Light-sensitive protecting groups for amines and alcohols: The photosolvolysis of n-substituted 7-nitroindolines

Article abstract of DOI:10.1055/s-2007-985580

Representative examples of primary and secondary amines were protected as urea derivatives 4 of 5-bromo-7-nitroindoline and even more efficiently as ureas 8 derived from 5,7-dinitroindoline, via high-yield reactions with carbamoyl chlorides 3 and 7, respectively. Deprotection of 4 or 8 was achieved in high yields by UV irradiation at room temperature in Pyrex vessels under neutral conditions and exclusion of air. In a similar manner the dinitroindolines serve as protecting groups for alcohols and phenols; the derived carbamates 5 and 9 can likewise be deprotected photochemically in high yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-985580

LETTER
2405
Light-Sensitive Protecting Groups for Amines and Alcohols:
The Photosolvolysis of N-Substituted 7-Nitroindolines
P
hotosolvolysis of
l
N-Sub
f
stituted-7
r
-Nitroin
e
dolines d Hassner,*a Diana Yagudayev,a Tarun K. Pradhan,a Abraham Nudelman,a Boaz Amitb
a
Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel
Fax +972(3)7384053; E-mail: hassna@mail.biu.ac.il
b
ProChon Biotech Ltd., Weizmann Science Park, Nes Ziona, 70400, Israel
Received 6 June 2007
philic attack. However, unlike o-nitrobenzyl derivatives,
the photochemistry of the 7-nitroindoline group appears
to involve hydrolysis of a very reactive acyl nitronate
intermediate A6–8 in the presence of water (Scheme 1). To
Abstract: Representative examples of primary and secondary
amines were protected as urea derivatives 4 of 5-bromo-7-nitro-
indoline and even more efficiently as ureas 8 derived from 5,7-di-
nitroindoline, via high-yield reactions with carbamoyl chlorides 3
and 7, respectively. Deprotection of 4 or 8 was achieved in high achieve an efficient synthesis of the required 7-nitroindo-
yields by UV irradiation at room temperature in Pyrex vessels under
lines and to ensure regioselective nitration at the C-7
neutral conditions and exclusion of air. In a similar manner the di-
position, it is common to have a substituent at C-5, (usu-
nitroindolines serve as protecting groups for alcohols and phenols;
ally Br, CH2CO2R, or NO2), and in some cases also a
the derived carbamates 5 and 9 can likewise be deprotected photo-
methoxy group at C-4.8
chemically in high yields.
Key words: alcohols, amines, protecting groups, photochemistry,
ureas, carbamates, indolines
Br
Br
hν
N
N
H2O
+
_
N
O
R
Facile protection and deprotection of functional groups
are important steps in synthesis and manipulation of
synthetic organic compounds and natural products. Fre-
quently, only the proper selection of protecting groups
combined with a good synthetic strategy can lead to a suc-
cessful total synthesis.1 Among various protecting groups,
photochemical deprotection offers the important
advantage of neutral conditions and absence of chemical
reagents.2
NO2
O
O
O
R
A
Br
RCOOH
+
N
H
NO2
2
In 1973, Amit and Patchornik reported the photolysis of
amides, derived from N-substituted o-nitroanilides, to fur-
nish free carboxylic acids in high yields.3 The photocleav-
age of the above amides formally follows the known
photoreduction reactions of aromatic nitro compounds
bearing substituents at the ortho position, where an oxy-
gen atom is transferred from the nitro group to the ortho
substituents.4 As a result of this rearrangement to the
oxygenated ortho substituent, o-nitrosoaniline and often
other photo side products were formed, which can inter-
fere with the isolation and purity of the product. To
improve the outcome of the photolysis, another light-sen-
sitive protecting group of carboxylic acids was devel-
oped.5 UV irradiation of amides, derived from 5-bromo-7-
nitroindoline, in the presence of water, furnished the free
carboxylic acids and the starting nitroindolines in good
yields, as shown in Scheme 1.
