Deallyloxy- and debenzyloxycarbonylation of protected alcohols, amines and thiols via a naphthalene-catalysed lithiation reaction

Article abstract of DOI:10.1016/j.tet.2005.07.055

The naphthalene-catalysed lithiation of Alloc- and Cbz-protected alcohols, amines and thiols in THF at 0°C led, after quenching with methanol, to the recovery of the free alcohols, amines and thiols in short reaction times and with very good yields. The selectivity for the removal of the Alloc- or the Cbz- group in a polyfunctionalised substrate has been studied. The selective reductive cleavage of a benzylic carbon-oxygen bond was achieved in the presence of an allylic carbon-oxygen or carbon-nitrogen bond. This method represents a great improvement in comparison with the previously reported deprotection procedures by dissolving metals, since it avoids the use of the toxic liquid ammonia and, therefore, the need to perform the reaction at low temperatures.

Full text of DOI:10.1016/j.tet.2005.07.055

Tetrahedron 61 (2005) 9319–9324
Deallyloxy- and debenzyloxycarbonylation of protected alcohols,
amines and thiols via a naphthalene-catalysed lithiation reaction
*
Cherif Behloul, David Guijarro and Miguel Yus
´ ´ ´ ´
Departamento de Quımica Organica, Facultad de Ciencias and Instituto de Sıntesis Organica (ISO), Universidad de Alicante,
Apdo. 99, 03080 Alicante, Spain
Received 21 June 2005; revised 15 July 2005; accepted 18 July 2005
Available online 9 August 2005
Abstract—The naphthalene-catalysed lithiation of Alloc- and Cbz-protected alcohols, amines and thiols in THF at 0 8C led, after quenching
with methanol, to the recovery of the free alcohols, amines and thiols in short reaction times and with very good yields. The selectivity for the
removal of the Alloc- or the Cbz- group in a polyfunctionalised substrate has been studied. The selective reductive cleavage of a benzylic
carbon–oxygen bond was achieved in the presence of an allylic carbon–oxygen or carbon–nitrogen bond. This method represents a great
improvement in comparison with the previously reported deprotection procedures by dissolving metals, since it avoids the use of the toxic
liquid ammonia and, therefore, the need to perform the reaction at low temperatures.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
functional groups present in the molecule to be
deprotected.8b
The allyloxycarbonyl (Alloc) and the benzyloxycarbonyl
(Cbz) are among the most useful protecting groups for
alcohols, amines and, to a lesser extent, thiols.1 They have
shown a wide application in organic synthesis, especially in
the fields of peptides,2 nucleotides,3 and carbohydrates.4
These blocking groups present the advantages that are easily
introduced (generally by acylation with allyl5a or benzyl
chloroformate5b in the presence of a base), deactivate the
nucleophilic properties of the protected heteroatom and can
readily be removed when needed. The Alloc group can be
cleaved by sodium in liquid ammonia,6 nickel tetracarbonyl
or several palladium complexes in the presence of an
external nucleophile in order to prevent the liberated
functional group from adding to the intermediate p-allyl
complex.7 Concerning the Cbz group, several methods have
been reported for its removal: palladium-catalysed hydro-
genolysis, reduction by electrolysis, dissolving metals or
alkali metal borohydrides, basic hydrolysis, treatment with
strong acids, boron trihalides or trimethylsilyl halides.8 A
mild deprotection of allylic and benzylic carbamates using
tetrabutylammonium fluoride has recently been reported.9
However, some of these methods require the use of toxic
reagents or expensive transition metal complexes and, in
some cases, side reactions have been observed with other
Our research group has extensively been studying an arene-
catalysed lithiation methodology.10,11 The use of an excess
of lithium powder and a 0 catalytic amount of an arene
[mainly naphthalene or 4,4 -di-tert-butylbiphenyl (DTBB)]
has allowed us to generate simple organolithium com-
pounds starting from non-halogenated materials,12 and
functionalised organolithium compounds13 by chlorine–
lithium exchange or by ring opening of heterocycles.14 The
application of this lithiation process to the reductive
cleavage of several allylic and benzylic carbon-heteroatom
bonds has led to methods for removal of some blocking
groups from protected alcohols, amines and thiols.15 In a
previous study, we were able to generate allylic and
benzylic organolithium reagents by reductive cleavage of
carbon–oxygen and carbon–nitrogen bonds in carbonates
and carbamates.16 These results prompted us to test the
application of our lithiation methodology to the removal of
the Alloc and Cbz groups. In this paper we report the
lithium-mediated naphthalene-catalysed reductive cleavage
of these two groups from several protected alcohols, amines
and thiols in short reaction times under very mild reaction
conditions, avoiding the use of the toxic liquid ammonia.
