Preparation of alcohols from sulfones and trialkylboranes

Article abstract of DOI:10.1016/S0040-4039(03)01025-6

The reaction of sulfone anions with trialkylboranes followed by thermal isomerization of the obtained boron compounds in the presence of excess borane-methyl sulfide complex and by alkaline hydroperoxide oxidation yields primary alcohols.

Full text of DOI:10.1016/S0040-4039(03)01025-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4451–4454
Preparation of alcohols from sulfones and trialkylboranes
Ce´lia Billaud,a Jean-Philippe Goddard,a Thierry Le Galla,* and Charles Mioskowskia,b,
*
aCEA-Saclay, Service de Marquage Mole´culaire et de Chimie Bioorganique, Baˆt. 547, 91191 Gif-sur-Yvette, France
bLaboratoire de Synthe`se Bio-Organique, UMR CNRS 7514, Faculte´ de Pharmacie, Universite´ Louis Pasteur, 74 route du Rhin,
BP 24, 67401 Illkirch, France
Received 14 April 2003; revised 18 April 2003; accepted 19 April 2003
Abstract—The reaction of sulfone anions with trialkylboranes followed by thermal isomerization of the obtained boron
compounds in the presence of excess borane–methyl sulfide complex and by alkaline hydroperoxide oxidation yields primary
alcohols. © 2003 Elsevier Science Ltd. All rights reserved.
Boron compounds are versatile reagents which are
widely employed as precursors for various functional-
ized organic compounds.1 Many trialkylboranes are
conveniently prepared by hydroboration of alkenes and
several methods can be used to convert them to other
boron compounds. Thus, thermal migration of
organoboranes leads to less substituted trialkylboranes
from isomeric, more substituted trialkylboranes.2,3
Also, the reaction of an organoborane with a nucle-
ophile bearing an a-leaving group can afford, after
rearrangement of the initially formed ate complex,
another boron compound, allowing the preparation of
other functionalized products.1 Nucleophiles that have
been employed to achieve such a conversion include
dihalomethane anions, dimethylsulfonium methylide,
dimethylsulfoxonium methylide and diazo compounds.4
contain a common phenyl moiety, and differ by the
absence or the presence of a R group in the sulfone
a-position. This group was expected to have an influ-
ence on the reaction of the corresponding anion with
boron compounds, as well as on the migration of the
boron. Benzyl sulfones were not employed because they
were reported to be less reactive than alkyl sulfones.
The reaction of the anions of the prepared sulfones
with triethylborane were studied at first (Table 1). It
was carried out in toluene rather than in THF, because
the latter solvent would be expected to react with boron
species at elevated temperatures. We observed that the
reaction from 2a proceeded very efficiently, leading,
In 1981, Uguen reported the successful reaction of
anions of sulfones substituted by a primary alkyl or
allylic group with trialkylboranes, for the preparation
of secondary alcohols.5 This is of great interest since
various sulfones can be easily prepared.6 In order to
broaden further the scope of this method, we envi-
sioned to combine it with the thermal isomerization of
organoboranes,2 which allows a boron atom to migrate
along a chain of carbon atoms (Scheme 1). In this
letter, we describe our first results on this subject.
Several alkyl phenyl sulfones 1, 2a–c were prepared in
good yields, as depicted in Scheme 2. These sulfones
Keywords: sulfone; borane; boron compound; alcohol.
* Corresponding authors. Tel.: +1-6908-7105; fax: +1-6908-7991
(T.L.G.); tel.: +3-9024-4297; fax: +3-9024-4306 (C.M.); e-mail:
legall@dsvidf.cea.fr; mioskow@aspirine.u-strasbg.fr
Scheme 1.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01025-6

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C. Billaud et al. / Tetrahedron Letters 44 (2003) 4451–4454
Scheme 2.
after 15 h at room temperature and subsequent oxida-
tion, to alcohol 3b in 78% yield. Higher temperatures
were needed for the reactions using 1, 2b (50°C) and 2c
(80°C), which led to lower yields of the corresponding
alcohols. The reaction from 2a and tributyl- and tri-
hexylborane worked also satisfactorily. It can be seen
that this method provides an easy access to tertiary
alcohols.
Scheme 3.
