Mild deprotection of tert-butyl carbamates of NH-heteroarenes under basic conditions

Article abstract of DOI:10.1080/00397910600634480

Aqueous methanolic potassium carbonate under reflux has been demonstrated to be a highly effective deprotective agent for the tert -butyl carbamates of indoles, indazoles, carbazole, thiazoloindole, and pyrrole. The method is a mild one and is particularly expeditious for NH-heteroarenes bearing electron-withdrawing groups. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600634480

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Mild Deprotection of tert‐Butyl Carbamates of
NH‐Heteroarenes under Basic Conditions
a
a
b
Manas Chakrabarty , Taraknath Kundu & Yoshihiro Harigaya
a
Department of Chemistry, Bose Institute, Kolkata, India
b
School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan
Published online: 20 Aug 2006.
To cite this article: Manas Chakrabarty , Taraknath Kundu & Yoshihiro Harigaya (2006): Mild Deprotection
of tert‐Butyl Carbamates of NH‐Heteroarenes under Basic Conditions, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:14, 2069-2077
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Synthetic Communications , 36: 2069–2077, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600634480
Mild Deprotection of tert-Butyl Carbamates
of NH-Heteroarenes under Basic Conditions
Manas Chakrabarty and Taraknath Kundu
Department of Chemistry, Bose Institute, Kolkata, India
Yoshihiro Harigaya
School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan
Abstract: Aqueous methanolic potassium carbonate under reflux has been demon-
strated to be a highly effective deprotective agent for the tert-butyl carbamates of
indoles, indazoles, carbazole, thiazoloindole, and pyrrole. The method is a mild one
and is particularly expeditious for NH-heteroarenes bearing electron-withdrawing
groups.
2 3
Keywords: Aqueous K CO /MeOH, N-Boc-heteroarenes, deprotection, reflux
The proper choice of a protective group and its mild deprotection are of prime
importance in the synthesis of polyfunctional molecules. Consequently, many
[1]
[2]
books and reviews have been published on the extant methods of protec-
tion and deprotection of various functional groups. Moreover, updated
[3]
reviews on this topic are also published periodically. Of the common func-
tionalities, amines, including those incorporated in nitrogen heteroarenes, are
important in the fields of heterocycles and peptides. The tert-butoxycarbonyl
group (Boc) is perhaps most widely used of the numerous protective agents
[4]
used for amines, and it is also for aminoacids in peptide chemistry
because of the stability of the tert-butyl carbamates to basic and weakly
acidic conditions. The amines are usually regenerated from their N-Boc
[1,5]
derivatives by strong protic or Lewis acids or thermolysis. The most
common reagent is trifluoroacetic acid neat or in dichloromethane solution.
Received in India January 12, 2006
Address correspondence to Manas Chakrabarty, Department of Chemistry, Bose
Institute, 93/1, A.P.C. Road, Kolkata 700009, India. Tel.: þ 91-33-23506619;
Fax: þ91-33-23506790; E-mail: chakmanas@yahoo.co.in
2
069

2
070
M. Chakrabarty, T. Kundu, and Y. Harigaya
In recent years, methods have also been developed for the cleavage of N-Boc
[6a]
derivatives utilizing acidic solid catalysts such as silica gel (thermally,
[
6b]
[6c]
under low pressure
or microwave irradiation,
[7a]
or doped with
[7b]
or montmorillonite K10 ). Very
[
Yb(OTf)3 ) and clays (kaolinitic
6d]
[
8a,b]
[8c]
[8d]
[8e]
LiBr,
recently, n-Bu NF,
4
In/MeOH,
CAN,
and so on have
also been employed effectively for the cleavage of N-Boc derivatives.
