Radical deoxygenation of tertiary alcohols via trifluoroacetates

Article abstract of DOI:10.1016/j.tetlet.2004.02.109

Trifluoroacetates of tertiary alcohols undergo deoxygenation by Ph ₂SiH₂ in the presence of (^tBuO)₂ in excellent yields of the deoxy products without affecting the stereochemistry at β-carbon.

Full text of DOI:10.1016/j.tetlet.2004.02.109

Tetrahedron
Letters
Tetrahedron Letters45 (2004) 3031–3033
Radical deoxygenation of tertiary alcohols via trifluoroacetates
Joong-Gon Kim,c Dae Hyan Choa,b and Doo Ok Janga,b,
*
aDepartment of Chemistry, Yonsei University, Wonju 220-710, South Korea
bCenter for Bioactive Molecular Hybrids, Yonsei University, Seoul 120-749, South Korea
cBiotechnology Division, Hanwha Chemical R&D Center, Daejeon 305-345, South Korea
Received 20 January 2004; revised 19 February 2004; accepted 23 February 2004
Abstract—Trifluoroacetatesof tertiary alcoholsundergo deoxygenation by Ph 2SiH2 in the presence of (tBuO)2 in excellent yieldsof
the deoxy products without affecting the stereochemistry at b-carbon.
Ó 2004 Elsevier Ltd. All rights reserved.
8
Deoxygenation of tertiary alcoholsin complicated
molecules is not an easy task in organic synthesis.
Dehydration/hydrogenation method affordsa product
that loses the original configuration of b-carbon center.1
bonatesof alcohol.s We have assumed that trifluoro-
acetate derivativesof tertiary alcoholshave thermal
stability and proper reactivity under radical reaction
conditions. We report herein a convenient and efficient
method of deoxygenating tertiary alcoholsvia trifluoro-
acetateswith diphenylsilane.
Radical deoxygenation of secondary and primary alco-
holsvia thionocarbonyl derivativeshasbeen proven a
useful synthetic method, especially for the synthesis of
complex molecules.2 However, the method isnot usit-
able for the deoxygenation of tertiary alcoholsbecause
of the thermal instability of thionocarbonyl derivatives.3
Although there isan example of uisng the thionocar-
bonyl derivative for the deoxygenation of tertiary alco-
hols, it requires special treatment and careful handling
to prevent the thermal elimination.4 The stability of
thionocarbonatesof tertiary alcoholsdependsupon the
structure of the substrates.
We chose 1-methyl cyclododecanol trifluoroacetate as a
model compound. Treatment of 1-methyl cyclododeca-
nol trifluoroacetate with Ph2SiH2 in the presence of
(tBuO)2 at 140 °C resulted in the formation of the
deoxygenated product, methylcyclododecane quantita-
tively. In order to find the optimal reaction conditions,
the reaction wascarried out under variousreaction
conditions. The yield of methyl cyclododecane was
measured by GLC analysis, and the results are shown in
Table 1. The optimal reaction conditionswere etsab-
lished with 3 equiv of Ph2SiH2 and 1 equiv of (tBuO)2 at
130 °C (entry 4). Although the reaction proceeded at
below 130 °C, prolonged reaction timesare needed
(entries5 and 6). We have also carried out the reaction
Consequently, research efforts on radical precursors for
the deoxygenation of tertiary alcoholshave been
reported, including the tertiary alcohol thioxoformates5
and oxalates.6 In spite of their potential utility, however,
they involve in the use of toxic and moisture sensitive
and thermally unstable reagents. Thus, there is a need to
develop suitable radical precursors for the deoxygen-
ation of tertiary alcohols. Recently, Roberts reported
that tertiary alcoholswere deoxygenated via their MOM
Table 1. Deoxygenation of 1-methylcyclododecyl trifluoroacetate with
Ph2SiH2 under variousreaction conditions
Entry
Ph2SiH2
(equiv)
(tBuO)2
(equiv)
Temperature Time Yield
(h)
(°C)
(GC, %)a
1
2
3
4
5
6
7
5
3
2
3
3
3
3
1
140
140
140
130
120
125
130
15
15
15
15
20
20
15
100
100
7
ethersby refluxing in octane in the presence of a thiol.
It hasbeen known that acetate derivativesof alcohols
are much more stable thermally than the thionocar-
1
1
86 (14)b
1
100
1
63 (35)b
89 (11)b
92 (8)b
1
0.5
Keywords: Radical; tert-Alcohol; Deoxygenation; Trifluoroacetate.
* Corresponding author. Tel.: +82-33-760-2261; fax: +82-33-760-2182;
e-mail: dojang@dragon.yonsei.ac.kr
a Analyzed by GC.
b Starting material.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.02.109

