Selective conversion of N-trichloroethoxycarbonyl (Troc) groups into N-acetyl groups in the presence of N-tert-butoxycarbonyl (Boc) protecting groups

Article abstract of DOI:10.1055/s-2003-39405

Deprotection of N-trichloroethoxycarbonyl (Troc) groups with zinc in acetic anhydride cleaves also N-tert-butoxycarbonyl (Boc) groups, thus liberating the amino groups, which are immediately N-acetylated. When this reaction is performed in the presence of triethylamine only Troc groups are selectively cleaved as demonstrated for several examples.

Full text of DOI:10.1055/s-2003-39405

1262
PAPER
Selective Conversion of N-Trichloroethoxycarbonyl (Troc) Groups into
N-Acetyl Groups in the Presence of N-tert-Butoxycarbonyl (Boc) Protecting
Groups
S
elective Conversi
i
onof
N
a
-Trichlor
o
n
ethoxycarbon
g
yl
G
roups in
m
to
N
-Acetyl
G
roup
i
ng Zhu, Richard R. Schmidt*
Fachbereich Chemie, Universität Konstanz, Fach M 725, 78457 Konstanz, Germany
Fax +49(7531)883135; E-mail: Richard.Schmidt@uni-konstanz.de
Received 19 February 2003; revised 2 April 2003
Abstract: Deprotection of N-trichloroethoxycarbonyl (Troc)
groups with zinc in acetic anhydride cleaves also N-tert-butoxycar-
bonyl (Boc) groups, thus liberating the amino groups, which are im-
mediately N-acetylated. When this reaction is performed in the
presence of triethylamine only Troc groups are selectively cleaved
as demonstrated for several examples.
Key words: protecting groups, orthogonality, cleavage, zinc,
amines
Protecting groups play a central role in modern organic
synthesis,1 and the selective removal or conversion of one
protecting group in the presence of another is of critical
importance in many synthetic sequences. The more selec-
tively a protecting group can be removed, the more useful
it becomes. We report herein an efficient procedure for the
selective conversion of N-trichloroethoxycarbonyl (Troc)
groups into N-acetyl groups in the presence of N-Boc pro-
tecting groups.
Among the various amine protecting groups, the Troc
group is one which is frequently used in organic synthe-
sis,1a especially in syntheses with amino sugar deriva-
tives.2 This is due to its stability under mild acidic and
Scheme 1
basic conditions and its ease of removal under specific
conditions; thus, this group is orthogonal to other amino
protecting groups which renders it ideal as a temporary
protecting group.3
Unexpectedly, when 1 was treated with Zn/Ac2O, the side
product 3 was produced in addition to the desired product
2, i.e. the N-Boc group of 1 was removed and the amino
group was converted into an N-acetyl group. Indeed, com-
pound 2 could be isolated from the mixture, but in low
yield, and compound 3 was obtained exclusively if the re-
action time was extended (Scheme 1). In the litera-
ture,2b,3,7 N-Troc groups have been used in combination
with N-Boc groups, but no specific reaction conditions
providing exclusive conversion of N-Troc into N-acetyl
groups in one-pot has been described3,7 or when Zn/Ac2O
was employed,2b the reaction mixture contained presum-
ably already some Et3N from the preceding reaction. We
anticipated that not Zn dust but ZnCl2, which was pro-
duced in situ after cleavage of N-Troc groups in this reac-
tion, cleaved the N-Boc groups. To verify this hypothesis,
compounds 4a and 4b were treated directly with ZnCl2, as
shown in Scheme 2. Expectedly, the N-Boc groups were
indeed removed completely within 2 hours to give the cor-
responding free amine products. Analogous deprotection
of N-Boc groups conducted with ZnBr2 in CH2Cl2 has al-
ready been reported.8
Removal of the N-Troc group can be carried out under a
number of conditions, e.g. with Zn/HOAc,4 Zn and acidic
buffer,5 Zn-Cu couple/HOAc,2c Cd-Pb/HOAc,3 or other
reduction methods. The only condition available for its
one-pot conversion into an N-acetyl group is Zn/
Ac2O.2a,b,6 The N-Boc group can be also selectively re-
moved with trifluoroacetic acid in the presence of N-Troc
groups.
In the course of our studies on the synthesis of glycopep-
tides, we required a mild and efficient method for the
transformation of 1 into 2, as shown in Scheme 1.
Synthesis 2003, No. 8, Print: 05 06 2003.