The N-Boc group is generally found to be resistant to cleavage under basic
conditions. In fact, two recent reports have shown that the N-Boc group was not
[
9a]
cleaved by a mild base, viz. K CO (CH CN/room temperature/24h) and
2
3
t
3
[9b]
not even by a strong base, viz. NaO Bu (PhCH /40 8C/12h). Nevertheless,
3
the regeneration of amines from their N-Boc derivatives using basic reagents
have been achieved in a few instances, for example, NaOMe/MeOH-THF for
[
10]
[11]
t
pyrroles,
THF for both aromatic and aliphatic primary amines,
Cs CO /imidazole (CH CN/70 8C/4-24h) mainly for the conversion of N,N-
Mg(OMe) /MeOH for lactams,
NaO Bu/moist THF or 2-Me-
2
[12]
and lately by
2
3
3
[13]
(
Boc) -a-amino acids to their NH-Boc derivatives. Of these, Cs CO /
2 3
imidazole/CH CN was reported to cleave N-Boc-indole and N-Boc-oxindole
(a lactam) to the respective parent heteroarene,
earlier reported to regenerate a few indoles from their N-Boc derivatives in
2
3
[13]
and NaOMe/MeOH was
[
14]
isolated cases. Thus, there does not appear to exist any generally applicable
basic reagent, particularly a mild one, for the cleavage of N-Boc-heteroarenes to
their parent NH-heteroarenes, in which we were interested.
In connecton with our recent work on the syntheses of a naturally
[
15]
[16]
[17]
occurring bisindolic enamide,
thiazoloindoles,
and indolyloxazoles,
we needed to develop a method for the cleavage of mainly the N-Boc-
indoles to regenerate indoles using mildly basic conditions. As a result of
our efforts, we have now been able to demonstrate that potassium carbonate
(
3 equiv) in methanol–water (3 : 1) under reflux efficiently deprotects the N-
Boc derivatives of several indoles (1a–i), carbazole (1j), a thiazoloindole
1k), two nitroindazoles (1l,m), and 2-formylpyrrole (1n) to regenerate the
(
parent heteroarenes (2a–n) in 80–98% isolated yields in 15 min–10 h. The
reactions are presented in Scheme 1 and the results in Table 1.
An analysis of the results immediately unveiled a correlation between the
electronic effects of the substituents on the heteroarenes and the reaction
periods. Thus, the presence of an electron-withdrawing group (NO in 1b,
2
1
l, and 1m; CHO in 1g and 1n) expedited the reactions (15–30 min),
whereas for indole (1a), the presence of an electron-donating group
NHCSNHMe in 1f; Br, OMe, NH , and Me in 1e, 1d, 1c, and 1 h, respectively)
(
2
in the heteroarenes decelerated the reactions (2.5–5 h). In the case of 3-methy-
lindole (1i), the reaction took an appreciably longer period (10 h), which is in
conformity with the well-known reduced activity at C-2, compared to that at
C-3, in the indole nucleus. Carbazole (1j) and the thiazoloindole (1k)
required intermediate time periods for the completion of the reactions.
To ascertain the effectiveness of the reagent for the cleavage of the N-Boc
derivatives of aromatic and aliphatic primary amines, the reagent was

Mild Deprotection of tert-Butyl Carbamates
2071
Scheme 1.
applied separately to the N-Boc derivatives of aniline, benzylamine, and b-phe-
nylethylamine under similar conditions. In all three cases, the reagent proved to
be abortive even after refluxing for 12 h, which pointed to the possibleuse of this
reagent for the selective deprotection of N-Boc-heteroarenes in the presence of
0
0
N-Boc aliphatic primary amines. Accordingly, N, N ,N -(Boc) -tryptamine (1o)
3
Table 1. Deprotection of N-Boc-heteroarenes by K CO /aq. MeOH/reflux
2
3
a
Yield(%)
of 2
Entry
N-Boc-heteroarenes (1)
Time
0
1
2
3
4
5
6
7
8
9
a: R ¼ R ¼ H
2.5 h
90
98
85
82
87
86
95
92
85
91
80
92
90
0
b: R ¼ H; R ¼ -NO
15 min
4.0 h
3.5 h
2
0
0
0
0
c: R ¼ H; R ¼ 5-NH
2
d: R ¼ H; R ¼ 5-OMe
e: R ¼ H; R ¼ -Br
3.0 h
2.5 h
f: R ¼ H; R ¼ NHCSNHMe
0
g: R ¼ 3-CHO; R ¼ H
20 min
5.0 h
0
h: R ¼ 2-Me; R ¼ H
0
i: R ¼ 3-Me; R ¼ H
10.0 h
1.0
2.0 h
1
1
1
1
1
1
0
1
2
3
4
5
j: Carbazole
k: A thiazoloindole
l: R ¼ 5-NO
15 min
20 min
30 min
3.0 h
2
m: R ¼ 6-NO
2
n: 2-Formylpyrrole
0
80
65 (2o) ;
0
b
o: N, N ,N -(Boc) -tryptamine
3
0
b
2
5 (2 o)
a
b
Yields of isolated pure products.