3032
J.-G. Kim et al. / Tetrahedron Letters 45 (2004) 3031–3033
at 100 °C with more active other hydridesusch as
n-tributyltin hydride and triphenyltin hydride affording
the corresponding alcohols in 88% and 89%, respec-
tively. The reaction with t-dodecanthiol/Ph2SiH2 or
N-ethylpiperidium hypophosphite at 100 °C did not
proceed at all. The results implied that the reaction did
not depend on the activity of hydrides, and a radical
intermediate of the reaction did not break up at 100 °C
to give an alkyl radical.
the products are obtained in high isolated yields. The
results show that the method is general for the deoxy-
genation of tertiary alcohols.
The reaction isapplicable to the deoxygenation of ter-
tiary alcoholsthat have a stereogenic center at b-carbon.
Thus, tertiary alcohols with a stereogenic center were
transformed into the deoxy products without interfering
with an adjacent chiral center asshown in Table 3.
The procedure wasapplied to the deoxygenation of
varioustertiary alcoholsto examine the scope and lim-
itations of the reaction. The results are presented in
Table 2. The reactionsare clean, and there are no side
reactionsusch aselimination reaction implying that
tertiary alcohol trifluoroacetatesare quite tsable ther-
mally. The experimental procedure isquite simple, and
In order to prove preserving the configuration of b-
position in the deoxy product, (2S)-1-tert-butyldiphen-
ylsilyoxy-2,3-dimethylbutane was deprotected with
tetrabutylammonium fluoride to obtain (2S)-2,3-
dimethyl-1-butanol in 93% yield, which gave the identical
spectroscopic data to an authentic sample (Scheme 1).9
Next, we tried to utilize the present method for more
complex substrates. The procedure used for the deoxy-
genation of a limonoid, xyloccensin K (1). Treatment of
xyloccensin K (1) with trifluoroacetic anhydride in the
presence of DMAP afforded trifluoroacetate 2 in 72%
Table 2. Deoxygenation of varioustertiary alcoholswith Ph 2SiH2
Ph2SiH2 (3 equiv), (tBuO)2 (1 equiv)
O
R3C O C CF3
R3C H
130 oC, 15 h
yield. The latter wastreated with Ph SiH2 in the pres-
2
Entry
1
Substrate
R3C–H (%)a
ence of (tBuO)2 at 130 °C giving the deoxy product 310 in
81% yield without epoxide ring opening.11 The result
implies that reducible functional groups such as ketones,
esters, and lactones are tolerance under the reaction
conditions.
O
C
O
O
CF3
90
O
C
F
C
3
2
3
4
5
6
90
84
86
88
82
Bu
Table 3. Deoxygenation of tertiary alcoholswith chiral center at
b-carbon with Ph2SiH2
O
O C CF3
Ph2SiH2 (3 equiv), (tBuO)2 (1 equiv)
O
R3C O
C
CF3
R3C H
130 oC, 15 h
O
Entry
Substrate
R3C–H (%)a
Bu
O C CF3
O
1
74
O
C CF3
O
C
O
CF3
O
O
O
C CF3
O
O
C
CF3
CF3
O
O
2
3
4
83
84
87
Bu
O
C
O
O
O
O C CF3
O
7
87
Ph
O
C
CF3
Si
Ph
Ph
Si
Ph
O
O
C
O
O
CF3
5
87
O C CF3
8
89
93
85
O
a Isolated yield.
Bu
O
O C CF3
9
u
B
F
4N
h
h
P
10
i
S
O
HO
O
O
P
C
93 %
CF3
a Isolated yield.
Scheme 1.