2. Results and discussion
Keywords: Lithium; Naphthalene; Allyloxycarbonyl; Benzyloxycarbonyl;
Deprotection; Alcohols; Amines; Thiols.
All protected substrates 1–3 (Scheme 1, Table 1) were
prepared from commercially available alcohols (for 1),
*
Corresponding author. Tel.: C34 965903548; fax: C34 965903549;
e-mail: yus@ua.es
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.07.055

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C. Behloul et al. / Tetrahedron 61 (2005) 9319–9324
phenol 4f, respectively, in yields ranging from 58 to 80%
(Table 1, entries 1, 4 and 7).
Having proved that our procedure was efficient for the
removal of both Alloc and Cbz groups from carbonates, a
competition experiment was performed in order to check if
any of these groups could be selectively cleaved in the
presence of the other one. 1,9-Nonanediol was mono-
protected with the Cbz group on one hydroxyl and the Alloc
group was introduced on the remaining hydroxyl. The
naphthalene-catalysed lithiation of the obtained dicarbonate
1g led to the recovery of the free diol 4g in almost
quantitative yield (Table 1, entry 8), showing that there was
no chemoselectivity in the process. Attempts to get some
selectivity at K78 8C did not change the result, the diol 4g
being obtained again.
Scheme 1. Reagents and conditions: (i) Li, C10H8 (8 mol%), THF, 0 8C; (ii)
H2O.
amines (for 2) or thiols (for 3) and the corresponding allyl or
benzyl chloroformate under basic reaction conditions.
Benzyl 1-decyl carbonate 1ab (Scheme 1 and Table 1, entry
2) was chosen as a model substrate. The reaction of
compound 1ab with an excess of lithium powder (1:9 molar
ratio) and a catalytic amount of naphthalene (1:0.16 molar
ratio; 8 mol%) in THF at 0 8C for 2 h gave, after quenching
the excess of lithium with methanol, the expected 1-decanol
4a in 86% yield (Table 1, entry 2). The reaction was
repeated at K30 and K78 8C, but yields did not improve.
Therefore, the temperature of 0 8C was chosen because of
the simpler experimental set-up (reaction cooled in an ice-
bath).
Our methodology was successfully applied to the deal-
lyloxy- and debenzyloxycarbonylation of protected second-
ary amines and thiols (Scheme 1 and Table 1, entries 9–16).
Both the Alloc and the Cbz groups could easily be removed
from the protected dioctylamines 2aa and 2ab, respectively,
in very good yields (Table 1, entries 9 and 10). The Cbz
group could selectively be eliminated in the protected
diallylamine 2b, which contains two allylic carbon–nitrogen
bonds that could also be cleaved under the lithiation reaction
conditions (Table 1, entry 11).18 N-Methylaniline 5c was
obtained in an excellent yield in the lithiation of substrate 2c
(Table 1, entry 12). We also tried the debenzyloxy-
carbonylation of a protected primary amine, but it failed.
Octylamine was protected with the Cbz group and the
removal of the latter was attempted following the same
procedure previously used by us in the deprotection of
tritylated primary amines,15c consisting in deprotonation
with n-butyllithium and treatment with trimethylsilyl
chloride before performing the lithiation step. Although
the starting material disappeared, neither octylamine nor
N-(trimethylsilyl)octylamine were detected in the crude
reaction mixture (GC–MS). Concerning sulfur-containing
substrates, the lithiation of the allylic and benzylic
Next, the process was extended to some other Cbz-protected
alcohols. Benzylic carbonates derived from 2-octanol (1b)
and 3,7-dimethyl-3-octanol (1d) were submitted to the
naphthalene-catalysed lithiation reaction under the same
experimental conditions and gave the corresponding free
alcohols 4b and 4d in excellent yields (Table 1, entries 3 and
5). However, the lithiation of benzyl geranyl carbonate 1e
under the same conditions only led to a 12% yield of
geraniol, probably due to a competitive cleavage of the
allylic geranyl-oxygen bond leading to the corresponding
hydrocarbon.17 The selective removal of the Cbz group was
achieved when the lithiation of 1e was performed at
K78 8C, which led to a 71% yield of geraniol (Table 1,
entry 6). The Alloc group of carbonates 1aa, 1c and 1f could
also be effectively cleaved under the typical lithiation
conditions, affording the deprotected alcohols 4a and 4c and
Table 1. Deallyloxy- or debenzyloxycarbonylation of compounds 1–3 via a naphthalene-catalysed lithiation. Preparation of compounds 4–6
Entry
Substrate
R1
Time (h)
Product
Yield (%)a
No.
X
R2
No.
