Cine-Substitution in the Stille Coupling: Evidence for the Carbenoid Reactivity of sp3-gem-Organodimetallic Iodopalladio-trialkylstannylalkane Intermediates

Article abstract of DOI:10.1021/ja037409j

Two complementary routes to sp³-gem-organodimetallic iodopalladio-trialkylstannanylalkanes are presented. Such intermediates have been proposed as Pd-carbenoid precursors in the Busacca-Farina cine-substitution mechanism in the Stille coupling. The decomposition of iodomethyltrialkylstannanes by Pd(0) catalysts was monitored by ¹H, ²D, and ¹¹⁹Sn NMR. The formation of ethylene, trace formaldehyde, and iodotrialkylstannanes was detected. When the reaction was carried out in the presence of norbornene, the corresponding cyclopropane was produced in good yield. These observations are consistent with the intermediacy of a Pd-carbenoid species. sp³-gem-Organodimetallic iodopalladio-trialkylstannanylalkane complexes were also prepared under stoichiometric conditions via transmetalation from tin to Pd(II). Me₃SnCH₂Sn(CH₂CH₂CH₂)₃ reacted with [(D-t-BPF)PdI]⁺I^-, yielding the (D-t-BPF)Pd(II)ICH₂SnMe₃ complex that dimerized to form ethylene and cyclopropanated norbornene. The carbenoid reactivity of iodopalladio-trialkylstannanylalkanes complexes validates the Busacca-Farina mechanism of the cine-substitution in the Stille coupling. Copyright

Full text of DOI:10.1021/ja037409j

Published on Web 09/27/2003
Cine-Substitution in the Stille Coupling: Evidence for the Carbenoid
Reactivity of sp3-gem-Organodimetallic Iodopalladio-trialkylstannylalkane
Intermediates
Eric Fillion* and Nicholas J. Taylor1
Department of Chemistry, UniVersity of Waterloo, Waterloo, Ontario, Canada N2L 3G1
Received July 19, 2003; E-mail: efillion@uwaterloo.ca
Scheme 1
Palladium-catalyzed cross-coupling reactions are general and
commonly used synthetic methods for the formation of carbon-
carbon bonds.2 The cross-coupling methodologies tolerate a wide
array of functional groups and display high regioselectivity and
stereospecificity. When vinylmetals are used as coupling partners,
however, a reversal of regioselectivity and formation of the cine-
substitution products is often observed. The cine-substitution is most
frequently encountered in the Stille coupling of R-substituted vinyl
stannanes,3 and methods overcoming this selectivity problem have
been reported.4
Two widely accepted cine-substitution mechanisms have been
postulated: the Kikukawa3g and the Busacca-Farina3d,e mecha-
nisms. The initial formation of a key sp3-gem-dimetallic Pd-
stannylalkane intermediate 2, via regioselective migratory insertion
of PhPd(II)X (X ) I, BF4) into the vinylstannane 1, is suggested
for both mechanistic pathways (Scheme 1).
formation of formaldehyde (δH ) 8.75) (<1%) (eq 1).9 More
Kikukawa proposed that intermediate 2 undergoes a â-hydride
elimination to afford the vinylstannane 3.3g Subsequent hydro-
palladation across the alkene with opposite regiochemistry followed
by anti elimination of Bu3SnBF4 and regeneration of the catalyst
leads to the cine-product 4. All efforts to detect and identify the
uncomplexed vinylstannanane 3 have been unsuccessful.
Labeling and crossover experiments by Busacca and Farina3d,e
provided evidence to support a mechanism involving an intermedi-
ate palladium-carbene 5, formed via a four-center transmetalation
of the gem-dimetallic intermediate 2 with loss of Bu3SnI (Scheme
1). A 1,3-hydride shift followed by reductive elimination afforded
the cine-substitution product 4.
importantly, when the decomposition of 6 was carried out in the
presence of a 5-fold excess of norbornene, exo-tricyclo[3.2.1.02,4]-
octane (8) was formed in 64% yield (eq 2).10 Ethylene and CH2O
were also present.11 These observations were consistent with the
intermediacy of a methylene carbenoid species.
