Use of pentamethyldisiloxane in the palladium-catalyzed cyclization/ hydrosilylation of functionalized dienes

Article abstract of DOI:10.1021/ol005810u

(Matrix presented) Pentamethyldisiloxane reacts with a range of functionalized dienes in the presence of a catalytic 1:1 mixture of (N-N)Pd(Me)Cl [N-N = 1,10-phenanthroline or (R)-(+)-4-isopropyl-2-(2-pyridinyl)-2-oxazoline] and NaBAr₄ [Ar = 3,

Full text of DOI:10.1021/ol005810u

ORGANIC
LETTERS
2000
Vol. 2, No. 10
1469-1471
Use of Pentamethyldisiloxane in the
Palladium-Catalyzed Cyclization/
Hydrosilylation of Functionalized Dienes
Tao Pei and Ross A. Widenhoefer*
Duke UniVersity, P. M. Gross Chemical Laboratory,
Durham, North Carolina 27708-0346
rwidenho@chem.duke.edu
Received March 14, 2000
ABSTRACT
Pentamethyldisiloxane reacts with a range of functionalized dienes in the presence of a catalytic 1:1 mixture of (N−N)Pd(Me)Cl [N−N )
1,10-phenanthroline or (R)-(+)-4-isopropyl-2-(2-pyridinyl)-2-oxazoline] and NaBAr4 [Ar ) 3,5-C H (CF3)2] to form the corresponding silylated
6
3
carbocycles in good yield and with good stereoselectivity. Treatment of these silylated carbocycles with excess KF and peracetic acid at room
temperature for 48 h formed the corresponding alcohols in excellent yield with retention of stereochemistry.
The use of a silyl moiety as a masked hydroxyl group has
become an important strategy in the synthesis of complex
alcohols and polyols.1 The utility of this approach stems from
the development of facile and high-yielding methods for both
the incorporation and unmasking of the silyl group and also
from the stability of organosilanes to varied reaction condi-
tions and chromatography.1 However, efficient unmasking
of the silyl group is restricted to those silanes which possess
a functional group. For example, the dimethylphenylsilyl
group can be unmasked in two steps by first cleaving the
phenyl group with an electrophile followed by oxidation with
peracid.2 Conversely, silanes which possess an allyl, alkoxy,
amino, or chloro group undergo oxidation in the absence of
an electrophile, leading to improved functional group com-
patibility.3 In addition, a general procedure for the oxidation
of both phenylsilanes and hindered alkoxysilanes employing
t-BuOOH under basic conditions has recently been devel-
oped.4
We recently reported the cyclization/hydrosilylation of
functionalized dienes catalyzed by a 1:1 mixture of (N-N)-
Pd(Me)Cl [N-N ) 1,10-phenanthroline (2a) or (R)-(+)-4-
isopropyl-2-(2-pyridinyl)-2-oxazoline (2b)] and NaBAr4 [Ar
) 3,5-C6H3(CF3)2] (2c) to form silylated carbocycles in good
yield and with high stereoselectivity (Scheme 1).5 Unfortu-
nately, efficient and general cyclization/hydrosilylation was
(1) Jones, G. R.; Landais, Y. Tetrahedron 1996, 52, 7599.
(2) Fleming, I.; Henning, R.; Plaut, H. J. Chem. Soc., Chem. Commun.
1984, 29. (b) Fleming, I.; Sanderson, P. E. J. Tetrahedron Lett. 1987, 28,
4229.
(3) Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M. Organometallics
1983, 2, 1694. (b) Tamao, K.; Ishida, N. J. Organomet. Chem. 1984, 269,
C37. (c) Tamao, K.; Ishida, N. Tetrahedron Lett. 1984, 25, 4249. (d) Magar,
S. S.; Fuchs, P. L. Tetrahedron Lett. 1991, 32, 7513. (e) Tamao, K. Ishida,
N.; Kumada, M.; J. Org. Chem. 1983, 48, 2120.
(4) Smitrovich, J. H.; Woerpel, K. A. J. Org. Chem. 1996, 61, 6044.
(5) (a) Widenhoefer, R. A.; DeCarli, M. A. J. Am. Chem. Soc. 1998,
120, 3805. (b) Stengone, C. N.; Widenhoefer, R. A. Tetrahedron Lett. 1999,
40, 1428. (c) Widenhoefer, R. A.; Stengone, C. N. J. Org. Chem. 1999, 64,
8681. (d) Widenhoefer, R. A.; Vadehra, A. Tetrahedron Lett. 1999, 40,
8499. (e) Perch, N. S.; Widenhoefer, R. A. J. Am. Chem. Soc. 1999, 121,
6960. (f) Perch, N. S.; Pei, T.; Widenhoefer, R. A. J. Org. Chem. In press.
10.1021/ol005810u CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/26/2000

