Synthesis of α-arylated allylsilanes through palladium-catalyzed γ-selective allyl-aryl coupling

Article abstract of DOI:10.1021/ol101114r

(Equation Presented). A palladium-catalyzed γ-selective allyl-aryl coupling between γ-silylated allylic esters and arylboronic acids produced α-arylated allylsilanes with E-alkene geometry. The reaction tolerated various functional groups in both the arylboronic acids and the allylic esters and afforded functionalized allylsilanes. The reaction of optically active allylic esters took place with excellent α-to-γ chirality transfer with syn stereochemistry to give chiral allylsilanes.

Full text of DOI:10.1021/ol101114r

ORGANIC
LETTERS
2010
Vol. 12, No. 15
3344-3347
Synthesis of r-Arylated Allylsilanes
through Palladium-Catalyzed γ-Selective
Allyl-Aryl Coupling
Dong Li, Tatsunori Tanaka, Hirohisa Ohmiya,* and Masaya Sawamura*
Department of Chemistry, Faculty of Science, Hokkaido UniVersity,
Sapporo 060-0810, Japan
ohmiya@sci.hokudai.ac.jp; sawamura@sci.hokudai.ac.jp
Received May 14, 2010
ABSTRACT
A palladium-catalyzed γ-selective allyl-aryl coupling between γ-silylated allylic esters and arylboronic acids produced r-arylated allylsilanes
with E-alkene geometry. The reaction tolerated various functional groups in both the arylboronic acids and the allylic esters and afforded
functionalized allylsilanes. The reaction of optically active allylic esters took place with excellent r-to-γ chirality transfer with syn stereochemistry
to give chiral allylsilanes.
Allylsilanes are useful reagents for the stereoselective carbon-
carbon bond formations.1 The development of facile and
efficient methods for the sythesis of allylsilanes is important.
In particular, the preparation of enantiomerically enriched
allylsilanes remains a challenge. Among a number of routes to
allylsilanes,2-13 two types of copper-mediated allylic sub-
stitution strategies, substitutions of γ-silylated allylic alcohol
derivatives with organocopper reagents14 and reactions of
allylic alcohol derivatives with silylcuprate reagents,15,16 are
particularly efficient and versatile because the substrates and
the reagents are readily available and the reactions are highly
reliable in terms of product yield and stereoselectivity. Even
these methods, however, are not secure from the problems
of the incompatibility with functional groups because the
organocopper reagents are prepared from basic organome-
tallic reagents such as Grignard or organolithium reagents,
and the silylcuprate reagents are also strongly basic.
(4) For Pd-catalyzed silylations of allylic substrates with disilanes, see:
(a) Matsumoto, Y.; Ohno, A.; Hayashi, T. Organometallics 1993, 12, 4051–
4055. (b) Hayashi, T.; Ohno, A.; Lu, S.; Matsumoto, Y.; Fukuyo, E.; Yanagi,
K. J. Am. Chem. Soc. 1994, 116, 4221–4226. (c) Tsuji, Y.; Kajita, S.; Isobe,
S.; Funato, M. J. Org. Chem. 1993, 58, 3607–3608. (d) Tsuji, Y.; Funato,
M.; Ozawa, M.; Ogiyama, H.; Kajita, S.; Kawamura, T. J. Org. Chem.
1996, 61, 5779–5787. (e) Moser, R.; Nishikata, T.; Lipshutz, B. H. Org.
Lett. 2010, 12, 28–31.
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Fleming, I.; Barbero, A.; Walter, D. Chem. ReV. 1997, 97, 2063–2192. (c)
Chabaund, L.; James, P.; Landais, Y. Eur. J. Org. Chem. 2004, 3173–3199.
(2) For Pd-catalyzed couplings between vinyl halides and silylmethyl
Grignard reagents, see: (a) Hayashi, T.; Konishi, M.; Ito, H.; Kumada, M.
J. Am. Chem. Soc. 1982, 104, 4962–4963. (b) Hayashi, T.; Konishi, M.;
Okamoto, Y.; Kabeta, K.; Kumada, M. J. Org. Chem. 1986, 51, 3772–
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ates, see: Hayashi, T.; Iwamura, H.; Uozumi, Y. Tetrahedron Lett. 1994,
35, 4813–4816.
(6) For Ni-catalyzed couplings of allylic ethers with chlorosilanes, see:
(a) Terao, J.; Watabe, H.; Watanabe, H.; Kambe, N. AdV. Synth. Catal.
