A new mild deprotecting method for O-benzylsulfonyl phenols and alcohols based on a DTBB-catalyzed lithiation

Article abstract of DOI:10.1055/s-2005-869907

A variety of alcohols and phenols, protected as the corresponding benzylsulfonic esters, were efficiently deprotected by selective reductive cleavage of the sulfur-oxygen bond, using an excess of lithium sand and a catalytic amount (5 mol%) of 4,4′-di-tert-butylbiphenyl (DTBB) as electron carrier, in THF at 0° C. This deprotection system was also efficient at -50 °C and was compatible with a wide range of other functional groups. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-869907

PAPER
1971
A New Mild Deprotecting Method for O-Benzylsulfonyl Phenols and Alcohols
Based on a DTBB-Catalyzed Lithiation
New
D
eprote
c
r
ting Me
t
a
hod for
O
-B
n
enzylsulfon
c
yl Phenols
i
and
A
l
s
a
Departamento de Química Orgánica, Facultad de Ciencias, and Instituto de Síntesis Orgánica (ISO), Universidad de Alicante,
Apdo. 99, 03080 Alicante, Spain
Fax +34(96)5903549; E-mail: yus@ua.es
Instituto de Investigaciones en Química Orgánica (INIQO), Departamento de Química, Universidad Nacional del Sur,
Avda. Alem 1253, 8000 Bahía Blanca, Argentina
b
Fax +54(291)4595187; E-mail: gradivoy@criba.edu.ar
Received 23 February 2005
On the other hand, the chemistry of benzylsulfonates has
been little studied, which is normally related to the study
of some general reaction mechanisms7 and very rarely as
protecting group.8 However, in 2003, Mioskowski et al.
Abstract: A variety of alcohols and phenols, protected as the corre-
sponding benzylsulfonic esters, were efficiently deprotected by se-
lective reductive cleavage of the sulfur–oxygen bond, using an
excess of lithium sand and a catalytic amount (5 mol%) of 4,4¢-di-
tert-butylbiphenyl (DTBB) as electron carrier, in THF at 0° C. This presented benzylsulfonyl as a valuable potential protect-
deprotection system was also efficient at –50 °C and was compati-
ble with a wide range of other functional groups.
ing group in phenol chemistry that was able to tune the re-
activity of phenolic substrates and stable under a variety
Key words: benzylsulfonyl, protecting group, alcohols, phenols,
reductive deprotection
of drastic reaction conditions and towards many common
reagents.9 This group was readily introduced using inex-
pensive commercially available benzylsulfonyl chloride
and Et3N or pyridine as a base, and could be mildly depro-
The hydroxyl group is one of the most versatile groups in tected using catalytic Raney nickel under hydrogen at
synthetic organic chemistry because of its easy transfor- room temperature. Unfortunately, this study was limited
mation to other functional groups through rearrange- to only one example, and therefore the scope and limita-
ments, oxidation, reduction, substitution, or elimination tions of the methodology remain unknown.
processes.1 However, appropriate hydroxyl protection,
Our continuous work on the active-metal based reduction
usually as alkyl or benzyl ethers, becomes necessary when
of functional groups has shown that alkyl, vinyl, aryl, and
we want to preserve this functionality from the influence
dienyl mesilates and triflates, can be effectively reduced
of different kinds of reagents in the course of multistep
with systems like NiCl2·2H2O–Li-arene (cat.)10 and
syntheses.2
CuCl2·2H2O–Li-arene (cat.),11 to give the corresponding
Sulfonates as protective groups for alcohols have been hydrocarbon structures. The reductive cleavage of the car-
scarcely studied and their use is practically restricted to bon–oxygen bond of alkyl triflates12 and that of allylic and
carbohydrates,3 whereas it is known that phenols can be benzylic mesylates13 was also accomplished in our group
easily protected as mesylates and tosylates.4 Some of the by a naphthalene-catalyzed lithiation.14
methods for deprotection of alkyl sulfonates involve pho-
We wish to report herein a new mild deprotection method
tolysis, reductive cleavage, and reaction with a metal hy-
for alcohols and phenols protected as benzylsulfonic es-
dride or organometallic reagent.3 Aryl sulfonates have
ters based on the use of lithium and a catalytic amount of
DTBB (4,4¢-di-tert-butylbiphenyl).
