Asymmetric diene cyclization/hydrosilylation/oxidation employing 1-tert-butyl-3,3-dimethyl-1,1-diphenyldisiloxane

Article abstract of DOI:10.1016/S0040-4039(00)01321-6

A 1:1 mixture of (N-N)Pd(Me)Cl [N-N=(R)-(+)-4-isopropyl-2-(2-pyridinyl)-2-oxazoline] (1) and NaBAr₄ [Ar=3,5-C₆H₃(CF₃)₂] catalyzed the asymmetric cyclization/hydrosilylation of functionalized 1,6-diene

Full text of DOI:10.1016/S0040-4039(00)01321-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 7597–7600
Asymmetric diene cyclization/hydrosilylation/oxidation
employing 1-tert-butyl-3,3-dimethyl-1,1-diphenyldisiloxane
Tao Pei and Ross A. Widenhoefer*
P.M. Gross Chemical Laboratory, Duke University, Durham, NC 27708-0346, USA
Received 1 August 2000; accepted 3 August 2000
Abstract
A 1:1 mixture of (NꢀN)Pd(Me)Cl [NꢀN=(R)-(+)-4-isopropyl-2-(2-pyridinyl)-2-oxazoline] (1) and
NaBAr4 [Ar=3,5-C6H3(CF3)2] catalyzed the asymmetric cyclization/hydrosilylation of functionalized
1,6-dienes with 1-tert-butyl-3,3-dimethyl-1,1-diphenyldisiloxane at −20°C to form silylated cyclopentanes
in good yield with up to 95% ee. These silylated carbocycles underwent oxidative cleavage of the CꢀSi
bond with H2O2 at room temperature to form the corresponding alcohols. © 2000 Elsevier Science Ltd.
All rights reserved.
We have been investigating the cyclization/hydrosilylation of functionalized dienes catalyzed
by mixtures of (NꢀN)Pd(Me)Cl [NꢀN=1,10-phenanthroline1 or (R)-(+)-4-isopropyl-2-(2-
pyridinyl)-2-oxazoline (1)]2 and NaBAr4 [Ar=3,5-C6H3(CF3)2]. Our initial procedures required
the use of HSiEt3 to achieve efficient and general cyclization/hydrosilylation, and the resulting
silylated carbocycles were therefore resistant to oxidative CꢀSi bond cleavage.3 In response to
this limitation, we recently identified pentamethyldisiloxane (HSiMe2OTMS) as an effective and
readily oxidized silane for use in palladium-catalyzed cyclization/hydrosilylation.4 Unfortu-
nately, the enantioselectivity of asymmetric cyclization/hydrosilylation employing
HSiMe2OTMS was significantly diminished relative to HSiEt3. For example, the reaction of
4,4-bis(trimethylacetoxymethyl)-1,6-heptadiene (2) with HSiEt3 catalyzed by 1/NaBAr4 formed
carbocycle 3 with 91% ee, while the reaction of 2 with HSiMe2OTMS in the presence of
1/NaBAr4 formed carbocycle 4 with only 82% ee (Table 1, entries 1 and 2). Therefore, we sought
to identify a silane which would give high enantioselectivity in asymmetric cyclization/hydrosily-
lation to form silylated carbocycles which would be reactive towards oxidation. Here we report
that 1-tert-butyl-3,3-dimethyl-1,1-diphenyldisiloxane (HSiMe2OTBDPS) serves as an effective
silane for the asymmetric cyclization/hydrosilylation/oxidation of 1,6-dienes, generating
(hydroxymethyl)cyclopentanes with up to 95% ee.
* Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01321-6

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Table 1
Asymmetric cyclization/hydrosilylation of 2 catalyzed by a 1:1 mixture of 1 and NaBAr4 (5 mol%) as a function
of silane
Entry
Silane
Carbocycle
Yield (%)
de (%)
ee (%)
1
2
3
HSiEt3
HSiMe2OTMS
HSiMe2OTBDPS
3
4
5
89
98
99
\95
\95
\95
91
82
95
The reaction of 2 and excess of HSiMe2OTBDPS5 catalyzed by a 1:1 mixture of 1 and
NaBAr4 (5 mol%) in CH2Cl2 at −20°C for 12 h led to the isolation of silylated carbocycle 5 in
99% yield with >95% de and 95% ee (Table 1, entry 3).6 Unfortunately, carbocycle 5 failed to
oxidize under the conditions previously employed for oxidation of the ꢀSiMe2OTMS group
(KF/AcOOH, 25°C, 48 h)4 and an alternative procedure was therefore required.7 To this end,
the reaction of 5 with a mixture of TBAF, KF, KHCO3, and 50% H2O2 in THF at room
temperature for 3 days led to the isolation of alcohol 6 in 73% yield (Scheme 1).8 In addition to
diene 2, a range of functionalized 1,6-dienes underwent asymmetric cyclization/hydrosilylation/
oxidation employing HSiMe2OTBDPS to give (hydroxymethyl)cyclopentanes in moderate to
good yield with high enantioselectivity (Table 2).
Scheme 1.
In summary, HSiMe2OTBDPS reacts with functionalized 1,6-dienes in the presence of
1/NaBAr4 to form silylated carbocycles with up to 95% ee. These silylated carbocycles undergo
oxidative cleavage of the CꢀSi bond with H2O2 at room temperature. The significant enhance-
ment of the enantioselectivity of palladium-catalyzed cyclization/hydrosilylation employing
HSiMe2OTBDPS relative to HSiEt3 and HSiMe2OTMS suggests that HSiMe2OTBDPS may be
of general use in catalytic asymmetric hydrosilylation. We are currently working towards the
development of more effective procedures for oxidation of the ꢀSiMe2OTBDPS group.

