Palladium-catalyzed carbene insertion into vinyl halides and trapping with amines

Article abstract of DOI:10.1021/ol070758o

Palladium is shown to catalyze the three-component coupling of vinyl halides, trimethytsilyldiazomethane, and amines to generate allylamines. The mechanism is believed to Involve formation of an R-Pd=CHSiMe₃ intermediate that undergoes migratio

Full text of DOI:10.1021/ol070758o

ORGANIC
LETTERS
2007
Vol. 9, No. 10
2047-2049
Palladium-Catalyzed Carbene Insertion
into Vinyl Halides and Trapping with
Amines
Sean K. J. Devine and David L. Van Vranken*
Department of Chemistry, 1102 Natural Sciences, UniVersity of California,
IrVine, California 92697-2025
daVid.VV@uci.edu
Received March 28, 2007
ABSTRACT
Palladium is shown to catalyze the three-component coupling of vinyl halides, trimethylsilyldiazomethane, and amines to generate allylamines.
The mechanism is believed to involve formation of an R Pd CHSiMe3 intermediate that undergoes migration of the vinyl ligand to the empty
p-orbital of the carbene ligand. The resulting
1-allylpalladium species forms an 3-allylpalladium intermediate that is trapped by the amine
nucleophile. Under the conditions tested, cyclic secondary amines and terminal vinyl iodides give the best results.
−
d
η
η
Palladium-catalyzed insertion of carbon monoxide and isoni-
triles into carbon-halogen bonds offers a powerful method
for joining molecular fragments through one-carbon units.1
There is growing interest in palladium-catalyzed reac-
tions that stitch together organic fragments using carbene
units.2 Bro¨ring and co-workers have shown that diazo
compounds can serve as precursors of palladium-carbene
complexes.3 Carbene formation is likely to proceed through
attack of the anionic diazo compound on a cationic Pd(II)
species (Scheme 1).
ligands donate into the empty orbital of the carbene, making
them resistant to this type of bond migration. We set out
to take advantage of migratory insertion of carbenes in
R-PddCHSiMe3 complexes as a way to effect three-
component couplings of vinyl halides, trimethylsilylcarbenes,
and amine nucleophiles (Scheme 2). 1-Trimethylsilyl sub-
Scheme 2. Migration of Vinyl Groups Generates
η3-Allylpalladium Intermediates That Are Subject to Attack
Scheme 1. Mechanism for Pd-Carbene Formation from
Diazo Compounds
stituents on η3-allylpalladium complexes direct attack of
nucleophiles to the opposite terminus, leading to vinylsilanes,
(1) (a) Brunet, J. J.; Chauvin, R. Chem. Soc. ReV. 1995, 24, 89-95. (b)
Goure, W. F.; Wright, M. E.; Davis, P. D.; Labadie, S. S.; Stille, J. K. J.
Am. Chem. Soc. 1984, 106, 6417-6422. (c) Ni, Y.; Montgomery, J. J. Am.
Chem. Soc. 2006, 128, 2609-2612. (d) Ishiyama, T.; Oh-e, T.; Miyaura,
N.; Suzuki, A. Tetrahedron Lett. 1992, 33, 4465-4468.
(2) (a) Greenman, K. L.; Carter, D. S.; Van Vranken, D. L. Tetrahedron
2001, 57, 5219-5225. (b) Greenman, K. L.; Van Vranken, D. L.
Tetrahedron 2005, 61, 6438-6441.
In most palladium-carbene complexes with anionic
ligands, R, cis to the carbene (e.g., R-PddCX2), the Pd-R
bonds tend to align with the empty p-orbital of the carbenes
an orientation that facilitates donation and ultimately bond
migration. The nitrogen lone pairs of N-heterocyclic carbene
(3) Bro¨ring, M.; Brandt, C. D.; Stellwag, S. Chem. Commun. 2003,
2344-2345.
10.1021/ol070758o CCC: $37.00
© 2007 American Chemical Society
Published on Web 04/19/2007

