Palladium-catalyzed regio- And stereoselective cross-coupling of Baylis-Hillman adducts and bimetals: A novel method for the synthesis of substituted allylsilanes and allylgermanes

Article abstract of DOI:10.1021/om0492451

Cross-coupling reactions between Baylis-Hill-man acetate adducts and bimetallic reagents (Si-Si, Ge-Ge) catalyzed by a phosphine-free palladium complex are described. 3-Substituted-2-carbonylallylsilanes and allylgermanes were isolated in high yields. The cross-coupling reactions are regio- and stereoselective.

Full text of DOI:10.1021/om0492451

762
Organometallics 2005, 24, 762-764
Notes
Palladium-Catalyzed Regio- and Stereoselective
Cross-Coupling of Baylis-Hillman Adducts and Bimetals:
A Novel Method for the Synthesis of Substituted
Allylsilanes and Allylgermanes
George W. Kabalka,* Bollu Venkataiah, and Gang Dong
Departments of Chemistry and Radiology, The University of Tennessee,
Knoxville, Tennessee 37996-1600
Received September 30, 2004
Scheme 1
Summary: Cross-coupling reactions between Baylis-Hill-
man acetate adducts and bimetallic reagents (Si-Si,
Ge-Ge) catalyzed by a phosphine-free palladium com-
plex are described. 3-Substituted-2-carbonylallylsilanes
and allylgermanes were isolated in high yields. The
cross-coupling reactions are regio- and stereoselective.
Allylmetal reagents have found widespread use in
organic synthesis.1 Their addition to carbonyl com-
pounds stereoselectively provides functionalized homo-
allylic alcohols that are used in synthesis of a variety
of complex natural products. In view of their synthetic
utility, the development of novel and efficient methods
for preparing functionalized allylmetal reagents in a
regio- and stereoselective fashion would be of great
utility. In continuation of our work on boron reactions,2
we recently reported that palladium-catalyzed coupling
reactions of bis(pinacolato)diboron and Baylis-Hillman
acetate adducts lead to functionalized allylborates.3 This
prompted us to examine the feasibility of coupling
Baylis-Hillman acetate adducts with bimetals of both
silicon and germanium (Scheme 1). The reaction would
provide a convenient synthetic method for preparing a
wide range of 2-carbonylallylmetal reagents that are
difficult to obtain by other methods.
transformations. Allylsilanes are extensively used in
carbonyl addition reactions1 and coupling reactions5 and
have been employed as key intermediates in the total
synthesis of natural products.6 Allylsilanes containing
a carbonyl group at the â-position (2-carbonylallylsi-
lanes) are unique in that they can react with both
electrophiles and nucleophiles.7 Tsuji reported a prepa-
ration of allylsilanes from allyl acetates and disilanes
in the presence of a palladium catalyst. Several other
methods for preparing allylsilanes catalyzed by transi-
tion metals are also known,8 but routes to 2-carbonyl-
allylsilanes are limited.7,9
The reaction of Baylis-Hillman acetate adduct 1 and
hexamethylsilane, 2 (in the presence of Pd), generates
2-methoxycarbonylallylsilanes 3 (Table 1) in high yields.
A variety of catalysts and solvent systems were exam-
ined in an effort to optimize reaction conditions. Highest
yields were obtained when reactions were carried out
in toluene using 4 mol % of Pd2(dba)3 at 50 °C. It is
noteworthy that acetates of Baylis-Hillman adducts can
The Baylis-Hillman reaction is a widely employed
carbon-carbon bond forming reaction.4 It is used to
convert simple starting materials into densely function-
alized products that are useful in a variety of synthetic
* To whom all correspondence should be addressed. Phone: (865)
974-3260. Fax: (865) 974-2997. E-mail: kabalka@utk.edu.
(1) For recent reviews on allylmetal chemistry see: (a) Denmark,
S. E.; Almstead, N. G. In Modern Carbonyl Chemistry; Otera, J., Ed.;
Wiley-VCH: Weinheim, 2000; Chapter 10. (b) Stereoselective Synthesis,
Methods of Organic Chemistry (Houben-Weyl), E21 ed.; Helmchen, G.,
Hoffmann, R., Mulzer, J., Schaumann, E., Eds.; Thieme: Stuttgart,
1996; Vol. 3, p 1357. (c) Denmark, S. E.; Fu, J. Chem. Rev. 2003, 103,
2763. (d) Kennedy, J. W. J.; Hall, D. G. Angew. Chem., Int. Ed. 2003,
42, 4732.
(2) (a) Yu, S.; Li, N.-S.; Kabalka, G. W. J. Org. Chem. 1999, 64, 5822.
(b) Kabalka, G. W.; Wu, Z.; Ju, Y. Org. Lett. 2002, 4, 3415. (c) Kabalka,
G. W.; Dong, G.; Venkataiah, B. Org. Lett. 2003, 5, 893. (d) Kabalka,
G. W.; Guchhait, S. K. Org. Lett. 2003, 5, 4129.
(3) Kabalka, G. W.; Venkataiah, B.; Dong, G. J. Org. Chem. 2004,
69, 5807.
(5) Hiyama, T. In Metal-Catalyzed-Cross-Coupling Reactions; Dieder-
ich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; Chapter 10.
(6) (a) Roberson, C. W.; Woerpel, K. A. J. Am. Chem. Soc. 2002, 124,
11246. (b) Peng, Z. H.; Woerpel, K. A. Org. Lett. 2002, 4, 2945. (c) Angle,
S. R.; El-Said, N. A. J. Am. Chem. Soc. 2002, 124, 3608. (d) Denmark,
S. E.; Fu, J. Org. Lett. 2002, 4, 1951.
(7) Kuroda, C.; Suzuki, H. Curr. Org. Chem. 2003, 7, 115.
(8) (a) Matsumota, H.; Yako, T.; Nagashima, S.; Moteig, T.; Nagai,
Y. J. Orgnomet. Chem. 1978, 148, 97. (b) Tsuji, Y.; Kajita, S.; Isobe,
S.; Fuanato, M. J. Org. Chem. 1993, 58, 3607. (c) Obora, Y.; Tsuji, Y.;
Kawamura, T. J. Am. Chem. Soc. 1993, 115, 10414. (d) Obara, Y.; Tsuji,
Y.; Kawamura, T. J. Am. Chem. Soc. 1995, 117, 9814. (e) Tsuji, Y.;
Funato, M.; Ozawa, M.; Ogiyama, H.; Kajita, S.; Kawamura, T. J. Org.
Chem. 1996, 61, 5779. (f) Wu, M.-Y.; Yang, F.-Y.; Cheng, C.-H. J. Org.
Chem. 1999, 64, 2471. (g) Yang, F.-Y.; Shanmugasundaram, M.;
Chuang, S.-Y.; Ku, P.-P.; Wu, M.-Y.; Cheng, C.-H. J. Am. Chem. Soc.
2003, 125, 12576. (h) Suginome, M.; Ito, Y. J. Organomet. Chem. 2003,
680, 43.
(4) (a) Drewes, S. E.; Ross, G. H. P. Tetrahedron 1988, 44, 4653. (b)
Basavaiah, D.; Dharmaroa, P.; Suguna, H. R. Tetrahedron 1996, 52,
8001. (c) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003,
103, 811.
(9) (a) Barbero, A.; GarcRa, C.; Pulido, F. J. Tetrahedron 2000, 56,
2739. (b) Takimoto, M.; Kawamura, M.; Mori, M. Synthesis 2004, 791.
10.1021/om0492451 CCC: $30.25 © 2005 American Chemical Society
Publication on Web 01/14/2005

