Development of a one-pot palladium-catalyzed hydrostannylation/Stille coupling protocol with catalytic amounts of tin

Full text of DOI:10.1021/jo981915n

9622
J . Org. Chem. 1998, 63, 9622-9623
Sch em e 1a
Develop m en t of a On e-P ot
P a lla d iu m -Ca ta lyzed Hyd r osta n n yla tion /
Stille Cou p lin g P r otocol w ith Ca ta lytic
Am ou n ts of Tin
Robert E. Maleczka, J r.,* and Ina Terstiege
Department of Chemistry, Michigan State University,
East Lansing, Michigan 48824
Received September 21, 1998
The Stille cross-coupling of vinyl halides with vinylstan-
nanes is a mild method for the stereoselective synthesis of
1,3-dienes, a structural unit that is often found in natural
products.1 Despite its wide use, this reaction bears some
problems. The vinyl halide and the vinyltin compound have
to be prepared stereoselectively in separate steps, prior to
their employment in the coupling reaction. Furthermore,
some vinyltins undergo protiodestannylation during chro-
matographic purification,2 and stoichiometric amounts of
toxic organotin halides are produced as a byproduct. There-
fore, we view the development of a one-pot protocol for the
stereoselective generation of vinyltins and their subsequent
cross-coupling, employing only catalytic amounts of tin, as
highly desirable.
Toward this end, Boden et al. have shown that upon the
complete palladium-mediated hydrostannylation of 1-bro-
moalkynes the addition of a further quantity of Pd catalyst
and a vinyl bromide could furnish the desired Stille product.3
This procedure represents a means of obviating the isolation
of the vinylstannane intermediate. However, the stepwise
nature of the sequence was prohibitive toward our own goal
of developing a protocol catalytic in tin in which all reaction
components are present at the beginning of the reaction
sequence.
a
Unless otherwise stated all yields refer to isolated products.
b
Based on 47% recovered vinylstannane.
While the Pd-catalyzed hydrostannylation is a well-
established synthetic tool,2b,4 the feasibility of carrying out
Pd-catalyzed hydrostannylations in the presence of a Stille
electrophile was by no means assured. We would need to
strike a balance between the catalyst requirements for high-
yielding hydrostannylations (strong σ-donor ligands such as
PPh3) and efficient cross-couplings (weaker σ-donor ligands).1c
Equally important was the need to minimize side reactions,
especially the Pd-mediated Bu3SnH reduction of vinyl
halides.5 Furthermore, understanding the regiochemical
consequence of Pd-catalyzed hydrostannylations remains an
active area of investigation.2b,6 As the focus of our study was
the combination of the hydrostannylation and cross-coupling
reactions, we wished to minimize any complications that
could arise from the hydrostannylation step being nonregi-
oselective. Therefore, we chose R-trisubstituted alkynes,
which are highly biased toward (E)-vinylstannanes upon Pd-
catalyzed hydrostannylation as our substrates.2b,6
Our initial experiments focused on the one-pot hydrostan-
nylation/Stille coupling utilizing Bu3SnH and (Ph3P)2PdCl2
as the catalyst. We were pleased to find that the reaction of
Bu3SnH with a variety of alkynes in the presence of 1.1 equiv
of bromostyrene and 0.3 mol % (PPh3)2PdCl2 resulted in
formation of the anticipated 1,3-dienes (Scheme 1) in yields
that were comparable or superior to that of the stepwise
variant.7
With the feasibility of the one-pot Pd-catalyzed hy-
drostannylation/Stille cross-coupling secured, we then fo-
cused on the employment of alternative sources for the
relatively expensive and unstable tin hydride. Hayashi et
al.8 have shown that tin hydride can be generated from (Bu3-
Sn)2O and polymethylhydrosiloxane (PMHS). These two
starting materials represent a stable and cheap storage form
of tributyltin hydride and have been shown to work well in
free-radical hydrostannylations of 1-alkynes.9 Furthermore,
PMHS has been used extensively by Fu and co-workers10
as the stoichiometric reducing agent in reactions catalytic
in tin. However, to the best of our knowledge, the (Bu3Sn)2O/
PMHS combination had never been reported for the in situ
(1) Stille, J . K. J . Am. Chem. Soc. 1987, 109, 813-817. (b) Stille, J . K.;
Simpson, J . H. J . Am. Chem. Soc. 1987, 109, 2138-2152. (c) Farina, V.;
Krishnamurthy, V.; Scott, W. J . Org. React. 1997, 50, 1-652.
