soc. 1998, 120, 900 ±
907.
O
O
RO
RO
O
N
N
Bn
R2
Bn
R1
1
2
Figure 1. Postulated intermediates in glycosylation reactions. R ˆ Bn,
R1 ˆ Me, R2 ˆ Ph; Bn ˆ benzyl.
[15] J. Burfeindt, M. Patz, M. Müller, H. Mayr, J. Am. Chem. Soc. 1998,
120, 3629 ± 3634.
[16] H. Mayr, A. R. Ofial, Tetrahedron Lett. 1997, 38, 3503 ± 3506.
[17] 1H NMR (400 MHz, CD2Cl2): d ˆ 1.98 (d, J ˆ 7.3 Hz, 2H, 4-H), 3.14 ±
3.47 (m, 2H, 1-H-anti, 3-H-anti), 4.02 (d, J ˆ 6.8 Hz, 2H, 1-H-syn, 3-H-
syn), 5.33 ± 5.46 (m, 1H, 2-H), 6.21 (d, J ˆ 15.7 Hz, 1H, 6-H), 6.41 ±
6.52 (m, 1H, 5-H), 7.11 ± 7.45 (m, Ph).
[18] a) A. Goliaszewski, J. Schwartz, Organometallics 1985, 4, 417 ± 419;
b) A. Goliaszewski, J. Schwartz, Tetrahedron 1985, 24, 5779 ± 5789; see
also: B. Henc, P. W. Jolly, R. Salz, S. Stobbe, G. Wilke, R. Benn, R.
Mynott, K. Seevogel, R. Goddard, C. Krüger, J. Organomet. Chem.
1980, 191, 449 ± 475.
be formed in the glycosylation reaction, is rather stable and
makes this donor unreactive. Generation of a free amine from
either NPhth or NHAc requires strongly basic conditions that
often cause partial decomposition of the product.[4] A number
of alternative amino protecting groups have therefore been de-
veloped. These include N-4,5-dichlorophthaloyl (NDCPhth),[5a]
N-tetrachlorophthaloyl (NTCPhth),[5b, c] N-2,2,2-trichloro-
ethoxycarbonyl (NTroc),[5d] N-trichloroacetyl (NCOCl3),[5e] N-
dichloroacetyl (NCOCHCl2),[5f] N-monochloroacetyl (NCO-
CH2Cl),[5g] N-trifluoroacetyl (NCOCF3),[5h] N-sulfonyl (NSO2-
Ph),[5i] N,N-diacetyl (NAc2),[5j] N-acetyl-N-2,2,2-trichloro-
ethoxycarbonyl (NAcTroc),[5k] and N-p-nitrobenzyloxycarbon-
yl (PNZ).[5l] These protecting groups have proven very useful.
In the course of a program on the preparation of N-linked
oligosaccharide analogues, we found that attempted synthesis
of the b-GalNPhth(1 !2)a ± Man linkage resulted in an
unusually high proportion of a-linked disaccharide, despite
the expected participation of the NPhth group. A similar
situation had been previously encountered.[6] A b:a mixture
(3:1, 75% yield) was formed on glycosylation of acceptor 7
with the tri-O-benzyl-NPhth-thioglycoside donor 8 (see
Scheme 1). This was presumably due to a ªmismatchº[7] in
the donor± acceptor pair, and we therefore sought out an
alternative donor that would not result in an intermediate
similar to the oxazolinium ion 1. In the search for such a
donor, we also recognized that the final deprotection step in
almost all synthetic schemes for oligosaccharides involves the
removal of persistent O-benzyl ether groups by hydrogenol-
ysis. We therefore elected to examine the N,N-dibenzyl-
thioglycoside donor 6 as a potential glycosylation agent.
2-Amino sugars bearing N-alkyl groups have not previously
been used as glycosylation donors, presumably because of the
expected problematic N-glycosylation.
The donors 6 and 8 were prepared as shown in Scheme 1.
Removal of the phthalimido group in 4 followed by O- and
N-benzylation with BnBr and NaH in DMF provided 6 in
85% overall yield. Treatment of 4, which is obtained from 3,[8]
with BnBr and NaH in the presence of Bu4NI in DMF gave 8
in high yield (88%).
To evaluate 6 as a glycosyl donor for the synthesis of the
2-amino-2-deoxy-b-d-galactopyranosyl-(1 !2)-a-d-manno-
pyranoside sequence, we condensed it with octyl 3,4,6-tri-O-
benzyl-a-d-mannopyranoside (7)[9] in the presence of the
neutral promoter dimethyl(methylthio)sulfonium tetrafluoro-
borate (DMTSBF4)[10] (Scheme 1). The glycosylation with 6
resulted in excellent b-selectivity (b:a ꢁ 13:1) and high yield
(86%). One-step deprotection of 10 by hydrogenolysis gave
the free amine 11 in 94% yield.
The 2-N,N-Dibenzylamino Group
as a Participating Group in the
Synthesis of b-Glycosides**
Hailong Jiao and Ole Hindsgaul*
2-Amino-2-deoxyglycopyranosides are important constitu-
ents of proteoglycans, glycoproteins, peptidoglycans, and
glycolipids, which are widely distributed in living organisms
or plants.[1, 2] Most are N-acetylated and are present in 1,2-
trans-glycosidic linkages. Numerous synthetic approaches to
this class of glycosidic linkage have been developed. Because
of its nucleophilicity, the amino functionality is always
protected during the glycosylation reaction to avoid N-glyco-
sylation, and the choice of protecting group can provide
control of stereoselectivity. The most commonly used method
for the construction of 1,2-trans-glycosidic linkages employs
2-amino sugar donors that contain a participating group as the
amino-protecting functionality. The ideal amino protecting
group should be stable and impart sufficient reactivity,
stereoselectivity, and high yield in glycosylation reactions.
Moreover, the protecting group should be readily removed
under mild conditions and in high yield.
Many amino protecting groups have been developed for the
1,2-trans-glycosylation of 2-amino sugars. The N-phthalimido
(NPhth)[3] group is most widely used for this purpose. The N-
acetamido (NHAc) group has also been used,[2] but the
oxazolinium intermediate 1 (Figure 1), which is presumed to
[*] Prof. O. Hindsgaul, H. Jiao
Department of Chemistry
University of Alberta
Edmonton, Alberta, T6G 2G2 (Canada)
Fax: (‡1)403-492-7705
E-mail: ole.hindsgaul@ualberta.ca
[**] We thank Dr. A. Morales-Isquierdo for measuring the high-resolution
mass spectra (ES) on a Macromass ZabSpec Hybrid Sector-TOF, and
Dr. A. Otter for recording the NMR spectra on a Varian-INOVA 600
spectrometer. This work was supported by PENCE and NSERC of
Canada.
We then investigated the behavior of 6 with the partially
protected galactopyranosides 12 ± 15,[9] which represent a
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