Synthesis of cyclic β-silylenones via oxidative rearrangement of tertiary α-hydroxy allylsilanes with PCC

Article abstract of DOI:10.1016/j.cclet.2010.10.018

An oxidative rearrangement of cyclic tertiary α-hydroxy allylsilanes has been carried out in refluxing ClCH₂CH₂Cl with pyridinium chlorochromate (PCC). The reaction provides a convenient method to synthesize cyclic β-silylenones in m

Full text of DOI:10.1016/j.cclet.2010.10.018

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 306–309
www.elsevier.com/locate/cclet
Synthesis of cyclic b-silylenones via oxidative rearrangement
of tertiary a-hydroxy allylsilanes with PCC
*
Xia Wu, Jian Lei, Zhen Lei Song
Key Laboratory of Drug-Targeting of Education Ministry and Department of Medicinal Chemistry,
West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Received 1 July 2010
Available online 22 December 2010
Abstract
An oxidative rearrangement of cyclic tertiary a-hydroxy allylsilanes has been carried out in refluxing ClCH2CH2Cl with
pyridinium chlorochromate (PCC). The reaction provides a convenient method to synthesize cyclic b-silylenones in modest to
excellent yields.
# 2010 Zhen Lei Song. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Pyridinium chlorochromate; Oxidative rearrangement; Cyclic b-silylenones
The oxidative rearrangement of tertiary allylic alcohols using various oxidants such as Cr(VI)-based reagents [1],
IBX [2] and TEMPO [3] to yield b-disubstituted a,b-unsaturated ketones is a key step of the alkylative carbonyl
transposition of a,b-unsaturated ketones [4]. The reaction is generally believed to proceed through a [3,3]-sigmatropic
rearrangement of the formed ester intermediates with leading to the efficient transposition of a carbonyl group from
one carbon to another. Although the reaction has been used widely in organic synthesis [5], to our knowledge, little
attention has been paid to the silylative carbonyl transposition of a,b-unsaturated ketones. We envisioned that such
oxidative rearrangement of cyclic tertiary a-hydroxy allylsilanes prepared readily from 1,2-addition of silyllithium to
a,b-unsaturated ketones might provide a convenient approach to cyclic b-silylenones, which are valuable synthons [6],
but still lack of general synthetic methods [7]. Herein, we report the realization of this process using pyridinium
chlorochromate (PCC) as an effective oxidant (Scheme 1).
According to Koreeda’s procedure, a-hydroxy allylsilane 1 was prepared in 94% yield via 1,2-addition of
PhMe2SiLi to cyclohexenone [8]. Oxidative rearrangement of 1 was performed initially by using 1.5 equivalent of
PCC in CH2Cl2 with Si2O as additives. After stirring at 0 8C for 3 h, b-silyl cyclohexenone 2 was obtained in 38%
yield (entry 1, Table 1). Increasing the amount of PCC to 3.0 equivalents led to the even worse result (entry 2, Table 1).
Effects of solvents were then investigated. While reactions using toluene and CHCl3 gave the poor yields (entries 3 and
4, Table 1), the one carried out in refluxing ClCH2CH2Cl resulted in 45% yield as well as dramatic increase of reaction
rate (entry 5, Table 1). Other oxidants such as Jones reagent, Collins reagents and IBX were also examined for the
reaction, but no better yields than the one using PCC were obtained (entries 6–8, Table 1).
* Corresponding author.
E-mail address: zhenleisong@scu.edu.cn (Z.L. Song).
1001-8417/$ – see front matter # 2010 Zhen Lei Song. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.10.018

[()TD$FIG]
X. Wu et al. / Chinese Chemical Letters 22 (2011) 306–309
SiPhMe2
307
HO SiPhMe2
PCC (1.5 equiv)
n
n
ClCH2CH2Cl, refluxing, 5 min
40-94%
O
R
R
n = 0, 1; R = H, alkyl
Scheme 1. Oxidative rearrangement of cyclic tertiary a-hydroxy allylsilanes with PCC.
