Room-temperature Hiyama cross-couplings of arylsilanes with alkyl bromides and iodides

Article abstract of DOI:10.1021/ja0349352

The first method for achieving Hiyama couplings of unactivated alkyl bromides and iodides is reported. The desired carbon-carbon bond formation proceeds under mild conditions (room temperature) with good functional-group tolerance. Copyright

Full text of DOI:10.1021/ja0349352

Published on Web 04/16/2003
Room-Temperature Hiyama Cross-Couplings of Arylsilanes with Alkyl
Bromides and Iodides
Jae-Young Lee and Gregory C. Fu*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
Received February 28, 2003; E-mail: gcf@mit.edu
Table 1. Effect of Reaction Parameters on the Hiyama
Cross-Coupling of an Alkyl Bromide
The palladium-catalyzed Hiyama coupling of organosilicon
compounds with organic halides and sulfonates is an important
method for producing carbon-carbon bonds.1,2 Relative to some
of the other organometallic reagents that are employed in cross-
coupling processes, organosilicon compounds can be attractive due
to their ease of handling and/or low toxicity. To date, nearly all
entry
conditions
yield (%)a
1
2
3
4% Pd(OAc)2, 8% PCy3, K3PO4‚H2O
5% Pd(OAc)2, 10% P(t-Bu)2Me, KOt-Bu
2.5% [(π-allyl)PdCl]2, 15% P(t-Bu)2Me, Me4NF,
3 Å molec. sieves
0
0
0
2
studies of the Hiyama reaction have focused on couplings of Csp -X
electrophiles (e.g., aryl and vinyl halides and triflates). In contrast,
we are unaware of examples of palladium-catalyzed Hiyama cross-
4
5
4% PdBr2, 10% P(t-Bu)2Me, 2.4 equiv of Bu4NF
10% P(t-Bu)2Me, 2.4 equiv of Bu4NF
4% PdBr2, 2.4 equiv of Bu4NF
4% PdBr2, 10% PPh3, 2.4 equiv of Bu4NF
4% PdBr2, 10% P(t-Bu)3, 2.4 equiv of Bu4NF
4% PdBr2, 10% P(i-Pr)2Me, 2.4 equiv of Bu4NF
4% PdBr2, 10% IMesHCl, 2.4 equiv of Bu4NFb
81 W
0
3
3
couplings of unactivated Csp -X electrophiles.
During the past two years, we have reported that Pd/PR3-based
(PR3 ) a bulky trialkylphosphine, such as P(t-Bu)2Me or PCy3)
catalyst systems can effect Suzuki reactions of alkyl bromides,
chlorides, and tosylates.4 Building on our initial observations, Beller
established that Pd/PR3 can achieve Kumada-Murahashi couplings
of alkyl chlorides,5 and we determined that Pd/PR3 can catalyze
Stille reactions of alkyl bromides.6 In this Communication, we de-
scribe the development of a method for accomplishing room-temp-
erature Hiyama cross-couplings of alkyl bromides and iodides (eq
1), thereby expanding the scope of this important process and pro-
viding further evidence of the versatility of Pd/PR3-based catalysts.
6
0
7
8
8
0
9
23
36
10
a Determined by GC versus a calibrated internal standard (average of
two runs). b IMesHCl: 1,3-bis(2,4,6-trimethylphenyl)imidazolium chloride.
Table 2. Palladium-Catalyzed Hiyama Cross-Couplings of Alkyl
Bromides at Room Temperature
Perhaps not surprisingly, under the conditions that we have
reported for achieving Suzuki reactions of alkyl bromides,4a,d we
observe essentially no cross-coupling of dodecyl bromide with
(MeO)3SiPh (Table 1, entries 1 and 2). Fluoride is a common
activating agent for Hiyama couplings, presumably through forma-
tion of a more reactive hypervalent silicate intermediate. We have
exploited Me4NF as an activator for Pd/P(t-Bu)2Me-catalyzed Stille
reactions of alkyl bromides;6 unfortunately, these conditions were
ineffective for the desired Hiyama cross-coupling (entry 3).
However, after an extensive investigation of reaction parameters,
we discovered that PdBr2/P(t-Bu)2Me/Bu4NF efficiently couples the
bromide with the organosilane at room temperature (entry 4).
Under otherwise identical conditions in the absence of PdBr2 or
P(t-Bu)2Me, none of the Hiyama product is generated (Table 1,
entries 5 and 6, respectively). Furthermore, PPh3 is an ineffective
ligand (entry 7). As we have observed for other cross-coupling
reactions of Csp -X electrophiles,4,6 the efficiency of carbon-carbon
3
bond formation is very dependent on the bulk of the trialkylphos-
phine. Thus, either increasing (P(t-Bu)2Me f P(t-Bu)3; entry 4 vs
entry 8) or decreasing (P(t-Bu)2Me f P(i-Pr)2Me; entry 4 vs entry
9) the steric demand of the phosphine leads to a substantial drop
in the yield of the coupling product. Interestingly, we have
determined that a carbene ligand, IMes, can furnish a modestly
effective catalyst (entry 10).
a Isolated yield, average of two runs.
Table 2). As illustrated in the table, a spectrum of functional groups,
including ethers, acetals, nitriles, esters, and amides, are compatible
with the cross-coupling conditions.7
Because of the oxygen sensitivity of many trialkylphosphines,
which can make their handling inconvenient, we have advocated
the use of the corresponding air- and moisture-stable phosphonium
With PdBr2/P(t-Bu)2Me/Bu4NF, we can achieve an array of
Hiyama reactions of alkyl bromides in fairly good yield (65-81%;
9
5616
