Practical One-Pot Di-O-silylation and Regioselective Deprotective Oxidation of 1O-O-Silyl Ether in 1O,2O-Diols

Full text of DOI:10.1021/jo9621175

2628
J . Org. Chem. 1997, 62, 2628-2629
Ta ble 1. Disilyla tion a n d /or Regioselective Dep r otective
Oxid a tion of Diols/Disilyl Eth er s
P r a ctica l On e-P ot Di-O-silyla tion a n d
Regioselective Dep r otective Oxid a tion of
yielda (%)
70
10-O-Silyl Eth er in 10,20-Diols†
entry
1
substrate
product
OTBDMS
OTBDMS
CHO
H9C4
OTBDMS
H9C4
S. Chandrasekhar,* Pradyumna K. Mohanty, and
Mohamed Takhi
8
8
1a
1b
1b
2
3
OH
64 (82)
68
Indian Institute of Chemical Technology,
Hyderabad 500 007, India
H9C4
OH
OTBDMS
OH
8
2a
OTBDMS
CHO
OTBDMS
Received November 12, 1996
Ph
Ph
Ph
6
6
3a
Oxidation of an alcohol to a carbonyl group constitutes
a very useful functional group transformation, and the
plethora of reagents for this transformation documented
in literature directly measures the importance with
which this functional group transformation has been
addressed.1 However, only a few reagents are chemose-
lective in oxidizing either a primary alcohol group or a
secondary alcohol group exclusively. Though a good
number of reagents are available for selective secondary
alcohol oxidation,2 primary alcohol oxidation is rather
poorly addressed3 wherein only RuCl2 (PPH3),3b Cp2-
ZrH2,3e and TEMPO3f performed the desired transforma-
tion with moderate to reasonable selectivity. Addition-
ally, no reagent combination has been reported for
simultanious oxidation of primary alcohol while protect-
ing the existing secondary alcohol in a single pot. Our
continued interest in developing new oxidation proce-
dures4 and reagents5 has prompted us to address this
issue wherein we believe judicious choice of the right
protective group and oxidation reagent should give a
reality to our hypothesis. Thus, the protection-oxidation
sequence in a single pot, starting from a 10,20-diol (where
10,20-diol contains both a primary and a secondary
alcohol) (eq 1) will increase the overall efficacy, which is
desirable in a long synthetic scheme. Accordingly, we
reasoned that if one chooses the trialkylsilyl group as the
protective group for a 10,20-diol and an oxidation reagent
that also incorporates an element that selectively cleaves
3b
OH
4
5
3b
65 (80)
72
6
4a
OTBDMS
OTBDMS
CHO
OTBDMS
6
5a
6
5b
5b
OH
6
68 (78)
OH
6
6a
7
8
CHO
72
70
THPO
OTBDMS
OTBDMS
THPO
6
6
7b
7a
CHO
MOMO
MOMO
6
6
8a
8b
PhCH2OTBDMS
PhCHO
9
72
66
9a
9b
10
CHO
Ph
OTBDMS
10a
Ph
10b
C11H23CH2OTBDMS
C11H23CHO
11
71
92
11a
11b
+
+
OTBDMS
12a
Ph
12a
CHO
12
69
TBDPSO
OTBDMS
TBDPSO
6
6
13b
13a
a
The yields in parentheses are based on recovery of correspond-
ing disilyl ethers.
† IICT Communication No. 3747.
(1) (a) Hudlicky, M. Oxidations in Organic Chemistry; American
Chemical Society: Washington, DC, 1990. (b) Cainelli, G.; Cardillo,
G. Chromium Oxidations in Organic Chemistry; Springer-Verlag: New
York, 1984. (c) Haines, A. H. Methods for the oxidation of organic
compounds, alcohols, alcohols derivatives etc; Academic: London, 1988.
(d) Griffith, W. P.; Ley, S. V. Aldrichim. Acta 1990, 23, 13-19.
(2) (a) Bovicelli, P.; Lupattelli, P.; Sanetti, A. Tetrahedron Lett. 1994,
35, 8477. (b) Posner, G. H.; Perfetti, R. B.; Runquist, A. W. Tetrahedron
Lett. 1976, 3499. (c) Ueno, Y.; Okawara, M. Tetrahedron Lett. 1976,
4597. (d) J ung, M. E.; Speltz, L. M. J . Am. Chem. Soc. 1976, 98, 7882.
