Palladium-catalyzed carbene insertion and trapping with carbon nucleophiles

Article abstract of DOI:10.1021/ol800431w

Palladium catalysts are shown to catalyze the three-component coupling of vinyl halides, trimethylsilyldiazomethane. and stabilized carbon nucleophiles. The reaction is believed to proceed through a palladium-carbene intermediate LX(R)Pd=CHSiMe₃ that undergoes migration of the vinyl substituent to the electrophilic carbene center to generate an ν³-allylpalladium intermediate. The allylpalladium intermediate is attacked by the carbon nucleophile to generate a vinylsilane product.

Full text of DOI:10.1021/ol800431w

ORGANIC
LETTERS
2008
Vol. 10, No. 10
1909-1911
Palladium-Catalyzed Carbene Insertion
and Trapping with Carbon Nucleophiles
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 February 25, 2008
ABSTRACT
Palladium catalysts are shown to catalyze the three-component coupling of vinyl halides, trimethylsilyldiazomethane, and stabilized carbon
nucleophiles. The reaction is believed to proceed through a palladium-carbene intermediate LX(R)PddCHSiMe3 that undergoes migration of
the vinyl substituent to the electrophilic carbene center to generate an η3-allylpalladium intermediate. The allylpalladium intermediate is attacked
by the carbon nucleophile to generate a vinylsilane product.
Vinylsilanes are versatile functional groups for electrophilic
substitution reactions. 5-Silyl-4-pentenoic acid derivatives
can be cyclized to give butyrolactones1 or extended to
generate precursors to polyene cyclizations.2 In the past,
5-trimethylsilyl-δ,γ-unsaturated carboxylic acid derivatives
have been made through either Ireland-Claisen rearrange-
ments3 or palladium-catalyzed allylic alkylation reaction.4,5
When beta hydrogens are present next to the η3-allylic
moiety, formation of dienes through elimination often
competes with allylic alkylation.
the migration of vinyl groups to carbene ligands generated
η3-allylpalladium intermediates that could be trapped with
cyclic secondary amines.6a In this work we show that a
related three-component coupling using stabilized carbon
nucleophiles can be used to construct 5-silyl-4-pentenoic acid
derivatives with two new carbon-carbon bonds.
Our mechanistic model for the reaction (Scheme 1) starts
with oxidative addition of palladium to the vinyl halide to
generate vinylpalladium complex a, followed by formation
of a palladium carbene b.10 Migration of the vinyl ligand to
the empty p orbital of the carbene ligand generates the η1-
allylpalladium complex c. Presumably, the η1-allylpalladium
complex generates an η3-allylpalladium intermediate d, that
is then attacked by the carbon nucleophile.
Diazo compounds can serve as carbene precursors in
palladium-catalyzed reactions.6–9 Previously, we showed that
(1) Miura, K.; Hayashida, J.; Takahashi, T.; Nishikori, H.; Hosomi, A.
J. Organomet. Chem. 2003, 686, 242–250.
(2) Burke, S. D.; Saunders, J. O.; Oplinger, J. A.; Murtiashaw, C. W.
Tetrahedron Lett. 1985, 26, 1131–1134.
Our initial attempt to realize this transformation using
styryl bromide 1 was met with a surprising palladium-
catalyzed transformation. When trimethylsilyl-diazomethane
and phenyl tri-n-butylstannane were added slowly to styryl
bromide 1 none of the desired vinylsilane was generated.
Instead, E,Z-diene 211 was isolated in 60% yield (Scheme
(3) Ireland, R. E.; Varney, M. D. J. Am. Chem. Soc. 1984, 106, 3668–
3670.
(4) Tsuji, J.; Yuhara, M.; Minato, M.; Yamada, H.; Sato, F.; Kobayashi,
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.
(5) Sakaguchi, K.; Yamada, T.; Ohfune, Y. Tetrahedron Lett. 2005, 46,
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.
(6) (a) Devine, S. K. J.; Van Vranken, D. L. Org. Lett. 2007, 9, 2047–
2049. (b) Greenman, K. L.; Van Vranken, D. L. Tetrahedron 2005, 61,
6438–6441. (c) Greenman, K. L.; Carter, D. S.; Van Vranken, D. L.
(9) (a) Ihara, E.; Haida, N.; Iio, M.; Inoue, K. Macromolecules 2003,
36, 36–41. (b) Ihara, E.; Kida, M.; Fujioka, M.; Haida, N.; Itoh, T.; Inoue,
Tetrahedron 2001, 57, 5219–5225
.
(7) (a) Peng, C.; Cheng, J. J.; Wang, J. B. J. Am. Chem. Soc. 2007,
129, 8708–8709. (b) Peng, C.; Wang, Y.; Wang, J. J. Am. Chem. Soc. 2008,
K. J. Polym. Sci. A: Polym. Chem. 2007, 45, 1536–1545.
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130, 1566–1567
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Ed. 2007, 46, 5587–5590
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(11) Mitsudo, T.; Fischetti, W.; Heck, R. F. J. Org. Chem. 1984, 49,
.
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10.1021/ol800431w CCC: $40.75
Published on Web 04/11/2008
2008 American Chemical Society