J. AM. CHEM. SOC. 2003, 125, 5616-5617
10.1021/ja0349352 CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Table 3. Room-Temperature Hiyama Cross-Couplings of Alkyl
Bromides with Arylsilanes
In summary, we have developed the first method for achieving
Hiyama couplings of unactivated alkyl bromides and iodides. The
desired carbon-carbon bond formation proceeds under mild
conditions (room temperature) with good functional-group tolerance.
Our current efforts are directed at further expanding the scope of
3
palladium-catalyzed couplings of Csp -X electrophiles.
Acknowledgment. Support has been provided by the National
Institutes of Health (National Institute of General Medical Sciences,
R01-GM62871), the Postdoctoral Fellowship Program of Korea
Science and Engineering Foundation, Merck, and Novartis. Funding
for the MIT Department of Chemistry Instrumentation Facility has
been furnished in part by NSF CHE-9808061 and NSF DBI-
9729592. We thank Johnson Matthey for supplying palladium
compounds.
Supporting Information Available: Experimental procedures and
compound characterization data (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
a Isolated yield, average of two runs.
salts as a convenient alternative.8,9 In the studies that we have
previously reported, the phosphine and the salt generally furnish
comparable reaction yields. As illustrated in Table 2, for our Hiyama
cross-coupling protocol, replacement of P(t-Bu)2Me with [HP(t-
Bu)2Me]BF4 still leads to formation of the desired products,
although in more modest yields for reactions of functionalized alkyl
bromides (e.g., entries 3, 5, and 6).
In addition to exploring the scope of this coupling method with
respect to the alkyl bromide (Table 2), we have also examined the
effect of variations in the structure of the arylsilane. As illustrated
in Table 3, an electronically and sterically diverse array of organo-
silanes undergo cross-coupling in the presence of PdBr2/P(t-Bu)2-
Me/Bu4NF. Among the substrates shown, electron-poor arylsilanes
are the least suitable reaction partners (entries 2, 6, and 10).
We have established that this method is not limited to Hiyama
cross-couplings of alkyl bromides; the same protocol is also
effective for reactions of iodides. Thus, PdBr2/P(t-Bu)2Me/Bu4NF
catalyzes the coupling of functionalized alkyl iodides in good
isolated yield at room temperature (eqs 2 and 3).
References
(1) For a review of the Hiyama reaction, see: Hiyama, T. In Metal-Catalyzed
Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH:
New York, 1998; Chapter 10. See also: Hiyama, T. J. Organomet. Chem.
2002, 653, 58-61.
(2) For some recent developments in Hiyama cross-coupling chemistry, see:
(a) Denmark, S. E.; Sweis, R. F. Acc. Chem. Res. 2002, 35, 835-846.
(b) Itami, K.; Nokami, T.; Yoshida, J.-i. J. Am. Chem. Soc. 2001, 123,
5600-5601 and references therein.
3
(3) For an overview of the difficulty of achieving coupling reactions of Csp -X
electrophiles, see: Cardenas, D. J. Angew. Chem., Int. Ed. 2003, 42, 384-
387. See also: Luh, T.-Y.; Leung, M.-k.; Wong, K.-T. Chem. ReV. 2000,
100, 3187-3204.
(4) (a) Netherton, M. R.; Dai, C.; Neuschu¨tz, K.; Fu, G. C. J. Am. Chem.
Soc. 2001, 123, 10099-10100. (b) Kirchhoff, J. H.; Dai, C.; Fu, G. C.
Angew. Chem., Int. Ed. 2002, 41, 1945-1947. (c) Netherton, M. R.; Fu,
G. C. Angew. Chem., Int. Ed. 2002, 41, 3910-3912. (d) Kirchhoff, J. H.;
Netherton, M. R.; Hills, I. D.; Fu, G. C. J. Am. Chem. Soc. 2002, 124,
13662-13663.
(5) Frisch, A. C.; Shaikh, N.; Zapf, A.; Beller, M. Angew. Chem., Int. Ed.
2002, 41, 4056-4059.
(6) Menzel, K.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 3718-3719.
(7) (a) Air-stable PdBr2(P(t-Bu)2Me)2 is equally effective. (b) The reaction
does not appear to be sensitive to the presence of small amounts of water,
but it is sensitive to the Pd:P(t-Bu)2Me ratio. (c) During the course of the
reaction, Pd(P(t-Bu)2Me)2 is the predominant phosphorus-containing
species. (d) These conditions are not effective for the coupling of the
following: more hindered alkyl bromides and iodides with PhSi(OMe)3
(<2% yield for the reaction of cyclohexyl bromide or cyclohexyl iodide);
(allyl)Si(OMe)3 or (vinyl)Si(OMe)3 with n-dodecyl bromide (<2% yield);
alkyl chlorides or alkyl tosylates with PhSi(OMe)3 (5% and 15% yield
for n-dodecyl chloride and n-dodecyl tosylate, respectively). (e) Under
these conditions, other arylsilicon compounds (e.g., PhSiCl3 and PhSiMe2-
Cl) do not cross-couple with n-dodecyl bromide (<2% yield).
(8) For examples in which phosphines and their corresponding phosphonium
salts can be used interchangeably in palladium-catalyzed coupling
processes, see: (a) Netherton, M. R.; Fu, G. C. Org. Lett. 2001, 3, 4295-
4298. (b) References 4d and 6.
(9) Strem Chemicals catalog numbers: P(t-Bu)2Me (#15-1020); [HP(t-
Bu)2Me]BF4 (#15-1023).
JA0349352
9
J. AM. CHEM. SOC. VOL. 125, NO. 19, 2003 5617