1
2
3
4
5
6
7
8
1aa
1ab
1b
1c
1d
1e
1f
1g
O
O
O
O
O
O
O
Me(CH2)9
CH2]CHCH2 2.0
4a
4a
4b
4c
4d
4e
4f
80
86
O99
74
Me(CH2)9
Me(CH2)5CH(Me)
c-C6H11
PhCH2
PhCH2
2.0
5.0
CH2]CHCH2 1.5
Pri(CH2)3C(Me)(Et)
Geranyl
PhCH2
PhCH2
5.0
2.5
81
71b
58
2,4,6-Me3C6H2
CbzO(CH2)9
Me(CH2)7
Me(CH2)7
CH2]CHCH2
Ph
Me(CH2)9
Me(CH2)9
c-C6H11
CH2]CHCH2 1.0
CH2]CHCH2 2.0
CH2]CHCH2 2.0
O
Me(CH2)7N
Me(CH2)7N
CH2]CHCH2N
MeN
S
S
S
S
4gc
5a
5a
5b
5c
6a
6a
6b
6c
O99
86
71
62
98
78
82
62
96
9
2aa
2ab
2b
10
11
12
13
14
15
16
PhCH2
PhCH2
PhCH2
5.0
1.0
1.0
2c
3aa
3ab
3b
CH2]CHCH2 2.0
PhCH2
PhCH2
1.0
1.0
3c
Ph
CH2]CHCH2 1.0
a Yield determined by quantitative GLC, using commercially available compound 4–6 and n-dodecane (internal standard) in the determination of response
factors.
b The reaction was performed at K78 8C.
c Compound 4gZ1,9-nonanediol.

C. Behloul et al. / Tetrahedron 61 (2005) 9319–9324
9321
thiocarbonates 3a–3c, derived from primary, secondary and
aromatic thiols, led to the formation of the parent thiols in
moderate to excellent yields (Table 1, entries 13–16). The
moderate yield obtained with benzyl cyclohexyl thio-
carbonate 3b could be attributed to some oxidation of the
obtained cyclohexanethiol to the corresponding disulfide
during the work-up, since the latter was detected in the
crude reaction mixture (GC–MS).
300 spectrophotometer using CDCl3 (unless otherwise
stated) as solvent and tetramethylsilane (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 detector. Infrared (FT-IR)
spectra were obtained on a Nicolet-Nexus spectro-
photometer. The purity of volatile compounds and the
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 nitrogen as carrier gas.
Concerning a possible reaction mechanism, we assume that
the reductive cleavage of the allylic (for Alloc) or benzylic
(for Cbz) carbon–oxygen bond takes place first, leading to
allyl- or benzyllithium and the corresponding alkyl lithium
carbonate (from 1), carbamate (from 2) or thiocarbonate
(from 3). Then, the latter carbonic acid derivatives
decarboxylate to give the corresponding lithium alkoxide
(from 1), amide (from 2) or sulfide (from 3). The final
quench with excess of methanol renders the expected
alcohols 4, amines 5 or thiols 6, respectively, and the
hydrocarbons propene (by protonolysis of allyllithium) or
toluene (by protonolysis of benzyllithium). The latter was
always detected (GC–MS) in all the reactions with Cbz-
protected substrates, which is in favour of the proposed
reaction mechanism.
4.2. Synthesis of the carbonates 1a–1f, carbamates 2 and
thiocarbonates 3. General procedure
n-BuLi (6.3 mL of a 1.6 M solution of n-BuLi in hexane,
10.0 mmol) was dropwise added to a stirred solution of the
corresponding alcohol (for 1a–1f), amine (for 2) or thiols
(for 3) (10.0 mmol) in anhydrous THF (10 mL) under Ar at
0 8C. Ten minutes after the addition had been completed,
allyl or benzyl chloroformate (10.0 mmol) was added
during ca. 5 min. After stirring for 2 h at the same
temperature, the crude reaction mixture was adsorbed on
basic aluminium oxide, transferred to a short column of
basic aluminium oxide and eluted with hexane. Evaporation
of the solvent (15 Torr) afforded the expected Alloc- and
Cbz-protected compounds 1a–1f, 2 and 3 in pure form.
Their corresponding physical, spectroscopic and analytical
data follow.
3. Conclusion
In conclusion, we have reported here a very efficient
procedure to remove the Alloc and the Cbz groups from
protected alcohols, amines and thiols under mild reaction
conditions. The methodology is applicable to aliphatic and
aromatic substrates. This deprotection procedure works very
efficiently even for branched alcohols and thiols. Concern-
ing amines, this reductive cleavage is only applicable to
carbamates bearing two substituents at the nitrogen atom.
This method has shown to be a very good alternative to the
reported methods to remove this two popular protecting
groups, since it uses safer reagents and simpler experimental
set-up conditions.