Separated by prep.TLC/silica gel/PE-EtOAc (4:1).

2
072
M. Chakrabarty, T. Kundu, and Y. Harigaya
Scheme 2.
was subjected to similar basic conditions, and the reaction was complete in 3 h.
Two products were formed, of which the major and the minor ones were ident-
0
0
0
0
ified as N -Boc-tryptamine (2o; 65%) and N , N -(Boc) -tryptamine (2 o; 25%),
2
respectively (Scheme 2). Thus, indolic N-deprotection took place in both the
0
cases along with N -mono-deprotection in the side chain in one case. Clearly,
the reagent was a selective one, and more important, it appears to have the
potential of being able to convert N, N-(Boc) -amines to NH-Boc-amines.
2
However, we did not check the generality of this observation.
To our knowledge, this is the first general method of regeneration of
several classes of NH-heteroarenes from their N-Boc derivatives using a
mildly basic reagent. The method is environmentally benign, involves a
simple workup, and employs an easy isolation procedure. Compared to the
[13]
latest Cs CO /imidazole-mediated method,
the present method is dis-
2
3
tinctly superior on at least two counts. First, the use of a stoichiometric
amount of imidazole creates waste, which renders the earlier method not eco-
friendly; our present method avoids the use of any such waste-creating
reagent. Second, the present method furnishes indole (from N-Boc-indole)
more efficiently (90% yield in 2.5 h) than does the other method (82% yield
in 24 h). Therefore, our method holds the promise of being widely used in
the field of NH-heteroarenes, which is particularly expeditious for those
NH-heteroarenes that bear electron-withdrawing groups at appropriate sites.
EXPERIMENTAL
Melting points (in Celsius) were recorded on a Toshniwal apparatus and are
uncorrected. The IR spectra (nujol, unless stated otherwise) were recorded
on a Nicolet Impact 410 FT-IR or a Perkin-Elmer-782 spectrophotometer,
1
13
the H (500 MHz) and C (125 MHz) NMR spectra (including DEPT 135)
on a Bruker DRX 500 NMR spectrometer, the LR EI-MS on a JEOL JMS-
AX505HA, and ESI-MS (þve; TOF) on a Micromass Q-Tofmicro mass spet-
rometer. The molecular formulae of all new compounds were determined
either by HR EI-MS on a JEOL JMS-700 MStation or a Micromass
Q-Tofmicro YA263 mass spectrometer or by elemental analyses. The analyti-
cal and preparative TLCs were carried out on silica gel G (Merck, India)
plates. PE refers to petroleum ether, bp 60–80 8C.

Mild Deprotection of tert-Butyl Carbamates
2073
Except for 1c, 1f, and 1k, all other N-Boc-heteroarenes were prepared
[
18]
following the literature procedure.
.
compound 1c was prepared from 1b
by reduction with NH NH H O, 10% Pd-C in refluxing methanol), 1f
(
from 1c (by condensation with MeNCS), and 1 k from 1f (by cyclization
2
2
2
[
16]
using NBS-DBU).
cially. Because 1a, h–i,
Compounds 2a–e, 2g–j, 2l–n were procured commer-
[19d]
[
19a]
[19b]
[19c]
[10]
[19e]
1d,
known compounds, their spectroscopic data are not presented here.
1g,
1j,
2K,
and 2o
are
General Procedure for Deprotection
A solution of K CO (0.414 g, 3 mmol) in MeOH-H O (3 : 1; ca. 15 mL) con-
2
2
3
taining the N-Boc-heteroarene (1 mmol) was refluxed on a steam bath until the
substrate was consumed (TLC). It was then diluted with water (10–15 mL),
methanol was distilled off, and the solution cooled to room temperature.
Either the resulting crystals were filtered (entries 2, 7, 10, 12, 13) or the
products extracted (for the rest) with CH Cl (3 ꢀ 20 mL). The pooled
2
2
extracts were washed with water until free from alkali, dried (anhyd.