Table 1
Screening of oxidative rearrangement conditions of a-hydroxy allylsilane 1
[DT$INLE]
SiPhMe
HO SiPhMe
2
2
oxidative rearrangement
O
1
2
Entrya
Oxidant (equiv.)
Solvent
Additives
Temperature (8C)
Time
Yield (%)b
1
2
3
4
5
6
7
8
PCC (1.5)
CH2Cl2
CH2Cl2
Toluene
CHCl3
SiO2
SiO2
SiO2
SiO2
SiO2
–
0
0
3 h
38
30
27
32
45
26
18
4
PCC (3.0)
5 h
PCC (1.5)
0
3 h
PCC (1.5)
0
3 h
PCC (1.5)
ClCH2CH2Cl
Acetone
CH2Cl2
DMSO
85
0
5 min
1 h
Jones reagent (1.5)
Collins reagent (2.0)
IBX (2.0)
–
0
2 h
–
55
1 h
a
Products were identified by 1H NMR, 13C NMR, IR and HRMS.
Isolated yield.
b
Table 2
Scope of cyclic tertiary a-hydroxy allylsilanes.
Entrya
1
Substrates
Products
Yield (%)b
45
Entry
Substrates
Products
Yield (%)
45
HO SiPhMe2
SiPhMe2
[
SiPhMe2
5
HO SiPhMe2
]
2
9
]
10
[DT$INLE]
1
O
(dr = 3:2)
O
Bn
Bn
[
]
E
[TD$INLE]
SiPhMe2
HO SiPhMe2
HO SiPhMe2
SiPhMe2
2
3
60
6
45
3
4
11
12
O
O
Ally
SiPhMe2
Ally
HO SiPhMe2
SiPhMe2
HO SiPhMe2
[TD$INLINE]
5
[DT$INLE]
6
[DT$INLE]
13
[DT$INLE]
14
40
52
7
8
47
94
(dr = 4:3)
O
O
[
[
[
[TD$INLE]
HO SiPhMe2
HO
SiPhMe2
SiPhMe2
SiPhMe2
4
15
16
7
8
(dr = 6:1)
O
O
a
Products were identified by 1H NMR, 13C NMR, IR and HRMS.
Isolated yield.
b

[()TD$FIG]
308
X. Wu et al. / Chinese Chemical Letters 22 (2011) 306–309
O
O
O
OH
OH
O
SiPhMe2
H
H
Cr
Cr
O
25%
45%
O
O
H
H
desilylation
SiPhMe2
SiPhMe2
O
2
cyclohexenone
C-1
C-1'
O
OH
SiPhMe2
Cr
94%
O
O
H
SiPhMe2
O
H
C-15
16
Scheme 2. Rationalization for the observed reactivity difference between a-hydroxy allylsilanes 1 and 15.
Having established optimal reaction conditions, we explored the scope of this approach. Reaction of 2-, 4- and 5-
methyl substituted cyclohexenone-derived allysilanes gave the corresponding b-silylenones in modest to good yields
(entries 2–4, Table 2). Additionally, other allylsilanes with benzyl, allyl and dimethyl groups located at 4-position are
also suitable for the reaction (entries 5–7, Table 2). Interestingly, when using cyclopentenone-derived allylsilane 15 as
substrate, the desired b-silylenone 16 was obtained in 94% yield (entry 8, Table 2). This result represents a sharp
contrast to 45% yield obtained in the reaction of 1, in which the main byproduct is cyclohexenone. The following
rationale for this observation was proposed by considering conformations of chromate intermediates of both 1 and 15
(Scheme 2). Due to the potential 1,3-diaxial interaction between H and chromate moiety in C-1, C-10 to a certain extent
becomes a competitive conformation which can undergo oxidative desilylation to give cyclohexenone. However, this
interaction does not exist obviously in C-15 featuring a much flatter conformation. Thus, C-15 seems to be
energetically more stable and leads to the observed high yield of 16.
