Oxidation of sterically hindered alkoxysilanes and phenylsilanes under basic conditions

Full text of DOI:10.1021/jo960921l

6
044
J . Org. Chem. 1996, 61, 6044-6046
Oxid a tion of Ster ica lly Hin d er ed
Alk oxysila n es a n d P h en ylsila n es u n d er
Ba sic Con d ition s
fluoride source or with less than 5 equiv of fluoride, both
the diol 2 and the dioxasilacyclohexane 3 were isolated
from the reaction mixture. Therefore, the fluoride source
J acqueline H. Smitrovich and K. A. Woerpel*
Department of Chemistry, University of California,
Irvine, California 92717-2025
Received May 20, 1996
Since its discovery, the oxidation of silanes to alcohols
is important for deprotection of the oxidized silane, not
for the oxidation itself. Proof that the reaction proceeded
with retention of configuration was obtained by compar-
1
has played an important role in organic synthesis. This
reaction permits the unique properties of organosilicon
compounds to be employed in a reaction sequence,
followed by oxidation of the carbon-silicon bond to
provide a hydroxyl moiety.2 However, the oxidation is
restricted to silanes that are substituted with a hetero-
atom and to phenylsilanes that can be refunctionalized
1
ing the X-ray structures of 1 and an acetal derivative of
9
2
.
After the successful oxidation of 1, the scope of the new
oxidation conditions was examined. Hindered alkoxysi-
lanes 4a ,b were prepared by treating the readily avail-
3
,4
to install a heteroatom.
Hindered silicon groups are
able chlorosilanes with the desired alcohol and triethyl-
resistant to oxidation,1 and many strategies for oxidizing
,5
amine.1
0,11
Treatment of silanes 4a -c with t-BuOOH
phenylsilanes employ strongly electrophilic conditions,
and base in DMF provided the alcohols in high yield (eq
6
which limit functional group compatibility. Conditions
2
, Table 1).12 Compared to previously reported condi-
for oxidizing hindered silanes or phenylsilanes under
nucleophilic conditions would complement current silane
oxidation methods and improve the versatility of this
important transformation. Herein we report new condi-
tions for the oxidation of silanes that are successful in
highly congested systems and for silyl groups that bear
no heteroatoms.
As part of our investigation of the insertion of alde-
hydes into silacyclopropanes, we prepared the oxasila-
cyclopentane 1, which we reasoned could be oxidized to
provide a synthesis of 1,3-diols.7 Subjection of 1 to
[
O]
1
1
R –SiR3
a–c
R OH
(2)
4
5
tions, improved yields were observed for diisopropoxysi-
lanes 4a ,c13 (entries 1, 3). Although n-decyl-tert-butoxy-
2 2
dimethylsilane (4b) was resistant to the H O oxidation,
submission to the new conditions provided the alcohol
in good yield (entry 2). Thus, even a hindered alkoxysilyl
1
4
moiety is the functional equivalent of a hydroxyl group.
A limitation of current methods for the oxidation of
phenylsilanes is that treatment with HBF , Br , or Hg-
OAc) is required to install a heteroatom prior to
oxidation.
standard silane oxidation conditions (aqueous H
2 2
O ,
KHCO , and KF) afforded only recovered starting mate-
3
4
2
rial, presumably due to the steric hindrance at the silicon
center. Furthermore, none of the other modifications of
the oxidation proved effective.1 These results are not
surprising, since it has been demonstrated that alkoxy-
(
2
3
,4
Because the use of acidic or electrophilic
reagents is incompatible with a variety of functional
groups, including olefins and amines, other methods have
1
,5,8
silanes bearing bulky substituents are unreactive.
been developed.1
5-20
We have found that treatment of
1
In contrast to the standard conditions, we chose to
employ polar aprotic media, a strong base, and 90% tert-
butyl hydroperoxide to facilitate nucleophilic attack on
both primary and secondary phenylsilanes with t-BuOOH
and KH provided good yields of the corresponding
2
silicon. Treatment of 1 with t-BuOOH, CsOH‚H O, and
(
8) Clive, D. L. J .; Cantin, M. J . Chem. Soc., Chem. Commun. 1995,
19-320.