Scheme 1
Over the years 5-bromo-7-nitroindoline (BNI) has been
used in a wide range of reactions including peptide syn-
thesis.9 Corrie et al. used the BNI group as a photocleav-
able (caged) precursor for releasing of neuroactive amino
acids, such as L-glutamate, in neutral aqueous solution.10
Furthermore, Corrie’s group examined the mechanism of
photolysis of N-acyl-7-nitroindolines and the finding that
in aqueous solution the photoproduct was 7-nitrosoindole,
implying a change in mechanism.6,11 Nicolaou et al.7 car-
ried out the photocleavage of the carboxyl functionality in
the presence of primary and secondary amines, which led
to amides in high yields. They also demonstrated for the
first time an intramolecular photo-induced cyclorelease
with a number of resins based on BNI urea derivatives.7
Bochet et al.8 described a photochemical protection of
amines as amides or as carbamates in neutral medium
using 7-dinitroindolines as substrates. Despite this com-
prehensive research and development in the use of the
photocleavable 7-nitroindoline group, its use was focused
mostly on protecting and/or activating the carboxylic acid
function.
By contrast with o-nitroanilides, the 7-nitroindoline
amides were cleaved by photosolvolysis. Undeniably, the
excited 7-nitro group activates the amide bond to nucleo-
SYNLETT 2007, No. 15, pp 2405–2409
1
7
.0
9
.2
0
0
7
Advanced online publication: 13.08.2007
DOI: 10.1055/s-2007-985580; Art ID: G18107ST
© Georg Thieme Verlag Stuttgart · New York

2406
A. Hassner et al.
LETTER
Amino functions are generally protected by conversion First, the BNI group 2, prepared by hydrolysis of N-
into amides and carbamates, which often do not provide acetyl-5-bromoindoline 1,3 was coupled via its carbamoyl
sufficient resistance to basic or acidic reaction conditions. chloride 3 with amines and alcohols (Scheme 2). The urea
Therefore a stronger bond, such as found in ureas, would derivatives 4a and 4b were obtained in good yields
be advantageous as a protecting group for the amino (Scheme 2, Table 1) from benzylamine and pyrrolidine,
moiety. On the other hand, the stability of ureas towards respectively, and we were able to cut down significantly
solvolytic conditions requires the use of rather vigorous the amounts of amine and DMAP to 10 equivalents. Still
conditions for its chemical cleavage. Hence, photolytic the aromatic amine, p-tert-butylaniline, was not nucleo-
cleavage of ureas would provide a specific and mild philic enough to react with 3 and had to be converted first
method for their deprotection under neutral conditions. into its amide anion by means of n-BuLi. Ureas 4 were
This may be of particular importance in photoresists or stable to dilute acid or base at room temperature.
UV curing of polymers.12 Except for the study by Nico-
The carbamate derivatives 5a–d were synthesized in over
90% yield by reaction of 3 with 2 equivalents of alcohols
by the same method as the urea derivatives 4 (Scheme 2,
Table 1).
Photolysis of ureas 4a–c, first attempted as reported3 for
amides 1, in a Rayonet apparatus with 350 nm lamps, re-
laou et al.,7 using diamines, there have been no attempts
for protection and deprotection of simple amines via urea
derivatives. Furthermore, there apparently are no compre-
hensive reports where 7-nitroindoline carbamates were
used as photolabile protecting groups of alcohols.