4.2.1. Allyl 1-decyl carbonate (1aa).21 Colourless oil;
yield: 22%; Rf 0.88 (hexane/ethyl acetate: 9/1); n (film)
1747 (C]O), 1256 cmK1 (CO); dH 0.88 (3H, t, JZ6.8 Hz,
Me), 1.00–1.51 [14H, m, Me(CH2)7], 1.53–1.82 (2H, m,
CH2CO), 4.12 (2H, t, JZ6.6 Hz, CH2CH2O), 4.63 (2H, d,
JZ6.9 Hz, CHCH2O), 5.21–5.44 (2H, m, CH2]C), 5.84–
6.03 (1H, m, CH]CH2); dC 14.1 (Me), 22.6, 28.6, 29.2,
29.3, 29.5, 30.9 (2C), 31.8 [Me(CH2)8], 68.0, 68.2 (2!CO),
118.8 (CH2]C), 131.5 (CH]C), 155.1 (C]O); m/z (DIP)
242 (MC, !1%), 203 (10), 141 (80), 140 (47), 112 (25),
111 (25), 99 (27), 98 (16), 97 (39), 85 (100), 84 (25), 83
(49), 82 (17), 71 (84), 70 (37), 69 (43), 68 (12), 57 (90), 56
(31), 55 (48), 43 (54), 42 (11), 41 (30).
4. Experimental
4.1. General
4.2.2. Benzyl 1-decyl carbonate (1ab).22 Colourless oil;
yield: 61%; Rf 0.38 (hexane); n (film) 3071, 3034, 1587
(HC]C), 1746 (C]O), 1261 cmK1 (CO); dH 0.88 (3H, t,
JZ6.9 Hz, Me), 1.18–1.44 [14H, m, Me(CH2)7], 1.58–1.73
(2H, m, CH2CO), 4.13 (2H, t, JZ6.8 Hz, CH2CH2O), 5.15
(2H, s, PhCH2), 7.26–7.43 (5H, m, ArH); dC 14.1 (Me),
22.6, 25.6, 28.6, 29.15, 29.2, 29.5 (2C), 31.8 [Me(CH2)8],
68.3 (CH2CO), 69.4 (PhCH2), 128.3 (2C), 128.4, 128.5
(2C), 135.3 (ArC), 155.2 (C]O); m/z (DIP) 292 (MC,
!1%), 286 (14), 273 (11), 272 (27), 271 (100), 257 (47),
239 (26), 195 (12), 194 (14), 193 (64), 149 (66), 135 (16),
129 (20), 128 (11), 116 (10), 111 (11), 97 (18), 89 (17), 85
(16), 83 (19), 73 (19), 71 (22), 69 (19), 61 (10), 60 (13), 57
(46), 56 (61), 55 (27), 43 (38), 41 (24).
All moisture sensitive reactions were carried out under
argon atmosphere. Commercially available anhydrous THF
(99.9%, water content %0.006%, Acros) was used as
solvent in all the reactions. All reagents used for the
synthesis of protected substrates 1–3 and naphthalene were
commercially available (Acros, Aldrich) and were used
without further purification. Lithium powder was prepared
according to the procedure described in Ref. 19. Com-
mercially available n-butyllithium was titrated with a 1 M
solution of sec-butanol in xylene using 1,10-phenanthroline
as indicator.20 All glassware was dried in an oven at 100 8C
and cooled to room temperature under Ar before use.
Column chromatography was performed with Merck silica
gel 60 (0.040–0.063 mm, 240–400 mesh). Thin-layer
chromatography (TLC) was performed on precoated silica
gel plates (Merck 60, F254, 0.25 mm). Nuclear magnetic
resonance (NMR) spectra were recorded on a Bruker ARX-
4.2.3. Benzyl 2-octyl carbonate (1b).23 Colourless oil;
yield: 70%; Rf 0.58 (hexane/ethyl acetate: 9:1); n (film)
3093, 3055, 3034, 1498 (HC]C), 1734 (C]O), 1263 cmK1
(CO); dH 0.87 (3H, t, JZ6.5 Hz, MeCH2), 1.17–1.75 [10H,

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C. Behloul et al. / Tetrahedron 61 (2005) 9319–9324
m, (CH2)5], 1.27 (3H, d, JZ6.1 Hz, MeCH), 4.68–4.85 (1H,
m, CHO), 5.14 (2H, s, PhCH2), 7.24–7.47 (5H, m, ArH); dC
14.0 (MeCH2), 19.8 (MeCO), 22.5, 25.15, 25.2, 29.0, 31.6
[(CH2)5], 69.2 (PhCH2), 75.6 (MeCO), 128.2 (2C), 128.3,
128.5 (2C), 135.4 (ArH), 154.8 (C]O); m/z (DIP) 264
(MC, 2%), 180 (14), 152 (56), 151 (26), 112 (13), 111 (11),
110 (10), 108 (58), 107 (70), 92 (19), 91 (100), 90 (13), 79
(26), 77 (11), 71 (30), 69 (10), 65 (14), 57 (30), 55 (10), 43
(19), 41 (13).