Table 2. Distribution of alcohols 4, 5, 6b after various
heating times
Entry
Reaction time (h)
Distribution of alcoholsa (%)
4b
5b
6b
1
2
3
2
4
6
8
6
6
28
16
14
64
78
80
An evaluation of the combination of the reaction of the
sulfone 2a with triethylborane and of the thermal
migration was then carried out. After proceeding as
before for the first step, the mixture was heated at
160°C in toluene, in a heavy-walled pressure tube
(Scheme 3). After 15 h and after usual oxidation,
alcohol 6b, which derives from the corresponding less
substituted borane, was obtained in 61% yield. In
another experiment under similar conditions, samples
of the reaction mixture were oxidized after various
a From the 1H NMR spectra of oxidized samples.
b Actually, two diastereomers.
then reaction of these compounds to more thermody-
namically stable trialkylboranes.
1
In order not to obtain any alkene as product, borane
(BH3) was added to the mixture before heating. This
also allowed to lessen the temperature needed for the
thermal migration of boron. After several tries, we
found that completion of the migration was obtained
after heating at 120°C for several days in the presence
of 9 equivalents of BH3·SMe2 complex. The results are
summarized in Table 3.
times, and the proportions of alcohols evaluated by H
NMR (Table 2). It should be noted that alcohol 3b that
would result from the oxidation of the initially formed
borane was not observed after 2 h heating, and that 4
and 5 are actually couples of diastereomers.
One drawback of this process is the presence of varying
amounts of alkene by-products (such as 7 and 8 in the
present instance) which in certain cases lowered signifi-
cantly the yield of the expected alcohol. Alkenes are
intermediates in the thermal isomerization of trialkyl-
boranes which is thought to proceed through alternat-
ing dehydroboration to alkenes and dialkylboranes and
Reactions using triethylborane all afforded the expected
alcohols, albeit after varying times of heating. Good
yields were obtained from sulfones 2a and 2b, but
compound 6d was obtained from the sterically more
Table 1. Preparation of alcohols 3a–f
Entry
Sulfone
R
R%
T (°C)
Yielda (%)
Alcoholb
1
2
3
4
5
6
1
H
Me
Et
CH2Ph
Me
Me
Et
Et
Et
Et
Bu
Hex
50
RT
50
80
RT
RT
58
78
54
53
82
79
3a
3b
3c
3d
3e
3f
2a
2b
2c
2a
2a
a Yield of chromatographed product.
b See Ref. 7 for the description of spectroscopic characteristics of alcohols 3a–f.

C. Billaud et al. / Tetrahedron Letters 44 (2003) 4451–4454
Table 3. Preparation of alcohols 6a–g
4453
Entry
Sulfone
R
Borane
n
Time (days)
Yielda (%)
Alcoholb
1
2
3
4
5
6
7
1
H
Me
Et
CH2Ph
H
Me
Me
BEt3
BEt3
BEt3
BEt3
BBu3
BBu3
BHex3
0
0
0
0
2
2
4
3
1.5
4
4
6
50
70
74
26
52
78
12
6a
6b
6c
6d
6e
6f
2a
2b
2c
1
2a
2a
5
5
6g
a Yield of chromatographed product.
b See Ref. 8 for the description of spectroscopic characteristics of alcohols 6a–g.
crowded sulfone 2c in only 26% yield after 4 days at
120°C. Preparation of alcohols from tributylborane
required longer reaction times under these conditions
(entries 5, 6). Finally, after 5 days at 120°C, alcohol 6g,
derived from the sulfone 2a and trihexylborane, was
isolated in 12% yield, perhaps reflecting either a lower
rate of deshydroboration or a lower reducing ability of
D. J. Am. Chem. Soc. 1980, 102, 7588–7590; (d) Truce, W.
E.; Mura, L. A.; Smith, P. J.; Young, F. J. Org. Chem.
1974, 39, 1449–1450; (e) Hooz, J.; Linke, S. J. Am. Chem.
Soc. 1968, 90, 5936–5937; (f) Pasto, D. J.; Wojtkowski, P.
W. Tetrahedron Lett. 1970, 215–218; (g) Kabalka, G. W.;
Maddox, J. T.; Bogas, E. J. Org. Chem. 1994, 59, 5530–
5531; (h) Goddard, J.-P.; Le Gall, T.; Mioskowski, C. Org.
Lett. 2000, 2, 1455–1456.
dihexylborane formed initially by deshydroboration.
5. Uguen, D. Bull. Soc. Chim. Fr. II 1981, 99–102.
6. Simpkins, N. S. Sulphones in Organic Synthesis; Pergamon
Press: Oxford, 1993.
In conclusion, we have shown that the reaction of
sulfone anions with trialkylboranes allows the efficient
preparation of tertiary alcohols. The scope of this reac-
tion was further extended by combining it with a
thermal migration in the presence of excess borane.