(2) (a) Hitchcock, S. A.; Mayhugh, D. R.; Gregory, G. S. Tetrahedron Lett.
1995, 36, 9085-9088. (b) Zhang, H. X.; Guibe´, F.; Balavoine, G. J . Org.
Chem. 1990, 55, 1857-1867.
(3) Boden, C. D. J .; Pattenden, G.; Ye, T. J . Chem. Soc., Perkin Trans. 1
1996, 2417-2419.
(4) (a) Ichinose, Y.; Oda, H.; Oshima, K.; Utimoto, K. Bull. Chem. Soc.
J pn. 1987, 60, 3468-3470. (b) Kikukawa, K.; Umekawa, H.; Wada, F.;
Matsuda, T. Chem. Lett. 1988, 881-884. (c) Zhang, H. X.; Guibe´, F.;
Balavoine, G. Tetrahedron Lett. 1988, 29, 619-626.
(5) (a) Taniguchi, M.; Takeyama, Y.; Fugami, K.; Oshima, K.; Utimoto,
K. Bull. Chem. Soc. J pn. 1991, 64, 2593-2595. (b) Baillargeon, V. P.; Stille,
J . K. J . Am. Chem. Soc. 1986, 108, 452-461.
(6) (a) Blaskovich, M. A.; Kahn, M. J . Org. Chem. 1998, 63, 1119-1125.
(b) Betzer, J .-F.; Delaloge, F.; Muller, B.; Pancrazi, A.; Prunet, J . J . Org.
Chem. 1997, 62, 7768-7780.
(7) Under conditions that are optimal for Stille couplings (ref 1c), the
yields of the hydrostannylation reactions decrease tremendously. Evidently,
in polar solvents (DMF or NMP) and with highly active catalysts such as
(MeCN)2PdCl2, the rate of the Pd-catalyzed vinyltin formation can no longer
compete against Pd-catalyzed conversion of Bu3SnH into hexabutylditin
(Mitchell, T. N.; Amamria, A.; Killing, H.; Rutschow, D. J . Organomet. Chem.
1986, 304, 257-265).
(8) Hayashi, K.; Iyoda, J .; Shiihara, I. J . Organomet. Chem. 1967, 10,
81-94.
(9) Corey, E. J .; Wollenberg, R. H. J . Org. Chem. 1975, 40, 2265-2266.
(10) (a) Lopez, R. M.; Hays, D. S.; Fu, G. C. J . Am. Chem. Soc. 1997,
119, 6949-6950. (b) Hays, D. S.; Fu, G. C. J . Org. Chem. 1996, 61, 4-5. (c)
Hays, D. S.; Scholl, M.; Fu, G. C. J . Org. Chem. 1996, 61, 6751-6752.
10.1021/jo981915n CCC: $15.00 © 1998 American Chemical Society
Published on Web 12/04/1998

Communications
J . Org. Chem., Vol. 63, No. 26, 1998 9623
Sch em e 2
Sch em e 3
formation and reaction of Bu3SnH in Pd-mediated processes.