been deprotected in a warm basic aqueous medium, by
electrolysis, or by reductive cleavage.4a However, most of
We first focused on the deprotection of a broad range of
these methods are relatively harsh or non-selective and
non-functionalized aryl benzylsulfonates. Thus, treatment
can compromise the coexistence of other functional
of mono-, di-, and trisubstituted phenyl benzylsulfonates
groups in the same molecule. Therefore, the development
with an excess of lithium sand (8:1 molar ratio) and a cat-
of mild and chemoselective protocols for the deprotection
alytic amount of DTBB (5.0 mol%) as electron carrier, in
of alkyl and aryl sulfonates is welcome. In this context,
THF at 0 °C, gave the corresponding deprotected phenols
Sabitha et al. described the selective cleavage of aryl
in 68–82% yield (Table 1, entries 1, 3, 5, and 6). Even
tosylates under microwave irradiation (3–6 min) using
2,4,6-trimethylphenyl benzylsulfonate, that could present
some steric hindrance, was reduced nicely (Table 1, entry
5). The methodology was also successfully applied to the
benzylsulfonate derived from a-naphthol (Table 1, entry
7) and the bis-benzylsulfonate derived from 2,2¢-biphenol
(Table 1, entry 8), the latter suffering double deprotection
in good yield. An attempt to completely deprotect the tris-
benzylsulfonate derived from 3,5-dihydroxybenzyl alco-
hol furnished 5-methylresorcinol due to the easiness of
KF/Al2O3.5 In a recent example, Carreira et al. have re-
ported the chemoselective and mild deprotection of aryl
mesylates with LDA at –78 °C and 0 °C.6
SYNTHESIS 2005, No. 12, pp 1971–1976
x
x.
x
x
.
2
0
0
5
Advanced online publication: 19.05.2005
DOI: 10.1055/s-2005-869907; Art ID: Z04205SS
© Georg Thieme Verlag Stuttgart · New York

1972
F. Alonso et al.
PAPER
cleavage at the benzylic carbon–oxygen bond, even at –50 longer reaction time (compare entries 3 and 4), which can
°C (Table 1, entry 9).
be considered as an advantage of the method for tempera-
ture-sensitive substrates.
It is noteworthy that by carrying out the reaction at 25 °C,
a decrease in the product yield was observed in the depro- In order to test our deprotection methodology with alkyl
tection of p-tolyl benzylsulfonate (compare entries 1 and benzylsulfonates, a protected primary and secondary alco-
2 in Table 1), due to the competition between the cleavage hol, as well as a doubly protected diol could be also depro-
of the sulfur–oxygen and carbon–oxygen bonds. On the tected using the same general protocol, the reaction rate
other hand, deprotection of 2,4-dimethylphenyl benzyl- being slower than for phenols (Table 1, entries 10–12).
sulfonate (Table 1, entry 4) at –50 °C gave the corre- Unfortunately, all attempts to protect tertiary alcohols
sponding phenol with the same yield and in a slightly
Table 1 Deprotection of Non-Functionalized Phenols and Alcohols
Entry
Starting material
Reaction conditions
Product
Temp (°C)
0
Time (h)
Structure
Yield (%)b
75
1
2
0.5
0.5
0.5
0.8
0.5
OSO2Bn
OH
OH
OH
OH
25
0
52c
71
73
82
OSO2Bn
OSO2Bn
OSO2Bn
3
4
5
–50
0
OSO2Bn
OH
tBu
tBu
6
0
0.5
68
OSO2Bn
OH
tBu
OH
tBu
OSO2Bn
7
8
0
0
0.5
4
70
70
OSO2Bn
OH
BnO2SO
HO
9
0
4
73
HO
OH
BnO2SO
OSO2Bn
BnO2SO
10
11
0
0
1
1
69
65
OSO2Bn
OH
OH
10
10
OSO2Bn
12
0
2.5
67
BnO2SO
OSO2Bn
HO
OH
7
7
a All isolated products were > 95% pure (GLC).
b Isolated yield after column chromatography (silica gel, hexane–EtOAc) unless otherwise stated, based on the starting benzylsulfonate.
c The reaction proceeded with total conversion of the starting material, 48% of toluene as byproduct. Product composition determined by GLC.