In addition to 1, a range of functionalized dienes reacted
with PMDS in the presence of 2a/2c and underwent
subsequent oxidation to form the corresponding (hydroxy-
methyl)carbocycles in excellent yields and with high dia-
stereoselectivity (Table 1). For example, diesters, diethers,
Scheme 1
Table 1. Cyclization/Hydrosilylation of Dienes Employing
PMDS Catalyzed by a 1:1 Mixture of 2a and 2c (5 mol %) in
DCE at 0 °C Followed by Oxidation with Excess KF and
AcOOH in DMF at Room Temperature for 2 days
achieved only with trialkylsilanes such as HSiEt3; dimeth-
ylphenylsilane functioned satisfactorily in some cases but
displayed poor generality, while silanes of the form HSiMe2X
(X ) allyl, OR, NR2, or Cl) were completely ineffective.
Therefore, we sought to identify a silane for use in palladium-
catalyzed diene cyclization/hydrosilylation which would
display good generality and which would cleave efficiently
under mild conditions. Here we report that pentamethyl-
disiloxane (PMDS)6 serves as an effective and readily
oxidized silane for use in the palladium-catalyzed cyclization/
hydrosilylation of functionalized dienes.7
Reaction of dimethyl diallylmalonate (1) and excess PMDS
catalyzed by a 1:1 mixture of 2a and 2c (5 mol %) in 1,2-
dichloroethane (DCE) at 0 °C for 10 min led to complete
consumption of the diene. The solvent was evaporated, and
the residue was extracted with hexane/EtOAc (24:1) and
filtered through a plug of silica gel to give silylated
carbocycle 3 in 98% yield (96% de, 95% pure) (Scheme 2).8
Scheme 2
Treatment of 3 with a large excess of KF and peracetic acid
in DMF at room temperature for 2 days followed by workup
and chromatography gave alcohol 4 in 92% yield (90% from
1) with complete retention of stereochemistry (Scheme 2).9
(6) Available from Gelest, Inc. (Tullytown, PA) for ca. $ 1/g.
(7) Tamao reported that an unspecified siloxy group (SiMe2OSiMe2R)
was oxidatively cleaved in 72% yield by a two-step procedure involving
acid hydrolysis followed by treament with 30% H2O2. No further details
or development of this procedure were reported.3b
a Yields refer to the two-step conversion of diene to isolated alcohol of
>95% purity. b Isomer ratio determined by capillary GC analysis. c E )
CO2Me.
(8) General procedure for cyclization/hydrosilylation: the diene (5.0
mmol) and pentamethyldisiloxane (2.15 g, 15.0 mmol) were added
sequentially to a solution of 2a (84 mg, 0.25 mmol) and 2c (259 mg, 0.25
mmol) in DCE (50 mL) at 0 °C. The resulting pale yellow solution was
stirred for either 10 min at 0 °C (Table 1, entries 1-6, 13) or at room
temperature for 1-12 h (Table 1, entries 7-12) to form a dark brown
solution. Solvent and excess silane were evaporated under vacuum, and
the brown residue was dissolved in hexane/EtOAc (24:1) and filtered through
a plug of silica gel. Concentration under vacuum gave the corresponding
silylated carbocycle as a colorless to pale yellow oil in 80-99% purity
which was oxidized without further purification. Although carbocycle 3
decomposed slightly upon silica gel chromatography, all other silylated
carbocycles displayed no significant sensitivity toward silica gel.
and protected diols underwent facile cyclization/hydrosily-
lation/oxidation to form alcohols in >70% overall yield as
a single diastereomer (Table 1, entries 1-5). Similarly,
dienes which possessed an aliphatic, aromatic, or functional
group at the terminal olefinic carbon atom also served as
1470
Org. Lett., Vol. 2, No. 10, 2000