9) Furthermore, each diastereomer of 1 was oxidized to a stere-
tetrabutylammonium fluoride in DMF at 70 °C afforded
3
the 1,3-diol 2 in 64% yield as a single diastereomer by
(
1
13
H and C NMR spectroscopy. In the absence of a
ochemically unique diol, and reference diols were prepared for com-
parison (ref 7).
(
10) El-Durini, N. M. K.; J ackson, R. A. J . Organomet. Chem. 1982,
32, 117-121.
11) Semenov, V. V.; Ladilina, E. Y.; Chesnokova, T. A.; Cherepen-
nikova, N. F. Zh. Obshch. Khim. 1991, 61, 1184-1195.
12) All yields represent material which proved to be pure by 1H
2
(
(
1
3
and C NMR spectroscopy and by GC.
13) (a) Beauchamp, T. J .; Powers, J . P.; Rychnovsky, S. D. J . Am.
(
Chem. Soc. 1995, 117, 12873-12874. (b) Beauchamp, T. J .; Rych-
novsky, S. D., University of California, Irvine, personal communication,
1
996.
(14) For an example of the use of hindered alkoxysilanes to control
(1) Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M. Organometallics
1
983, 2, 1694-1696.
the stereochemistry in a cyclization reaction, see: Lipshutz, B. H.;
Tirado, R. J . Org. Chem. 1994, 59, 8307-8311.
(15) Magar, S. S.; Fuchs, P. L. Tetrahedron Lett. 1991, 32, 7513-
7516.
(16) Murakami, M.; Suginome, M.; Fujimoto, K.; Nakamura, H.;
Andersson, P. G.; Ito, Y. J . Am. Chem. Soc. 1993, 115, 6487-6498.
(17) Taber, D. F.; Yet, L.; Bhamidipati, R. S. Tetrahedron Lett. 1995,
36, 351-354.
(18) Landais, Y.; Planchenault, D.; Weber, V. Tetrahedron Lett.
1995, 36, 2987-2990.
(19) Knolker, H. J .; Wanzl, G. Synlett 1995, 378-382.
(20) Hunt, J . A.; Roush, W. R. Tetrahedron Lett. 1995, 36, 501-
504.
(
2) J ones, G. R.; Landais, Y. Tetrahedron 1996, 52, 7599-7662.
3) Fleming, I.; Henning, R.; Plaut, H. J . Chem. Soc., Chem.
(
Commun. 1984, 29-31.
4) Fleming, I.; Sanderson, P. E. J . Tetrahedron Lett. 1987, 28,
229-4232.
5) Andrey, O.; Landais, Y.; Planchenault, D. Tetrahedron Lett. 1993,
4, 2927-2930.
6) For example, see: Pearson, W. H.; Postich, M. J . J . Org. Chem.
994, 59, 5662-5671.
7) Bodnar, P. M.; Palmer, W. S.; Shaw, J . T.; Smitrovich, J . H.;
Sonnenberg, J . D.; Presley, A. L.; Woerpel, K. A. J . Am. Chem. Soc.
995, 117, 10575-10576.
(
4
3
1
(
(
(
1
S0022-3263(96)00921-8 CCC: $12.00 © 1996 American Chemical Society

Notes
J . Org. Chem., Vol. 61, No. 17, 1996 6045
Ta ble 1. Oxid a tion of Alk oxysila n es 4
yield of 5 (%)
(lit. procedure)
entry
compd
R1
n-decyl
n-decyl
SiR3
yield of 5 (%)a
b
1
2
3
4a
4b
4c
SiMe(O-i-Pr)2
SiMe2(O-t-Bu)
SiMe(O-i-Pr)2
81
90
75
0
44
c,d
94
a
t-BuOOH, CsOH‚H2O, DMF, 70 °C unless otherwise noted. H2O2, KHCO3, KF, 1:1 THF/MeOH, reflux. c t-BuOOH, KH, TBAF,
b
d
DMF, 23 °C. Reference 13.