Notes
Organometallics, Vol. 24, No. 4, 2005 763
Table 1. Pd-Catalyzed Coupling of Baylis-Hillman
Adduct 1 and Disilanea
Table 2. Reaction of Baylis-Hillman Adduct 1 and
Hexamethyldigermanium (4) in the Presence of Pd
Catalysta
R
X
productb
yield (%)c
Z:Ed
phenyl
Me
3a
3b
3c
3d
3e
3f
3g
3h
3i
87
84
82
80
69
86
85
64
73
100
96:4
100
97:3
92:8
94:6
98:2
92:8e
100:0
R
productb
yield (%)c
Z:Ed
100
p-methylphenyl
p-methoxyphenyl
p-chlorophenyl
o-chlorophenyl
1-furyl
Me
phenyl
5a
5b
5c
5d
5e
5f
84
82
85
80
70
81
76
64
Me
p-methylphenyl
p-methoxyphenyl
p-chlorophenyl
o-chlorophenyl
1-furyl
98:2
97:3
Me
Me
92:8
Me
95:5
1-naphthyl
n-octyl
phenyl
Me
100:0e
100:0
85:15e
Me
1-naphthyl
5g
5h
Phenyl
n-octyl
a Reactions carried out for 5 h at 50 °C using 4 mol % of Pd
catalyst. b All products exhibited satisfactory spectral (1H, 13C) and
elemental data. c Isolated yields. d E/Z ratio determined by 1H
NMR. e Reaction time was 10 h.
a Reactions carried out for 5 h at 50 °C using 4 mol % of Pd
catalyst. b All products exhibited satisfactory spectral (1H, 13C) and
elemental data. c Isolated yields. d E/Z ratio determined by 1H
NMR. e Reaction time was 10 h.
be silylated under mild conditions. It has been reported
that allyl acetates will couple with disilanes only in the
presence of chloride salt and at high temperatures,8b,e
clearly indicating that Baylis-Hillman adducts are more
reactive. Several types of Baylis-Hillman adducts readily
participate in the reaction, as shown in Table 1. Baylis-
Hillman adducts derived from aryl aldehydes, het-
eroaryl aldehydes, and aliphatic aldehydes are readily
transformed into the corresponding allylsilanes.
We then extended the methodology to the preparation
of functionalized allylgermanes. Relative to other allyl-
metals, few studies focused on the synthesis of allylger-
manes have been reported.10 Notably, allylgermanes
have been used in allylation reactions with carbonyl11
and imine12 compounds and in [3 + 2] cycloaddition13
reactions. Baylis-Hillman acetate adduct 1 reacted with
hexamethyldigermanium 4 in the presence of a Pd
catalyst to form allylgermane 5 (Table 2). Reactions
proceed readily at 50 °C, and the allylgermane products
form in high yields. To the best of our knowledge, this
is the first reported synthesis of 2-carbonylallylgerma-
nium compounds.
Scheme 2
Scheme 3
Reaction of the Baylis-Hillman adduct 6 derived from
methylvinyl ketone and hexamethyldisilane, 2, gave a
(1:1) mixture of (Z)-allylsilane 7 and its regioisomer 8,
in 83% yield, whereas the reaction of 6 with hexameth-
yldigermanium, 4, yielded only 9 in 80% yield (Scheme
2).
The stereochemistry of the allylmetals was deter-
mined to be Z using 1H and 13C NMR spectroscopy and
by comparison with the literature.9,14 Only trace quanti-
ties of the E isomers were detected. The Z selectivity is
presumably a consequence of thermodynamic control.
As outlined in Scheme 3, the reaction most likely
proceeds via the oxidative addition of palladium to the
Baylis-Hillman adduct (1 or 6) to produce the π-allyl
palladium complex 10. Addition of the bimetal reagents
(10) (a) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207. (b)
Jeganmohan, M.; Shanmugasundaram, M.; Cheng, C.-H. Chem. Com-
mun. 2003, 1746.
(11) Denmark, S. E.; Almstead, N. G. J. Org. Chem. 1991, 56, 6485.
(12) (a) Akiyama, T.; Iwai, J. Synlett 1998, 273. (b) Akiyama, T.;
Iwai, J.; Kagoshima, H. Chem. Commun. 1999, 2191.
(13) Akiyama T. Chem. Commun. 1997, 2357.
(14) (a) Pornet, J.; Rayadh, A.; Miginia, L. Tetrahedron Lett. 1986,
27, 5479. (b) Suzuki, H.; Kuroda, C. J. Chem. Res., Synop. 2003, 310.
to 10 would afford 11, which could equilibrate (anti vs
syn). Presumably the steric requirements of the carbonyl
group lead to the formation of the thermodynamically