In conclusion, we have described a convenient approach to various cyclic b-silylenones by an oxidative
rearrangement of cyclic tertiary a-hydroxy allylsilanes with PCC in refluxing ClCH2CH2Cl [9]. Improvement of the
protocol and the related application in organic synthesis are ongoing in our group.
Acknowledgments
This research was supported by the National Natural Science Foundation of China (No. 20802044), and RFDP (No.
200806101091).
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X. Wu et al. / Chinese Chemical Letters 22 (2011) 306–309
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[9] General procedure: To a magnetically stirred slurry of pyridinium chlorochromate (PCC) (97 mg, 0.45 mmol) and silica gel (finer than 200
mesh, 97 mg) in 1 mL 1,2-dichloroethane was added a solution of 15 (65 mg, 0.3 mmol) in 0.5 mL of 1,2-dichloroethane at 85 8C. The resulting
dark red-black mixture was stirred for 5 min and diluted with an equal volume of ether. The following filtration through a pad of silica,
concentration under reduced pressure and purification of the crude residue via silica gel flash column chromatography (gradient eluent: 5–10%
EtOAc in petroleum ether) afforded pure 16 (61 mg) as a yellow oil in 94% yield. Spectral data of products: 2: 1H NMR (400 MHz, CDCl3): d
7.45 (m, 5H), 6.29 (t, 1H, J = 1.6 Hz), 2.41 (t, 2H, J = 6.8 Hz), 2.31 (m, 2H), 1.96 (m, 2H), 0.43 (s, 6H); 13C NMR (100 MHz, CDCl3): d 198.5,
165.9, 136.9, 135.6, 133.9, 129.6, 128.1, 38.1, 28.0, 23.5, ꢀ4.2; IR (neat) cmꢀ1: 3064, 3016, 2952, 2927, 2864, 1675, 1585, 1454, 1424, 1330,
1253; HRMS (MALDI, m/z) calcd. for C14H18OSiNa (M+Na)+: 253.1025, found 253.1017. 4: 1H NMR (400 MHz, CDCl3): d 7.42 (m, 5H), 2.40
(t, 2H, J = 6.8 Hz), 2.34 (m, 2H), 1.93 (m, 2H), 1.76 (t, 3H, J = 2.0 Hz), 0.45 (s, 6H); 13C NMR (100 MHz, CDCl3): d 198.7, 156.1, 143.8, 137.5,
133.6, 129.3, 128.0, 38.2, 31.0, 23.7, 16.0, ꢀ1.7; IR (neat) cmꢀ1: 3063, 3005, 2948, 2928, 2863, 1670, 1585, 1426, 1377, 1340, 1254; HRMS
(MALDI, m/z) calcd. for C15H20OSiNa (M+Na)+: 267.1181, found 267.1185. 6: 1H NMR (400 MHz, CDCl3): d 7.44 (m, 5H), 6.22 (s, 1H), 2.61
(m, 1H), 2.55 (m, 1H), 2.35 (m, 1H), 2.08 (m, 1H), 1.79 (m, 1H), 1.05 (d, 3H, J = 7.2 Hz), 0.47 (s, 3H), 0.46 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 198.4, 170.4, 136.6, 136.2, 133.9, 129.6, 128.0, 33.9, 32.0, 30.7, 18.9, ꢀ2.9, ꢀ3.2; IR (neat) cmꢀ1: 3063, 2960, 2927, 2863, 1676,