153.0 (C]O); m/z (DIP) 220 (MC, 8%), 136 (23), 135
(100), 97 (17), 91 (33), 85 (28), 83 (15), 71 (35), 70 (12), 69
(16), 57 (44), 56 (12), 55 (18), 43 (26), 41 (37); HRMS: MC,
found 220.1098. C13H16O3 requires 220.1099.
4.2.8. N-(Allyloxycarbonyl)dioctylamine (2aa).25 Colour-
less oil; yield: 41%; Rf 0.60 (hexane/ethyl acetate: 9:1); n
(film) 3082, 1649 (HC]C), 1705 (C]O), 1237 cmK1 (CO);
dH 0.88 (6H, t, JZ6.6 Hz, 2!Me), 1.14–1.38, 1.41–1.61
[20H and 4H, respectively, 2m, 2!Me(CH2)6], 3.06–3.30
(4H, m, 2!CH2N), 4.59 (2H, d, JZ5.3 Hz, CH2O), 5.20,
5.31 (1H each, 2d, JZ10.1, 17.2 Hz, respectively,
CH2]C), 5.81–6.02 (1H, m, CH]C); dC 14.1 (2C, 2!
Me), 22.6 (2C), 26.8 (2C), 29.2 (2C), 29.3 (2C), 29.4 (2C),
31.8 (2C) [2!Me(CH2)6], 46.9 (2C, 2!CN), 65.6 (CO),
118.8 (CH2]C), 133.4 (CH]C), 155.1 (C]O); m/z (DIP)
325 (MC, !1%), 269 (27), 268 (100), 241 (16), 240 (86),
142 (26), 71 (28), 57 (28), 43 (13).
4.2.4. Allyl cyclohexyl carbonate (1c). Colourless oil;
yield: 44%; Rf 0.40 (hexane/ethyl acetate: 9:1); n (film)
1742 (C]O), 1651 (HC]C), 1254 cmK1 (CO); dH 1.06–
2.11 (10H, m, 5!CH2 ring), 4.47–4.73 (1H, m, CHO), 4.62
(2H, d, JZ4.5 Hz, CH2O), 5.15–5.42 (2H, m, CH2]C),
5.80–6.04 (1H, m, CH]C); dCZ23.0, 25.2 (2C), 31.6 (2C)
(5!CH2 ring), 68.1 (CH2O), 89.2 (CHO), 118.7 (CH2]C),
131.8 (CH]C), 154.5 (C]O); m/z (DIP) 184 (MC, 5%),
183 (30), 149 (15), 143 (12), 141 (15), 137 (12), 135 (18),
127 (18), 125 (21), 123 (15), 113 (17), 112 (12), 111 (39),
109 (21), 99 (26), 98 (16), 97 (48), 96 (14), 95 (28), 91 (12),
85 (78), 84 (21), 83 (83), 82 (28), 81 (32), 71 (75), 70 (25),
69 (55), 67 (29), 57 (100), 56 (21), 55 (72), 43 (55), 41 (64);
HRMS: MCKC4H5O2, found 99.0813. C6H11O requires
99.0810.
4.2.9. N-(Benzyloxycarbonyl)dioctylamine (2ab).26
Colourless oil; yield: 68%; Rf 0.56 (hexane/ethyl acetate:
9:1); n (film) 3065, 3032, 1498 (HC]C), 1704, 1643
(C]O), 1237 cmK1 (CO); dH 0.88 (6H, t, JZ7.0 Hz, 2!
Me), 1.07–1.38, 1.40–1.66 [20H and 4H, respectively, 2m,
2!Me(CH2)6], 3.13–3.32 (4H, m, 2!CH2N), 5.12 (2H, s,
PhCH2), 7.07–7.46 (5H, m, ArH); dC 14.1 (2C, 2!Me),
22.6 (2C), 26.8 (2C), 29.2 (2C), 29.3 (2C), 29.4 (2C), 31.8
(2C) [2!Me(CH2)6], 46.9, 47.5 (2!CN), 66.7 (CO),
127.65 (2C), 127.7, 128.3 (2C), 137.1 (ArC), 156.1
(C]O); m/z (DIP) 375 (MC, 5%), 269 (24), 268 (100),
240 (35), 232 (42), 170 (25), 142 (20), 91 (74), 71 (33), 57
(31), 43 (14).