(e) J ung, M. E.; Brown, R. W. Tetrahedron Lett. 1978, 2771. (f)
Tomioka, H.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1982, 23, 539.
(g) Kaneda, K.; Kawanishi, Y.; Itsukawa, K.; Teranishi, S. Tetrahedron
Lett. 1983, 24, 5009. (h) Trost, B. M.; Masuyama, Y. Tetrahedron Lett.
1984, 25, 173. (i) Kanemoto, S.; Saimoto, H.; Oshima, K.; Nozaki, H.
Tetrahedron Lett. 1984, 25, 3317. (j) Kim, K. S.; Song, Y. H.; Lee, N.
H.; Hahn, C. S. Tetrahedron Lett. 1986, 27, 2875. (k) Kim, K. S.;
Chung, S.; Cho, I. H.; Hahn, C. S. Tetrahedron Lett. 1989, 30, 2559.
(3) (a) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J . Org. Chem.
1987, 52, 2559. (b) Tomioka, H.; Takai, K.; Oshima, K.; Nozaki, H.
Tetrahedron Lett. 1981, 22, 1605. (c) Singh, J .; Kalsi, P. S., J awanda,
G. S.; Chhabra, B. Chem. Ind. 1986, 751. (d) Siedlecka, R.; Skarze-
wlski, J .; Mitochowski, J . Tetrahedron Lett. 1990, 31, 2177. (e) Nakano,
T.; Terada, T.; Ishii, Y.; Ogawa, M. Synthesis 1986, 774. (f) Semmel-
hack, M. F.; Chou, C. S.; Cortes, D. A. J . Am. Chem. Soc. 1983, 105,
4492.
10-O-silyl ether,6 the task could become practical. After
a careful study of the literature of chromium-based
oxidation reagents and extensive experimentation, we
have choosen to utilize freshly prepared quinolinium
fluorochromate7 (QFC) as the selective deprotection-
oxidation reagent to serve our needs. To our utmost
satisfaction, we were successful in achieving the desired
selective deprotective oxidation with QFC (eq 2). The
results are presented herein.
In an initial study, 1,10-bis-O-(tert-butyldimethylsilyl)-
tetradecane (Table 1, entry 1) was subjected to QFC
oxidation, and we observed a clean deprotective oxidation
of 10-O-silyl ether to aldehyde in 70% yield without
effecting the 20-O-silyl ether. Similarly, treatment of 1,-
10-tetradecanediol (Table 1, entry 2) with 2.5 equiv of
(6) For references pertaining to oxidative deprotection of O-silyl
ethers see: (a) Muzart, J . Synthesis 1993, 11. (b) Wilson, N. S.; Keay,
B. A. J . Org. Chem. 1996, 61, 2918. (c) Cossio, F. P.; Aizpurua, J . M.;
Palomo, C. Can. J . Chem. 1986, 64, 225. (d) Piva, O.; Amougay, A.;
Pete, J . P. Tetrahedron Lett. 1991, 32, 3993. (e) Liu, H. J .; Han, I. S.
Synth. Commun. 1985, 15, 759.
(4) (a) Chandrasekhar, S.; Yadav, J . S.; Sumithra, G.; Rajashaker,
K. Tetrahedron Lett. 1996, 37, 6603. (b) Chadrasekhar, S.; Sumithra,
G.; Yadav, J . S. Tetrahedron Lett. 1996, 37, 1645.
(5) Chandrasekhar, S.; Takhi, M.; Mohapatra, S. Synth. Commun.,
in press.
(7) Murugesan, V.; Pandurangan, A. Ind. J . Chem. 1992, 31(B), 377.