Art Id.1437-210X,E;2003,0,08,1262,1266,ftx,en;T01603SS.pdf.
© Georg Thieme Verlag Stuttgart · New York

PAPER
Selective Conversion of N-Trichloroethoxycarbonyl Groups into N-Acetyl Groups
1263
Each substrate (1 mmol) was treated under the same con-
ditions; it was dissolved in Ac2O (5 mL) containing Et3N
(2 mmol). Freshly activated Zn dust (20 mmol) was added
and the resulting mixture was sonicated in an ultrasonic
cleaning bath below room temperature until TLC indicat-
ed complete consumption of the starting material.
The results, summarized in Table 1, indicate that under
the above reaction conditions, N-Troc groups can be se-
lectively converted into N-acetyl groups in the presence of
N-Boc protecting groups. Initially, experiments were run
with 1-N-Troc-6-N-Boc-hexadiamine (5). A clean con-
version occurred within 2 hours and the acetamide 109
was obtained in almost quantitative yield without any ef-
fect on the N-Boc group. Excellent yields were also
achieved for the selective conversion of N-Troc into N-
acetyl groups in compounds 6 and 7. Moreover, the stabil-
ity of the N-Boc group under these conditions was con-
firmed when 7 was sonicated for 5 hours and the desired
product 12 was still obtained in 87% yield. The reaction
conditions were again so mild to inhibit the cleavage of
the N-Boc group in 8, even in the presence of two N-Boc
groups, and the -GlcNAc containing glycopeptide 13
was obtained in 81% yield. Notably, the Troc group of
thioglycoside 9 was also selectively converted into 14 in
76% yield under sonication conditions and both the ben-
zylidene and tert-butyl groups survived these conditions.
Scheme 2
In order to inhibit the formation of 3, we considered that
1 might be converted only into 2 if additional base was
present in the mixture to neutralize the ZnCl2 produced
during the course of the reaction . Thus, treatment of 1
with a large excess of Zn dust in Ac2O in the presence of
2 equivalents of Et3N for 8 hours did indeed give the de-
sired glycopeptide 2 in much better yield as indicated on
TLC. Subsequent optimization revealed that the reaction
time could be reduced noticeably from 8 to 3 hours if a
classic ultrasonic cleaning bath was applied instead of a
normal stirrer and 2 was obtained in 87% yield after chro-
matographic purification.
To examine the scope of this procedure, some properly
protected substrates for this purpose were prepared and
subjected to the above sonication conditions (Table 1).
Table 1 Selective Conversion of N-Troc Groups into N-Ac Groups
Substrate
Time (h)
3
Product
Yield (%)
87
2
2
95
Troc-Lys(Boc)-OMe (6)
Ac-Lys(Boc)-OMe (11)10
quant
Troc-Lys(Boc)-Val-OMe (7)
2
5
Ac-Lys(Boc)-Val-OMe (12)
96
87
3
81
2
76
Synthesis 2003, No. 8, 1262–1266 ISSN 1234-567-89 © Thieme Stuttgart · New York

1264
X. Zhu, R. R. Schmidt
PAPER
13C NMR (CDCl3, 62.8 MHz): = 156.0, 154.6, 95.7, 79.1, 74.4,
41.0, 40.2, 30.0, 29.6, 28.4, 26.14, 26.10.
groups in a one-pot reaction, using a very simple ultra- MALDI-MS: m/z = 413.5 [MNa+], 429.6 [MK+].
In summary, N-Troc groups have been selectively con-
verted into N-acetyl groups in the presence of N-Boc
sound treatment with Zn in an Ac2O/Et3N mixture. This
procedure renders the Troc group a versatile temporary
protecting group particularly in peptide and glycopeptide
synthesis.
Anal. Calcd for C14H25Cl3N2O4 (391.7): C, 42.93; H, 6.43; N, 7.24.
Found: C, 42.91; H, 6.35; N, 7.24.
Troc-Lys(Boc)-OMe (6)
[ ]D +3.0 (c = 1.0 CHCl3).
1H NMR (CDCl3, 250 MHz): = 5.70 (d, J = 7.7 Hz, 1 H), 4.74 (AB
peak, J = 12.0 Hz, 2 H), 4.58 (br s, 1 H), 4.38 (m, 1 H), 3.77 (s, 3
H), 3.12 (m, 2 H), 1.92–1.69 (m, 2 H), 1.45 (m, 4 H), 1.44 (s, 9 H).