Na SO ), and filtered, and the filtrate was evaporated to residue. The
resulting residue was purified by crystallization from PE-CH Cl and ident-
2
4
2
2
ified either by direct comparison (mp, mixed mp, co-TLC) with an
authentic sample (for known compounds) or by the usual spectroscopic and
elemental analyses (for new products).
Data
1
7
b: Mp 110–112 8C; IR: 1737, 1515, 1458, 1327, 1285, 1157, 1029,
2
1 1
46 cm ; H NMR (CDCl ): d 1.69 (9H, s), 6.70 (1H, d, J ¼ 3.5 Hz), 7.73
3
(
1H, d, J ¼ 3.5 Hz), 8.19 (1H, dd, J ¼ 9 Hz, J ¼ 2.5 Hz), 8.25 (1H, d,
1
2
1
3
J ¼ 9 Hz), 8.47 (1H, d, J ¼ 2.5 Hz); C NMR: d 28.5 (NCO CMe ), 85.5
2 3
(NCO CMe ), 108.2, 115.6, 117.6, 119.8, 129.2 (all Ar-CH), 130.7, 138.7,
2 3
1
44.1 (all Ar-C), 149.3 (carbamate CO); ESI-MS (þve; TOF): m/z (%) 285
(M þ Na; 14), 263 (M þ H; 23), 206 (100), 161 (17); HR EI-MS: m/z
þ
2
63.0261 (M þ H ). Calcd. for C H N O : 263.1028.
1
3 15 2 4
1
c: Brown liquid; IR (neat): 3443, 3363, 1719, 1629, 1478, 1454, 1357, 1286,
2
133, 1028, 859, 812 cm ; H NMR (CDCl ): d 1.64 (9H, s), 3.69 (2H, s),
1 1
1
6
3
.38 (1H, d, J ¼ 3.5 Hz), 6.71 (1H, dd, J ¼ 8.5 Hz, J ¼ 2 Hz), 6.83 (1H,
1
1
2
3
d, J ¼ 2 Hz), 7.49 (1H, s), 7.90 (1H, br); C NMR: d 28.6 (NCO CMe ),
2
3
8
1
3
3.6 (NCO CMe ), 106.6, 107.1, 114.1, 116.1, 126.7 (all Ar-CH), 129.7,
2 3
þ
32.0, 142.0 (all Ar-C), 150.1 (carbamate CO); EI-MS: m/z (%) 232 (M ;
3), 176 (100), 132 (92), 131 (28), 104 (10), 57 (43), 41 (15). Anal. calcd.
for C H N O : C, 67.24; H, 6.90; N, 12.07. Found: C, 67.20; H, 6.88; N,
1
3 16 2 2
1
2.08.

2
074
d: Mp 74–76 8C (lit.
IR: 1732, 1613, 1586, 1533, 1447, 1281, 1122, 1023, 837, 804, 764, 724 cm
M. Chakrabarty, T. Kundu, and Y. Harigaya
[
19b]
1
mp 75–76 8C; no spectroscopic data were given);
2
1
;
1
H NMR (CDCl ): d 1.63 (9H, s), 3.79 (3H, s), 6.45 (1H, d, J ¼ 3.5 Hz), 6.91
3
(1H, dd, J ¼ 9 Hz, J ¼ 2 Hz), 6.99 (1H, d, J ¼ 2 Hz), 7.54 (1H, s), 8.02 (1H,
br); C NMR: d 28.6 (NCO CMe ), 56.0 (OCH ), 83.8 (NCO CMe ), 103.9,
1
2
1
3
2
3
3
2
3
1
07.5, 113.4, 116.2, 126.9 (all Ar-CH), 130.3, 131.1, 156.3 (all Ar-C), 150.1
þ
(
carbamate CO); EI-MS: m/z (%) 247 (M ; 34), 191 (100), 147 (47), 132 (38),
þ
57 (48), 41 (12); HR EI-MS: m/z 247.1211 (M ). Calcd. for C H NO :
1
4
17
3
247.1209.