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1983, 24, 5661–5664. (b) Hayashi, T.; Kebeta, K. Tetrahedron Lett. 1985,
26, 3023–3026. (c) Hayashi, T.; Hengrasmee, S.; Matsumoto, Y. Chem.
Lett. 1990, 1377–1380. (d) Hayashi, T.; Matsumoto, Y. Tetrahedron:
Asymmetry 1990, 1, 151–154. (e) Hayashi, T.; Han, J. W.; Takeda, A.;
Tang, J.; Nohmi, K.; Mukaide, K.; Tsuji, H.; Uozumi, Y. AdV. Synth. Catal.
(7) For Pd-catalyzed silaborations of allenes, see: (a) Ohmura, T.;
Taniguchi, H.; Suginome, M. J. Am. Chem. Soc. 2006, 128, 13682–13683.
See also: (b) Suginome, M.; Matsumoto, A.; Ito, Y. J. Am. Chem. Soc.
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(8) For Pd-catalyzed allyl transfer reactions from silyl-substituted
homoallyl alcohols to aryl halides, see: Hayashi, S.; Hirano, K.; Yorimitsu,
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.
10.1021/ol101114r  2010 American Chemical Society
Published on Web 07/02/2010

Herein, we report a palladium-catalyzed γ-selective
allyl-aryl coupling between γ-trimethylsilyl-substituted al-
lylic esters and arylboronic acids,17-19 which appears to be
a versatile route to R-arylated allylsilanes.2,3b,5,7,8,14,15,16f The
reaction is compatible with various functional groups in both
arylboronic acids and γ-silylated allylic esters, affording
functionalized allylsilanes. Optically active allylic esters
reacted with excellent R-to-γ chirality transfer with syn
stereochemistry to give chiral allylsilanes.
[1a/2a/Pd(OAc)2/1,10-phenanthroline/AgSbF6 1:1.5:0.1:0.12:
0.1, 60 °C, 18 h].17 The reactions afforded (E)-1-phenyl-2-
alkenylsilane 3a in 71 and 59% isolated yields in THF and
ClCH2CH2Cl (DCE), respectively (84 and 78% convn of 1a),
with excellent E/Z (>99:1) selectivity (Table 1, entries 1 and
Table 1. Optimization of Reaction Conditionsa
In the studies to optimize reaction conditions, we used
γ-trimethylsilyl-substituted allylic ester 1a having an o-meth-
oxybenzoyloxy leaving group.20 The allylic ester 1a was readily
prepared in a three-step procedure involving an addition of
lithium trimethylsilylacetylide to an aldehyde and Red-Al
reduction21 followed by acylation. Initially, 1a and phenylbo-
ronic acid (2a) (1.5 equiv) were subjected to the standard
reaction conditions for the palladium-catalyzed γ-selective
allyl-aryl coupling between allylic ester and arylbornic acids
(9) For silylene insertions into allylic ethers, see: Bourque, L. E.; Cleary,
P. A.; Woerpel, K. A. J. Am. Chem. Soc. 2007, 129, 12602–12603
.
(10) For reactions of silyl chlorides with allylic samarium reagents, see: Takaki,
K.; Kusudo, T.; Uebori, S.; Nishiyama, T.; Kamata, T.; Yokoyama, M.;
Takehira, K.; Makioka, Y.; Fujiwara, Y. J. Org. Chem. 1998, 63, 4299–
4304
.
(11) For Ireland-Claisen rearrangements of (Z)-vinylsilanes, see: (a)
Panek, J. S.; Clark, T. D. J. Org. Chem. 1992, 57, 4323–4326. (b) Sparks,
M. A.; Panek, J. S. J. Org. Chem. 1991, 56, 3431–3438
(12) For Wittig olefinations of R-silylaldehyde, see: Bhushan, V.; Lohray,
B. B.; Enders, D. Tetrahedron Lett. 1993, 34, 5067–5070
.
.
(13) For Rh- or Cu-catalyzed carbenoid insertions into Si-H bonds,
see: (a) Davies, H. M.; Hansen, T.; Rutberg, J.; Bruzinski, P. R. Tetrahedron
Lett. 1997, 38, 1741–1744. (b) Bulugahapitiya, P.; Landais, Y.; Parra-
Rapado, L.; Planchenault, D.; Weber, V. J. Org. Chem. 1997, 62, 1630–
1641. (c) Wu, J.; Chen, Y.; Panek, J. S. Org. Lett. 2010, 12, 2112–2115
.
(14) For substitutions of γ-silylated allylic alcohol derivatives with
organocopper reagents, see: (a) Smitrovich, J. H.; Woerpel, K. A. J. Am.