S0022-3263(96)02117-2 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 8, 1997 2629
addition of BuMgBr onto 10-O-(tert-butyldimethylsilyl)decan-1-
al9 followed by desilylation using HF-pyridine.10 4a (Table 1,
entry 4) was prepared by addition of PhMgBr onto 8-O-(tert-
butyldimethylsilyl)octan-1-al followed by desilylation. 6a (Table
1, entry 6) was prepared by addition of vinylmagnesium bromide
onto 8-O-(tert-butyldimethylsilyl)octan-1-al followed by desily-
lation. 7a (Table 1, entry 7) was prepared from 1,8-octanediol
by monotetrahydropyranylation11 followed by silylation. 8a
(Table 1, entry 8) was prepared from 1,8-octanediol by mono-
O-silylation followed by MOM protection.12 9a , 10a , 11a , and
12a (Table 1, entries 9-12) were prepared by silylation of
commercial alcohols obtained from Aldrich. 1a , 3a , and 5a
(Table 1, entries 1, 3, and 5) were prepared from the correspond-
ing diols 2a , 4a , and 6a , respectively. 13a (Table 1, entry 12)
was prepared from commercial 1,8-octanediol by monosilylation
with 1 equiv of tert-butyldimethylsilyl chloride followed by a
second silylation with tert-butyldiphenylsilyl chloride.
Op tim ized Disilyla tion a n d Selective Desilyla tion -
Oxid a tion P r oced u r e. To a solution of 1,10-tetradecanediol
(2a , 0.55 g, 2.41 mmol) in dry CH2Cl2 (8 mL) were added
imidazole (0.41 g, 5.94 mmol) and TBDMSCl (0.91 g, 6.01 mmol).
The reaction mixture was stirred at room temperature for 12 h
(monitored by TLC, 25% EtOAc in hexane) followed the addition
of QFC (1.81 g, 7.22 mmol) and dry DMF13 (0.2 mL) and the
resulting mixture stirred for a further 12 h. The reaction
mixture was diluted with n-hexane (20 mL) and filtered through
a small pad of silica gel. Evaporation of the volatiles followed
by flash chromatography using silica gel (5% EtOAc in hexane
as the eluent) furnished 0.53 g of pure 10-O-(tert-butyldimeth-
ylsilyl)tetradecan-1-al (1b) (64%, Rf 0.5), and 0.22 g of 1,10-bis-
O-(tert-butyldimethylsilyl)tetradecane (1a ) (20%, Rf 0.8) was
recovered.
Op tim ized Selective Dep r otection -Oxid a tion P r oce-
d u r e. To 1,10-bis-O-(tert-butyldimethylsilyl)tetradecane (1a ,
0.65 g, 1.41 mmol) in dry CH2Cl2 (8 mL) were added QFC (1.05
g, 4.22 mmol) and DMF (0.2 mL) and the resulting mixture
stirred at ambient temperature for 15 h. Usual workup (vide
supra) furnished 0.34 g of the desired 10-O-(tert-butyldimeth-
ylsilyl)tetradecan-1-al (1b) (70%).
10-O-(ter t-b u t yld im et h ylsilyl)t et r a d eca n -1-a l (1b ): 1H
NMR (CDCl3) δ 0.00 (s, 6H), 0.91 (br s, 12H), 1.20-170 (br m,
16H), 2.41 (t, 2H, J ) 5 Hz), 3.60 (t, 2H, J ) 3 Hz), 9.78 (s, 1H);
IR (film) 1720 cm-1; MS 314 (M+, 5), 255 (75), 199 (20).
8-O-(ter t-bu tyld im eth ylsilyl)-8-p h en ylocta n -1-a l (3b): 1H
NMR (CDCl3) δ 0.20 (s, 6H), 1.10 (s, 9H), 1.41-1.90 (br m, 10H),
2.55 (t, 2H, J ) 5 Hz), 4.78 (t, 2H, J ) 4 Hz), 7.30-7.50 (m,
5H), 9.90 (s, 1H); IR (film) 1725 cm-1. Anal. Calcd for C20H34O2-
Si: C, 71.80; H, 10.24. Found: C, 71.90; H, 10.30.
OTBDMS
CHO
(1) TBDMSCl/imidazole
OH
(2) Quinolinium fluorochromate
(1)
(2)
CH2OH
R
n
R
n
B
A
Quinolinium
OTBDMS
CH2OTBDMS
fluorochromate
B
R
n
tert-butyldimethylsilyl chloride (TBDMSCl) and imida-
zole in CH2Cl2 for 12 h followed by addition of 3 equiv of
freshly prepared8 QFC for a further 24 h has also resulted
in a similar product with identical yield. To prove the
generality of these reagent combinations two free diols
(Table 1, entries 4 and 6) have been subjected to this one-
pot protection-deprotection oxidation sequence with
consistant efficacy. Also, few prepared silyl ethers (Table
1, entries 3 and 5) were deprotectively oxidized with QFC.