4.2.5. Benzyl 3,7-dimethyl-3-octyl carbonate (1d).
Colourless oil; yield: 87%; Rf 0.68 (hexane/ethyl acetate:
9:1); n (film) 3088, 3066, 3034, 1580, 1498 (HC]C), 1740
(C]O), 1263 cmK1 (CO); dH 0.75–0.99 (9H, m, 2!MeCH
and MeCH2), 1.07–1.61 [7H, m, CHMe and (CH2)3], 1.41
(3H, s, MeC), 1.63–1.96 (2H, m, CH2Me), 5.09 (2H, s,
PhCH2), 7.24–7.50 (5H, m, ArH); dC 8.0, 22.5, 23.0, 27.8
(4!Me), 21.2, 30.6, 37.6, 39.1 [(CH2)3 and CH2Me], 68.6
(PhCH2), 87.1 (CO), 128.1 (2C), 128.2, 128.5 (2C), 135.8
(ArC), 153.3 (C]O); m/z (DIP) 292 (MC, !1%), 181 (16),
180 (11), 140 (29), 91 (100), 85 (12), 71 (13), 70 (17), 57
(13), 43 (11); HRMS: MC, found 292.2064. C18H28O3
requires 292.2038.
4.2.10. N-(Benzyloxycarbonyl)diallylamine (2b).27
Colourless oil; yield: 65%; Rf 0.23 (hexane/ethyl acetate:
9:1); n (film) 3082, 3060, 3028, 1651, 1591, 1503 (HC]C),
1744, 1702 (C]O), 1241 cmK1 (CO); dH 3.77–3.99 (4H, m,
2!CH2N), 5.15 (2H, s, PhCH2), 5.01–5.25 (4H, m, 2!
CH2]C), 5.67–5.86 (2H, m, 2!CH]CH2), 7.26–7.50
(5H, m, ArH); dC 46.2, 49.1 (2!CN), 67.1 (PhCH2), 116.7,
117.1 (2!CH2]C), 127.7 (2C), 128.4 (2C), 128.5, 136.8
(ArC), 133.4 (2C, 2!CH]CH2), 156.0 (C]O); m/z (DIP)
231 (MC, 3%), 181 (12), 180 (37), 151 (33), 107 (57), 92
(31), 91 (100), 79 (36), 77 (17), 65 (17).
4.2.6. Benzyl geranyl carbonate (1e).24 Colourless oil;
yield: 26%; Rf 0.50 (hexane/ethyl acetate: 9:1); n (film)
3082, 3055, 3033, 1596, 1498 (HC]C), 1744 (C]O),
1255 cmK1 (CO); dH 1.60, 1.68, 1.71 (3H each, 3s, 3!Me),
1.99–2.12 [4H, m, (CH2)2], 4.54–4.74 (2H, m, CHCH2O),
4.99–5.20 (3H, m, CH]CMe2 and PhCH2), 5.33–5.46 (1H,
m, CHCH2O), 7.29–7.42 (5H, m, ArH); dC 16.5, 17.7, 25.7
(3!Me), 26.2, 39.5 [(CH2)2], 66.5 (CHCO), 69.6 (PhCH2),
117.8, 123.6 (2!CH]CMe), 131.7, 135.3 (2!C]CH),
128.2 (2C), 128.25, 128.5 (2C), 142.8 (ArC), 155.1 (C]O);
m/z 288 (MC, !1%), 136 (29), 135 (12), 121 (26), 108 (12),
107 (18), 93 (41), 92 (20), 91 (100), 80 (15), 79 (15), 77
(15), 69 (81), 68 (50), 67 (16), 65 (10).
4.2.11. N-(Benzyloxycarbonyl)-N-methylaniline (2c).28
Colourless oil; yield: 62%; Rf 0.28 (hexane/ethyl acetate:
9:1); n (film) 3088, 3063, 3032, 1598, 1497 (HC]C), 1749,
1708 (C]O), 1298 cmK1 (CO); dH 3.31 (3H, s, Me), 5.15
(2H, s, PhCH2), 6.99–7.51 (10H, m, ArH); dC 38.4 (Me),
67.2 (PhCH2), 126.6 (2C), 126.8, 127.6, 127.8 (2C), 128.3
(2C), 128.8 (2C), 136.6, 138.9 (ArC), 155.4 (C]O); m/z
(DIP) 241 (MC, 58%), 197 (65), 196 (17), 181 (11), 120
(28), 106 (14), 92 (28), 91 (100), 77 (28), 65 (24).