764 Organometallics, Vol. 24, No. 4, 2005
Notes
methyldisilane 2 (1.1 mmol) were added to a two-necked
round-bottomed flask. The system was evacuated and purged
with nitrogen gas. Toluene (4 mL) and 4 mol % of Pd2(dba)3
(36 mg) were added. The reaction mixture was stirred at 50
°C. After completion of the reaction (TLC), the mixture was
concentrated and purified by column chromatography to give
the desired product 3.
General Procedure for the Synthesis of Allylgermanes
5. The Baylis-Hillman acetate adduct 1 (1 mmol) and hexa-
methyldigermanium 4 (1.1 mmol) were added to a two-necked
round-bottom flask The system was evacuated and purged
with nitrogen gas. Toluene (4 mL) and 4 mol % of Pd2(dba)3
(36 mg) were added. The reaction mixture was stirred at 50
°C. After completion of the reaction (TLC monitor), the mixture
was concentrated and purified by column chromatography to
give the desired product 5.
more stable Z-allylmetal products that are produced by
reductive elimination.
In conclusion, we have developed the palladium-
catalyzed coupling of Baylis-Hillman acetate adducts
with bimetallic reagents (Si-Si, Ge-Ge). The method
leads to functionalized allylmetal reagents in excellent
yields. The catalytic reaction proceeds with high regio-
and stereoselectivity under mild conditions. Phosphine-
free Pd catalyzes the reaction, and no additional base
or ligand is required.
Experimental Section
General Considerations. All glassware was dried in an
oven at 120 °C and flushed with dry nitrogen. Reactions were
carried out under a nitrogen atmosphere. All reagents were
purchase from Aldrich Chemical Co. and used as received.
Baylis-Hillman adducts were prepared according to literature
procedures. Products were purified by flash chromatography
using silica gel (60 C, 230, 400 mesh) with hexanes and ethyl
acetate (hexanes/EtOAc, 20:1) as eluent. Elemental analyses
Acknowledgment. We thank the Department of
Energy and the Robert H. Cole Foundation for support
of this research.
1
were performed by Atlantic Microlabs Inc., Norcross, GA. H
NMR and 13C NMR spectra were recorded in CDCl3 on Bruker
250 MHz and Varian 300 MHz instruments with chemical
shifts reported relative to TMS.
Supporting Information Available: 1H and 13C spectral
and elemental analyses. This material is available free of
charge via the Internet at http://pubs.acs.org.
General Procedure for the Synthesis of Allylsilanes
3. The Baylis-Hillman acetate adduct 1 (1 mmol) and hexa-
OM0492451