Chem. Soc. 1998, 120, 12998–12999. (b) Smitrovich, J. H.; Woerpel, K. A.
J. Org. Chem. 2000, 65, 1601–1614. (c) Kacprzynski, M. A.; May, T. L.;
Kazane, S. A.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2007, 46, 4554–
4558. See also: (d) Tanigawa, Y.; Fuse, Y.; Murahashi, S. Tetrahedron
Lett. 1982, 23, 557–560
.
(15) Fleming et al. developed the silylations of allylic alcohol derivatives
with silylcuprate reagents, see: (a) Fleming, I.; Newton, T. W. J. Chem.
Soc., Perkin Trans. 1 1984, 1805–1808. (b) Fleming, I.; Thomas, A. P.
J. Chem. Soc., Chem. Commun. 1985, 411–413. (c) Fleming, I.; Thomas,
A. P. J. Chem. Soc., Chem. Commun. 1986, 1456–1457. (d) Fleming, I.;
Higgins, D.; Lawrence, N. J.; Thomas, A. P. J. Chem. Soc., Perkin Trans.
1 1992, 3331–3349. (e) Dieter, R. K. Modern Organocopper Chemistry;
Krause, N., Ed.; Wiley-VCH: Weinheim, Germany, 2002; pp 79-144.
(16) For other silylations of allylic substrates with silylcuprate reagents,
see: (a) Laycock, B.; Kitching, W.; Wickham, G. Tetrahedron Lett. 1983,
24, 5785–5788. (b) Clive, D. L. J.; Zhang, C.; Zhou, Y.; Tao, Y. J.
Organomet. Chem. 1995, 489, C35–C37. (c) Lipshuz, B. H.; Sclafani, J. A.;
Takanami, T. J. Am. Chem. Soc. 1998, 120, 4021–4022. (d) Oestreich, M.;
Auer, G. AdV. Synth. Catal. 2005, 347, 637–640. (e) Schmidtmann, E. S.;
Oestreich, M. Chem. Commun. 2006, 3643–3645. (f) Vyas, D. J.; Oestreich,
a Conditions: Pd(OAc)2 (10 mol %), ligand (12 mol %), AgSbF6 (10
mol %), 1a (0.25 mmol), 2a (0.375 mmol), solvent (1.5 mL), 60 °C, 18 h.
b Conditions: Pd(OAc)2 (10 mol %), Phen (12 mol %), AgSbF6 (10 mol
%), BQ (20 mol %), 1 (0.25 mmol), phenylboronic acid (0.375 mmol),
DCE (1.5 mL), 60 °C, 18 h. c Determined by 1H NMR analysis of the crude
materials. d NMR yield. The yield in parentheses was isolated yield.
M. Chem. Commun. 2010, 568–570
.
2). Although no R-substitution product was formed, the reaction
produced a smaller amount (12%) of desilylated exomethylene
compound (4aa) having a phenyl group at the ꢀ-position with
the acyloxy leaving group intact. Addition of a substoichiometric
amount (20 mol %) of 1,4-benzoquinone (BQ) to the reaction
mixture with DCE solvent resulted in complete consumption
of 1a, but failed to improve the yield of the coupling product
3a (70% isolated yield) (entry 3, conditions A).22 When the
reaction was performed on a 2.7 mmol scale (1.0 g) under
condition A, the coupling product 3a was obtained in 68%
isolated yield (3a/4aa 84:16).
(17) For the Pd-catalyzed γ-selective and stereospecific allyl-aryl
coupling between allylic esters and arylboronic acids, see: (a) Ohmiya, H.;
Makida, Y.; Tanaka, T.; Sawamura, M. J. Am. Chem. Soc. 2008, 130,
17276–17277. (b) Ohmiya, H.; Makida, Y.; Li, D.; Tanabe, M.; Sawamura,
M. J. Am. Chem. Soc. 2010, 132, 879–889
(18) For an approach to allenylsilanes by the Rh-catalyzed coupling
between propargylic carbonates and a silylboronate, see: Ohmiya, H.; Ito,
.
H.; Sawamura, M. Org. Lett. 2009, 11, 5618–5620
.
(19) For the Cu-catalyzed γ-selective and stereospecific allyl-aryl and
allyl-alkyl couplings with organoboron compounds, see: (a) Ohmiya, H.;
Yokokawa, N.; Sawamura, M. Org. Lett. 2010, 12, 2438–2440. (b) Ohmiya,
H.; Yokobori, U.; Makida, Y.; Sawamura, M. J. Am. Chem. Soc. 2010,
132, 2895–2897
.