Synthesis 2005, No. 12, 1971–1976 © Thieme Stuttgart · New York

PAPER
New Deprotecting Method for O-Benzylsulfonyl Phenols and Alcohols
1973
(e.g. t-BuOH and 1-adamantanol) with the benzylsulfonyl be driven toward the chemoselective deprotection in 30
group were unsuccessful.
minutes of reaction time, whereas longer reaction times
led to the products of combined deprotection–hydrodeha-
logenation processes (Table 2, entries 4–7). We must
highlight that the methoxycarbonyl group, or even the
most reactive formyl and nitro groups, remained un-
touched under the reductive conditions; the corresponding
chemoselective deprotected products were obtained in
high isolated yields (Table 2, entries 8–10).
The second part of this study focused on the chemoselec-
tive deprotection of a series of aryl benzylsulfonates bear-
ing different functional groups. Thus, when o-allylphenyl
benzylsulfonate was subjected to the above-described
protocol, a 1:1 mixture of the expected product together
with o-propylphenol was obtained. The method showed to
be compatible with the presence of the methoxy or fluoro
substituents, the inert carbon–fluorine bond remaining in- The fact that we have observed the formation of toluene
tact even at longer reaction times (4–6 h). In the case of as by-product in all the experiments allows us to suggest
the benzylsulfonic esters of p-chloro- or p-bromophenol, that the cleavage of the benzylsulfonyl group proceeds
the desulfonylation process proved to be faster than the through a mechanism similar to those reported in the liter-
halogen–lithium exchange. Therefore, the reaction could
Table 2 Deprotection of Functionalized Phenols
Entry
Starting material
Reaction time (h)a Productb
Structure
Yield (%)c
50d
1
1
OSO2Bn
OH
2
0.5
78
OH
OSO2Bn
OCH3
OCH3
3
4
5
6
7
8
0.5
0.5
0.5
1.5
1.5
0.5
60
OSO2Bn
OH
F
F
79
OSO2Bn
OH
Cl
Cl
Br
68
OSO2Bn
OSO2Bn
OSO2Bn
OH
Br
Cl
Br
85e
81e
88
OH
OH
OH
OH
OSO2Bn
CHO
CHO
NO2
9
0.5
0.5
74
80
OSO2Bn
NO2
10
80
CO2Me
HO
BnO2SO
CO2Me
a All reactions were carried out at 0 °C.
b All isolated products were > 95% pure (GLC).
c Isolated yield after column chromatography (silica gel, hexane–EtOAc) unless otherwise stated, based on the starting benzylsulfonate.
d The reaction proceeded with total conversion of the starting material, 50% of o-propylphenol was obtained as byproduct. Product composition
determined by GLC.
e GLC yield.
Synthesis 2005, No. 12, 1971–1976 © Thieme Stuttgart · New York

1974
F. Alonso et al.
PAPER
IR (KBr): 3064, 2986, 2932, 1500, 1363 (SO2), 1170 (SO2), 858,
702 cm–1.
1H NMR (300 MHz): d = 2.18, 2.31 (2 × s, 6 H, 2 × CH3), 4.56 (s, 2
H, CH2), 6.93–7.09 (m, 3 H, ArH), 7.39–7.59 (m, 5 H, ArH).
13C NMR (75 MHz): d = 15.3 (CH3), 19.7 (CH3), 56.2 (CH2), 120.7,
126.6, 127.9, 128.2, 129.9, 130.0, 131.3, 135.8, 144.6 (12 × ArC).
MS: m/z (%) = 276 (2.27) [M+], 212 (15), 91 (100), 65(10).
ature for the reductive cleavage of p-toluenesulfonates
and p-toluenesulfonamides.15
In conclusion, we have found a new procedure to cleave
aryl and alkyl benzylsulfonates under mild reaction con-
ditions, which enlarges the advantages of benzylsulfonyl
as a protecting group in synthetic organic chemistry,
where in addition, its deactivating properties can be help-
ful for tuning the reactivity of phenolic substrates. The
lithium–DTBB deprotection system demonstrated to be
very effective with a representative variety of non-func-
tionalized phenol and alcohol derivatives. The methodol-
ogy proved to be compatible with the presence of alkoxy,
halogen, aldehyde, nitro, or ester functionalities on the
phenol moiety, thus allowing the chemoselective depro-
tection in good yields. The fact that this new deprotecting
system is effective at temperatures ranging from 0 °C to
–50 °C, enlarges its synthetic applicability to temperature
sensitive organic compounds.
HRMS: m/z calcd for C15H16O3S: 276.3562; found: 276.3558.
2,4,6-Trimethylphenyl Benzylsulfonate (Table 1, entry 5)
Yield: 391 mg (89%); white solid; mp 92–93 °C (EtOH).