We describe herein the efficient use of the 7-nitroindoline
quired several days. Much more efficient for us was a 150
group as a photocleavable protecting group of amines or
W UV Hanau lamp, placing the samples in Pyrex tubes
alcohols, under neutral conditions, via urea or carbamate
approximately 1–1.5 cm from the UV lamp. Furthermore,
derivatives, respectively.
removal of air prior to the irradiation was important and
Initial studies to obtain BNI ureas 4 from corresponding was carried out by bubbling argon for one hour into the
carbamates 5 by reaction with amines were disappointing. solution of the urea in degassed dichloromethane–diox-
When we tried direct functionalization of BNI 2 under ane–water (8·10–2 M). The photoreactions were monitored
mild conditions by means of 4-nitrophenyl chloroformate by UV, since the product BNI 2 displays a maximum at
at room temperature mainly starting material was ob- much longer wavelengths (ca. 440 nm) than the parent
tained.13 This is apparently because the 7-nitro substituent ureas or carbamates (ca. 360 nm) as shown in Figure 1 and
diminishes reactivity at the indoline N, both by electron Figure 2.
withdrawal and steric hindrance. This was also apparent
After the irradiation, the products were purified by chro-
by the fact that carbamate 5a, which we finally obtained
matography to furnish indoline 2 (no nitroso product was
by reaction of 5-bromoindoline with 4-nitrophenyl
detected) and the free amines RNR1H or alcohols ROH in
chloroformate, followed by nitration, reacted only
high yields as shown in Table 1. Photolysis of carbamates
sluggishly with benzylamine. Since subsequent nitration
5 required less time (7–9 h) than photolysis of ureas 4
(12–14 h).
of carbamates or ureas derived from 5-bromoindoline is
not a desirable pathway for protection of alcohols or
amines, we adopted carbamoyl chloride 3 as our starting
Though we had been able to scale down the large excess
of amine as well as of DMAP from 50 to 10 equivalents in
point for the preparation of ureas 4 (see Scheme 2), in
the synthesis of the ureas 4, we felt that the more electron-
spite of the fact that reaction of 3 with ethylene diamine7
poor and more readily prepared 5,7-dinitroindoline 613
may offer an advantage. Indeed, reaction of the acid
required 50 equivalents of the diamine.
Br
Br
Br
Br
d
c
a, b
N
N
N
63–89%
94%
R
N
H
93%
N
R
Cl
NO2
NO2
R1
NO2
O
O
O
2
3
1
4a, R1 = H; R = PhCH2
4b, R, R1 = (CH2)4
b, e, a
40%
f
89–93%
Br
4c, R1 = H; R = p-t-BuC6H4
hν
88–89%
5a, R = p-NO2C6H4
N
hν
90–92%
R
O
RNHR1
NO2
O
ROH
5b, R = PhCH2
5c, R = p-MeC6H4CH2
5d, R = o-(TBS-OCH2)C6H4
Scheme 2 Reagents: (a) NaNO3, TFA; (b) 20% HCl, MeOH; (c) triphosgene, pyridine, CH2Cl2; (d) RR1NH, CH2Cl2, 4-DMAP or BuLi;
(e) ClCOOC6H4NO2; (f) ROH, CH2Cl2, 4-DMAP.
Synlett 2007, No. 15, 2405–2409 © Thieme Stuttgart · New York

LETTER
Photosolvolysis of N-Substituted 7-Nitroindolines
2407
Table 1 Synthesis and Photolysis of 4, 5, 8, and 9 by Protection and
Photodeprotection of Amines and Alcohols in the Presence of Water
at Room Temperaturea
Protection
Deprotection (hn)
Compound PR1NH
or ROH
Yield Time Yield (RNR1H
(%)
(h)
or ROH)
NH2
4a
89
13
89
NH
4b
4c
87
63
12
14
88
88
Figure 1 UV Spectra of the irradiation product of urea 4 at various
reaction times (2.6·10–5 M, CH2Cl2).
t-Bu
NH2
OH
5b
5c
93
91
8
9
90
90
OH
OH
OTBS
5d
89
7
92
NH2
8a
8b
98
96
5
5
95
93
EtO2C
NH2
H2NOC
HO
Figure 2 UV Spectra of the irradiation product of carbamate 5 at
various reaction times (2.6·10–5 M, CH2Cl2).