(20) For the screening of leaving groups, see Supporting Information.
The superiority of this leaving group for the allyl-aryl coupling between
γ-arylated allylic esters and arylboronic acids, see ref 17b.
Our ligand screening with substituted 1,10-phenanthrolines
revealed that disubstitutions at the 4,7- or 5,6-positions have
(21) Jones, T. K.; Denmark, S. E. Org. Synth. 1985, 64, 182–185.
Org. Lett., Vol. 12, No. 15, 2010
3345

significant impacts on suppressing the ꢀ-phenylation. Most
strikingly, the reaction with 4,7-diphenyl-1,10-phenanthroline
(bathophenanthroline) in the absence of BQ gave no ꢀ-pheny-
lation product, but unfortunately the reaction stopped at a low
conversion (62%) of 1a, resulting in a moderate yield of the
allylsilane 3a (57% by 1H NMR, 52% isolated, Table 1, entry
4, conditions B). The conversion and yield were not improved
even with a prolonged reaction time. Smaller but still significant
ligand effects in suppressing the ꢀ-phenylation were observed
with 4,7-dimethyl-, 4,7-dihydroxy-, and 5,6-dimethyl-1,10-
phenanthrolines (entries 5-7). In sharp contrast, 2,9-dimeth-
ylphenanthroline, which has an increased steric demand around
the N,N′-coordination site, afforded only the ꢀ-phenylation
product (4aa) in low yield (entry 8).
conditions B. It should be noted that the elimination of BQ (20
mol %) from conditions A resulted in a significant decrease in
the yield of 3. Since the side product (4) could easily be
separated from the allylsilanes 3 by silica gel chromatography,
conditions A seems to be more practical when higher isolated
yields of 3 are obtained.
Table 2 illustrated that a variety of functional groups such
as MeO, CF3, Cl, ketone, aldehyde, thiophene, silyl ether, ester,
and OH were compatible with the synthesis of R-arylated
allylsilanes (entries 1-5 and 7-10). Importantly, the functional
groups are tolerated in both allylic esters (1) and arylboronic
acids (2). A heteroarylboronic acid such as 3-thiopheneboronic
acid (2h) participated in the coupling (entry 7). The free hydroxy
group in substrate 1d did not inhibit the reaction, giving the
corresponding hydroxylated allylsilane 3d (entry 10). These
functional groups in the substrates caused capricious effects on
the yields of 3 and the 3/4 selectivities.
The formation of 4aa can be explained by invoking the
aryl-Pd insertion across the C-C double bond with the
“reverse” site selectivity (Scheme 1). Thus, the reverse selectiv-
The tolerance of the reaction toward steric demand in both
allylic esters (1) and arylboronic acids (2) is shown in Table
2, entries 6 and 11-13. o-Tolylboronic acid (2g) was coupled
with 1a albeit with a low yield (56%, entry 6, conditions
A). The allylic esters 1e and 1f with Bu and bulkier i-Pr
groups, respectively, instead of the phenylethyl group in 1a,
were phenylated at the R-position effectively (71 and 75%,
entries 11 and 12, conditions A). The tertiary alcohol
derivative 1g was converted to γ,γ-disubstituted allylsilane
3g with a moderate yield (61%, entry 13, conditions B).
The reaction of an optically active γ-silylated allylic ester
(S)-1e (99% ee) and phenylboronic acid (1a) in the presence
of Pd(OAc)2, 1,10-phenanthroline, AgSbF6, and BQ in DCE
at 40 °C afforded the allylsilane 3e in 63% yield (Scheme 2).
Scheme 1. Possible Pathways to 3 and 4
ity is induced by an interaction between the σ[C(γ)-Pd] and
the σ*[Si-C(Me)] orbitals in the addition product A′. The
ꢀ-hydride elimination of A′ forms styrylsilane B: This process
may be described as the elimination of H+ and a Pd(0) species.
Then, protodesilylation of B (with H+ or [Pd-H]+) gives the
exomethylene compound 4.23 The pronounced substituent
effects at the 4,7- and 5,6-positions of the phenanthroline ligands
may be explained by the steric repulsion between the ligand
substituents and the proximal Me3Si group in A′.