13C NMR (CDCl3, 62.8 MHz): = 172.3, 156.0, 154.2, 95.2, 78.9,
74.3, 53.8, 52.2, 39.7, 31.5, 29.3, 28.2, 22.1.
The solvents were purified according to the standard procedures.
Petroleum ether used had a bp range 35–80 °C. TLC was performed
on plastic plates coated with silica gel 60 F254. Detection was
achieved by treatment with a solution of ammonium molybdate (20
g) and cerium(IV) sulfate (0.4 g) in 10 or 15% H2SO4 (400 mL), and
heating at 150 °C. Flash chromatography was carried out on silica
gel (Baker 30–60 mm) at a pressure of 0.3–0.4 bar. Optical rotations
were determined at 21 °C with a Perkin-Elmer 241/MC polarimeter
(1 dm cell). NMR spectra were recorded with Bruker AC 250 (250
MHz) instrument by using tetramethylsilane as internal standard.
MS spectra were recorded with a MALDI-compact (Kratos) instru-
ment in the positive mode using 2,5-dihydroxybenzoic acid in diox-
ane as matrix. Elemental analyses were performed in the
Microanalysis unit at the Fachbereich Chemie, Universität Kon-
stanz.
MALDI-MS: m/z = 472.4 [MK+].
Troc-Lys(Boc)-Val-OMe (7)
[ ]D –5.0 (c = 1.0 CHCl3).
1H NMR (CDCl3, 250 MHz): = 6.66 (d, J = 8.5 Hz, 1 H), 5.95 (d,
J = 7.7 Hz, 1 H), 4.72 (m, 3 H), 4.50 (dd, J = 8.8, 4.9 Hz, 1 H), 4.22
(m, 1 H), 3.71 (s, 3 H), 3.09 (m, 2 H), 2.15 (m, 1 H), 1.91–1.62 (m,
2 H), 1.42 (m, 4 H), 1.40 (s, 9 H), 0.88 (t, J = 7.3 Hz, 6 H).
13C NMR (CDCl3, 62.8 MHz): = 172.1, 171.5, 156.0, 154.4, 95.3,
78.9, 74.4, 57.1, 54.8, 52.0, 39.6, 32.0, 30.8, 29.3, 28.3, 22.2, 18.8,
17.6.
N-tert-Butoxycarbonyl-S-[3,4,6-tri-O-acetyl-2-deoxy-2-(2,2,2-
trichloroethoxycarbonylamino)- -D-glucopyranosyl]-L-ho-
mocysteinyl-l-alanine Benzyl Ester (1); Typical Procedure
To a solution of Boc-Hcy-Ala-OBn (440 mg, 1.1 mmol) in 10% aq
Na2CO3 (15 mL) was added a solution of 3,4,6-tri-O-acetyl-2-
deoxy-2-(2,2,2-trichloroethoxycarbonylamino)- -bromo-D-glu-
copyranose (1.1 g, 2.1 mmol) in EtOAc (15 mL). After the addition
of Bu4NHSO4 (1.5 g, 4.4 mmol), the mixture was vigorously stirred
at r.t. for 8 h. The mixture was diluted with EtOAc, washed succes-
sively with sat. aq NaHCO3 and brine, dried (MgSO4) and concen-
trated to give a crude product which was purified by flash column
chromatography (petroleum ether–EtOAc, 2:1→1:1). Compound 1
was obtained as a white solid (850 mg, 90%); [ ]D –20.9 (c = 1.0
CHCl3).
1H NMR (CDCl3, 250 MHz): = 7.40 (m, 5 H), 6.80 (d, J = 7.0 Hz,
1 H), 5.96 (d, J = 10.0 Hz, 1 H), 5.29 (t, J = 9.9 Hz, 1 H), 5.23 (s, 2
H), 5.14 (d, J = 10.0 Hz, 1 H), 5.09 (t, J = 9.5 Hz, 1 H), 4.90 (d,
J = 12.0 Hz, 1 H), 4.68 (m, 3 H), 4.40 (m, 1 H), 4.25 (dd, J = 12.2,
4.6 Hz, 1 H), 4.11 (dd-like, J = 12.4, 2.1 Hz, 1 H), 3.79 (m, 1 H),
3.64 (m, 1 H), 2.90 (m, 1 H), 2.72 (m, 1 H), 2.09, 2.04, 2.02 (3 s, 9
H), 1.90 (m, 1 H), 1.75 (m, 1 H), 1.45 (d, J = 7.8 Hz, 3 H), 1.43 (s,
9 H).
MALDI-MS: m/z = 557.0 [MNa+], 572.9 [MK+].