Ta ble 2. Oxid a tion of Sila n es 6
ture, number of equivalents of reagents, and solvent
systems and by addition of fluoride ion were unsuccessful.
In conclusion, a new set of conditions for the oxidation
of the C-Si bond has been developed. The conditions
yield of 5 (%)a
entry
compd
R
SiR3
1
2
3
4
5
6a
6b
6c
6d
6e
n-decyl
n-decyl
cyclododecyl
n-decyl
n-decyl
SiMePh2
SiMe2Ph
SiMe2Ph
SiMe2H
SiMe3
84
82
80
82
37
b
(excess t-BuOOH and KH or CsOH‚H
2
O in DMF or NMP)
have been shown to be more reactive than the standard
c
protocol for hindered alkoxysilanes.1 The procedure is
a
t-BuOOH, KH, NMP, 70 °C unless otherwise noted. b t-
also applicable to the oxidation of arylsilanes, permitting
c
BuOOH, KH, NMP, TBAF, 70 °C. t-BuOOH, KH, 1:1:2 THF/
the oxidation of these compounds in one step and provid-
toluene/NMP, 120 °C.
3,4
ing an alternative to the known conditions.
Silanes
containing functional groups such as phenyl rings, al-
kenes, and tertiary amines, which can be incompatible
alcohols in one step (eq 3, Table 2). Since the nonpolar
21
with acidic or electrophilic reagents, can be oxidized by
using the new method. Consequently, hindered phenyl
and alkylsilanes may find broadened use as hydroxyl
equivalents in organic synthesis.
[
O]
1
1
R –SiR3
a–e
R OH
(3)
6
5
starting materials were only marginally soluble in DMF,
N-methylpyrrolidinone (NMP) was employed as the
solvent. The stronger base KH was necessary for con-
sumption of all starting material. Both mono- and
diphenylsilanes were oxidized under the conditions in
good yield (entries 1-3). The yield of the oxidation of
the secondary phenylsilane 6c (80%) is comparable to
that obtained (77%) by following the Fleming protocol
Exp er im en ta l Section
Gen er a l. All reactions were carried out under an atmosphere
of nitrogen in glassware which had been flame-dried under a
stream of nitrogen. Liquid chromatography was performed
using forced flow (flash chromatography) of the indicated solvent
system on EM Reagents silica gel (SiO ) 60 (230-400) mesh.
2
Coupling constants for 1H NMR spectra are reported in hertz.
THF was distilled from sodium and benzophenone ketyl. DMF
, KF).3 The utility of these
4 2 2 3
HBF and then H O , KHCO
(
was distilled from CaH
NMP was stirred over CaSO
Å molecular sieves. Silanes were purchased from United
2
and stored over 4 Å molecular sieves.
basic oxidation conditions for the oxidation of phenylsi-
lanes is illustrated by an application in a natural product
synthesis. The silane 7, prepared by Molander and
Nichols using an organoyttrium-promoted cyclization/
4
, filtered, distilled, and stored over
4
Chemical Technologies and used without further purification.
The preparation of silanes 4a , 6b, 6c, and 6e is provided as
supporting information. Microanalyses were performed by
Atlantic Microlab (Atlanta, GA).
ter t-Bu toxy-n -d ecyld im eth ylsila n e (4b).11 To a stirred
solution of chloro-n-decyldimethylsilane (7.4 mL, 0.030 mol) in
mL of toluene were added t-BuOH (14.0 mL, 0.076 mol) and
triethylamine (10.6 mL, 0.153 mol). The reaction was heated
at reflux for 20 h. After the reaction was cooled to 25 °C, 100
silylation reaction, could not be oxidized under acidic
conditions.21 However, when 7 was submitted to these
basic conditions, (()-epilupinine (8) was provided in 57%
isolated yield (eq 4).21 This result demonstrates that
tertiary amines are compatible with this protocol.