4.2.7. Allyl 2,4,6-trimethylphenyl carbonate (1f). Colour-
less oil; yield: 64%; Rf 0.55 (hexane/ethyl acetate: 9:1); n
(film) 3088, 3068, 1650, 1607, 1486 (HC]C), 1759
(C]O), 1245 cmK1 (CO); dH 2.59, 2.69 (6H and 3H,
respectively, 2s, 3!Me), 5.18 (2H, d, JZ5.8 Hz,
CHCH2O), 5.67–5.92, (2H, m, CH2]C), 6.32–6.52 (1H,
m, CH]CH2), 7.29 (2H, s, 2!ArH); dC 16.0 (2C), 20.7
(3!Me), 69.0 (CH2O), 119.2 (CH2]C), 131.3
(CH]CH2), 129.3 (2C), 129.6 (2C), 135.6, 146.2 (ArC),
4.2.12. O-Allyl S-(1-decyl) thiocarbonate (3aa). Colour-
less oil; yield: 81%; Rf 0.33 (hexane); n (film) 3082, 1648
(HC]C), 1744, 1713 (C]O), 1138 cmK1 (CO); dH 0.88
(3H, t, JZ6.6 Hz, Me), 1.15–1.46, 1.55–1.71 [14H and 2H,
respectively, 2m, Me(CH2)8], 2.86 (2H, t, JZ7.3 Hz,
CH2S), 4.71 (2H, d, JZ5.8 Hz, CH2O), 5.28, 5.37 (1H
each, 2d, JZ10.5, 17.2 Hz, respectively, CH2]C),
5.83–6.03, (1H, m, CH]C); dC 14.1 (Me), 22.6, 28.7,

C. Behloul et al. / Tetrahedron 61 (2005) 9319–9324
9323
29.1, 29.3, 29.4, 29.5, 29.7, 31.0, 31.9 [(CH2)9], 67.6 (CO),
118.9 (H2C]C), 131.6 (CH]C), 171.1 (C]O); m/z (DIP)
258 (MC, !1%), 201 (49), 174 (10), 173 (68), 172 (29),
140 (16), 99 (17), 97 (18), 85 (92), 83 (20), 71 (79), 69 (23),
57 (100), 55 (37), 43 (61), 42 (14), 41 (32); HRMS: MC,
found 258.1654. C14H26O2S requires 258.1654.
adsorbed on basic aluminium oxide, transferred to a short
column of basic aluminium oxide and eluted with hexane.
Evaporation of the solvent (15 Torr) gave the pure
diprotected diol 1g in 26% yield. The corresponding
physical, spectroscopic and analytical data follow.
4.3.1. Benzyl 9-(allyloxycarbonyloxy)-1-nonyl carbonate
(1g). Colourless oil; yield: 26%; Rf 0.50 (hexane/ethyl
acetate: 9:1); n (film) 3060, 3028, 1645, 1497 (HC]C),
1747 (C]O), 1259 cmK1 (CO); dH 1.13–1.74 [14H, m,
(CH2)7CO], 4.13 (2H, t, JZ6.6 Hz, 1!CH2CH2O), 4.57–
4.68 (4H, m, CH2CH and 1!CH2CH2O), 5.17 (2H, s,
PhCH2), 5.28, 5.39 (1H each, 2d, JZ10.3, 17.7 Hz,
respectively, CH2]C), 5.85–6.01 (1H, m, H2C]CH),
7.31–7.42 (5H, m, ArH); dC 14.1 (2C), 23.3 (2C), 25.7
(2C), 39.0 [(CH2)7CO], 68.3 (2C), 69.6, 74.3 (4!CO),
118.8 (CH2]C), 128.3 (2C), 128.5, 128.6 (2C), 131.7
(ArC), 131.5 (CH]CH2), 155.2 (2C, 2!CZO); m/z (DIP)
378 (MC, 1%), 125 (14), 108 (16), 107 (79), 92 (11), 91
(100), 83 (31), 81 (15), 69 (56), 57 (15), 55 (27), 41 (27);
HRMS: MC, found 378.2050. C21H30O6 requires 378.2042.
4.2.13. O-Benzyl S-(1-decyl) thiocarbonate (3ab). Colour-
less oil; yield: 62%; Rf 0.33 (hexane); n (film) 3099, 3065,
3033, 1498 (HC]C), 1744, 1710 (C]O), 1134 cmK1
(CO); dH 0.88 (3H, t, JZ6.6 Hz, Me), 1.14–1.45, 1.50–1.71
[14H and 2H, respectively, 2m, Me(CH2)8], 2.86 (2H, t, JZ
7.5 Hz, CH2S), 5.22 (2H, s, PhCH2), 7.18–7.44, (5H, m,
ArH); dC 14.1 (Me), 22.7, 28.7, 29.1, 29.3, 29.4, 29.5, 29.7,
31.1, 31.9 [(CH2)9], 68.7 (CO), 128.3 (2C), 128.4, 128.6
(2C), 135.3 (ArC), 171.3 (C]O); m/z (DIP) 264 (MC, 7%),
201 (16), 181 (49), 180 (30), 179 (16), 174 (11), 173 (88),
172 (12), 165 (12), 97 (21), 92 (59), 91 (100), 85 (26), 83
(15), 77 (11), 71 (23), 69 (17), 65 (20), 57 (32), 55 (28), 43
(34), 41 (30); HRMS: MC, found 308.1809. C18H28O2S
requires 308.1810.