N -{N-tert-Butoxycarbonyl-S-[3,4,6-tri-O-acetyl-2-deoxy-2-
(2,2,2-trichloroethoxycarbonylamino)- -D-glucopyranosyl]-l-
cysteinyl}-N -tert-butoxycarbonyl-L-lysine Methyl Ester (8)
This compound was prepared following the typical procedure given
for compound 1 in 92% yield; [ ]D –14.1 (c = 1.0 CHCl3).
1H NMR (CDCl3, 250 MHz): = 7.05 (d, J = 6.7 Hz, 1 H), 5.96 (d,
J = 6.1 Hz, 1 H), 5.69 (d, J = 7.0 Hz, 1 H), 5.25 (t, J = 9.9 Hz, 1 H),
5.09 (t, J = 9.8 Hz, 1 H), 4.75 (m, 4 H), 4.52 (m, 1 H), 4.41 (m, 1
H), 4.23 (m, 2 H), 3.80 (m, 2 H), 3.78 (s, 3 H), 3.06 (m, 4 H), 2.10,
2.04, 2.02 (3 s, 9 H), 1.80 (m, 2 H), 1.46, 1.44 (2 s, 18 H), 1.42 (m,
4 H).
13C NMR (CDCl3, 62.8 MHz): = 172.3, 170.6, 170.4, 170.3,
169.3, 156.0, 155.2, 154.3, 95.4, 84.8, 80.3, 79.1, 76.0, 74.4, 73.2,
68.5, 62.3, 54.8, 54.3, 52.5, 52.2, 40.1, 32.5, 31.6, 29.3, 28.4, 28.2,
20.6, 20.5.
MALDI-MS: m/z = 947.9 [MNa+].
Anal. Calcd for C35H55Cl3N4O16S (926.2): C, 45.39; H, 5.98; N,
6.05. Found: C, 45.58; H, 5.99; N, 5.99.
13C NMR (CDCl3, 62.8 MHz): = 172.7, 171.3, 170.6, 170.3,
169.2, 155.4, 154.1, 135.1, 128.4, 128.2, 127.9, 95.4, 84.5, 79.9,
75.6, 74.2, 73.2, 68.5, 67.1, 62.0, 54.9, 52.5, 48.0, 32.5, 28.1, 26.7,
20.5, 20.4, 17.5.
Phenyl 4,6-O-Benzylidene-3-O-(N-tert-butoxycarbonyl-O-tert-
butyl-L-threonyl)-2-deoxy-2-(2,2,2-trichloroethoxycarbonyl-
amino)-1-thio- -D-glucopyranoside (9)
Prepared by coupling Boc-Thr(t-Bu)-OH with the corresponding
sugar under the known DCC/HOBt condition in 71% yield; [ ]D
–31.1 (c = 1.0 CHCl3).
MALDI-MS: m/z = 897.5 [MK+].
Preparation of 5, 6 and 7; General Procedure
1H NMR (CDCl3, 250 MHz): = 7.53–7.30 (m, 10 H), 6.10 (d,
J = 6.8 Hz, 1 H), 5.72 (t, J = 9.3 Hz, 1 H), 5.65 (d, J = 10.4 Hz, 1
H), 5.50 (s, 1 H), 5.29 (d, J = 8.3 Hz, 1 H), 4.83, 4.65 (AB peak,
J = 12.0 Hz, 2 H), 4.38 (m, 1 H), 4.10 (m, 2 H), 3.81 (t, J = 9.7 Hz,
1 H), 3.70 (m, 2 H), 3.11 (m, 1 H), 1.44 (d, J = 4.7 Hz, 9 H), 1.16
(d, J = 6.3 Hz, 3 H), 0.87 (s, 9 H).
To a stirred solution of the appropriate free amine (1.0 mmol) in an-
hyd CH2Cl2 (15 mL) was added TrocCl (0.2 mL) followed by N,N-
diisopropylethylamine (0.35 mL). The mixture was stirred for 2 h at
r.t., and then the solvent was evaporated. The residue was purified
by flash column chromatography (petroleum ether–EtOAc) to give
the corresponding N-Troc protected compound.
MALDI-MS: m/z = 813.6 [MNa+], 829.6 [MK+].