8
mL of saturated aqueous NH
was extracted with 3 × 100 mL of Et
layers were washed with 50 mL of brine, dried (Na
4
Cl was added, and the mixture
O. Combined organic
SO ), and
2
2
4
concentrated in vacuo to afford a yellow liquid, which was
purified by flash chromatography (3:97 EtOAc/hexanes) to yield
the product as a colorless liquid. Further purification by bulb-
to-bulb distillation (0.05 mmHg, 85 °C) afforded the product as
1
a colorless liquid (4.91 g, 60%): H NMR (CDCl
3
, 500 MHz) δ
1
0
2
2
.29 (m, 16H), 1.24 (s, 9H), 0.88 (t, 3H, J ) 7.0), 0.54 (m, 2H),
The unfunctionalized silanes 6d ,e were also found to
oxidize under the new conditions (Table 2). For these
substrates, use of THF as a cosolvent was necessary for
dissolution of the starting material. When silane 6d was
treated with t-BuOOH and KH in 1:1 THF/NMP, n-
decanol was obtained in 82% yield. In fact, treatment of
n-decyltrimethylsilane (6e) with t-BuOOH and KH in
.09 (s, 6H); 13C NMR (CDCl
, 125 MHz) δ 71.9, 33.6, 32.1, 32.0,
3
9.73, 29.67, 29.44, 29.40, 23.5, 22.7, 18.8, 14.1, 0.95; IR (neat)
959, 2923, 2854, 1462, 1388, 1363, 1249, 1200, 1051, 1024, 839,
-
1
776 cm ; HRMS (CI/isobutane) m/ z calcd for C16
H
37OSi (M +
+
H) 273.2610, found 273.2613. Anal. Calcd for C16
0.51; H, 13.31. Found: C, 70.57; H, 13.36.
n -Decyld ip h en ylm eth ylsila n e (6a ). To a cooled (0 °C)
H36OSi: C,
7
solution of n-decyldimethylchlorosilane (5.2 mL, 20 mmol) in 20
mL of THF was added phenylmagnesium chloride (2.0 M
solution in THF, 40 mL, 80 mmol) by syringe. The reaction
mixture was stirred for 36 h. The thick tan slurry was diluted
1
:1:2 THF/toluene/NMP afforded decanol in 37% yield
1
(50% conversion by H NMR spectroscopy), demonstrat-
ing that even tetraalkylsilanes can be oxidized. Attempts
to increase conversion by varying the reaction tempera-
with 30 mL of saturated aqueous NH
vacuo. The resultant white slurry was extracted with 4 × 30
mL of Et O. The combined organic layers were washed with 10
mL of brine, dried (Na SO ), and concentrated in vacuo to afford
6.1 g of a golden oil, which was flushed through a pad of SiO
(hexanes) to give 5.01 g of a clear, colorless liquid. Purification
4
Cl and concentrated in
2
(
21) Molander and Nichols have employed the oxidation protocol
reported here as their final step of an expeditious synthesis of
epilupinine in the accompanying paper: Molander, G. A.; Nichols, P.
J . J . Org. Chem. 1996, 61, 6040-6043.
2
4
2

6
046 J . Org. Chem., Vol. 61, No. 17, 1996
Notes
by bulb-to-bulb distillation (120-160 °C, 0.05 mmHg) afforded
partitioned between 5 mL of H
2
O and 10 mL of Et
2
O. The layers
1
the product as a colorless liquid (4.99 g, 74%): H NMR (CDCl
3
,
were separated, and the aqueous layer was extracted with 2 ×
10 mL of Et O. The combined organic layers were washed with
O and 5 mL of brine, dried (MgSO ), and
5
2
00 MHz) δ 7.50 (m, 4H), 7.32 (m, 6H), 1.29 (m, 16H), 1.05 (m,
2
H), 0.87 (t, 3H, J ) 6.7), 0.53 (s, 3H); 13C NMR (CDCl
, 125
10 × 1 mL of H
3
2
4
MHz) δ 137.5, 134.4, 129.0, 127.7, 33.6, 31.9, 29.63, 29.58, 29.3,
2
2
HRMS (CI/isobutane) m/ z calcd for C23
found 337.2367. Anal. Calcd for C23
Found: C, 81.64; H, 10.12.
concentrated in vacuo to afford 0.057 g of a yellow oil. The oil
9.2, 23.8, 22.7, 14.2, 14.1, -4.5; IR (neat) 3068, 3048, 2955,
was purified by flash chromatography (25:75 to 35:65 EtOAc/
hexanes) to yield the product as a colorless oil (0.019 g, 64%):
-
1
923, 2853, 1465, 1427, 1250, 1190, 1169, 787, 730, 699 cm
;
+
1
H
H
33Si (M - H) 337.2352,
34Si: C, 81.56; H, 10.14.