Iodomethylstannatrane (6) displayed an enhanced reactivity in
the oxidative insertion reaction as compared with ICH2SnBu3 and
ICH2SnMe3.12 The cyclopropanation of norbornene (9-fold excess)
by ICH2SnBu3 catalyzed by Pd(P(t-Bu)3)2 (25 mol %) yielded 8 in
71% yield (based on 33% conversion after 15 days). In addition,
C2H4, CH2O, MeSnBu3 (δΗ CH3 ) 0.11) (24%), and CH2(SnBu3)2
(δΗ CH2 ) -0.16) (5%) were formed.13
The synthetic importance of the Stille coupling demands that
the cine-substitution mechanism be clearly established.
Providing that the â-hydride shift is not an available reaction
pathway, the preparation of the sp3-gem-dimetallic halo-Pd(II)/
trialkylstannylalkane species should lead to Pd-stabilized carbenes
following the Busacca-Farina mechanism, and further react in
reactions typical of metal-carbenes.5 This Communication reports
two approaches for the preparation of gem-dimetallic iodopalladio-
trialkylstannylalkane complexes as Pd-carbenoid precursors to probe
the cine-substitution mechanism in the Stille coupling.
Our initial efforts were directed at generating sp3-gem-dimetallic
iodo-Pd/trialkylstannylalkane species by oxidative insertion of Pd(0)
catalysts into iodomethyltrialkylstannanes. It was anticipated that
the decomposition of iodomethyltrialkylstannanes by Pd(0) catalysts
would lead to the formation of ethylene by dimerization of the car-
benoid intermediate. To test this hypothesis, iodomethylstannatrane6
(6) (δΗ ) 1.68, δSn ) -29.1) was decomposed in benzene-d6 in
the presence of Pd(P(t-Bu)3)2 (25 mol %) at room temperature for
36-48 h.7 The reactions were carried out in sealed NMR tubes
and monitored by 1H and 119Sn NMR spectroscopy.8 Most reward-
ingly, the presence of ethylene (δΗ ) 5.24) (not quantified) and
iodostannatrane (7) (δSn ) -57.8) was detected, with competitive
Further insights into the metal-carbenoid mechanism were gained
from observations made with the deuterium-labeled d2-6. The d2-
methylene singlet (δD ) 1.68) of d2-6 decreased while a set of
signals appeared when treated with Pd(P(t-Bu)3)2 (25 mol %) and
excess norbornene. H NMR established the clean formation of
tricycle d2-8, CD2O, and C2D4 (eq 3).14
2
The need for a Pd(0) catalyst in these reactions was confirmed
by treating 6 with 50 to up to 200 mol % of P(t-Bu)3 in the absence
9
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J. AM. CHEM. SOC. 2003, 125, 12700-12701
10.1021/ja037409j CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
(2) (a) Diedrich, F., Stang, P. J., Eds. Metal-Catalyzed, Cross Coupling
Reactions; Wiley-VCH: Weinheim, 1998. (b) Farina, V.; Krishnamurthy,
V.; Scott, W. J. Org. React. 1998, 50, 1-657. (c) Miyaura, N.; Suzuki,
A. Chem. ReV. 1995, 95, 2457-2483.
or presence of a 10-fold excess of norbornene. No decomposition
of 6 or formation of cyclopropane 8, ethylene, or formaldehyde
was detected after several days at room temperature, ruling out
phosphine-mediated decomposition mechanisms.
(3) (a) Flohr, A. Tetrahedron Lett. 1998, 39, 5177-5180. (b) Quayle, P.;
Wang, J.; Xu, J. Tetrahedron Lett. 1998, 39, 489-492. (c) Chen, S.-H.
Tetrahedron Lett. 1997, 38, 4741-4744. (d) Farina, V.; Hossain, M. A.
Tetrahedron Lett. 1996, 37, 6997-7000. (e) Busacca, C. A.; Swestock,
J.; Johnson, R. E.; Bailey, T. R.; Musza, L.; Rodger, C. A. J. Org. Chem.
1994, 59, 7553-7556. (f) Stork, G.; Isaacs, R. C. A. J. Am. Chem. Soc.
1990, 112, 7399-7400. (g) Kikukawa, K.; Umekawa, H.; Matsuda, T. J.
Organomet. Chem. 1986, 311, C44-C46.