1
e: Mp 58–60 8C; IR: 1739, 1573, 1533, 1275, 1248, 1162, 1082, 1023,
2
1 1
7
64 cm ; H NMR (CDCl ): d 1.66 (9H, s), 6.49 (1H, d, J ¼ 3.5 Hz), 7.38
3
(
1H, dd, J ¼ 9 Hz, J ¼ 1.5 Hz), 7.57 (1H, d, J ¼ 3.5 Hz), 7.67 (1H, d,
2 3
1
2
1
3
J ¼ 1.5 Hz), 8.01 (1H, br d, J ¼ 8 Hz); C NMR: d 28.5 (NCO CMe ),
8
1
4.5 (NCO CMe ), 106.8, 116.9, 123.9, 127.4 (ꢀ2) (all Ar-CH), 116.3,
2
3
32.6, 134.3 (all Ar-C), 149.8 (carbamate CO); EI-MS: m/z (%) 297
þ
(
M þ 2; 18), 295 (M ; 18), 241 (40), 239 (40), 224 (10), 222 (10), 197
(63), 195 (66), 116 (27), 115 (27), 57 (100), 41 (53); HR EI-MS: m/z
þ
95.0197 (M ). Calcd. for C H NO Br: 295.0208.
13 14 2
79
2
1
f: Mp 172–174 8C (dec.); IR: 3363, 3169, 1719, 1547, 1469, 1327, 1299,
21 1
1
155, 1049, 764 cm ; H NMR (DMSO-d ): d 1.61 (9H, s), 2.89 (3H, d,
6
J ¼ 4.5 Hz), 6.68 (1H, d, J ¼ 3.5 Hz), 7.19 (1H, d, J ¼ 8.5 Hz), 7.49 (1H, br
s), 7.56 (1H, s), 7.65 (1H, d, J ¼ 3.5 Hz), 7.96 (1H, d, J ¼ 8.5 Hz), 9.50
1
3
(
1H, br s);
C NMR: d 27.6 (NCO CMe ), 31.3 (N-CH ), 83.8
2 3 3
(
NCO CMe ), 107.5, 114.7, 116.7, 121.5, 126.6 (all Ar-CH), 130.4, 131.9,
2 3
1
3
1
33.7 (all Ar-C), 149.0 (carbamate CO), 181.3 (C 55 S); EI-MS: m/z (%)
þ
05 (M ; 100), 249 (45), 216 (29), 215 (28), 205 (26), 193 (48), 176 (69),
32 (76), 131 (32), 74 (25), 57 (86), 41 (25). Anal. calcd. for C H N O S:
1
5 19 3 2
C, 59.01; H, 6.23; N, 13.77. Found: C, 59.07; H, 6.21; N, 13.80.
1
k: Mp 180–182 8C (dec.); IR (KBr): 3232, 1733, 1621, 1562, 1426, 1367,
2
1
1
1
278, 1154, 763 cm ; H NMR (CDCl ): d 1.68 (9H, s), 3.12 (3H, d,
3
J ¼ 5.5 Hz), 5.92 (1H, br s), 6.50 (1H, d, J ¼ 3.5 Hz), 7.51 (1H, d,
1
3
J ¼ 8.5 Hz), 7. 64 (1H, d, J ¼ 3.5 Hz), 8.10 (1H, d, J ¼ 8.5 Hz); C NMR:
d 27.2 (NCO CMe ), 31.3 (N-CH ), 83.3 (NCO CMe ), 104.7, 112.8, 114.9,
2
3
3
2
3
1
26.0 (all Ar-CH), 120.5, 123.4, 130.3, 148.1, 166.9 (all Ar-C), 149.1
þ
(
carbamate CO); EI-MS: m/z (%) 303 (M ; 28), 247 (100), 203 (35), 202
17), 175 (13), 174 (25), 57 (26), 41 (11). Anal. calcd. for C H N O S: C,
(
1
5 17 3 2
59.40; H, 5.61; N, 13.86. Found: C, 59.33; H, 5.60; N, 13.89.
2
1
1
l: Mp 128–130 8C; IR: 1765, 1613, 1527, 1341, 1295, 1149, 1029, 830 cm
;
1
H NMR (DMSO-d ): d 1.45 (9H, s), 7.98 (1H, d, J ¼ 9 Hz), 8.17 (1H, dd,
6
1
3
J ¼ 9 Hz, J ¼ 2 Hz), 8.40 (1H, s), 8.60 (1H, d, J ¼ 2 Hz); C NMR: d
1
2
2
8.4 (NCO CMe ), 86.5 (NCO CMe ), 115.6, 119.5, 124.5, 141.8 (all
2 3 2 3

Mild Deprotection of tert-Butyl Carbamates
2075
Ar-CH), 126.2, 142.1, 144.5 (all Ar-C), 148.7 (carbamate CO); ESI-MS (þve;
TOF): m/z (%) 286 (M þ Na; 100), 264 (M þ H; 3), 230 (20), 208 (36), 179
(22), 123 (75). Anal. calcd. for C H N O : C, 54.75; H, 4.94; N, 15.97.