3
H NMR (CDCl , 500 MHz) δ 7.36-7.24 (m, 5H), 5.04 (d, 1H, J
) 1.7), 3.83 (quintet, 1H, J ) 6.3) 3.15 (br s, 1H), 2.56 (br s,
1H), 1.84 (m, 1H), 1.31 (d, 3H, J ) 6.2), 0.82 (d, 3H, J ) 7.0);
1
3
n -Decyld im eth ylsila n e (6d ). LiAlH
was added to 20 mL of THF. Chloro-n-decyldimethylsilane (2.5
mL, 10.1 mmol) was added to the LiAlH suspension dropwise
4
(0.377 g, 20.2 mmol)
3
C NMR (CDCl , 125 MHz) δ 142.6, 128.0, 127.0, 126.1, 75.0,
70.9, 45.5, 21.9, 11.5; IR (thin film) 3355, 2975, 2896, 1453, 1380,
-
1
4
1199, 1144, 1102, 1072, 1000, 974, 926, 887, 742, 702 cm
;
+
by syringe over 2 min. The resultant suspension was stirred at
room temperature for 12 h. After the suspension was cooled to
HRMS (CI/isobutane) m/ z calcd for (M + H) 181.1228, found
181.1225. Anal. Calcd for
Found: C, 73.09; H, 9.04.
11 16 2
C H O : C, 73.30; H, 8.95.
0
°C, excess LiAlH
mL of H O, 0.77 mL of 15% NaOH, and 2.3 mL of H
resultant white slurry was filtered through celite, washing with
Et O. The filtrate was concentrated in vacuo to a colorless
liquid. Purification by bulb-to-bulb distillation (0.05 mmHg, 80
C) afforded the product as a colorless liquid (1.62 g, 80%): 1
NMR (CDCl , 300 MHz) δ 3.83 (septet, 1H, J ) 3.5), 1.38 (m,
6H), 0.86 (t, 3H, J ) 6.5), 0.56 (m, 2H), 0.05 (d, 3H, J ) 3.5);
4
was quenched by successive addition of 0.77
2
2
O. The
(1R*,2S*,3R*)-1,2-Dioxa -4,5-d im eth yl-6-p h en yl-2-d i-ter t-
bu tylsila cycloh exa n e (3). Using the procedure given for 2
with oxasilacyclopentane 1 (0.050g, 0.164 mmol), tert-butyl
hydroperoxide (90%, 0.080 mL, 0.740 mmol), KH (0.126 g, 0.820
mmol, 26% dispersion washed with 3 × 1 mL of hexanes), and
4
2
°
H
3
n-Bu NF (0.043 g, 0.164 mmol) afforded the product as a white
1
1
solid (0.028 g, 53%): mp 69-70 °C; H NMR (CDCl , 500 MHz)
3
1
3
C NMR (CDCl
3
, 125 MHz) δ 33.3, 32.0, 29.7, 29.6, 29.44, 29.40,
δ 7.21-7.36 (m, 5H), 5.48 (d, 1H, J ) 2.7), 4.69 (dq, 1H, J ) 6.4,
2.4), 1.82 (m, 1H), 1.23 (d, 3H, J ) 6.7), 1.13 (s, 9H), 1.12 (s,
2
1
4.4, 22.7, 14.2, 14.1, -4.4; IR (neat) 2957, 2923, 2854, 2112,
-1
13
466, 1249, 887, 835, 768 cm ; HRMS (CI/isobutane) m/ z calcd
9H), 0.67 (d, 3H, J ) 7.2); C NMR (CDCl , 125 MHz) δ 143.5,
3
+
for C12
for C12
H
H
27Si (M - H) 199.1882, found 199.1888. Anal. Calcd
127.9, 126.4, 125.2, 78.7, 73.3, 43.3, 28.8, 27.9, 23.6, 22.0, 20.8,
4.6; IR (KBr) 3064, 2970, 2861, 1474, 1449, 1388, 1366, 1209,
28Si: C, 71.93; H, 14.10. Found: C, 72.03; H, 14.06.