Scheme 1
.
Mechanistic Model for Three-Component Coupling
with Carbon Nucleophiles
Scheme 3
.
Optimization of Reaction Conditions for
Three-Component Coupling
to generate a mixture of dienes. Other bases were ineffective.
DBU gave none of the desired vinylsilane. With O,N-bis-
(trimethylsilyl)acetamide as the base the yield of vinylsilane
was 2%. By increasing the amount of malonate, addition of
malonate to the η3-allylpalladium intermediate was favored
over competitive addition of the diazo compound. When the
addition of trimethylsilyldiazomethane was stretched out over
17 h, instead of 10 h, the yield of the desired vinylsilane
was decreased, and diene products akin to those formed in
Scheme 2 were apparent by NMR. Yields increased progres-
sively with the inclusion of more malonate, which is the least
expensive component of the reaction mixture (Scheme 3).
Ultimately, our isolated yields reached 89.5% through a
judicious choice of temperature and stoichiometry.
2) along with a 73% yield of biphenyl. Palladium catalyzed
homocouplings of E-styrylbromides have been observed
before,12 and can be attributed to the carbapalladation of the
highly reactive styryl bromide by the vinylpalladium bro-
mide, followed by ꢀ-elimination of PdBr2, which is reduced
back to Pd(0) by the arylstannane. With this problem in mind,
we turned our attention away from aryl-substituted alkenes
and arylstannane nucleophiles to vinyl halides with aliphatic
substituents and enolate nucleophiles. Indeed, this combina-
tion of starting materials is expected to give a much more
interesting class of products.
Scheme 2. Heck Dimerization Outcompetes Carbene Insertion
Scheme 4. Substrate Variation
We turned to a three-component coupling of vinyl iodide
3a, 2 equiv of sodium diethylmalonate, and 1.5 equiv
trimethylsilyldiazomethane, added by syringe pump. The
malonate anion is generated by treatment of diethyl malonate
with sodium hydride. Excess sodium malonate anion helps
to neutralize the equivalent of hydroiodic acid that is
generated in the reaction. The yield for this initial reaction
was poor 24% and 30% of the vinyl iodide starting material
was present in the final reaction mixture (Scheme 3). Other
products present in the crude product mixture were consistent
with addition of the diazo compound, which is also a
stabilized carbanion, to the η3-allylpalladium intermediate
(12) (a) Tietze, L. F.; Petersen, S. J. Org. Chem. 2000, 9, 1827–1830.
(b) Wakioka, M.; Nagao, M.; Ozawa, F. Organometallics 2008, 27, 602–
608.
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Org. Lett., Vol. 10, No. 10, 2008

We next set out to explore the functional group tolerance
of the reaction. The reaction seems to require the Z vinyl
halide. When the reaction was attempted using E-3a, the
desired vinylsilane was produced in only 11% yield and most
of the vinyl iodide was recovered. One explanation for the
superiority of Z vinyl halides is that steric compression
accelerates the migration of the vinyl group to the carbene.
Vinyl bromides appear to be as effective as vinyl iodides.
The reaction even works with disubstituted vinyl iodide 3c
to generate a highly congested quaternary center. Nitriles
and silyl ethers are well tolerated as indicated by the
formation of adducts 4d and 4e, respectively (Scheme 4).
In no case did we observe products resulting from further
alkylation of the malonate product. Indeed, when diethyl
2-methylmalonate was employed none of the desired prod-
ucts were generated under the standard conditions. Bro-
mostyrene 1 was still a poor substrate under the optimized
conditions due to formation of diene products.
olefin, or stereospecifically halodesilylated to produce the
haloalkene.13 To favor protodesilylation of the vinylslane
over cyclization of the ester carbonyl,1 1 equiv of pTsOH•H2O
was used (Scheme 6).
Scheme 6. Protodesilylation Reveals a Terminal Olefin
Bromodesilylation of vinylsilane 4a was attempted under
the two-step conditions of Kobayashi.14 However, bromo-
lactonization competed with bromine addition even in the
presence of 1 equiv of n-Bu4N+Br-. When malononitrile
derivative 6a was used as a substrate the desired vinyl
bromide was isolated as a 7:1 ratio of E and Z isomers
(Scheme 7). The ability to start with a vinyl halide and,
through a two-step sequence of carbene insertion/bromode-
silylation, regenerate a vinyl halide holds particular promise
for iterative carbene insertions.
Scheme 5. Application of Other Stabilized Carbon Nucleophiles
Scheme 7. Halodesilylation Regenerates a Vinyl Halide
In conclusion, we have developed a new three-component
coupling using Z vinyl halides, trimethylsilyldiazomethane,
and stabilized carbon nucleophiles to generate vinylsilanes.
Acknowledgment. This work was supported by ACS PRF
42780-AC1.
We next explored the ability of other stabilized carbanions,
similar to diethyl malonate, to participate in the reaction
(Scheme 5). Solubility limited the number of equivalents that
could be employed in the reaction without changing the
concentration of the other reagents. Thus, with only 6 equiv
of nucleophile/base, ethyl cyanoacetate gave only 47% yield
of vinylsilane 5a as a 1.2:1 mixture of diastereomers.
Surprisingly, malononitrile gave an even higher yield of
vinylsilane 6a with fewer equivalents of the nucleophile.
Vinylsilanes are valuable synthetic intermediates. For
example, they can be protodesilylated to reveal the parent
Supporting Information Available: Experimental pro-
cedures and spectral data for compounds 2, 3a-e, and 4a-e.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL800431W
(13) Mori, M.; Kaneta, N.; Shibasaki, M. J. Organomet. Chem. 1994,
464, 35–40.
(14) Kobayashi, Y.; Nakayama, Y.; Mizojiri, R. Tetrahedron 1998, 54,
1053–1062.
Org. Lett., Vol. 10, No. 10, 2008
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