NH2
8c
95
90
6
4
90
87
MeO2C
chloride 7, the analogue of 3 synthesized from 6 and tri-
phosgene, proceeded readily with a number of amines,
including amino acid derivatives, requiring only 1 equiv-
alent of amine and 1.5–2.5 equivalents of DMAP and
producing ureas 8a–e in high yield (Scheme 3, Table 1).
The reaction proceeded even with an aromatic amine
(p-methoxyaniline) without requiring conversion into its
lithio derivative. In a similar manner we obtained carb-
amates 9a–d by reaction of a number of alcohols and a
phenol in high yield. It is noteworthy that the amino alco-
hol, serine methyl ester, furnished exclusively the urea
derivative 8c via reaction of the more nucleophilic amine.
NH
8d
MeO
NH2
8e
9a
9b
87
80
87
7
3
3
80
92
90
Me(CH2)6CH2OH
OH
OH
9c
85
95
2
2
88
90
Photocleavage of the 5,7-dinitroindoline ureas 8a–e and
carbamates 9a–d proceeded under neutral conditions at
room temperature for 2–7 h in Pyrex tubes in the presence
of water and was followed by UV as described for ana-
logues 4 and 5 to provide pure free amines and alcohols,
respectively, in excellent yields (see Table 1). Further-
more, the photolysis of the 5,7-dinitro derivatives re-
quired less time than for the 5-bromo-7-nitro derivatives.
OH
9d
OTBS
a Compounds 4 were prepared using 10 equiv of amine, 5 using 2
equiv of alcohol, while for 8 or 9 1 equiv of amine or alcohol was
used.
In conclusion, the 5-bromo-7-nitroindoline moiety 2 was
successfully used to protect primary and secondary ali-
phatic amines and an aromatic amine, in good yields, as
urea derivatives 5. Deprotection of 4 was achieved photo-
chemicaly in high yield at room temperature in Pyrex
vessels under neutral conditions and exclusion of air. In a
similar manner protection and deprotection of alcohols
was carried out via carbamates 5. However, since forma-
tion of the urea derivatives 4 necessitated 10 equivalents
of the amine, a more efficient protecting group was found
to be 5,7-dinitroindoline 7, which required only one
Synlett 2007, No. 15, 2405–2409 © Thieme Stuttgart · New York

2408
A. Hassner et al.
LETTER
O2N
O2N
O2N
c
b
80–95%
N
N
90–98%
N
R
R
O
R
N
NO2
O
NO2
NO2
R1
O
6, R = H
8a, R1 = H; R = EtO2C-CH2
8b, R1 = H; R = H2N(O)C-CH(Me)
8c, R1 = H; R = HOCH2CH(COOMe)
8d, R, R1 = (CH2)5
a
9a, R = (CH2)7CH3
9b, R = Cyclopentyl
9c, R = PhCH2
95%
7, R = COCl
9d, R = o-(TBS-OCH2)C6H4
8e, R1 = H; R = p-MeOC6H4
hν
hν
ROH
88–92%
80–95%
RNHR1
Scheme 3 Reagents: (a) triphosgene, pyridine, CH2Cl2; (b) RR1NH, 4-DMAP, CH2Cl2; (c) ROH, 4-DMAP, CH2Cl2.
yellow oil (93% yield). 1H NMR (CDCl3): d = 7.76 (m, 1 H), 7.49
(m, 1 H), 7.38–7.34 (m, 5 H), 5.19 (s, 2 H, CH2O), 4.24 (t, J = 7.7
Hz, 2 H, CH2N), 3.15 (t, J = 7.7 Hz, 2 H, CH2CH2N). 13C NMR
(CDCl3): d = 154.1, 143.5, 139.9, 136.5, 135.1, 130.3, 128.5, 127.9,
127.6, 123.4, 116.5, 65.9, 45.6, 24.3. HRMS: m/z calcd for
C16H13BrN2O4: 377.1921; found: 377.191 [M]+.
equivalent of amine. In this manner 5,7-dinitroindoline
urea and carbamate derivatives 8 and 9 were readily pre-
pared. Photolysis of ureas 8 and carbamates 9 furnished
free amines, amino acid derivatives, and alcohols, respec-
tively, in high yield under mild and neutral conditions.