Found: C, 54.72; H, 4.95; N, 15.95.
12 13 3 4
1
m: Mp 134–136 8C; IR: 1738, 1534, 1410, 1300, 1372, 1253, 1160, 1082,
2
1
1
1
025, 890, 784 cm ; H NMR (CDCl ): d 1.76 (9H, s), 7.88 (1H, dd,
3
J ¼ 9 Hz, J ¼ 1 Hz), 8.20 (1H, dd, J ¼ 9 Hz, J ¼ 2 Hz), 8.30 (1H, d,
1
2
1
2
1
3
J ¼ 1 Hz), 9.12 (1H, s); C NMR: d 28.4 (NCO CMe ), 86.8 (NCO CMe ),
2
3
2
3
1
11.5, 119.0, 122.1, 139.2 (all Ar-CH), 129.4, 139.2, 148.5 (all Ar-C), 148.7
(
carbamate CO); ESI-MS (þve; TOF): m/z (%) 286 (M þ Na; 86), 264
(
M þ H; 3), 230 (13), 208 (100), 164 (48). Anal. calcd. for C H N O : C,
1
2 13 3 4
5
4.75; H, 4.94; N, 15.97. Found: C, 54.70; H, 4.93; N, 15.95.
2
1
1
n: Mp 50–52 8C; IR: 1750, 1655, 1541, 1249, 1124, 1024, 844, 758 cm
;
1
H NMR (CDCl ): d 1.64 (9H, s), 6.28 (1H, t, J ¼ 3 Hz), 7.18–7.19 and
3
1
3
7
8
.43–7.44 (1H, m each), 10.32 (1H, s); C NMR: d 28.3 (NCO CMe ),
2 3
6.1 (NCO CMe ), 112.0, 121.5, 127.1 (all Ar-CH), 135.1 (Ar-C), 148.7
2
3
(
(
carbamate CO), 182.7 (CHO); ESI-MS (þve; TOF): m/z (%) 218
M þ Na; 47), 196 (M þ H; 2); 162 (73), 140 (100), 96 (55), 68 (19); HR
þ
EI-MS: m/z 196.0724 (M þ H ). Calcd. for C H NO : 196.0974.
1
0
14
3
2
1
1
o: Mp 76–78 8C; IR: 1732, 1699, 1367, 1255, 1082, 864, 744 cm
;
H NMR (CDCl ): d 1.48 (18H, s), 1.65 (9H, s), 2.97 and 3.86 (2H, t
1
3
each, J ¼ 7.5 Hz), 7.24 and 7.30 (1H, t each, J ¼ 7.5 Hz), 7.39 (1H, s), 7.61
1
3
(
1H, d, J ¼ 7.5 Hz), 8.11 (1H, ill-split d); C NMR: d 25.0 (CH ),
2
2
8.4 (2 ꢀ NCO CMe ), 28.6 (1 ꢀ NCO CMe ), 46.7 (CH2), 82.6
2 3 2 3
2
3
2
3
(
(
2 ꢀ NCO CMe ), 83.7 (1 ꢀ NCO CMe ), 115.6, 119.4, 122.8, 123.6, 124.7
all Ar-CH), 118.0, 131.0, 135.9 (all Ar-C), 150.1 (1 ꢀ carbamate CO),
þ
1
52.9 (2 ꢀ carbamate CO); EI-MS: m/z (%) 460 (M ; 23), 404 (5), 360 (6),
260 (23), 248 (36), 204 (76), 187 (53), 143 (87), 130 (70), 57 (100), 41 (24);
HR EI-MS: m/z 460.2567 (M ). Calcd. for C H N O : 460.2574.