4.2.14. O-Benzyl S-cyclohexyl thiocarbonate (3b).
Colourless oil; yield: 74%; Rf 0.25 (hexane); n (film)
3099, 3064, 3032, 1591, 1503 (HC]C), 1705 (C]O),
1132 cmK1 (CO); dH 1.10–2.10 (10H, m, 5!CH2 ring),
3.28–3.43 (1H, m, CHS), 5.21 (2H, s, PhCH2), 7.15–7.43
(5H, m, ArH); dC 25.4, 25.8 (2C), 33.1 (2C) (5!CH2 ring),
44.4 (CS), 68.4 (CO), 128.2 (2C), 128.3, 128.5 (2C), 135.3
(ArC), 170.8 (C]O); m/z (DIP) 250 (MC, 9%), 181 (28),
180 (17), 92 (70), 91 (100), 83 (17), 81 (18), 79 (13), 77
(24), 65 (34), 55 (28), 41 (22); HRMS: MC, found
250.1024. C14H18O2S requires 250.1028.
4.4. Naphthalene-catalysed lithiation of compounds 1–3.
Preparation of products 4–6. General procedure
A solution of the protected substrate 1–3 (1.0 mmol) in THF
(2 mL) was dropwise added to a green suspension of lithium
powder (63 mg, 9.0 mmol) and naphthalene (20 mg,
0.16 mmol) in THF (5 mL), under Ar, at 0 8C. After stirring
at the same temperature for the time indicated in Table 1,
methanol (5 mL) was carefully added, the cooling bath was
removed and the reaction was stirred till it reached room
temperature. The yields of the deprotected products were
determined by quantitative GLC. Commercially available
alcohols 4, amines 5, thiols 6, n-dodecane (internal
standard) and n-hexadecane (internal standard for 4f) were
used in the determination of response factors. Compounds
4–6 (commercially available) were characterised by
comparison of their physical and spectroscopic data with
authentic samples.
4.2.15. O-Allyl S-phenyl thiocarbonate (3c). Colourless
oil; yield: 57%; Rf 0.70 (hexane/ethyl acetate: 9:1); n (film)
3078, 3055, 1636, 1583, 1479 (HC]C), 1726 (C]O),
1135 cmK1 (CO); dH 4.72 (2H, d, JZ5.8 Hz, CH2O), 5.28,
5.31 (1H each, 2d, JZ10.5, 17.2 Hz, respectively,
CH2]C), 5.78–6.01 (1H, m, CH]CH2), 6.93–7.74 (5H,
m, ArH); dC 68.2 (CO), 117.6 (CH2]C), 129.6, 129.8 (2C),
134.8 (2C), 135.9 (ArC), 133.5 (C]CH2), 169.4 (C]O);
m/z (DIP) 194 (MC, 2%), 165 (15), 150 (15), 149 (77), 137
(10), 135 (64), 125 (15), 124 (69), 123 (100), 111 (13), 110
(39), 109 (50), 97 (14), 91 (17), 85 (13), 83 (12), 79 (11), 77
(22), 71 (14), 69 (17), 65 (16), 57 (22), 55 (13), 51 (13), 45
(26), 43 (12), 41 (21); HRMS: MC, found 194.0415.
C10H10O2S requires 194.0402.
Acknowledgements
This work was financially supported by the DGI of the
´
Spanish Ministerio de Educacion y Ciencia (project no.
CTQ2004-01261) and the Generalitat Valenciana (project
no. GRUPOS03/135). C.B. thanks the University of
Alicante for a fellowship.
4.3. Preparation of diprotected nonane-1,9-diol 1g
n-BuLi (6.3 mL of a 1.6 M solution of n-BuLi in hexane,
10.0 mmol) was dropwise added to a stirred solution of
nonane-1,9-diol (1.635 g, 10.0 mmol) in anhydrous THF
(10 mL) at 0 8C. Five minutes after the addition had been
completed, benzyl chloroformate (1.5 mL, 10.0 mmol) was
added during ca. 5 min. After stirring for 10 min at the same
temperature, the same amount of n-BuLi as above was
dropwise added, the reaction mixture was stirred for 5 min
and allyl chloroformate (1.1 mL, 10.0 mmol) was added
during ca. 5 min. The reaction was then stirred for 5 min, the
cooling bath was removed and stirring was continued at
room temperature for 2 h. The crude reaction mixture was
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