IR (KBr): 3037, 2990, 2943, 1495, 1347 (SO2), 1114 (SO2), 855,
699 cm–1.
1H NMR (300 MHz): d = 2.24 (s, 6 H, 2 × CH3), 2.27 (s, 3 H, CH3),
4.63 (s, 2 H, CH2), 7.05 (s, 2 H, ArH), 7.41–7.47 (m, 3 H, ArH),
7.51–7.58 (m, 2 H, ArH).
13C NMR (75 MHz): d = 17.6 (2 × CH3), 21.0 (CH3), 58.2 (CH2),
128.2, 129.3, 129.6, 130.3, 131.4, 132.2, 136.9, 144.7 (12 × ArC).
MS: m/z (%) = 290 (12.6) [M+], 135 (10), 91 (100), 65(10).
HRMS: m/z calcd for C16H18O3S: 290.3831; found: 290.3817.
All moisture-sensitive reactions were carried out under N2 atmo-
sphere. Anhydrous THF was freshly distilled from sodium/ben-
zophenone ketyl. Other solvents used were purified prior to use by
standard methods.16 All compounds used for the synthesis of the
corresponding benzylsulfonates were of the best available grade
(Aldrich, Fluka, Merck) and were used without further purification.
Column chromatography was performed with Merck silica gel 60
(0.040–0.063 mm, 240–400 mesh). TLC was performed on precoat-
ed silica gel plates (Merck 60, F254, 0.25 mm). NMR spectra were
recorded on a Bruker ARX-300 spectrometer using CDCl3 (unless
otherwise stated) as solvent and TMS as internal reference. Mass
spectra (EI) were obtained at 70 eV on a Hewlett Packard HP-5890
GC–MS instrument equipped with a HP-5972 selective mass detec-
tor. FT-IR spectra were obtained on a Nicolet–Nexus spectrometer.
The purities of volatile compounds and chromatographic analyses
(GC) were determined with a Shimadzu GC-9A instrument
equipped with a flame-ionization detector and a 2 m column (1.5%
OV17 9A SUS Chrom 103 80/1000), using N2 as carrier gas.
3,5-Di-tert-butylphenyl Benzylsulfonate (Table 1, entry 6)
Yield: 420 mg (78%); white solid; mp 88–90 °C (EtOH).
IR (KBr): 3037, 2966, 2916, 1611, 1584, 1479, 1421, 1374 (SO2),
1157 (SO2), 877, 699 cm–1.
1H NMR (300 MHz): d = 1.31 (s, 18 H, 6 × CH3), 4.53 (s, 2 H, CH2),
6.92–6.98 (m, 3 H, ArH), 7.33–7.59 (m, 5 H, ArH).
13C NMR (75 MHz): d = 31.7 (6 × CH3), 35.4 (2 × C), 57.1 (CH2),
116.5, 121.4, 128.1, 129.3, 129.6, 131.3, 149.7, 153.3 (12 × ArC).
MS: m/z (%) = 360 (2.14) [M+], 296 (12), 91 (100).
HRMS: m/z calcd for C21H28O3S: 360.5175; found: 360.5169.
2-(2-Benzylsulfonyloxyphenyl)phenyl Benzylsulfonate (Table 1,
entry 8)
Yield: 259 mg (66%); white semi-solid.
IR (KBr): 3033, 2978, 2935, 1600, 1576, 1479, 1370 (SO2), 1165
(SO2), 878, 866, 792, 780 cm–1.
1H NMR (300 MHz, acetone-d6): d = 4.38 (s, 4 H, 2 × CH2), 7.27–
7.61 (m, 18 H, ArH).
13C NMR (75 MHz, acetone-d6): d = 56.6 (2 × CH2), 121.9, 126.3,
127.4, 128.1, 128.3, 129.3, 129.8, 130.4, 131.9, 146.6 (24 × ArC).
MS: m/z = 494 (0.28) [M+], 430 (10), 281 (10), 253 (10), 207 (51),
91 (100), 65 (10).