When a mixture of 10-O-silyl ether and 20-O-silyl ether
(Table 1, entry 11) was exposed to QFC, only the 10-O-
silyl ether was deprotected and oxidized to aldehyde; no
trace of 20-O-silyl ether cleavage or ketone formation was
observed. In the case of substrates (Table 1, entries 7
and 8) where acid-sensitive protective groups are present,
other than deprotective oxidation, no THP ether cleavage
(Table 1, entry 7) and MOM ether cleavage (Table 1,
entry 8) were noticed. This stability of acid-labile groups
amply shows that QFC is reasonably neutral and silyl
deprotection was achieved with fluoride. Incidentally, 20-
benzylic and allylic ethers are also unaffected (Table 1,
entries 3 and 5), whereas 10-benzylic and allylic ethers
under went smooth deprotection-oxidation (Table 1,
entries 9 and 10). Surprisingly, 10-O-(tert-butyldiphenyl-
silyl) ether resisted the deprotection-oxidation (Table 1,
entry 12).
In summary, a new functional group transformation
has been developed wherein a series of four transforma-
tions, viz., 10-O-silyl protection, 20-O-silyl protection, 10-
O-desilylation, and oxidation of a 10-alcohol have been
achieved in a single vessel. We believe this technique
will attract a wide range of synthetic organic chemists,
especially those who are in the field of complex natural
products synthesis. Efforts are currently underway to
prepare new oxidation reagents that can cleave and
oxidize other ether protective groups.
8-O-(ter t-bu tyld im eth ylsilyl)-9-d ecen -1-a l (5b): 1H NMR
(CDCl3) δ 0.00 (s, 6H), 0.91 (s, 9H), 1.20-1.81 (m, 10H), 2.39 (t,
2H, J ) 6 Hz), 3.85-4.10 (m, 1H), 4.91-5.15 (m, 2H), 5.61-
5.85 (m, 1H), 9.75 (s, 1H); IR (film) 1735 cm-1. Anal. Calcd for
C
16H32O2Si: C, 67.55; H, 11.34. Found: C, 67.70; H, 11.40.
Exp er im en ta l Section
Gen er a l Meth od s. Crude products were purified by column
chromatography on silica gel of 60-120 mesh. 1H NMR were
obtained in CDCl3 at 200 MHz. Chemical shifts are given in
ppm with respect to internal TMS, and J values are quoted in
Hz. Infrared spectra were obtained neat, and only the most
significant absorptions in cm-1 are indicated. N,N-Dimethyl-
formamide and dichloromethane were distilled over CaH2 prior
to use. All reactions were carried out under an atmosphere of
nitrogen using dry glassware.
Ack n ow led gm en t. Two of us (P.K.M. and M.T.) are
thankful to CSIR (New Delhi) for financial assistance.
J O9621175
(9) Luengo, J . I.; Konialiam-Beck, A.; Levy, M. A.; Brandt, M.;
Eggleston, D. S.; Holt, D. A. BioMed. Chem. Lett. 1994, 4, 321.
(10) Nicolaou, K. C.; Webber, S. E. Synthesis 1986, 453.
(11) Vig, O. P.; Vig, A. K.; Gauba, A. L.; Gupta, K. C. J . Indian Chem.
Soc. 1975, 52(6), 541.
(12) Guindan, Y.; Yoakim, C.; Mortan, H. E. J . Org. Chem. 1984,
49(21), 3912.
Sta r tin g Ma ter ia ls. QFC was prepared following the lit-
erature procedure.7 2a (Table 1, entry 2) was prepared by
(13) The amount of DMF addition is critical, since more DMF
generally resulted in partial formation of alcohol along with desired
aldehyde.
(8) Once prepared, the Quinolinium fluorochromate (stored in a
plastic container in the dark) is active for 2 weeks.