Radical deoxygenation of alcohols via their S-methyl dithiocarbonate derivatives with di-n-butylphosphine oxide as hydrogen atom donor

Article abstract of DOI:10.1055/s-1998-1582

Various S-methyl dithiocarbonates of tertiary and secondary alcohols are readily deoxygenated in high isolated yields by radical deoxygenation with di-n-butylphosphine oxide and various radical initiators in boiling dioxane. Primary alcohols react similarly in boiling xylenes.

Full text of DOI:10.1055/s-1998-1582

January 1998
SYNLETT
39
Radical Deoxygenation of Alcohols via Their S-Methyl Dithiocarbonate Derivatives with
Di-n-butylphosphine Oxide as Hydrogen Atom Donor
a
a
b
Doo Ok Jang *, Dae Hyan Cho and Derek H. R. Barton
aDepartment of Chemistry, Yonsei University, Wonju 220-710, Korea
bDepartment of Chemistry, Texas A&M University, College Station, TX 77843, USA
Fax 82 371 763 4323; dojang@dragon.yonsei.ac.kr
Received 21 October 1997
Abstract: Various S-methyl dithiocarbonates of tertiary and secondary
alcohols are readily deoxygenated in high isolated yields by radical
deoxygenation with di-n-butylphosphine oxide and various radical
initiators in boiling dioxane. Primary alcohols react similarly in boiling
xylenes.
Reactions for the selective replacement of hydroxyl groups by hydrogen
atoms are very important in many areas of natural product chemistry.
Although a number of ionic reactions for the deoxygenation of alcohols
have been reported, radical deoxygenation of alcohols (Barton-
McCombie reaction) is the most frequently used.1 The radical
deoxygenation is particularly suitable for the replacement of a sterically
hindered hydroxyl group by a hydrogen without elimination and
2
rearrangement. Various thiocarbonyl precursors (1: X = methylthio,
2
2
3
4
p-methylphenoxy,5
phenyl,
imidazolyl,
phenoxy,
methoxy,
7
pentafluorophenoxy, p-fluorophenoxy, and amidyl8) which are
reduced to the corresponding deoxygenated products under radical
reaction conditions are used in the Barton-McCombie reaction (Scheme
6
1). Among them, S-methyl dithiocarbonate, phenyl thionocarbonate and
p-fluorophenyl thionocarbonate derivatives of alcohols are the most
frequently used due to their reactivity and ease of preparation.
Scheme 1
Organotin hydrides have been used commonly as radical hydrogen
sources in the radical deoxygenation of alcohols. However, they are
very toxic, and it is difficult to remove the tin byproduct completely
from the desired products. Consequently, they are not suitable for large
scale work and unacceptable for pharmaceutical applications.
Therefore, it is very important to find alternatives for tin hydrides. There
have been several efforts to replace organotin hydrides with other
in the presence of AIBN (0.5 eq) was heated to reflux, cyclododecane
(2c) was obtained in 94 % yield (Table 1, entry 1). In the absence of
initiator only an 8 % yield of cyclododecane (2c) was obtained, thus
providing evidence for the radical chain mechanism. To establish the
optimal conditions, various radical initiators were examined. The results
are summerized in Table 1.
7-9
radical hydrogen sources. It has been reported recently that silanes,
dialkyl phosphites1
0,12
and hypophosphorous acid
11,12
can be used as
hydrogen donors and radical chain carriers in the radical deoxygenation
of alcohols. Among them, the phosphorus compounds (dialkyl
phosphites and hypophosphorous acid) are almost ideal as hydrogen
atom donors and radical chain carriers. However, dialkyl phosphites
need benzoyl peroxide to initiate the reaction. Hypophosphorous acid is
not applicable in moisture sensitive substrates because of the difficulties
in removing the water completely. We report herein a new radical
hydrogen donor for the radical deoxygenation of alcohols.
Radical deoxygenation of alcohols can be accomplished with di-n-
1
3
butylphosphine oxide affording the corresponding deoxygenated
products in high isolated yields. The advantages of the process are the
applicability of various radical initiators, not using an excess of the
radical hydrogen donor and complete exclusion of moisture.
When
a solution of the S-methyl dithiocarbonate derivative of
cyclododecanol (2a) and di-n-butylphosphine oxide (1.5 eq) in dioxane