Synthesis of the Starting Benzylsulfonates; General
Procedure17
To a stirred solution of Et3N (1.0 mmol) and the corresponding phe-
nol or alcohol (1.0 mmol) in THF (10 mL) under N2 in a water-ice
bath, was slowly added a solution of a-toluenesulfonyl chloride (1.0
mmol) in THF (3 mL). The reaction mixture was then stirred for an
additional hour. The precipitated triethylamine hydrochloride was
filtered off, and the filtrate was washed several times with dilute
HCl, dried over Na2SO4, and then evaporated under reduced pres-
sure. The resulting solid was recrystallized from 95% EtOH to af-
ford the corresponding crystalline or semi-solid product. The
following known compounds, included in Tables 1 and 2, were
characterized by comparison of their chromatographic and spectro-
scopic data (1H, 13C NMR, and MS) with those described in the lit-
erature: p-tolyl benzylsulfonate (Table 1, entries 1 and 2),17 1-
naphthyl benzylsulfonate (Table 1, entry 7),18 9-benzylsulfonyloxy-
nonyl benzylsulfonate (Table 1, entry 12),19 p-chlorophenyl benzyl-
HRMS: m/z calcd for C26H22O6S2: 494.5891; found: 494.5874.
3-Benzylsulfonyloxy-5-benzylsulfonyloxymethylphenyl Benzyl-
sulfonate (Table 1, entry 9)
Yield: 362 mg (75%); white semi-solid; mp 120–122 °C (EtOH).
IR (KBr): 3064, 2947, 1592, 1452, 1360 (SO2), 1172 (SO2), 951,
834, 807, 699 cm–1.
1H NMR (300 MHz, acetone-d6): d = 4.69 (s, 2 H, CH2O), 4.91 (s,
4 H, 2 × PhCH2SOAr), 5.26 (s, 2 H, PhCH2SOCH2Ar), 7.10–7.67
(m, 18 H, ArH).
13C NMR (75 MHz, acetone-d6): d = 57.4 (PhCH2SOCH2Ar), 57.9
(2 × PhCH2SOAr), 71.4 (CH2O), 117.8, 121.6, 127.8, 129.2, 129.8,
129.9, 130.0, 130.1, 130.4, 131.5, 132.2, 132.4, 139.5, 151.3 (24 ×
ArC).
sulfonate (Table 2, entries
4
and 6),20 p-bromophenyl
benzylsulfonate (Table 2, entries 5 and 7),17 and o-nitrophenyl ben-
zylsulfonate (Table 2, entry 9).20
For new compounds, physical and spectroscopic data are as follows.
2,4-Dimethylphenyl Benzylsulfonate (Table 1, entries 3 and 4)
Yield: 390 mg (94%); white solid; mp 132–134 °C (EtOH).
HRMS: m/z calcd for C28H26O9S3: 602.7070; found: 602.7092.
Synthesis 2005, No. 12, 1971–1976 © Thieme Stuttgart · New York

PAPER
New Deprotecting Method for O-Benzylsulfonyl Phenols and Alcohols
1975
2
Dodecyl Benzylsulfonate (Table 1, entry 10)
Yield: 420 mg (86%); white solid; mp 48–50 °C (EtOH).
13C NMR (75 MHz): d = 57.3 (CH2), 116.9 (d, JC–F = 23.5 Hz,
3
ArC), 124.1 (d, JC–F = 8.8 Hz, ArC), 127.6, 129.4, 129.8, 131.3,
(ArC), 145.3 (d, JC–F = 2.9 Hz, ArC), 161.4 (d, 1JC–F = 246.5 Hz,
4
IR (KBr): 3025, 2920, 2850, 1560, 1471, 1456, 1355 (SO2), 1172
(SO2), 963, 854, 722, 699 cm–1.
1H NMR (300 MHz): d = 0.91 (t, J = 7.2 Hz, 3 H, CH3), 1.20–1.80
[m, 20 H, (CH2)10], 4.06 (t, J = 6.4 Hz, 2 H, CH2O), 4.34 (s, 2 H,
PhCH2), 7.34–7.55 (m, 5 H, ArH).
ArC).
MS: m/z = 266 (0.29) [M+], 202 (10), 91 (100), 83 (10), 65 (12).
HRMS: m/z calcd for C13H11FO3S: 266.2929; found: 266.2942.
2-Formylphenyl Benzylsulfonate (Table 2, entry 8)
Yield: 215 mg (65%); white semi-solid.
13C NMR (75 MHz): d = 14.5 (CH3), 23.1, 25.7, 29.4, 29.6, 29.7,
29.8, 29.9, 30.0, 32.3 [(CH2)10], 57.2 (PhCH2), 71.7 (CH2O), 128.5,
129.2, 129.4, 131.0 (6 × ArC).