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Table 2
Asymmetric cyclization/hydrosilylation of dienes employing HSiMe2OTBDPS catalyzed by a 1:1 mixture of 1
and NaBAr4 (5 mol%) in CH2Cl2 at −20°C for 12 h, followed by oxidation with excess TBAF, KF, KHCO3,
and 50% H2O2 in THF at room temperature for 3 days
Acknowledgements
This work was supported by grants from the National Institutes of Health (GM59830-01) and
the donors of the Petroleum Research Fund, administered by the American Chemical Society
(33131-G1). 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.
References
1. (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, 1451. (c) Widenhoefer, R. A.; Stengone, C. N. J. Org. Chem. 1999, 64, 8681. (d)
Widenhoefer, R. A.; Vadehra, A. Tetrahedron Lett. 1999, 40, 8499.
2. (a) Perch, N. S.; Widenhoefer, R. A. J. Am. Chem. Soc. 1999, 121, 6960. (b) Perch, N. S.; Pei, T.; Widenhoefer,
R. A. J. Org. Chem. 2000, 65, 3836.
3. Jones, G. R.; Landais, Y. Tetrahedron 1996, 52, 7599.
4. Pei, T.; Widenhoefer, R. A. Org. Lett. 2000, 2, 1469.
5. Synthesis of HSiMe2OTBDPS. Saturated aqueous NaHCO3 (120 mL) was added to a solution of TBDPSCl (13.0
mL, 50.0 mmol) and dimethylchlorosilane (16.6 mL, 150.0 mmol) in THF (120 mL) at 0°C, the mixture was
warmed slowly to room temperature, and stirred overnight. Work-up and chromatography gave HSiMe2OTBDPS
1
(12.6 g, 80%) as a colorless oil. H NMR: l 7.69–7.66 (m, 4H), 7.42–7.36 (m, 6H), 4.97 (septet, J=2.8 Hz, 1H),
1.06 (s, 9H), 0.27 (s, 3H), 0.26 (s, 3H). 13C{1H} NMR: l 136.1, 135.2, 129.7, 127.9, 27.0, 19.7, 1.4.

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6. Synthesis of 5. Diene 2 (172 mg, 0.53 mmol) and HSiMe2OTBDPS (0.50 g, 1.60 mmol) were added sequentially
to a solution of 1 (11 mg, 0.03 mmol) and NaBAr4 (27 mg, 0.03 mmol) in CH2Cl2 (6 mL) under nitrogen at −20°C
and maintained at this temperature for 12 h. Evaporation of solvent and chromatography gave 5 as a colorless oil
1
(335 mg, 99%). H NMR: l 7.68–7.61 (m, 4H), 7.40–7.30 (m, 6H), 3.86–3.82 (m, 4H), 1.78 (dd, J=6.8, 13.2 Hz,
1H), 1.69 (dd, J=6.8, 13.2 Hz, 1H), 1.43–1.26 (m, 2H), 1.17 (s, 9H), 1.16 (s, 9H), 1.03 (s, 9H), 0.99–0.93 (m, 3H),
0.85 (d, J=6.0 Hz, 3H), 0.30 (dd, J=11.0, 14.6 Hz, 1H), 0.10 (s, 3H), 0.09 (s, 3H). 13C{1H} NMR: l 178.8, 178.7,
136.2, 135.4, 129.7, 127.8, 68.5, 44.0, 43.4, 42.4, 41.8, 41.0, 39.2, 27.5, 27.1, 22.9, 19.5, 17.7, 2.0, 1.6.
7. The following conditions also failed to oxidize the ꢀSiMe2OTBDPS group: (1) AcOOH/DMF/KF/25°C; (2)
AcOOH/AcOH/HgOAc2/25°C; (3) AcOOH/DMF/KHF2/25°C; (4) t-BuOOH/CsOH/DMF/TBAF/25°C; (5)
AcOOH/Py-HF/DMF/KF/25°C.
8. Synthesis of 6.4 A suspension of 5 (364 mg, 0.57 mmol), TBAF (1.0 M in THF, 5.0 mL, 5 mmol), KF (410 mg,
7.0 mmol), KHCO3 (120 mg, 1.2 mmol) and H2O2 (50% wt) (0.70 mL, 12.0 mmol) was stirred at room temperature
for 3 days. Water/EtOAc work-up, followed by chromatography gave 6 (143 mg, 73%) as a colorless oil.
.