This should be of interest in the field of organic
synthesis.
7. Typical experimental procedure: To a solution of sulfone
2a (200 mg, 0.77 mmol, 1 equiv.) in toluene (3 ml) at
−78°C was added dropwise n-BuLi (0.34 ml of 2.5 M
solution in hexanes, 0.85 mmol, 1.1 equiv.). The colorless
solution became yellow immediately. The solution was
stirred for 15 min at −78°C, then 15 min at room temper-
ature. At −78°C, tributylborane (1.15 ml of 1 M solution
in THF, 1.15 mmol, 1.5 equiv.) was added and the mixture
was stirred 15 min at −78°C then at room temperature.
After a certain time, the yellow solution lost its color and
a white precipitate appeared. The mixture was stirred at
room temperature for 15 h. At 0°C, 30% H2O2 (1.5 ml),
3N NaOH (1.5 ml) and EtOH (1.5 ml) were added. The
solution was stirred for 6 h, then extracted with ether. The
organic layers were washed with 1N HCl, dried over
anhydrous MgSO4 and concentrated by rotary-evapora-
tion. Purification by column chromatography on silica gel
(pentane/diethyl ether: 9/1) yielded alcohol 3e (120.7 mg,
82%) as a colorless oil. Spectral data for compounds
described in Table 1. Entry 1 (3a: 1-phenyl-2-butanol): IR
References
1. For reviews, see: (a) Pelter, A.; Smith, K.; Brown, H. C.
Borane Reagents; Academic Press: London, 1988; (b)
Vaultier, M.; Carboni, B. In Comprehensive Organometal-
lic Chemistry; Abel, E. W.; Stone, F. G. A.; Wilkinson, G.;
McKillop, A. Eds.; Pergamon: Oxford, 1995; Vol. 11, pp.
191–276.
2. (a) Hennion, G. F.; McCusker, P. A.; Ashby, E. C.;
Rutkowski, A. J. J. Am. Chem. Soc. 1957, 79, 5190–5191;
(b) Brown, H. C.; Subba Rao, B. C. J. Org. Chem. 1957,
22, 1137–1138; (c) Brown, H. C.; Zweifel, G. J. Am. Chem.
Soc. 1966, 88, 1433–1439.
3. (a) Field, L. D.; Gallagher, S. P. Tetrahedron Lett. 1985,
26, 6125–6128; (b) Wood, S. E.; Rickborn, B. J. Org.
Chem. 1983, 48, 555–562; (c) Lhermitte, F.; Knochel, P.
Angew. Chem., Int. Ed. 1998, 37, 2460–2461; (d) Laaziri,
H.; Bromm, L. O.; Lhermitte, F.; Gschwind, R. M.;
Knochel, P. J. Am. Chem. Soc. 1999, 121, 6940–6941.
4. See, for example: (a) Tufariello, J. J.; Lee, L. T. C. J. Am.
Chem. Soc. 1966, 88, 4757–4759; (b) Tufariello, J. J.;
Wojtkowski, P.; Lee, L. T. C. J. Chem. Soc., Chem.
Commun. 1967, 505–506; (c) Matteson, D. S.; Majumbar,
1
(NaCl) w=3384, 2929, 1455, 974, 740, 699 cm−1; H NMR
(300 MHz, CDCl3) l 7.38–7.22 (m, 5H), 3.8–3.75 (m, 1H),
2.88 (dd, J=4.3 Hz, J=13.4 Hz, 1H), 2.66 (dd, J=8.5 Hz,
J=13.4 Hz, 1H), 1.7–1.5 (m, 2H), 1.53 (broad s, 1H), 1.02
(t, J=7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) l 138.7,