MS: m/z (%) = 340 (0.05) [M+], 172 (10), 91 (100), 65 (10), 55 (11),
41 (13).
IR (KBr): 3067, 3033, 2978, 2932, 1700, 1603, 1456, 1366 (SO2),
1157 (SO2), 1064, 877, 773, 699 cm–1.
1H NMR (300 MHz): d = 4.66 (s, 2 H, CH2), 7.37–7.70 (m, 9 H,
ArH), 9.95 (s, 1 H, CHO).
13C NMR (75 MHz): d = 57.8 (CH2), 122.5, 123.8, 127.2, 127.9,
128.8, 129.4, 129.6, 130.0, 131.3, 147.3 (12 × ArC), 188.3 (CO).
MS: m/z (%) = 276 (0.42) [M+], 121 (10), 91 (100), 65 (21), 39 (11).
HRMS: m/z calcd for C19H32O3S: 340.5273; found: 340.5185.
Cyclohexyl Benzylsulfonate (Table 1, entry 11)
Yield: 294 mg (77%); white semi-solid.
IR (KBr): 3032, 2935, 2862, 1585, 1464, 1347 (SO2), 1168 (SO2),
939, 904, 695 cm–1.
HRMS: m/z calcd for C14H12O4S: 276.3129; found: 276.3205.
1H NMR (300 MHz): d = 1.10–1.87 [m, 10 H, (CH2)5], 3.95 (m, 1
H, CH), 4.24 (s, 2 H, PhCH2), 7.23–7.39 (m, 5 H, ArH).
Methyl 4-(4-Benzylsulfonyloxyphenyl)benzoate (Table 2, entry
10)
Yield: 454 mg (70%); white solid; mp 165–166 °C (EtOH).
13C NMR (75 MHz): d = 23.8, 25.3, 33.0 [(CH2)5], 58.0 (PhCH2),
82.4 (CH), 126.9, 128.7, 129.3, 131.1 (6 × ArC).
MS: m/z (%) = 254 (1.70) [M+], 92 (14), 91 (100), 82 (23), 67 (49),
IR (KBr): 3064, 3033, 3005, 2955, 1720, 1603, 1495, 1429, 1348
(SO2), 1145 (SO2), 1118, 842, 768, 703 cm–1.
1H NMR (300 MHz): d = 3.95 (s, 3 H, CH3), 4.57 (s, 2 H, CH2),
7.22, 7.60 (2 × d, J = 8.8 Hz, 4 H, ArH), 7.41–7.53 (m, 5 H, ArH),
7.61, 8.11 (2 × d, J = 8.2 Hz, 4 H, ArH).
65 (13), 55 (12), 54 (24), 41 (18), 39 (19).
HRMS: m/z calcd for C13H18O3S: 254.3501; found: 254.3477.
2-Allylphenyl Benzylsulfonate (Table 2, entry 1)
Yield: 341 mg (78%); white solid; mp 63–65 °C (EtOH).
13C NMR (75 MHz): d = 52.5 (CH3), 57.4 (CH2), 122.8, 127.4,
127.6, 129.1, 129.4, 129.7, 129.8, 130.6, 131.3, 139.5, 144.5, 149.6
(18 × ArC), 167.2 (C=O).
IR (KBr): 3079, 2978, 2939, 1638, 1487, 1366 (SO2), 1157 (SO2),
873, 790, 706 cm–1.
MS: m/z (%) = 382 (1.28) [M+], 318 (11), 139 (12), 91 (100), 65
(10).
1H NMR (300 MHz): d = 3.22 (m, 2 H, CH2CH=CH2), 4.48 (s, 2 H,
PhCH2), 4.87–5.02 (m, 2 H, CH2CH=CH2), 5.70–5.86 (m, 1 H,
CH), 6.97–7.18 (m, 4 H, ArH), 7.30–7.43 (m, 5 H, ArH).
HRMS: m/z calcd for C21H18O5S: 382.4369; found: 382.4407.
Deprotection of Benzylsulfonates Using the Li–DTBB (cat.)
System; General Procedure
13C NMR (75 MHz): d = 33.0 (CH2CH=CH2), 56.5 (PhCH2), 115.5
(CH2CH=CH2), 121.1, 126.1, 126.4, 126.6, 127.9, 128.3, 129.8,
129.9, 132.2, 146.2 (12 × ArC), 136.1 (CH).