which are useful intermediates for stereospecific organic
transformations.4
observed in other palladium-catalyzed reactions of amines,
such as arylation,5 CO insertion,6 and allylic alkylations.7
Initially, we explored the three-component coupling of
various amines with a readily synthesized vinyl iodide,
1-((Z)-4-iodobut-3-enyl)benzene (1a), and trimethylsilyldia-
zomethane using Pd2dba3•CHCl3 as the catalyst precursor
(Scheme 3) and adding the diazo compound by syringe pump
A number of different haloalkenes were subjected to the
palladium-catalyzed three-component coupling with piperi-
dine and trimethylsilyldiazomethane to generate the corre-
sponding allylamines in varying yields (Scheme 4). Terminal
Scheme 4. Three-Component Coupling of Vinyl Halides,
Trimethylsilyldiazomethane, and Piperidine
Scheme 3. Three-Component Coupling of Vinyl Iodide 1a,
Trimethylsilyldiazomethane, and Amines
vinyl iodides give the best results. Surprisingly, the vinyl
iodide 1b effectively generated tertiary allylic amine 3 in
55% yield. Unfortunately, the yield of allylamine 4 generated
from the internal vinyl iodide 1c was low, although these
achiral products are arguably less interesting than the chiral
amines generated from terminal vinyl halides. The vinyl
bromide 1d gave a lower yield of the corresponding
allylamine 2c. An attempt to perform the reaction on oct-
1-enyl triflate gave none of the desired allylamine, implying
that halide is important for the reaction. At present, the role
of the halide ion is unclear.
over 10 h. The results using benzylamine as a nucleophile
gave the desired vinylsilane 2a in 19% yield; about half of
the starting material remained unreacted, implying low
catalyst turnover.
Cyclic, secondary amines such as pyrrolidine and piperi-
dine gave better results than benzylamine. The yield of
allylamine 2b was dramatically improved by addition of
potassium carbonate and addition of phenylboronic acid to
reduce any PdX2 salts that might be degrading the diazo
compound. However, the improved yield did not extend to
other amines. Piperidine generated high yields of the desired
vinylsilane 2c. Morpholine (pKa′ 8.4) gave a lower yield of
vinylsilane than piperidine (pKa′ 11.2), but good results were
achieved by doubling the stoichiometry of morpholine.
Higher stoichiometries of amine did not lead to better results
with benzylamine. Instead, the yield of vinylsilane 2a
increased to 30% by dropping to 2 equiv of benzylamine
and increasing the temperature to 66 °C. In general, the
variation in yields does not correlate with the basicity of the
amines in organic solvents. This lack of correlation has been
A mechanistic model that is consistent with our results
and observations involves initial oxidative addition to form
a vinylpalladium halide complex a (Scheme 5). Addition of
the diazo compound to this electrophilic complex would
generate a vinylpalladium carbene b. Migration of the vinyl
group to the carbene center, which is now precedented in a
number of stoichiometric transformations,8 would generate
an η1-allylpalladium complex c. Importantly, for chiral
(5) Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald, S. L. J.
Org. Chem. 2000, 65, 1158-1174.
(6) Ozawa, F.; Soyama, H.; Yanagihara, H.; Aoyama, I.; Takino, H.;
Izawa, K.; Yamamoto, A. J. Am. Chem. Soc. 1985, 107, 3235-3245.
(7) Hierso, J.-C.; Fihri, A.; Amardeil, R.; Meunier, P.; Doucet, H.;
Santelli, M. Tetrahedron 2005, 61, 9759-9766.
(4) Inami, H.; Ito, T.; Urabe, H.; Sato, F. Tetrahedron Lett. 1993, 34,
5919-5922.
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Org. Lett., Vol. 9, No. 10, 2007

fragment assembly, generation of chiral centers through
carbene insertion, and regiocontrolled allylic alkylation.
Simple palladium(II) salts are active catalysts for polym-
erization of ethyl diazoacetate with loss of nitrogen.10 While
not optimized for ethyl diazoacetate, the three-component
coupling seems to work well (Scheme 7), in spite of the
Scheme 5. Proposed Catalytic Cycle
Scheme 7. Synthesis of γ-Amino Acids through Carbene
Insertion
potential for polymerization. Clearly, as long as the Pd(II)
complex has a migratable alkyl ligand, migratory insertion
can win out over polymerization of the diazo compound.
These results suggest that other diazo compounds might be
effective in related palladium-catalyzed processes.
This communication shows the exciting potential for
palladium-catalyzed carbene insertions to generate allyl-
amines using vinyl halides and diazo compounds. While there
is strong analogy with palladium-catalyzed CO insertion
processes, the potential for complex molecule synthesis and
asymmetric induction adds new dimensions to these pro-
cesses.
products such as 2c, 3, and 4, the stereochemistry is set in
this migratory insertion step and cannot be lost through η1-
η3-η1 interconversions. Control of this key migration step
represents an attractive target for asymmetric induction.
Isomerization to the more stable η3-allylpalladium complex
d, with anti substituents, may precede nucleophilic attack to
give the E vinylsilanes 2 and 3 that are observed as products.
Vinylsilanes are valuable intermediates for stereospecific
electrophilic substitution reactions; even protodesilylation
generates a useful terminal olefin. After the trimethylsilyl
group directs attack of the nucleophile to the more hindered
position of the η3-allylpalladium complex, it can be removed
from the product (Scheme 6). Other recently developed
palladium-catalyzed reactions for generating hindered R,R-
disubstituted allylic amines from achiral substrates have not
yet been shown to proceed with high levels of enantiose-
lection.9 This new approach combines the power of allylic
Acknowledgment. This work was supported by ACS
PRF 42780-AC1.
Supporting Information Available: Experimental pro-
cedures and spectral data for compounds 2-6. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL070758O
(8) (a) Danopoulos, A. A.; Tsoureas, N.; Green, J. C.; Hursthouse, M.
B. Chem. Commun. 2003, 756-757. (b) Albe`niz, A. C.; Espinet, P.;
Manrique, R.; Perez-Mateo, A. Angew. Chem., Int. Ed. 2002, 41, 2363-
2366. (c) Sole, D.; Vallverdu, L.; Solans, X.; Font-Bardia, M.; Bonjoch, J.
Organometallics 2004, 23, 1438-1447.
Scheme 6. Access to R,R-Disubstituted Tertiary Allylic
Amines
(9) (a) Faller, J. W.; Wilt, J. C. Organometallics 2005, 24, 5076-5083.
(b) Faller, J. W.; Wilt, J. C. Org. Lett. 2005, 7, 633-636. (c) Watson, L.
D. G.; Yudin, A. K. J. Am. Chem. Soc. 2005, 127, 17516-17529.
(10) Ihara, E.; Haida, N.; Iio, M.; Inoue, K. Macromolecules 2003, 36,
36-41.
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