5,7-Dinitroindoline-1-carbonyl Chloride (7)
A solution of dinitroindoline 68 (1.05 g, 5 mmol), pyridine (0.8 mL,
10 mmol), and triphosgene (1 g, 5 mmol) in anhyd CH2Cl2 (50 mL)
was stirred for 24 h at r.t. The mixture was washed with 5% HCl (3
× 30 mL), H2O, and dried (Na2SO4). The residue left after removal
of solvent under reduced pressure was sufficiently pure for the next
5-Bromo-7-nitroindoline-1-carbonyl Chloride (3)
To a solution of nitroindoline 2 (1.00 g, 4.1 mmol) and pyridine
(0.66 mL, 2 equiv) in CH2Cl2 (15 mL) at 0 °C, triphosgene (0.40 g,
1/3 equiv) was added. The mixture was then allowed to warm to r.t.
for ca. 30 min and was washed with 1 N HCl, diluted with CH2Cl2,
dried over MgSO4, and concentrated to give 3 as an orange powder
1
step. Yield 95%; mp 158–159 °C. H NMR (300 MHz, CDCl3):
d = 8.58 (d, J = 1.8 Hz, 1 H), 8.28 (d, J = 1.8 Hz, 1 H), 4.59 (t,
J = 8.4 Hz, 2 H, CH2N), 3.44 (t, J = 8.4 Hz, 2 H, CH2CH2). 13C
NMR (300 MHz, CDCl3): d = 147.0, 143.8, 139.4, 139.4, 138.0,
124.0, 120.0, 53.8, 27.9. HRMS (CI, CH4): m/z (%) calcd for
C9H6ClN3O5: 271.000; found: 270.998 (82) [M]+, 209.023 (100)
[MH – COCl]+.
1
(1.18 g, 94% yield), mp 121–122 °C. H NMR (CDCl3): d = 7.75
(m, 1 H), 7.53 (m, 1 H), 4.40 (t, J = 5.9 Hz, 2 H), 3.20 (t, J = 5.9 Hz,
2 H). 13C NMR (CDCl3): d = 146.8, 139.1, 132.6, 132.6, 132.36,
125.9, 118.2, 53.3, 28. Due to the high moisture sensitivity of 3, no
HRMS was obtained.
General Procedure for the Synthesis of Ureas 4
General Procedure for the Synthesis of Dinitrocarbamates 8
An amine (1 equiv) was added to the stirred mixture of 7 (1 equiv)
and 4-DMAP (1.5–2.5 equiv) in anhyd CH2Cl2. The mixture was
stirred at r.t. for 1–5 h, then washed with 5% HCl solution, H2O, and
dried (Na2SO4).
To a solution of 3 (1.10 g, 3.6 mmol) in CH2Cl2 (15 mL), amine (10
equiv), and 4-DMAP (10 equiv) were added and the mixture was
stirred in the dark overnight at r.t. It was then washed with 3% HCl
and 3% NaHCO3 solution, extracted with CH2Cl2, dried over
MgSO4, and concentrated in vacuo. The residue was crystallized
from CHCl3 to get pure compound 4.
2-[(1-Carbamoyl-5,7-dinitroindoline)]-3-hydroxypropionic
Acid Methyl Ester (8c)
1-(Benzylcarbamoyl)-5-bromo-7-nitroindoline (4a)
Synthesized from L-serine methyl ester hydrochloride (1.55 g, 10
mmol), compound 7 (2.71 g, 10 mmol), and 4-DMAP (3 g, 25
mmol) in anhyd CH2Cl2 (30 mL). The residue after removal of sol-
vent afforded pure 8c in 95% yield; mp 169 °C. 1H NMR (300 MHz,
acetone-d6): d = 8.46 (d, J = 2.4 Hz, 1 H), 8.30–8.29 (m, 1 H), 6.95
(d, J = 7.8 Hz, 1 H, NHCH), 4.57–4.42 (m, 3 H), 4.29 (s, 1 H, OH),
3.97 (dd, J = 11.0, 4.5 Hz, 1 H, CH2O), 3.87 (dd, J = 11.0, 4.5 Hz,
Synthesized from 3 and benzylamine in 89% yield; mp 182–183 °C.