Envisioning that halopalladio-trialkylstannylalkane intermedi-
ates may be alternatively accessed under stoichiometric condi-
tions via transmetalation from tin to Pd(II) led to the synthesis
of Me3SnCH2Sn(CH2CH2CH2)3N (9) (δΗ CH2 ) -0.29).15 It
was postulated that the stannatrane moiety of 9 would trans-
metalate preferentially with Pd(II)I2 complexes, giving cis-
Pd(II)I(CH2SnMe3) intermediates that would dimerize and cyclo-
propanate alkene.16 Indeed, treatment of a benzene-d6 solution of
9 and norbornene (9 equiv) with cationic [Pd(II)I]+I- complex 10
(1.05 equiv) at 55 °C for 6 days provided tricycle 8 in 36% yield,
C2H4 (not quantified), iodostannatrane (7), Me3SnI (δΗ CH3 ) 0.11)
(59%), and Me4Sn (δΗ CH3 ) 0.05) (12%) (based on 80%
conversion) (eq 4).17
(4) (a) Han, X. H.; Stoltz, B. M.; Corey, E. J. J. Am. Chem. Soc. 1999, 121,
7600-7605. (b) Allred, G. D.; Liebeskind, L. S. J. Am. Chem. Soc. 1996,
118, 2748-2749.
(5) (a) Zaragoza Do¨rwald, F. Metal Carbenes in Organic Chemistry; Wiley-
VCH: Weinheim, 1999. Pd-carbenes have been proposed in various
transformations, see: (b) Nevado, C.; Charruault, L.; Michelet, V.; Nieto-
Oberhuber, C.; Mun˜oz, M. P.; Me´ndez, M.; Rager, M.-N.; Geneˆt, J.-P.;
Echavarren, A. M. Eur. J. Org. Chem. 2003, 706-713. (c) Sierra, M. A.;
del Amo, J. C.; Manchen˜o, M. J.; Go´mez-Gallego, M. J. Am. Chem. Soc.
2001, 123, 851-861. (d) Kozawa, Y.; Mori, M. Tetrahedron Lett. 2001,
42, 4869-4873. (e) Monteiro, N.; Balme, G. J. Org. Chem. 2000, 65,
3223-3226. (f) Monteiro, N.; Gore´, J.; Hemelryck, B. V.; Balme, G.
Synlett 1994, 447-449.
(6) Jensen, M. S.; Yang, C.; Hsiao, Y.; Rivera, N.; Wells, K. M.; Chung, J.
Y. L.; Yasuda, N.; Hughes, D. L.; Reider, P. J. Org. Lett. 2002, 2, 1081-
1084.
(7) Oxidative insertion of Pd(0) into the sp3-carbon-halide bond, see: (a)
Netherton, M. R.; Dai, C.; Neuschu¨tz, K.; Fu, G. C. J. Am. Chem. Soc.
2001, 123, 10099-10100. (b) Luh, T.-Y.; Leung, M.-k.; Wong, K.-T.
Chem. ReV. 2000, 100, 3187-3204.
(8) The yields were determined by 1H NMR spectroscopy using mesitylene
or 1,4-dioxane as an internal standard.
As illustrated in Scheme 2, oxidative insertion of Pd(0) into the
C-I bond18 of 6, ICH2SnBu3, or ICH2SnMe3 and reaction of Pd(II)
complex 10 with 9 converge to the key intermediate cis-iodo-
(methyltrialkylstannane)Pd(II) complexes 12. These intermediates
12 rapidly react and are not detectable on the NMR time scale.
Formation of ethylene occurs by dimerization of intermediate 12.19
The dimetallic 12 reacts with the residual O2 present in solution to
generate CH2O and with norbornene, providing tricycle 8.20-22
(9) Decomposition of the gem-dimetallic Me3SiCH2WCl5 at 20 °C in benzene
led to the formation of ethylene (not quantified), Me3SiCl (29-33%),
(CH3)3SiCH2Cl (24-25%), (Me3SiCH2)2 (18-22%), and Me4Si (24-
26%). An intermediate tungsten-stabilized carbene was suggested to
rationalize the formation of (CH3)3SiCl and ethylene, see: Dolgoplosk,
B. A.; Makovetskii, K. L.; Oreshkin, I. A.; Tinyakova, E. I.; Svergun, V.
I. Dokl. Akad. Nauk SSSR 1975, 223, 1369-1370.
(10) Cinnamyl methyl ether did not provide the corresponding cyclopropane,
and styrene yielded cyclopropylbenzene in 5% yield. Coordination of the
olefin with the Pd center has been reported to be essential in the
cyclopropanation reaction by Pd-carbenes and the efficiency of the reaction
greatly affected by sterics, see: Anciaux, A. J.; Hubert, A. J.; Noels, A.