N-(tert-Butoxycarbonyl)-N -(2,2,2-trichloroethoxycarbon-
yl)hexane-1,6-diamine (5)
Anal. Calcd for C35H45Cl3N2O10S (792.2): C, 53.07; H, 5.73; N,
3.54. Found: C, 53.24; H, 6.07; N, 3.86.
1H NMR (CDCl3, 250 MHz): = 5.15 (br s, 1 H), 4.73 (s, 2 H), 4.57
(br s, 1 H), 3.23 (q, J = 6.6 Hz, 2 H), 3.10 (m, 2 H), 1.60–1.33 (m,
8 H), 1.44 (s, 9 H).
Synthesis 2003, No. 8, 1262–1266 ISSN 1234-567-89 © Thieme Stuttgart · New York

PAPER
Selective Conversion of N-Trichloroethoxycarbonyl Groups into N-Acetyl Groups
1265
N-Acetyl-S-(3,4,6-tri-O-acetyl-2-acetamido-2-deoxy- -D-glu-
copyranosyl)-L-homocysteinyl-L-alanine Benzyl Ester (3)
Glycoside 1 (1.2 g, 1.4 mmol) was dissolved in Ac2O (17 mL),
freshly activated Zinc dust (0.4 g) was added, and the suspension
was stirred for 8 h. The mixture was filtered through Celite and the
filtrate was concentrated under vacuo to give the crude product. Pu-
rification by flash column chromatography (EtOAc–MeOH, 15:1)
afforded 3 (793 mg, 85%) as a white amorphous solid; [ ]D –39.5
(c = 1.0 CHCl3–MeOH, 1:1).
Ac-Lys(Boc)-OMe (11)10
[ ]D +12.0 (c = 1.0 CHCl3).
1H NMR (CDCl3, 250 MHz): = 6.28 (d, J = 7.2 Hz, 1 H), 4.60 (m,
2 H), 3.75 (s, 3 H), 3.10 (q like, 2 H), 2.04 (s, 3 H), 1.91–1.65 (m, 2
H), 1.44 (s, 9 H), 1.40 (m, 4 H).
13C NMR (CDCl3, 62.8 MHz): = 172.9, 170.2, 156.0, 78.7, 52.0,
51.8, 39.7, 31.4, 29.3, 28.1, 22.6, 22.2.
MALDI-MS: m/z = 324.8 [MNa+], 340.8 [MK+].
1H NMR (CDCl3/CD3OD, 250 MHz): = 8.10 (d, J = 6.8 Hz, 1 H),
7.76 (d, J = 8.9 Hz, 1 H), 7.61 (d, J = 8.0 Hz, 1 H), 7.35 (m, 5 H),
5.25 (t, J = 9.7 Hz, 1 H), 5.19 (m, 2 H), 5.08 (t, J = 9.6 Hz, 1 H),
4.82 (d, J = 10.5 Hz, 1 H), 4.53 (m, 2 H), 4.25 (dd, J = 12.4, 4.4 Hz,
1 H), 4.13 (m, 1 H), 3.93 (t, J = 10.3 Hz, 1 H), 3.77 (m, 1 H), 2.72
(m, 2 H), 2.08, 2.04, 2.01, 1.95 (4 s, 15 H), 1.95 (m, 2 H), 1.46 (d,
J = 7.3 Hz, 3 H).
Ac-Lys(Boc)-Val-OMe (12)
[ ]D –22.1 (c = 1.0 CHCl3).
1H NMR (CDCl3, 250 MHz): = 6.66 (d, J = 8.3 Hz, 1 H), 6.35 (d,
J = 7.5 Hz, 1 H), 4.74 (br s, 1 H), 4.49 (m, 2 H), 3.75 (s, 3 H), 3.12
(m, 2 H), 2.20 (m, 1 H), 2.03 (s, 3 H), 1.80 (m, 2 H), 1.45 (m, 4 H),
1.44 (s, 9 H), 0.92 (t, J = 6.8 Hz, 6 H).
13C NMR (CDCl3, 62.8 MHz): = 172.4, 171.6, 171.5, 171.3,
171.0, 170.7, 169.6, 135.1, 128.3, 128.1, 127.8, 83.6, 75.3, 73.6,
68.4, 66.9, 62.0, 53.0, 51.3, 48.0, 31.9, 26.0, 22.3, 22.2, 20.3, 20.2,
16.7.