A mixture of DTBB (176 mg, 0.1 mmol) and lithium sand (56 mg,
8 mmol) in THF (5 mL) was stirred at r.t. until the reaction mixture
turned dark green (5–20 min) indicating the formation of the lithium
arenide. The reaction flask was immersed in a temperature-con-
trolled bath at 0 °C and the corresponding benzylsufonate (1.0
mmol) in THF (5 mL) was slowly added with a syringe. After total
conversion of the starting material (TLC, GLC, IR), the resulting
suspension was diluted with Et2O (20 mL) and successively washed
with 10% HCl, water and brine (20 mL each). The organic layer was
dried over Na2SO4, the solvents were evaporated (15 Torr), and the
resulting residue was purified by column chromatography (silica
gel, hexane–EtOAc). For some products, the dried organic layer
was analyzed by GLC using an internal standard (toluene or p-
cresol, see Table footnotes). The deprotected phenols or alcohols
were fully characterized by comparison of their chromatographic
and spectral data with those of the corresponding commercially
available pure samples, used as substrates for the synthesis of the
starting benzylsulfonates.
MS: m/z (%) = 288 (0.98) [M+], 133 (17), 91 (100), 65 (10).
HRMS: m/z calcd for C16H18O3S: 288.3672; found: 288.3723.
3-Methoxyphenyl Benzylsulfonate (Table 2, entry 2)
Yield: 379 mg (90%); white solid; mp 66–67 °C (EtOH).
IR (KBr): 3079, 2982, 2943, 1607, 1580, 1491, 1363 (SO2), 1172
(SO2), 943, 858, 699 cm–1.
1H NMR (300 MHz): d = 3.66 (s, 3 H, CH3), 4.41 (s, 2 H, CH2),
6.55–6.58, 6.62–6.67, 6.71–6.76, 7.12–7.19 (4 × m, 4 H, ArH),
7.29–7.40 (m, 5 H, ArH).
13C NMR (75 MHz): d = 54.5 (CH3), 55.8 (CH2), 106.9, 112.1,
112.9, 126.3, 127.9, 128.2, 129.1, 129.9, 149.1, 159.7 (12 × ArC).
MS: m/z (%) = 278 (3.19) [M+], 214 (13), 91 (100), 65 (10).
HRMS: m/z calcd for C14H14O4S: 278.3288; found: 278.3291.
4-Fluorophenyl Benzylsulfonate (Table 2, entry 3)
Yield: 367 mg (69%); white solid; mp 69–71 °C (EtOH).
Acknowledgment
We thank the CONICET (grant no. 705/2004) and SGCyT-UNS
(Project 24/ZQ01) from Argentina for financial support. Y. M. also
thanks the CONICET for a doctoral fellowship. This work was also
generously supported by the Dirección General de Enseñanza Supe-
rior (DGES) of the Spanish Ministerio de Educación y Ciencia
IR (KBr): 3079, 2986, 2939, 1601, 1499, 1382 (SO2), 1157 (SO2),
877, 815, 706 cm–1.
1H NMR (300 MHz): d = 4.53 (s, 2 H, CH2), 7.00–7.13 (m, 4 H,
ArH), 7.40–7.52 (m, 5 H, ArH).
Synthesis 2005, No. 12, 1971–1976 © Thieme Stuttgart · New York

1976
F. Alonso et al.
PAPER
(MEC; grant no. BQU2001-0538) and the Generalitat Valenciana
(GV; project no. GRUPOS03/35).
(10) (a) Radivoy, G.; Alonso, F.; Yus, M. Tetrahedron 1999, 55,
14479. (b) For a review about the NiCl2–Li-arene (cat.) as a
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(11) (a) Radivoy, G.; Alonso, F.; Moglie, Y.; Vitale, C.; Yus, M.
Tetrahedron 2005, 61, 3859. For other applications of the
CuCl2·2H2O–Li-arene (cat.) reducing system, see:
(b) Alonso, F.; Vitale, C.; Radivoy, G.; Yus, M. Synthesis
2003, 443. (c) Alonso, F.; Moglie, Y.; Radivoy, G.; Vitale,
C.; Yus, M. Appl. Catal. A: Gen. 2004, 271, 171.
(12) Alonso, E.; Ramón, D. J.; Yus, M. Tetrahedron 1996, 52,
14341.
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Synthesis 2005, No. 12, 1971–1976 © Thieme Stuttgart · New York