1H NMR (CDCl3): d = 7.82 (m, 1 H), 7.46 (m, 1 H), 7.36–7.31 (m,
5 H), 5.02 (br s, 1 H, NH), 4.48 (d, J = 6.5 Hz, 2 H), 4.13 (t, J = 8.1
Hz, 2 H), 3.24 (t, J = 8.1 Hz, 2 H). 13C NMR (CDCl3): d = 161.3,
142.4, 142.2, 138.3, 131.7, 128.9, 127.9, 127.84, 125.8, 120.5,
50.58, 45, 28.8. HRMS: m/z calcd for C16H14BrN3O3: 375.0232;
found: 375.023 [M]+ .
1 H, CH2O), 3.71 (s, 3 H, CH3O), 3.50–3.41 (m, 2 H, CH2CH2). 13
C
NMR (300 MHz, acetone-d6): d = 171.5, 155.4, 143.3, 142.5, 139.6,
137.9, 123.9, 120.4, 62.9, 57.1, 52.5, 52.2, 28.7. HRMS (CI, CH4):
m/z (%) calcd for C13H14N4O8: 354.081; found: 355.087 (12)
[MH]+.
General Procedure for the Synthesis of Carbamates 5
To a solution of 3 (1.10 g, 3.6 mmol) in CH2Cl2 (15 mL), alcohol (2
equiv), and 4-DMAP (2 equiv) were added and the reaction mixture
was left in the dark overnight at r.t. It was then washed with 3% HCl
and 3% NaHCO3 solution, extracted with CH2Cl2, dried over
MgSO4, and concentrated.
General Procedure for the Synthesis of Dinitrocarbamates 9
A respective alcohol (1 equiv) was added to the stirred solution of 7
(1 equiv) and 4-DMAP (1.2 equiv) in anhyd CH2Cl2. The mixture
was stirred at r.t. for 3–8 h, then washed with 5% HCl solution, H2O,
and dried (Na2SO4).
1-Benzyloxycarbonyl-5-bromo-7-nitroindoline (5b)
Synthesized from 3 and benzyl alcohol. The crude carbamate was
chromatographed on silica gel (EtOAc–hexane, 7:1) to get 5b as a
Synlett 2007, No. 15, 2405–2409 © Thieme Stuttgart · New York

LETTER
Photosolvolysis of N-Substituted 7-Nitroindolines
2409
5,7-Dinitroindoline-1-carboxylic Acid 2-(tert-Butyldimethyl-
silanyloxymethyl)phenyl Ester (9d)
References and Notes
Synthesized from 2-(tert-butyldimethylsilanyloxy-methyl)phenol14
(2.38 g, 10 mmol), 7 (2.71 g, 10 mmol), and 4-DMAP (1.46 g, 12
mmol) in anhyd CH2Cl2 (30 mL) at r.t. for 3 h. The residue afforded
after removal of solvent pure 9d in 95% yield; mp 161–162 °C. 1H
NMR (300 MHz, CDCl3): d = 8.58 (d, J = 1.5 Hz, 1 H), 8.28 (d,
J = 1.5 Hz, 1 H), 7.54–7.51 (m, 1 H), 7.33–7.26 (m, 2 H), 7.16–7.12
(m, 1 H), 4.73 (s, 2 H, CH2O), 4.57 (t, J = 8.4 Hz, 2 H, CH2N), 3.41
(t, J = 8.4 Hz, 2 H, CH2CH2), 0.91 (s, 9 H, CCH3), 0.084 (s, 6 H,
SiCH3). 13C NMR (300 MHz, CDCl3): d = 150.8, 147.4, 143.3,
140.2, 138.3, 133.2, 128.2, 128.2, 126.7, 123.5, 123.3, 121.6, 120.2,
60.4, 50.8, 28.1, 25.8, 18.3, –5.3. HRMS (CI, CH4): m/z (%) calcd
for C22H27N3O7Si: 473.162; found: 473.168 (13) [M]+, 416.091 (66)
[M – tBu]+.
