Pd-catalyzed synthesis of allylic silanes from allylic ethers

Article abstract of DOI:10.1021/ol9023908

Chemical Equation Presented Allylic phenyl ethers serve as electrophiles toward Pd(O) en route to a variety of allylic silanes. The reactions can be run at room temperature in water as the only medium using micellar catalysis

Full text of DOI:10.1021/ol9023908

ORGANIC
LETTERS
2010
Vol. 12, No. 1
28-31
Pd-Catalyzed Synthesis of Allylic
Silanes from Allylic Ethers
Ralph Moser, Takashi Nishikata, and Bruce H. Lipshutz*
Department of Chemistry & Biochemistry, UniVersity of California,
Santa Barbara, California 93106
lipshutz@chem.ucsb.edu
Received October 16, 2009
ABSTRACT
Allylic phenyl ethers serve as electrophiles toward Pd(0) en route to a variety of allylic silanes. The reactions can be run at room temperature
in water as the only medium using micellar catalysis.
Allylic silanes are among the most important and widely used
reagents in organic synthesis.1 Well known transformations,
such as the Hosomi-Sakurai reaction,2 or Hiyama cou-
plings,3 underscore their value as building blocks, in
particular for complex natural product syntheses.1 Although
a vast array of synthetic methods for the preparation of allylic
silanes now exists,4,5 further development of selective entries
to allylic silanes are still of considerable interest. Tsuji
described a general silylation reaction of allylic esters with
organodisilanes in the presence of a palladium catalyst at
100 °C.6 Terao and Kambe reported the synthesis of allylic
silanes from chlorosilanes and allylic ethers using palladium
or nickel catalysts and an excess of Grignard reagents.7
Takaki utilized allylic ethers en route to allylic silanes via
allylic samarium reagents.8 Recently, Woerpel reported
metal-catalyzed insertions of highly reactive silylenes into
allylic ethers to provide allylic silanes.9
(1) For recent reviews, see: (a) Curtis-Long, M. J.; Aye, Y. Chem.sEur.
J. 2009, 15, 5402. (b) Gawronski, J.; Wascinska, N.; Gajewy, J. Chem.
ReV. 2008, 108, 5227. (c) Chabaud, L.; James, P.; Landais, Y. Eur. J. Org.
Chem. 2004, 3173. (d) Denmark, S. E.; Fu, J. Chem. ReV. 2003, 103, 2763.
(e) Kennedy, J. W. J.; Hall, D. G. Angew. Chem., Int. Ed. 2003, 42, 4732.
For recent applications to syntheses of natural products, see: (f) Lowe, J. T.;
Panek, J. S. Org. Lett. 2008, 10, 3813. (g) Youngsaye, W.; Lowe, J. T.;
Pohlki, F.; Ralifo, P.; Panek, J. S. Angew. Chem., Int. Ed. 2007, 46, 9211.
(2) Hosomi, A.; Miura, K. Bull. Chem. Soc. Jpn. 2004, 77, 835.
(3) (a) Denmark, S. E.; Werner, N. S. J. Am. Chem. Soc. 2008, 130,
16382. (b) Hatanaka, Y.; Yasuo, E.; Hiyama, T. J. Am. Chem. Soc. 1991,
113, 7075.
(6) (a) Tsuji, Y.; Funato, M.; Ozawa, M.; Ogiyama, H.; Kajita, S.;
Kawamura, T. J. Org. Chem. 1996, 61, 5779. (b) Tsuji, Y.; Kajita, S.; Isobe,
S.; Funato, M. J. Org. Chem. 1993, 58, 3607.
(4) (a) Barbero, A.; Pulido, F. J. Acc. Chem. Res. 2004, 37, 817. (b)
Sarkar, T. K. Science of Synthesis, Vol. 4; Georg Thieme Verlag: Stuttgart,
2002; pp 837-925. (c) Sarkar, T. K. Synthesis 1990, 969. (d) Sarkar, T. K.
Synthesis 1990, 1101.
(7) (a) Naitoh, Y.; Bando, F.; Terao, J.; Otsuki, K.; Kuniyasu, H.; Kambe,
N. Chem. Lett. 2007, 36, 236. (b) Terao, J.; Watabe, H.; Watanabe, H.;
Kambe, N. AdV. Synth. Catal. 2004, 346, 1674.
(8) Takaki, K.; Kusudo, T.; Uebori, S.; Nishiyama, T.; Kamata, T.;
Yokoyama, M.; Takehira, K.; Makioka, Y.; Fujiwara, Y. J. Org. Chem.
1998, 63, 4299.
(5) Selected metal catalyzed silylations: (a) Simon, M.-O.; Martinez,
R.; Geneˆt, J.-P.; Darses, S. AdV. Synth. Catal. 2009, 351, 153. (b) Tobisu,
M.; Kita, Y.; Ano, Y.; Chatani, N. J. Am. Chem. Soc. 2008, 130, 15982.
(c) Li, Z.; Yang, C.; Zheng, H.; Qiu, H.; Lai, G. J. Organomet. Chem.
2008, 693, 3771. (d) Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K.
J. Am. Chem. Soc. 2007, 129, 12650. (e) Shintani, R.; Ichikawa, Y.; Hayashi,
T.; Chen, J.; Nakao, Y.; Hiyama, T. Org. Lett. 2007, 9, 4643. (f) Kabalka,
G. W.; Venkataiah, B.; Dong, G. Organometallics 2005, 24, 762. (g)
Suginome, M.; Ito, Y. J. Organomet. Chem. 2003, 680, 43. (h) Obora, Y.;
Tsuji, Y.; Kawamura, T. J. Am. Chem. Soc. 1995, 117, 9814. (i) Obora,
Y.; Tsuji, Y.; Kawamura, T. J. Am. Chem. Soc. 1993, 115, 10414. (j)
Matsumoto, H.; Yako, T.; Nagashima, S.; Motegi, T.; Nagai, Y. J.
Organomet. Chem. 1978, 148, 97.
(9) (a) Bourque, L. E.; Haile, P. A.; Loy, J. M. N.; Woerpel, K. A.
Tetrahedron 2009, 65, 5608. (b) Bourque, L. E.; Cleary, P. A.; Woerpel,
K. A. J. Am. Chem. Soc. 2007, 127, 12602.
(10) Allylic amination: (a) Mora, G.; Piechaczyk, O.; Le Goff, X. F.;
Le Floch, P. Organometallics 2008, 27, 2565. (b) Murakami, H.; Minami,
T.; Ozawa, F. J. Org. Chem. 2004, 69, 4482. (c) Takahashi, K.; Miyake,
A.; Hata, G. Bull. Chem. Soc. Jpn. 1972, 45, 230. Cross-couplings: (d)
Yasui, H.; Mizutani, K.; Yorimitsu, H.; Oshima, K. Tetrahedron 2006, 62,
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Lett. 2007, 48, 5963.
10.1021/ol9023908  2010 American Chemical Society
Published on Web 12/01/2009