Our experiments (Scheme 1) showed that treatment of
1-alkynes with a mixture of (Bu3Sn)2O11 and PMHS in the
presence of bromostyrene and Pd resulted in hydrostanny-
lation of the alkyne and subsequent Stille coupling, provid-
ing the dienes in yields that were comparable to the direct
employment of Bu3SnH.12
Able to perform a one-pot hydrostannylation/Stille reac-
tion, either with Bu3SnH or in situ generated tin hydride,
and having established the compatibility of PMHS with the
other components in the reaction mixture, we next focused
on the in situ conversion of the tributyltin halide Stille
byproduct into a tin oxide. We believed that by efficiently
effecting such a transformation our protocol could be made
catalytic in tin as PMHS reduction of the newly formed
Sn-O bond would regenerate Bu3SnH and thus establish
the catalytic cycle (Scheme 2).13
To accomplish this task, we clearly need an oxygen
nucleophile that would be unreactive toward PMHS. During
this study, we found that tin chloride in the presence of
aqueous Na2CO3 and PMHS forms tin hydride, with little
decomposition of the silane.14 With this information in hand,
we returned to our hydrostannylation/Stille sequence where
we clearly demonstrated the ability to recycle the tin with
an average turnover of 2.5 (Scheme 3).15 When we employed
aqueous Na2CO3, PMHS, and only 4 mol % of tin chloride,
five turnovers of tin were achieved, providing the 1,3-diene
in 22% yield.16 Furthermore, when the tin load was in-
creased to 20%, product yields approached that of the overall
stepwise protocol despite an 80% reduction in tin. We view
these results as somewhat remarkable in that the tin species
has to undergo four separate reaction steps in one turnover.
Our study demonstrates the feasibility of a one-pot
tandem Pd-catalyzed hydrostannylation/Stille coupling with
either Bu3SnH or (Bu3Sn)2O and PMHS serving as the tin
hydride source. Furthermore, we have shown that with the
addition of Na2CO3 it is possible to carry out this fairly
complex sequence of reactions with catalytic amounts of tin.
Further studies to improve the turnover numbers and
overall yields are ongoing in order to apply this methodology
to more complex and less accessible substrates.
Ack n ow led gm en t. Generous support was provided by
the NIH (HL-58114), Abbott Laboratories (Diagnostics
Division), and MSU through an All University Research
Initiation Grant and startup funds for R.E.M. We also
thank Mr. Michael Rice for running important control
experiments.
Su p p or tin g In for m a tion Ava ila ble: Spectroscopic data for
all new compounds pictured as well as selected experimental
procedures (19 pages).
(11) The generation of a full 2 equiv of Bu3SnH from one molecule of
(Bu3Sn)2O occurs only at elevated temperatures (ref 8). Therefore, under
our reaction conditions a 2-fold excess of bistributyltin oxide is required
for complete consumption of the alkyne.
(12) We observed no evidence of palladium-mediated hydrosilylation with
PMHS, although other silanes, such as phenylsilane, did show a propensity
for hydrosilylation.
(13) The use of catalytic quantities of tin salts and equimolar amounts
of NaBH4 has proven an effective means for the in situ conversion of tin
halides to tin hydrides in free radical reactions ((a) Corey, E. J .; Suggs, J .
W. J . Org. Chem. 1975, 40, 2554-2555. (b) Curran, D. P. Synthesis 1988,
489-513 and references therein). For our purposes though, this method
appeared less than ideal as hydride reducing agents are known to reduce
Pd(II) intermediates (Tsuji, J . Palladium Reagents and Catalysts; Wiley:
Toronto, 1995; p 148). Furthermore, strong hydride donors would severely
curtail the broad functional group tolerance normally associated with the
Stille reaction.
J O981915N
(14) More basic metal alkoxides (NaOMe, NaOPh, etc.) reacted with
PMHS. Not surprisingly, application of such alkoxides to the hydrostan-
nylation/Stille coupling with catalytic amounts of tin was largely unsuc-
cessful.
(15) The same reaction sequence absent tin produced no Stille coupling
products, ruling out the Pd-mediated coupling of a transient vinylsilane
with the halide ((a) Hosomi, A.; Kohra, S.; Tominaga, Y. Chem. Pharm.
Bull. 1988, 36, 4622-4625. (b) Hatanaka, Y.; Hiyama, T. J . Org. Chem.
1988, 53, 918-920).
(16) During our study of the catalytic reactions (2-furyl3P)2Pd and diethyl
ether proved to be the Pd catalyst and solvent of choice.