129.5, 128.6, 126.5, 74.1, 43.6, 29.7, 10.1. Entry 2 (3b:
2-methyl-1-phenyl-2-butanol): IR (NaCl) w=3438, 2970,
1
1456, 1146, 928, 715 cm−1; H NMR (300 MHz, CDCl3) l
7.31–7.24 (m, 5H), 2.8 (d, J=13.4 Hz, 1H), 2.74 (d,
J=13.4 Hz, 1H), 1.53 (q, J=7.3 Hz, 2H), 1.29 (broad s,

4454
C. Billaud et al. / Tetrahedron Letters 44 (2003) 4451–4454
1H), 1.15 (s, 3H), 0.99 (t, J=7.3 Hz, 3H); 13C NMR (75
Spectral data for compounds described in Table 2: Entry 1
MHz, CDCl3) l 137.7, 130.6, 128.2, 126.4, 72.7, 47.6, 34.2,
26, 8.4. Entry 3 (3c: 3-benzyl-3-pentanol): IR (NaCl) w=
(6a: 4-phenyl-1-butanol): IR (NaCl) w=3339, 2934, 1453,
1061, 745, 698; H NMR (300 MHz, CDCl3) l 7.31–7.14
1
3464, 2965, 1455, 1137, 705 cm−1 1H NMR (300 MHz,
;
(m, 5H), 3.53 (t, J=6.4 Hz, 2H), 2.57 (t, J=7.3 Hz, 2H),
1.67–1.51 (m, 5H); 13C NMR (75 MHz, CDCl3) l 142.2,
128.3, 128.2, 125.6, 62.5, 35.5, 32.2, 27.4. Entry 2 (6b:
3-methyl-4-phenyl-1-butanol): IR (NaCl) w=3341, 2924,
1454, 1055, 737, 699; 1H NMR (300 MHz, CDCl3) l
7.5–7.3 (m, 5H), 3.94–3.80 (m, 2H), 2.73 (dd, J=6.1 Hz,
J=13.4 Hz, 1H), 2.54 (dd, J=7.9 Hz, J=13.4 Hz, 1H),
2.04–1.95 (m, 1H), 1.9–1.8 (m, 1H), 1.66–1.55 (m, 1H),
1.37 (broad s, 1H), 1.08 (d, J=6.7 Hz, 3H); 13C NMR (75
MHz, CDCl3) l 141.1, 129.3, 128.3, 125.9, 61.2, 43.9, 39.5,
31.7, 19.6. Entry 3 (6c: 3-benzyl-1-pentanol): IR (NaCl)
CDCl3) l 7.32–7.23 (m, 5H), 2.76 (s, 2H), 1.48 (q, J=7.3
Hz, 4H), 1.21 (broad s, 1H), 0.94 (t, J=7.3 Hz, 6H); 13C
NMR (75 MHz, CDCl3) l 137.9, 130.5, 128.2, 126.3, 75.5,
47.8, 30.4, 7.9. Entry 4 (3d: 1,1-dibenzyl-1-propanol): IR
1
(NaCl) w=3570, 2935, 1452, 1115, 1026, 750, 704 cm−1; H
NMR (300 MHz, CDCl3) l 7.37–7.26 (m, 10H), 2.84 (s,
4H), 1.41 (q, J=7.3 Hz, 2H), 1.36 (broad s, 1H), 1.05 (t,
J=7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) l 137.3,
130.6, 128.0, 126.3, 74.4, 44.8, 30.6, 8.3. Entry 5 (3e:
2-methyl-1-phenyl-2-hexanol): IR (NaCl) w=3438, 2934,
1
1
1457, 1376, 1144, 730, 701; H NMR (300 MHz, CDCl3) l
w=3340, 2928, 1426, 1058, 734, 699; H NMR (300 MHz,
7.36–7.22 (m, 5H), 2.81 (d, J=13.4 Hz, 1H), 2.74 (d,
J=13.4 Hz, 1H), 1.50–1.35 (m, 7H), 1.16 (s, 3H), 0.96 (t,
J=6.7 Hz, 3H); 13C NMR (75 MHz, CDCl3) l 137.6,
130.5, 128.1, 126.3, 72.4, 47.9, 41.5, 26.5, 26.2, 23.2, 14.1.
Entry 6 (3f: 2-methyl-1-phenyl-2-octanol): IR (NaCl) w=
3440, 2930, 1458, 1137, 931, 701; 1H NMR (300 MHz,
CDCl3) l 7.34–7.22 (m, 5H), 2.81 (d, J=12.8 Hz, 1H),
2.74 (d, J=12.8 Hz, 1H), 1.42–1.33 (m, 11H), 1.17 (s, 3H),
0.93 (t, J=6.7 Hz, 3H); 13C NMR (75 MHz, CDCl3) l
137.6, 130.4, 129.9, 126.2, 72.4, 47.9, 41.8, 31.8, 29.8, 26.3,
23.9, 22.5, 13.9.