Despite the advantages of less reactive allylic ethers, for
example, stability toward nucleophilic attack and resistance to
strongly acidic and basic conditions, their use in allylation
chemistry remains quite rare.10-12 Moreover, such silylation
reactions reported to date tend to require strictly anhydrous
conditions.4-9
Herein we disclose an exceptionally mild entry to allylic
silanes made possible by micellar catalysis13 in water at room
temperature from the combination of allylic ethers and
disilanes (Scheme 1).
was essential for activation of the disilane; under these new
conditions, catalysis between cinnamyl phenyl ether (1a) and
hexamethyldisilane (2a) proceeds at ambient temperature in the
complete absence of organic solvent. Consistent results were
best achieved in the presence of excess Et3N (4 equiv; entries
5, 6), although the amounts of base could be reduced without
significant loss in reactivity. Curiously, other amine bases led
to little-to-no conversion (entry 7), whereas K2CO3 gave
reasonable results (entry 8). Control experiments in the absence
of PTS, or in Et3N as solvent, confirmed the essential role of
the surfactant.
To explore the scope of this Pd-catalyzed silylation, various
allylic phenyl ethers were examined (Table 2). While (E)-
cinnamyl phenyl ether (1a) gave mainly the E-olefinic product
3a (entry 1; also Table 1, entry 4), the (Z)-educt 1b afforded
the corresponding cinnamyl silane 3a in high yield with
decreased stereoselectivity, also favoring the (E)-isomer (entry
2). Cinnamyl derivatives 1c and 1d, i.e., those bearing an
electron-donating methoxy substituent in either the meta or ortho
position, readily underwent the silylation reaction, the latter
substitution pattern showing a strong preference for the E-
product 3c (entries 3, 4). Surprisingly, alkyl substituted allylic
phenyl ether 1e did not undergo full conversion under the
optimized conditions. Ultimately, use of a mixed catalyst system
consisting of PdCl2(PPh3)2 and PdCl2(DPEphos)15 gave the long
Scheme 1
An initial investigation focused on the reaction of cinnamyl
phenyl ether (1a) with hexamethyldisilane (2a) in 2 wt %
PTS/H2O at room temperature (PTS ) polyoxyethanyl
R-tocopheryl sebacate).14 Among several palladium catalysts
screened, those bearing monodentate phosphine ligands or
ligandless sources gave poor results; only PdCl2(PPh3)2 led
to a moderate level of conversion (Table 1, entry 1).
Table 2. Pd-Catalyzed Silylation Reactions with
Hexamethyldisilanea
Table 1. Optimization of Pd-Catalyzed Silylation Reactionsa
entry
catalyst
base (equiv) convn (%)b l:bb E:Zb
1
2
3
4
5
6
7
8
PdCl2(PPh3)2
Et3N (6)
Et3N (6)
Et3N (6)
Et3N (6)
Et3N (4)
Et3N (2)
aminesd
K2CO3 (3)
44
40
60
25:1 19:1
7:1 25:1
24:1 25:1
PdCl2(DtBPF)
PdCl2(DiPPF)
PdCl2(DPEphos)
PdCl2(DPEphos)
PdCl2(DPEphos)
PdCl2(DPEphos)
PdCl2(DPEphos)
100 (91)c 25:1 10:1
95
95
0
25:1 10:1
25:1 10:1
73
25:1 13:1
a Reaction conditions: 1a (1.0 equiv, 0.25 mmol), 2a (1.5 equiv), catalyst
(3 mol %), base, 2 wt % PTS/H2O (1.5 mL), rt, 20 h. b Determined by
d
GCMS and H NMR. c Isolated yield. nBu3N and EtiPr2N were used.
1
However, reaction in the presence of bidentate ligands afforded
generally better results (entries 2, 3), and in the case of
preformed complex PdCl2(DPEphos), full conversion with
associated high isolated yield and excellent regioselectivity could
be realized (entry 4). In previously reported silylations of more
reactive allylic acetates, heating in organic solvents (e.g., DMF)6
a All reactions were carried out on 0.25 mmol scale. b l:b and E:Z ratio
determined by GCMS and 1H NMR methods. c Isolated yield after column
chromatography. d 6 mol % catalyst and 4 equiv NEt3 were used.
e PdCl2(PPh3)2 (1.5 mol %) and PdCl2(DPEphos) (1.5 mol %) were used.
Org. Lett., Vol. 12, No. 1, 2010
29