F.; Petiniot, N.; Teyssie´, P. J. Org. Chem. 1980, 45, 695-702.
(11) When the decomposition of 6 was catalyzed by Pd(PPh3)4 (25 mol %) at
room temperature for 48-72 h, 1H NMR showed the formation of C2H4,
CH2O, and iodostannatrane (7) with subsequent appearance of styrene,
in up to 38% yield. Such rearrangement of palladium(II) complexes has
been previously reported, see: Morita, D. K.; Stille, J. K.; Norton, J. R.
J. Am. Chem. Soc. 1995, 117, 8576-8581 and the Supporting Information.
(12) Alkylstannatranes in the Stille coupling, see: Vedejs, E.; Haight, A. R.;
Moss, W. O. J. Am. Chem. Soc. 1992, 114, 6556-6558.
Scheme 2
(13) Similar results were obtained with ICH2SnMe3.
(14) In some run, the dehalogenated byproduct, methylstannatrane, was
detected.
In conclusion, two complementary routes to sp3-gem-dimetallic
iodopalladio(II)-trialkylstannylalkane complexes have been reported.
These species exhibit carbenoid reactivity undergoing dimerization
and alkene cyclopropanation, therefore validating the Busacca-
Farina cine-substitution mechanism. Efforts to develop the synthetic
potential of these species are now underway in our laboratories
and will be reported in due course.
(15) Me3SnCH2Sn(CH2CH2CH2)3N was selected for simplification of the 1H
NMR, and for its ease of synthesis and purification.
(16) The transmetalation of alkylstannatrane with Pd(II) complexes was initially
explored by treating (PPh3)2PdCl2 with 6 to cleanly give (PPh3)2PdCl-
(CH2I) as observed by 1H NMR. This Pd(II) complex decomposed over
5 days to C2H4, CH2O, and propene as reported by McCrindle, see ref
20.
(17) The bidentate 1,1′-bis(di-tert-butylphosphino)ferrocene ligand (D-t-BPF)
was rationally selected to lead to a cis-PdI(CH2SnMe3) complex following
transmetalation, see: Mann, G.; Shelby, Q.; Roy, A. H.; Hartwig, J. F.
Organometallics 2003, 22, 2775-2789.
Acknowledgment. The authors would like to thank NSERC
(Canada) and the University of Waterloo for financial support. This
research was supported by an award from Research Corporation.
Dr. V. Farina, Dr. C. Busacca, and Dr. M. Eriksson are thanked
for sharing unpublished results and helpful discussions.
(18) Insertion into the C-Sn bond has been excluded because CH2(SnBu3)2
was inert to Pd(P(t-Bu)3)2.
(19) No experimental data are available, suggesting the loss of halotrialkyltin
prior to dimerization, cyclopropanation, or O2 trapping.
(20) Chloro(chloromethyl) Pd(II) complexes dimerize and undergo oxidation
to CH2O under air, see: McCrindle, R.; Ferguson, G.; McAlees, A. J.;
Arsenault, G. J.; Gupta, A.; Jennings, M. C. Organometallics 1995, 14,
2741-2748.
Supporting Information Available: Procedures,1H, 2H, and 119Sn
NMR spectra, and tables of crystallographic data for 10 (PDF and CIF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
(21) (a) Bernardi, F.; Bottoni, A.; Miscione, G. P. Organometallics 2001, 20,
2751-2758. (b) Bernardi, F.; Bottoni, A.; Miscione, G. P. Organometallics
2000, 19, 5529-5532.
(22) When R3Sn is stannatrane (Scheme 2), 12 displays an enhanced carbenoid
character in comparison to Bu3Sn and Me3Sn that is a direct reflection of
its superior transmetallating ability; the carbene products were cleanly
formed, and no or trace of dehalogenated byproduct was observed.
References
(1) Corresponding author concerning the X-ray crystal structure.
JA037409J
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