oxazoline catalysts. For example, reaction of 1 and PMDS
catalyzed by a 1:1 mixture of 2b and 2c (5 mol %) at -20
°C for 12 h led to the isolation of 3 in near quantitative yield.
Carbocycle 3 was oxidized with KF and peracetic acid to
form 4 in 93% overall yield with 98% de and 75% ee (Table
2, entry 1). Preliminary results point to the generality of
asymmetric cyclization/hydrosilylation employing PMDS and
precatalyst 2b (Table 2, entries 2-5). However, the enan-
tioselectivity of the carbocycles formed under these condi-
tions was slightly lower than that obtained by employing
HSiEt3 and 2b, which may be due to the smaller size of
PMDS relative to HSiEt3.10
Table 2. Asymmetric Cyclization/Hydrosilylation of Dienes
Employing PMDS Catalyzed by a 1:1 Mixture of 2b and 2c (5
mol %) at -20 °C in CH2Cl2 for 12 h Followed by Oxidation
with Excess KF and AcOOH in DMF at Room Temperature for
2 days
In summary, the reaction of pentamethyldisiloxane (PMDS)
and functionalized dienes is catalyzed by palladium phenan-
throline complex 2a and chiral palladium pyridine-oxazoline
complex 2b to form silylated carbocycles in excellent yield
and with high stereoselectivity. With the exception of 3, the
silylated carbocycles are stable toward silica gel chroma-
tography and undergo oxidation in high yield at room
temperature with complete retention of stereochemistry.9
Because of these characteristics, PMDS may have useful
applications outside the scope of palladium-catalyzed cy-
clization/hydrosilylation. We are currently working toward
the identification of disiloxane derivatives which will
improve the enantioselectivity of the asymmetric procedure
and/or enhance the stability of the silylated carbocycles
toward hydrolysis and silica gel chromatography.
a Yields refer to the isolated alcohol of >95% purity. b Isomer ratio
determined by capillary GC. c ee determined by chiral GC of the silylated
carbocycle. d ee determined by 19F NMR analysis of the corresponding
Mosher ester. e ee determined by 1H NMR analysis of the purified silylated
carbocycle employing Eu(hfc)3.
Acknowledgment is made to the National Institutes of
Health (GM59830-01) and the donors of the Petroleum
Research Fund (33131-G1), administered by the American
Chemical Society, for support of this research. R.W. thanks
the Camille and Henry Dreyfus Foundation and DuPont for
new faculty awards and the Alfred P. Sloan Foundation for
a research fellowship. We thank Mr. Carmine N. Stengone
for performing some initial experiments.
effective substrates, as did dienes which possessed an allylic
substituent (Table 1, entries 6-11). In addition, the cycliza-
tion/hydrosilylation/oxidation protocol was amenable to the
synthesis of substituted pyrrolidines (Table 1, entry 12) and
cyclohexane derivatives (Table 1, entry 13).
The reaction of PMDS with functionalized dienes was also
effectively catalyzed by optically active palladium pyridine-
Supporting Information Available: Experimental pro-
cedures and spectroscopic and analytical data for new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(9) General procedure for oxidation: a suspension of the silylated
carbocycle (1.75 mmol), KF (0.81 g, 14.0 mmol), and peracetic acid (32
wt % in acetic acid, 5.0 mL, 21.0 mmol) in DMF (14 mL) was stirred at
room temperature for 48 h. Water (20 mL) was added, and the resulting
suspension was extracted with ethyl acetate. The combined organic extracts
were washed with 10% Na2SO3 and saturated NaHCO3, dried (Na2SO4),
concentrated, and chromatographed on silica gel to give the pure alcohol
as a colorless oil.
OL005810U
(10) For example, under comparable conditions, the enantioselectivity
of the cyclization/hydrosilylation of 1 catalyzed by a mixture of 2b and 2c
increased in the order HSiMe2Et (82% ee) < HSiEt3 (87% ee) < HSiMe2-
CMe3 (89% ee).
Org. Lett., Vol. 2, No. 10, 2000
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