chain allylic silane 3d in good yield, again favoring the E-isomer
(entry 5). Each of these Pd-catalyzed allylic silylation reactions
occurred with excellent regioselectivity favoring the corre-
sponding linear products.
The alternative allylic dimethylphenylsilanes 3e-k (Table
3) could also be prepared in an analogous fashion, using
commercially available 1,2-diphenyltetramethyl-disilane (2b).
In general, these cross-couplings are both efficient and more
selective than those forming the corresponding TMS deriva-
tives. For example, (E)-cinnamyl phenyl ether (1a) gave
product 3e in high yield with an E:Z ratio of >25:1 (entry
1), although the (Z)-isomer 1b gave the same 3:1 preference
favoring the (E)-derivative (entry 2; compare with Table 2,
entry 2). Substitution on the aryl ring in cinnamyl phenyl
ethers, whether electron-donating (entries 4, 6) or -withdraw-
ing (entries 5, 7), seemingly independent of location on the
ring gave the corresponding allylic silanes in high yields and
with excellent regio- and stereoselectivity. Dibenzylamine-
substituted methallyl substrate 1i also smoothly undergoes
silylation (entry 8).
When the silylation reaction of alkyl substituted allylic
phenyl ether 1e was carried out in pure MeOH, essentially
no conversion was observed (Scheme 2). In PTS/H2O,
Table 3. Pd-Catalyzed Silylations with Disilane 2ba
Scheme 2
however, the desired product allylic dimethylphenylsilane
3l was isolated in high yield (cat Pd ) 3 mol %
PdCl2(DPEphos); 4:1 E:Z). Thus, while nanomicelles are
clearly involved when water is the medium,14 it is not yet
known how PTS behaves in alcoholic solvent.
The relative reactivity of an allylic acetate compared
to an allylic phenyl ether is as expected: reaction first
occurs at the former site. Under optimized conditions, the
combination of catalytic [allylPdCl]2 ligated by Xantphos
gave chemoselective amination of allylic acetate 4 (Scheme
3). Without isolation, introduction of PdCl2(DPEphos) and
Scheme 3
disilane 2b resulted in silylation at the allylic ether
fragment. This 1-pot amination/silylation sequence, done
in its entirety in water at room temperature, could be
applied to generation of dibenzylaminated methallylsilane
3k, and amino acid-substituted allylic silane 3m in good
overall yields.
Scheme 4 illustrates one pathway accounting for the
observed silylations, although details on the mechanism await
further investigation. Initial oxidative addition of Pd(0) to
a All reactions were carried out on 0.25 mmol scale. b l:b and E:Z ratio
determined by GCMS and 1H NMR methods. c Isolated yield after column
chromatography. d 10 mol % PdCl2(DPEphos) used.
30
Org. Lett., Vol. 12, No. 1, 2010