(1) (a) Kocienski, P. J. Protecting Groups, 3rd ed.; Thieme:
New York, 2004. (b) Greene, T. W.; Wuts, P. G. Protective
Groups in Organic Synthesis, 3rd ed.; Wiley: New York,
1999, 369. (c) Greene, T. W.; Wuts, P. G. Protective Groups
in Organic Synthesis, 3rd ed.; Wiley: New York, 1999, 494.
(2) See: Bochet, C. G. J. Chem. Soc., Perkin Trans. 1 2002, 125;
and references cited therein.
(3) Amit, B.; Patchornik, A. Tetrahedron Lett. 1973, 24, 2205.
(4) Morisson, H. A. The Chemistry of the Nitro and Nitroso
Groups, Part 1; Feuer, H., Ed.; Interscience: New York,
1970, 185.
(5) Amit, B.; Ben-Efraim, D. A.; Patchornik, A. J. Am. Chem.
Soc. 1976, 98, 843.
(6) Papageorgiou, G.; Ogden Barth, A.; Corrie, J. E. T. D. C.
J. Am. Chem. Soc. 1999, 121, 6503.
(7) Nicolaou, K. C.; Safina, B. S.; Winssinger, N. Synlett 2001,
900.
(8) (a) Helgen, C.; Bochet, C. G. J. Org. Chem. 2003, 68, 2483.
(b) Helgen, C.; Bochet, C. G. Synlett 2001, 1968.
(9) Papageorgiou, G.; Corrie, J. E. T. Tetrahedron 2000, 56,
8197.
(10) Pass, S.; Amit, B. J. Am. Chem. Soc. 1981, 103, 7674.
(11) Morrison, J.; Wan, P.; Corrie, J. E. T.; Papageorgiou, G.
Photochem. Photobiol. Sci. 2002, 1, 960.
(12) See, for instance: (a) Frechet, J. M. J.; Cameron, J. F.;
Chung, C. M.; Haque, S. A.; Willson, C. G. Polym. Bull.
(Berlin) 1993, 30, 369. (b) Beecher, J. E.; Cameron, J. F.;
Frechet, J. M. J. J. Mat. Chem. 1992, 2, 811.
(13) Previously, carbamate derivatives of 7-nitroindolines have
been obtained by prior deprotonation with NaH (ref. 8).
(14) Sefkow, M.; Kaatz, H. Tetrahedron Lett. 1999, 40, 6561.
General Procedure for Deprotection of Urea and Carbamate
Derivatives 4, 5, 8, or 9 by Irradiation
The respective carbamate or urea derivative (300–400 mg) in
CH2Cl2–dioxane–H2O (5:10:1) at a concentration of 8·10–2 M was
deoxygenated by bubbling argon into the mixture for 1 h followed
by irradiation at r.t. with a 150 W UV Hanau lamp in Pyrex tubes at
a distance of 1–1.5 cm from the UV lamp for the time indicated in
Table 1. Free amines, alcohols, and nitroindolines (no nitrosoindole
derivatives were observed) were isolated by silica gel chromatogra-
phy of the crude products, after removal of solvent under reduced
pressure, and identified by comparison with authentic compounds.
Acknowledgment
Support of this research by the Marcus Center for Medicinal and
Pharmaceutical Chemistry at Bar-Ilan University is gratefully ack-
nowledged.
Synlett 2007, No. 15, 2405–2409 © Thieme Stuttgart · New York

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