4
0
LETTERS
SYNLETT
References and Notes
(
1) a) Hartwig, W. Tetrahedron 1983, 39, 2609. b) Ramaiah, M.
Tetrahedron 1987, 43, 3541. c) Curran, D. P. Synthesis 1988, 417.
d) Idem, ibid. 1988, 489.
(2) Barton, D. H. R.; McCombie, S. W. J. Chem. Soc., Perkin Trans. I
1
975, 1574.
3) Robins, M. J.; Wilson, J. S.; Hansske, F. J. Am. Chem. Soc. 1983,
05, 4059.
(
1
(4) Prisbe, E. J.; Martin, J. C. Synth. Commun. 1985, 15, 401.
(5) Heibl, J.; Zbiral, E. Tetrahedron Lett. 1990, 31, 4007.
(6) Barton, D. H. R.; Jaszberenyi, J. Cs. Tetrahedron Lett. 1989, 30,
2
619.
(7) Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. Cs. Tetrahedron
Lett. 1990, 31, 4681.
(
8) a) Nishiyama, K.; Oba, M.; Oshimi, M.; Sugawara, T.; Ueno, R.
Tetrahedron Lett. 1993, 23, 3745. b) Oba, M.; Nishiyama, K.
Synthesis 1994, 624.
(
9) a) For tris(trimethylsilyl)silane, references cited therein:
Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188. b) Kirwan, J.
N.; Roberts, B. P.; Willis, C. R. Tetrahedron Lett. 1990, 31, 5093.
c) Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. Cs. Synlett 1991,
4
35. d) Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. Cs.
Tetrahedron Lett. 1991, 32, 7187. e) Cole, S. J.; Kirwan, J. N.;
Roberts, B. P.; Wills, C. R. J. Chem. Soc., Perkin Trans. I 1991,
103. f) Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. Cs.
Tetrahedron Lett. 1992, 33, 6629. g) Barton, D. H. R.; Jang, D.
O.; Jaszberenyi, J. Cs. Tetrahedron 1993, 49, 2793. h) Barton, D.
H. R.; Jang, D. O.; Jaszberenyi, J. Cs. Tetrahedron 1993, 49,
The reaction was applied for the deoxygenation of various alcohols.
Tertiary and secondary alcohols were smoothly converted into the
corresponding hydrocarbons (Table 2, entries 1-4). S-Methyl
dithiocarbonate derivative of a sterically hindered alcohol such as 7a
needed at least 3.0 eq of di-n-butylphosphine oxide to obtain the
deoxygenated product efficiently (entries 5 and 6). As expected, a much
higher temperature was needed for the deoxygenation of primary
alcohols (entries 7-10).
7
193.
(10) Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. Cs. Tetrahedron
Lett. 1992, 33, 2311.
(11) Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. Cs. Tetrahedron
Lett. 1992, 33, 5709.
(
12) Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. Cs. J. Org. Chem.
1993, 58, 6838.
Interestingly, p-fluorophenyl thionocarbonate derivatives of alcohols
which are reactive to tri-n-butyltin hydride and silanes showed poor
reactivity. Under the standard conditions, p-fluorophenyl
thionocarbonate derivative of cyclododecanol 2b gave cyclododecane
(
13) Preparation of di-n-butylphosphine oxide: To a solution of diethyl
phosphite (4.6 mL, 36.2 mmol) in dry ether (10 mL) was added
n
BuMgCl (2.0 M solution, 53.4 mL, 108.6 mmol) at 15 oC. The
(2c) in 7 % yield along with 90 % of recovered 2b.
mixture was heated to reflux for 30 min. After cooling to room
In summary, di-n-butylphosphine oxide can be used for the
deoxygenation of S-methyl dithiocarbonate derivatives of various
alcohols as an alternative for organotin hydrides with various radical
initiators under anhydrous conditions.
temperature, the mixture was stirred with 25% H SO4 (44 mL)
2
and H O (80 mL) for 1 hr. The reaction mixture was washed with
2
saturated K CO3 and H O. The organic layer was dried over
2
2
anhydrous MgSO . After filtration, the solvent was removed and
4
Typical procedure: A solution of the starting S-methyl dithiocarbonate
the residue was recrystallyzed in dry hexanes to give di-n-
butylphosphine oxide in 60 % ( 3.5 g): mp 64 C (lit. : 66 C), H
o
14
o
1
6
a (100 mg, 0.21 mmol) and di-n-butylphosphine oxide (51 mg, 0.32
t
t
mmol) in dry dioxane (1 mL) under argon was treated with BuOO Bu
0.01 mL, 0.05 mmol) twice (8 hr interval) during reflux. The reaction
NMR (CDCl3) δ 1.37-3.50 (m, 18H), 6.84 (d, JP-H = 686 Hz, 1H).
31
(
P NMR (CDCl3) δ 38.6.
(14) Rauhut, M. M.; Currier, H. A. J. Org. Chem. 1961, 26, 4626.
was followed by TLC. When the reaction was completed, the solvent
was evaporated in vacuum and the product was isolated by column
chromatography on silica gel (eluent: hexanes) affording 76 mg (97 %)
of cholestane (6b).
Acknowledgements: We thank the Korea Science and Engineering
Foundation (Grant No. 961-0302-010-1) for the financial support of this
work.