Scheme 2. Synthesis of Chiral Allylsilanes and Their
Lewis-Acid-Mediated Addition to an Aldehyde
The γ-selective palladium-catalyzed reaction was capable of
affording a variety of R-arylated allylsilanes (Table 2). All
substrate combinations listed in Table 2 were subjected to both
reaction conditions, conditions A (Pd/Phen/Ag/BQ/DCE) and
conditions B (Pd/Bathophen/Ag/THF). While conditions A
afforded higher yields of 3 in most cases (entries 1-7 and
9-12), the selectivity for 3 over 4 was generally higher with
The subsequent addition of 3e to isobutyraldehyde in the
presence of TiCl4 afforded homoallylic alcohol (3S,4S)-5e (99%
ee) without a loss of enantiomeric purity.1a,2a The diastereomer
ratio with respect to the consecutive stereogenic centers was
>20:1 (E/Z > 99:1). Under the identical conditions, the
reaction of (S)-1f (99% ee), which contains a bulkier R-i-Pr
group, gave (R)-3f with 98% ee, suggesting that the R-to-γ
chirality transfer is not significantly influenced by the steric
demand of the R-substituent.
(22) Generally, conditions A afforded higher yields of 3 than the
conditions shown in Table 1, entry 1. For example, the reaction between
1a and 2c under the conditions shown in Table 1, entry 1, afforded the
coupling product 3ac in 51% isolated yield, while the conditions A afforded
3ac in 82% (Table 2, entry 2).
(23) ThestyrylsilaneBshouldbemoresusceptibletoprotonation-desilylation
than 1 because the aryl group stabilizes a positive charge of the corre-
sponding carbocation intermediate. The protodesilylation process may be
mediated by Pd species, see: (a) Fillion, E.; Taylor, N. J. J. Am. Chem.
Soc. 2003, 125, 12700–12701. (b) Busacca, C. A.; Swestock, J.; Johnson,
R. E.; Bailey, T. R.; Musza, L.; Rodger, C. A. J. Org. Chem. 1994, 59,
7553–7556. (c) Farina, V.; Hossain, M. A. Tetrahedron Lett. 1996, 37, 6997–
7000. (d) Gordillo, A.; de Jesu´s, E.; Lo´pez-Mardomingo, C. J. Am. Chem.
Soc. 2009, 131, 4584–4585.
The 1,2-syn-selectivity for the arising stereogenic centers
suggests that the addition of the allylsilanes 3e and 3f to the
aldehyde proceeded through an acyclic antiperiplanar transition
3346
Org. Lett., Vol. 12, No. 15, 2010

Table 2. Synthesis of R-Arylated Allylsilanes (3) through Pd-Catalyzed Allyl-Aryl Coupling
a Conditions A: Pd(OAc)2 (10 mol %), Phen (12 mol %), AgSbF6 (10 mol %), BQ (20 mol %), 1 (0.25 mmol), 2 (0.375 mmol), DCE (1.5 mL), 60 °C,
18 h. b Conditions B: Pd(OAc)2 (10 mol %), Bathophen (12 mol %), AgSbF6 (10 mol %), 1 (0.25 mmol), 2 (0.375 mmol), THF (1.5 mL), 60 °C, 18 h.
c
d
1
1
Isomeric ratio (E/Z > 99:1). Determined by H NMR analysis of the crude materials. Determined by H NMR analysis of the crude materials.
state.1a,2a On the basis of the established 1,3-anti stereo-
chemical pathway of Lewis-acid-mediated SE′ reactions of
allylsilanes,24 the absolute configuration of the chiral allyl-
silanes 3e and 3f was deduced to R. Accordingly, it revealed
that R-to-γ chirality transfer in the Pd-catalyzed allyl-aryl
coupling proceeded with syn stereochemistry. This stereo-
chemistry coincides with the stereochemical outcome previ-
ously observed in the parent Pd-catalyzed allyl-aryl cou-
pling, which can be rationalized by the C-C double bond
insertion into the aryl-Pd bond and syn-ꢀ-acyloxy elimina-
tion with the assistance of intramolecular coordination of
the acyloxy group to the palladium center.17
arylboronic acids is a versatile, functional group-tolerable
approach to R-arylated allylsilanes, while the yields are only
moderate. The excellent R-to-γ chirality transfer with syn-
stereochemistry allowed the preparation of chiral allylsilanes
from optically active allylic esters.
Acknowledgment. This work was supported by Grants-
in-Aid for Scientific Research (B) (No. 21350020) and for
Young Scientists (B) (No. 21750086), JSPS.
Supporting Information Available: Experimental details
and characterization data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
In conclusion, a palladium-catalyzed γ-selective allyl-aryl
coupling between γ-trimethylsilyl-substituted allylic esters and
(24) Denmark, S. E.; Almstead, N. G. J. Org. Chem. 1994, 59, 5130–
5132.
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