CDCl3) l 7.30–7.16 (m, 5H), 3.68–3.65 (m, 2H), 2.63 (dd,
J=7.3 Hz, J=13.4 Hz, 1H), 2.53 (dd, J=7.3 Hz, J=13.4
Hz, 1H), 1.8–1.65 (m, 1H), 1.6–1.53 (m, 2H), 1.40 (broad
s, 1H), 1.38–1.25 (m, 2H), 0.93 (t, J=7.3 Hz, 3H); 13C
NMR (75 MHz, CDCl3) l 141.2, 129.1, 128.1, 125.7, 61.1,
40.2, 36.0, 25.8, 10.7, 3.60. Entry 4 (6d: 3,3-dibenzyl-1-
propanol): IR (NaCl) w=3338, 3026, 2926, 1600, 1451,
1
1047, 746, 699; H NMR (300 MHz, CDCl3) l 7.40–7.15
(m, 10H), 3.64 (t, J=6.7 Hz, 2H), 2.75–2.50 (m, 4H),
2.25–2.05 (m, 1H), 1.57 (dt, J=6.1 Hz, J=6.7 Hz, 1H),
1.25 (m, 2H), 1.24 (broad s, 1H); 13C NMR (75 MHz,
CDCl3) l 140.8, 129.1, 128.2, 125.8, 60.8, 40.5, 38.6, 36.1.
Entry 5 (6e: 6-phenyl-1-hexanol): IR (NaCl) w=3338,
8. Typical experimental procedure: In a heavy-walled pres-
sure tube, at −78°C, n-BuLi (0.34 ml of 2.5 M solution in
hexanes, 0.85 mmol, 1.1 equiv.) was added dropwise to a
solution of sulfone 2a (200 mg, 0.77 mmol, 1 equiv.) in
toluene (3 ml). The colorless solution became yellow
immediately. The solution was stirred 15 min at −78°C,
then 15 min at room temperature. At −78°C, tributylbo-
rane (1.15 ml of 1 M solution in THF, 1.15 mmol, 1.5
equiv.) was added and the mixture was stirred for 15 min
at −78°C then at room temperature. After some time, the
yellow solution lost its color and a white precipitate
appeared. The mixture was stirred at room temperature
for 15 h. Then BH3·SMe2 complex (3.5 ml of 2 M solution
in THF, 6.93 mmol, 9 equiv.) was added. The tube was
tightly closed and heated at 120°C for 5 days. At 0°C, 30%
H2O2 (1.5 ml), 3N NaOH (1.5 ml) and EtOH (1.5 ml) were
added. The solution was stirred for 6 h, then extracted
with ether. The organic layers were washed with 1N HCl,
dried over anhydrous MgSO4 and concentrated by rotary-
evaporation. Purification by column chromatography on
silica gel (pentane/diethyl ether: 9/1) yielded alcohol 6f
(115.8 mg, 78%) as a colorless oil.
1
2930, 1455, 1054, 745, 698; H NMR (300 MHz, CDCl3) l
7.34–7.21 (m, 5H), 3.64 (t, J=6.6 Hz, 2H), 2.64 (t, J=7.9
Hz, 2H), 1.8–1.4 (m, 9H); 13C NMR (75 MHz, CDCl3) l
134.9, 128.3, 128.2, 125.5, 62.8, 35.8, 32.6, 31.3, 29.0, 25.5.
Entry 6 (6f: 5-methyl-6-phenyl-1-hexanol): IR (NaCl) w=
3338, 2928, 1455, 1053, 739, 699; 1H NMR (300 MHz,
CDCl3) l 7.3–7.15 (m, 5H), 3.64 (t, J=6.1 Hz, 2H), 2.66
(dd, J=6.1 Hz, J=13.4 Hz, 1H), 2.40 (dd, J=8.5 Hz,
J=13.4 Hz, 1H), 1.85–1.80 (m, 1H), 1.84 (broad s, 1H),
1.60–1.20 (m, 6H), 0.9 (d, J=6.7 Hz, 3H); 13C NMR (75
MHz, CDCl3) l 141.3, 129.0, 127.9, 125.5, 62.7, 43.5, 36.3,
34.8, 32.8, 23.2, 19.2. Entry 7 (6g: 7-methyl-8-phenyl-1-
octanol): IR (NaCl) w=3335, 2927, 1456, 1055, 738, 699;
1H NMR (300 MHz, CDCl3) l 7.31–7.14 (m, 5H), 3.65 (t,
J=6.7 Hz, 2H), 2.64 (dd, J=6.1 Hz, J=13.4 Hz, 1H),
2.37 (dd, J=7.9 Hz, J=13.4 Hz, 1H), 1.75–1.65 (m, 1H),
1.60–1.58 (m, 2H), 1.57–1.34 (m, 9H), 0.86 (d, J=6.7 Hz,
3H); 13C NMR (75 MHz, CDCl3) l 141.6, 129.1, 128.0,
125.5, 63.0, 43.7, 36.6, 34.9, 32.7, 29.6, 27.0, 25.7, 19.4.