þ
2
5 36 2 6
2
f: Mp 158–160 8C; IR: 3356, 3224, 3177, 1560, 1520, 1314, 1261, 1043,
2
1 1
7
58, 724 cm ; H NMR (DMSO-d ): d 2.86 (3H, d, J ¼ 4 Hz), 6.40 (1H,
6
s), 6.90 (1H, d, J ¼ 8 Hz), 7.21 (1H, br s), 7.34 (1H, s), 7. 35 (1H, d,
1
3
J ¼ 8 Hz), 7.37 (1H, s), 9.34 (1H, br s), 11.09 (1H, s); C NMR: d 32.3
(N-CH ), 102.2, 112.5, 117.7, 120.5, 127.0 (all Ar-CH), 128.6, 130.5, 134.9,
3
þ
1
82.2 (all Ar-C); EI-MS: m/z (%) 205 (M ; 100), 174 (16), 172 (29), 171
32), 157 (15), 156 (15), 132 (87), 116 (15), 104 (23), 89 (13), 74 (13); HR
(
EI-MS: m/z 205.0674 (M ). Calcd. for C H N S: 205.0673.
þ
1
0 11 3
0
21 1
o: Mp 122–124 8C; IR: 3317, 1732, 1255, 1142, 864, 738 cm ; H NMR
2
(
CDCl ): d 1.46 (18H, s), 3.04 and 3.87 (2H, t each, J ¼ 7 Hz), 6.99 (1H, s),
3
7
.11 and 7.17 (1H, t each, J ¼ 7.5 Hz), 7.34 and 7.67 (1H, d each, J ¼ 8 Hz),

2
076
M. Chakrabarty, T. Kundu, and Y. Harigaya
1
.14 (1H, s); C NMR: d 25.3 (CH ), 28.4 (NCO CMe ), 47.5 (CH ), 82.5
3
8
2
2
3
2
(
NCO CMe ), 111.5, 119.3, 119.7, 122.3, 122.5 (all Ar-CH), 113.4, 128.0,
2 3
þ
1
36.6 (all Ar-C), 152.9 (carbamate CO); EI-MS: m/z (%) 360 (M ; 13),
2
60 (23), 248 (36), 204 (27), 203 (10), 187 (10), 159 (11), 143 (74), 130
þ
(
100), 57 (26); HR EI-MS: m/z 360.2035 (M ). Calcd. for C H N O :
2
0 28 2 4
360.2049.
ACKNOWLEDGMENTS
The authors sincerely thank the Director, Bose Institute for laboratory facili-
ties; the Council for Scientific and Industrial Research, Govt. of India, for
providing a fellowship (T.K.); and B. Majumder, NMR facilities, and
P. Dey, microanalytical laboratory, both of Bose Institute, for recording the
spectra.
REFERENCES
1
. (a) Kocienski, P. J. Protecting Groups; George Thieme Verlag: Stutttgart, 1994;
b) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis;
rd Ed.; John Wiley & Sons: New York, 1999.
(
3
2
. (a) Carpino, L. A. Acc. Chem. Res. 1973, 6, 191; (b) Kunz, H.; Waldmann, H. Pro-
tecting Groups in Comprehensive Organic Synthesis; Trost, B. M., Flemming, I.,
Eds.; Pergamon Press: Oxford, 1991; pp. 631–701; (c) Schelhaas, M.;
Waldmann, H. Angew. Chem. Int. Ed. Engl. 1996, 35, 2056.
3
4
5
. (a) Jarowinski, K.; Kocienski, P. J. J. Chem. Soc., Perkin Trans. 1 2001, 2109;
(
b) Spivey, A. C.; Srikaran, R. Ann. Rep. Prog. Chem., Sect. B 2001, 97, 41.
. Bodanszky, M. In Principles of Peptide Chemistry; Springler-Verlag: New York,
984; p. 49.
1
. (a) Bose, D. S.; Lakshiminarayana, V. Synthesis 1999, 66; (b) Bose, D. S.;
Kumar, K. K.; Reddy, A. V. N. Synth. Commun. 2003, 33, 445; (c) Li, B.;
Bemish, R.; Buzon, R. A.; Chiu, C. K.-F.; Colgan, S. T.; Kissel, W.; Le, T.;
Leeman, K. R.; Newell, L.; Roth, J. Tetrahedron Lett. 2003, 44 (8113), and refer-
ences cited therein.