5′′17 suggests that σ-allyl palladium species 5 and/or 5′ more
likely undergoes transmetallation with disilane to give allyl
silyl palladium complex 6 and/or 6′, leading to the corre-
sponding branched and/or linear products, respectively,
strongly favoring the latter.
Scheme 4
In conclusion, new technology has been developed for Pd-
catalyzed formation of allylic silanes from allylic ethers.
These cross-couplings are very efficient, and occur under
“green” conditions: without heat, without organic solvent,
and within a micellar environment where water is the only
external medium. Readily available disilanes serve as the
stoichiometric source of silicon. Both the regio- as well as
stereoselectivity associated with the catalysis are well-
controlled. Further applications of micellar catalysis to
transition metal chemistry are currently underway and will
be reported in due course.
Acknowledgment. We thank the NIH (GM 86485) for
support and Johnson Matthey for supplying Pd catalysts.
Supporting Information Available: Experimental pro-
cedures and characterization of all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
allylic ether 1, aided by presumably high concentrations
within micellar nanoreactors,16 produces allyl palladium
intermediates 5, 5′ and 5′′, each containing the bidentate
ligand. Slow transmetalation of a π-allyl palladium complex
OL9023908
(12) Li, C.-J. Chem. ReV. 2005, 105, 3095.
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Tamaru, Y. In PerspectiVes in Organopalladium Chemistry for the XXI
Century; Tsuji, J., Ed.; Elsevier Science: Switzerland, 1999; p 215. (c) Tsuji,
J. In Palladium Reagents and Catalysts, InnoVations in Organic Synthesis;
Wiley: New York, 1995; p 290. (d) Masuyama, Y. in AdVances in Metal-
Organic Chemistry, Vol. 3; Liebeskind, L. S., Ed.; JAI Press: Greenwich,
CT, 1994; p 255. (e) Trost, B. M.; Verhoeven, T. R. In ComprehensiVe
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(14) (a) Nishikata, T.; Lipshutz, B. H. Org. Lett. 2009, 11, 2377. For a
review, see: (b) Lipshutz, B. H.; Ghorai, S. Aldrichimica Acta 2008, 41,
58, and references cited therein.
(15) We cannot explain this synergistic effect at this stage.
(16) Dynamics of Surfactant Self-Assemblies; Micelles, Microemulsions,
Vesicles, and Lyotropic Phases; Zana, R., Ed.; Surfactant Science Series
125; Taylor & Francis: Boca Raton, FL, 2005.
(17) Hegedus, L. S. in Organometallics in Synthesis, 2nd ed.; Schlosser,
M., Ed.; Wiley: New York, 2004; p 1185.
Org. Lett., Vol. 12, No. 1, 2010
31