J.-G. Kim et al. / Tetrahedron Letters 45 (2004) 3031–3033
3033
References and notes
O
O
1. Barton, D. H. R.; Ollis, W. D. Comprehensive Organic
Chemistry; Pergamon: Oxford, 1979; p 579.
O
H
MeO
2. (a) Motherwell, W. B.; Crich, D. Free Radical Chain
Reactions in Organic Synthesis; Academic: London, 1992;
(b) Curran, D. P. Synthesis 1988, 417; (c) Ramaiah, M.
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1983, 39, 2609; (e) Graham, A. E.; Thomas, A. V.; Yang,
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H. Tetrahedron Lett. 2002, 43, 5921.
O
O
X
O
1: X = OH
2: X = OC(O)CF3
3: X = H
3. Nace, H. R. Org. React. 1962, 12, 57.
4. (a) Barton, D. H. R.; Parekh, S. I.; Tse, C. L. Tetrahedron
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Tetraheron Lett. 1993, 34, 6673.
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In summary, this paper describes a convenient and
practical procedure for the radical deoxygenation of
tertiary alcoholsvia their trifluoroacetatesiunsg
Ph2SiH2. Thismethod iscompatible with acid labile
acetals and silyl ethers. This procedure also provides
simplicity and high yields of the deoxy products, which
makes it attractive for the synthesis of complex mole-
cules.
7. Dang, H.-S.; Franchi, P.; Roberts, B. P. Chem. Commun.
2000, 499.
8. (a) Sano, H.; Taketa, T.; Migita, T. Synthesis 1988, 402;
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Tetrahedron Lett. 2001, 42, 1073.
Typical procedure for deoxygenation of trifluoroace-
tatesof
tert-alcohols: (2S)-1-(tert-Butyldiphenyl-
silyl)oxy-2,3-dimethylbutane. A mixture of trifluoro-
acetate of (2S)-1-(tert-butyldiphenylsilyl)oxy-2,3-di-
methylbutanol (180 mg, 0.4 mmol), diphenylsilane
(220 mg, 1.2 mmol) and di-tert-butylperoxide (50 mg,
0.4 mmol) wassealed in an ampule under argon atmo-
sphere. After heating at 130 °C for 15 h, the mixture was
purified by silica gel column chromatography giving
157 mg (87%) of the title compound. 1H NMR
(300 MHz, CDCl3) d 0.78 (dd, J ¼ 3:2, 11.2 Hz, 6H),
0.84 (d, J ¼ 6:8 Hz, 3H), 1.06 (s, 9H), 1.51 (m, 1H), 1.69
(m, 1H), 3.34 (dd, J ¼ 6:8, 9.5 Hz, 2H), 7.49–7.68 (m,
10H); 13C NMR (75 MHz, CDCl3) d 11.8, 16.8, 17.4,
19.7, 20.2, 22.5, 29.4, 60.9, 127.3, 130.4, 133.2, 134.1.
Anal. Calcd for C22H32OSi: C, 83.47; H, 10.19. Found:
C, 82.24; H, 10.10.
9. Masamune, S.; Kim, B.; Petersen, J. S.; Sato, T.; Veenstra,
S. J. Am. Chem. Soc. 1985, 107, 4549.
20
D
CHCl3); IR (CHCl3): 2971, 2879, 1723, 1459, 1375, 1263,
10. Spectroscopic data of compound 3: ½aŠ þ 98:7 (c, 0.12
1
1171, 1027 cmꢀ1; H NMR (300 MHz, CDCl3): d 0.69 (s,
3H), 0.94 (s, 3H), 1.08 (s, 3H), 1.16 (s, 3H), 1.39–1.43 (m,
1H), 1.65–1.73 (m, 4H), 1.90–2.0 (m, 2H), 2.09–2.30 (m,
4H), 2.50 (dd, J ¼ 6:0, 6.0 Hz, 1H), 2.95 (dd, J ¼ 2:7,
10.5 Hz, 1H), 3.14 (t, J ¼ 5:7 Hz, 1H), 3.69 (s, 3H), 4.24 (d,
J ¼ 5:7 Hz, 1H), 6.35 (s, 1H), 6.47 (s, 1H), 7.44 (s, 1H),
7.52 (s, 1H); 13C NMR (75 MHz, CDCl3): d 17.2, 19.8,
20.2, 21.6, 28.0, 32.0, 32.9, 37.3, 42.8, 48.8, 51.7, 52.0, 52.1,
53.5, 80.6, 81.2, 89.1, 110.2, 118.3, 120.3, 141.5, 143.3,
164.9, 166.2, 174.5, 215.1; Anal. Calcd. for C27H34O7: C,
68.92; H, 7.28; O, 23.80. Found: C, 69.85; H, 7.14; O,
23.87.
11. For examplesof the ring opening of an oxirane by an
adjacent carbon centered radical: (a) Barton, D. H. R.;
Hay-Motherwell, R. S.; Motherwell, W. B. J. Chem. Soc.
Perkin Trans. 1 1981, 2363; (b) Bowman, W. B.; Marples,
B. A.; Zaidi, N. A. Tetrahedron Lett. 1989, 30, 3343.
Acknowledgements
This work was supported by Korea Research Founda-
tion Grant (KRF-2002-015-CP0214).