6
. (a) Wensbo, D.; Amby, U.; Gronowitz, S. Tetrahedron 1995, 51, 10323;
(
b) Apelqvist, T.; Wensbo, D. Tetrahedron Lett. 1996, 37, 1471; (c) Siro, J. G.;
Martin, J.; Garcia-Navio, J. L.; Remulnan, M. J.; Vaquero, J. J. Synlett 1998, 147;
d) Kotsuki, H.; Ohishi, T.; Araki, T.; Arimura, K. Tetrahedron Lett. 1998, 39, 4869.
. (a) Sabu, K. R.; Sukumar, R.; Lalithambika, M. Bull. Chem. Soc. Jpn. 1993, 66,
535; (b) Shaikh, N. S.; Gajare, A. S.; Deshpande, V. H.; Bedekar, A. V. Tetrahe-
(
7
8
3
dron Lett. 2000, 41, 385.
. (a) Routier, S.; Sauge, L.; Ayerbe, N.; Coudert, G.; M e´ rour, J.-Y. Tetrahedron Lett.
2
002, 43, 589; (b) Jacquemard, U.; B e´ n e´ teau, V.; Lefoix, M.; Routier, S.;
M e´ rour, J.-Y.; Coudert, G. Tetrahedron 2004, 60, 10039; (c) Yadav, J. S.;
Reddy, B. V.S.; Reddy, K. S.; Reddy, K. B. Tetrahedron Lett. 2002, 43, 1549;
(
d) Hwu, J. R.; Jain, M. L.; Tsai, F.-W.; Balakumar, A.; Hakimelahi, G. H.;

Mild Deprotection of tert-Butyl Carbamates
2077
Tsay, S.-C. Arkivoc 2002, ix, 28; (e) Hern a´ ndez, J. N.; Ramirez, M. Z.;
Martin, V. S. J. Org. Chem. 2003, 68, 743.
. (a) Amjad, M.; Knight, D. W. Tetrahedron Lett. 2004, 45, 539; (b) Denmark, S. E.;
9
Baird, J. D. Org. Lett. 2004, 6, 3652.
0. Hasan, I.; Marinelli, E. R.; Li-Ching, C. L.; Fowler, F. W.; Levy, A. B. J. Org.
Chem. 1981, 46, 157.
1
1
1
1. Wei, Z.-Y.; Knaus, E. E. Tetrahedron Lett. 1994, 35, 847.
2. Tom, N. J.; Simon, W. M.; Frost, H. N.; Ewing, M. Tetrahedron Lett. 2004, 45,
905.
1
1
3. Mohapatra, D. K.; Durugkar, K. A. Arkivoc 2005, xiv, 20.
4. (a) Doyle, K. J.; Moody, C. J. Synthesis 1994, 1021; (b) Kutschy, P.; Dzurilla, M.;
Takasugi, M.; T o¨ r o¨ k, M.; Achbergerov a´ , I.; Homzov a´ , R.; R a´ cov a´ , M. Tetrahe-
dron 1998, 54, 3549.
1
1
5. Chakrabarty, M.; Basak, R.; Harigaya, Y. Synthesis 2003, 2011.
6. Chakrabarty, M.; Kundu, T.; Arima, S.; Harigaya, Y. Tetrahedron Lett. 2005, 46,
2
865.
7. Chakrabarty, M.; Basak, R.; Harigaya, Y.; Takayanagi, H. Tetrahedron 2005, 61,
793.
8. (a) Grehn, L.; Ragnarsson, U. Angew. Chem., Int. Ed. Engl. 1984, 23, 296;
b) Rawal, V. H.; Cava, M. P. Tetrahedron Lett. 1985, 26, 6141.
9. (a) Dhanak, D.; Reese, C. B. J. Chem. Soc., Perkin Trans. 1 1986, 2181;
b) Clark, R. D.; Muchowski, J. M.; Souchet, M.; Repke, D. B. Synlett 1990,
1
1
1
1
(
(
207; (c) Shin, S.; Takahashi, N.; Yonezawa, Y. Chem. Pharm. Bull. 1990, 38,
2020; (d) Diep, V.; Dannenberg, J. J.; Franck, R. W. J. Org. Chem. 2003, 68,
7907; (e) Benson, S. C.; Lee, L.; Yang, L.; Snyder, J. K. Tetrahedron 2000, 56,
1165.