1584, 1456, 1422, 1331, 1257; HRMS (MALDI, m/z) calcd. for C15H20OSiNa (M+Na)+: 267.1181, found 267.1172. 8: 1H NMR (400 MHz,
CDCl3): d 7.43 (m, 5H), 6.25 (s, 1H), 2.41 (m, 1H), 2.36 (m, 2H), 2.03 (m, 1H), 1.68 (m, 1H), 1.12 (d, 3H, J = 6.8 Hz), 0.43 (s, 6H); 13C NMR
(50 MHz, CDCl3): d 201.4, 164.7, 136.5, 134.2, 133.9, 133.7, 133.2, 129.6, 128.1, 41.6, 31.7, 27.8, 22.9, 15.1, ꢀ4.1, ꢀ4.2; IR (neat) cmꢀ1: 3051,
2957, 2925, 2856, 1676, 1588, 1456, 1427, 1374, 1253; HRMS (MALDI, m/z) calcd. for C15H20OSiNa (M+Na)+: 267.1181, found 267.1176. 10:
1H NMR (400 MHz, CDCl3): d 7.44 (m, 5H), 7.23 (m, 5H), 6.29 (t, 1H, J = 1.6 Hz), 3.34 (m, 1H), 2.52 (m, 2H), 2.37 (m, 1H), 2.21 (m, 1H), 1.93
(m, 1H), 1.58 (m, 1H), 0.42 (s, 6H); 13C NMR (50 MHz, CDCl3): d 199.7, 164.9, 140.0, 136.7, 135.6, 133.9, 129.7, 129.2, 128.3, 128.1, 128.0,
48.4, 35.3, 27.9, 27.7, ꢀ4.1, ꢀ4.2; IR (neat) cmꢀ1: 3062, 3023, 2923, 2856, 1953, 1887, 1816, 1672, 1596, 1494, 1451, 1426, 1339, 1253; HRMS
(MALDI, m/z) calcd. for C21H24OSi Na (M+Na)+: 343.1494, found 343.1496. 12: 1H NMR (400 MHz, CDCl3): d 7.44 (m, 5H), 6.26 (m, 1H),
5.76 (m, 1H), 5.03 (m, 2H), 2.61 (m, 1H), 2.41 (m, 1H), 2.32 (m, 2H), 2.08 (m, 2H), 1.66 (m, 1H), 0.43 (s, 6H); 13C NMR (100 MHz, CDCl3): d
199.9, 164.9, 136.6, 136.1, 135.6, 133.9, 129.6, 128.1, 116.7, 46.1, 33.7, 28.1, 27.6, ꢀ4.1, ꢀ4.2; IR (neat) cmꢀ1: 3070, 3012, 2923, 2857, 1674,
1587, 1427, 1339, 1255; HRMS (MALDI, m/z) calcd. for C17H22OSi Na (M+Na)+: 293.1338, found 293.1341. 14: 1H NMR (400 MHz, CDCl3):
d 7.45 (m, 5H), 0.43 (s, 6H), 6.19 (t, 1H, J = 2.0 Hz), 2.32 (m, 2H), 1.78 (t, 2H, J = 6.0 Hz), 1.09 (s, 6H); 13C NMR (50 MHz, CDCl3): d 203.6,
163.5, 135.8, 135.5, 133.9, 129.6, 128.1, 41.0, 37.0, 25.4, 24.1, ꢀ4.1; IR (neat) cmꢀ1: 3065, 3015, 2962, 2917, 1673, 1588, 1455, 1426, 1383,
1307, 1253; HRMS (MALDI, m/z) calcd. for C16H22OSiNa (M+Na)+: 281.1338, found 281.1336. 16: 1H NMR (400 MHz, CDCl3): d 7.45 (m,
5H), 6.39 (t, 1H, J = 2.0 Hz), 2.69 (m, 2H), 2.33 (m, 2H), 0.49 (s, 6H); 13C NMR (50 MHz, CDCl3): d 211.2, 182.4, 142.4, 135.2, 133.7, 129.7,
128.1, ꢀ35.0, 31.9, 3.9; IR (neat) cmꢀ1: 3052, 2957, 2921, 1708, 1430, 1252; HRMS (MALDI, m/z) calcd. for C13H16OSi Na (M+Na)+:
239.0868, found 239.0878.