-
1
Rep r esen ta tive Oxid a tion P r oced u r e: Oxid a tion of
Cyclod od ecylp h en yld im eth ylsila n e 6c to Cyclod od eca n ol.
To a cooled (0 °C) solution of KH (0.335 g, 2.92 mmol, 35%
dispersion in mineral oil washed with 3 × 5 mL of hexanes) in
1155, 1004, 967, 846, 732, 651 cm ; HRMS (CI/isobutane) m/ z
+
calcd for C19H33O Si (M + H) 321.2250, found: 321.2249. Anal.
2
Calcd for C19H32O Si: C, 71.18; H, 10.08. Found: C, 70.97; H,
2
9.98.
1
.5 mL of NMP was added tert-butyl hydroperoxide (90%, 0.320
mL, 2.90 mmol) dropwise. After the solution was warmed to 25
C, a solution of 6c (0.144 g, 0.476 mmol) in 3.0 mL of NMP
was added dropwise. After 10 min, n-Bu NF (0.267 g, 1.02
mmol, hydrate lyophilized from benzene) was added. The
reaction mixture was heated at 70 °C for 10 h. After the mixture
Ack n ow led gm en t. This research was supported by
University of California Cancer Research Coordinating
Committee funds. Acknowledgment is also made to the
Donors of the Petroleum Research Fund, administered
by the American Chemical Society, for support of this
research. We thank Professor Scott D. Rychnovsky and
Thomas J . Beauchamp (University of California, Irvine)
for providing data for their oxidation of silane 4c.
Professor Gary A. Molander and Paul J . Nichols (Uni-
versity of Colorado, Boulder) are gratefully acknowl-
edged for discussions about their application of this
protocol. We thank Charles V. Nicolasvu for technical
assistance and J ared T. Shaw for helpful discussions.
°
4
was cooled to 25 °C, 1.0 g of Na
mL of H
O. The mixture was washed with 4 × 10 mL of
t-BuOMe. The combined organic layers were washed with 4 ×
mL of H
O, 2 × 2 mL of NaOH, and 5 mL of brine, dried
MgSO ), and concentrated in vacuo to afford a tan solid.
2 2 3
S O was added, followed by 3
2
1
2
(
4
Purification by flash chromatography (hexanes to 10:90 EtOAc/
hexanes) afforded the product as a white solid (0.070 g, 80%).
1
13
H and C NMR spectra, GC, and TLC were consistent with
those of an authentic sample of cyclododecanol.
1R*,2S*,3R*)-1-P h en yl-2-m eth yl-1,3-bu ta n ed iol (2). To
a cooled (0 °C) solution of tert-butyl hydroperoxide (90%, 0.207
O (0.331
(
g, 2.30 mmol) in 1.3 mL of DMF was added CsOH‚H
2
Su p p or tin g In for m a tion Ava ila ble: Preparation of si-
lanes 4a , 6b, 6c, and 6e; experimental procedure for oxidation
of 7 to 8 (3 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
g, 1.97 mmol). After the mixture was warmed to 25 °C, a
solution of oxasilacyclopentane 1 (0.050 g, 0.164 mmol) in 0.8
mL of DMF was added dropwise by syringe. After 10 min, n-Bu -
4
NF (0.214 g, 0.82 mmol, hydrate, lyophilized from benzene) was
added. The reaction mixture was heated at 75 °C for 8 h. After
the mixture was cooled to 25 °C, Na
2 2 3
S O was added, and the
solvent was removed in vacuo. The resultant oily solid was
J O960921L