13C NMR (CDCl3, 62.8 MHz): = 172.4, 171.9, 170.3, 156.0, 78.7,
57.4, 52.7, 51.9, 39.8, 31.9, 30.4, 29.3, 28.2, 22.7, 22.2, 18.8, 17.6.
MALDI-MS: m/z = 424.0 [MNa+], 440.1 [MK+].
Anal. Calcd for C19H35N3O6 (401.5): C, 56.84; H, 8.79; N, 10.47.
Found: C, 56.61; H, 8.79; N, 10.41.
MALDI-MS: m/z = 689.8 [MNa+], 705.9 [MK+].
Anal. Calcd for C30H41N3O12S·3H2O (721.8): C, 49.92; H, 5.73; N,
5.82. Found: C, 49.77; H, 5.86; N, 6.05.
N -[N-tert-Butoxycarbonyl-S-(3,4,6-tri-O-acetyl-2-acetamido-
2-deoxy- -D-glucopyranosyl)-L-cysteinyl]-N -tert-butoxycarbo-
nyl-L-lysine Methyl Ester (13)
Selective Conversion of N-Troc Groups into N-Ac Groups;
General Procedure
[ ]D –31.1 (c = 1.0 CHCl3).
Freshly activated Zn dust (0.65 g) was added to a solution of the ap-
propriate N-Troc derivative (0.5 mmol) in Ac2O (6 mL) containing
Et3N (0.14 mL). The reaction vessel was then sonicated in a classic
ultrasonic cleaning bath below r.t. until the disappearance of start-
ing material, as determined by TLC (typically 2–3 h). At this time
the mixture was filtered through Celite, the filtrate was evaporated
and the residue was chromatographed (petroleum ether–EtOAc) to
give the corresponding N-Ac compound.
1H NMR (CDCl3, 250 MHz): = 7.11 (d, J = 7.2 Hz, 1 H), 6.12 (d,
J = 8.3 Hz, 1 H), 5.69 (d, J = 7.3 Hz, 1 H), 5.13 (m, 2 H), 4.74 (m,
1 H), 4.70 (d, J = 10.5 Hz, 1 H), 4.53 (m, 1 H), 4.42 (m, 1 H), 4.23–
4.12 (m, 3 H), 3.78 (s, 3 H), 3.77 (m, 1 H), 3.05 (m, 4 H), 2.09, 2.04,
2.03, 1.96 (4 s, 12 H), 1.80 (m, 2 H), 1.46, 1.44 (2 s, 18 H), 1.42 (m,
4 H).
13C NMR (CDCl3, 62.8 MHz): = 172.4, 170.9, 170.7, 170.5,
170.3, 169.3, 156.1, 155.2, 85.0, 80.4, 79.2, 76.2, 73.7, 68.3, 62.3,
54.4, 52.9, 52.5, 52.3, 42.8, 40.2, 32.4, 31.7, 29.4, 28.4, 28.3, 23.2,
22.4, 20.6.
N-tert-Butoxycarbonyl-S-(3,4,6-tri-O-acetyl-2-acetamido-2-
deoxy- -D-glucopyranosyl)-L-homocysteinyl-L-alanine Benzyl
Ester (2)
MALDI-MS: m/z = 814.8 [MNa+], 830.7 [MK+].
[ ]D –26.5 (c = 1.0 CHCl3).
Anal. Calcd for C34H56N4O15S (792.9): C, 51.50; H, 7.12; N, 7.07.
Found: C, 51.97; H, 7.19; N, 6.78.
1H NMR (CDCl3, 250 MHz): = 7.37 (m, 5 H), 7.23 (d, J = 7.2 Hz,
1 H), 6.24 (d, J = 8.5 Hz, 1 H), 5.34 (t, J = 9.7 Hz, 1 H), 5.29 (d,
J = 8.1 Hz, 1 H), 5.20 (AB peak, J = 12.3 Hz, 2 H), 5.08 (t, J = 9.6
Hz, 1 H), 4.92 (d, J = 10.3 Hz, 1 H), 4.61 (m, 1 H), 4.39 (m, 1 H),
4.25 (dd, J = 12.3, 4.7 Hz, 1 H), 4.12 (dd, J = 12.3, 2.1 Hz, 1 H),
3.82 (m, 1 H), 3.70 (m, 1 H), 2.79 (m, 2 H), 2.08, 2.04, 2.03, 1.96 (4
s, 12 H), 1.95 (m, 2 H), 1.45 (d, J = 7.4 Hz, 3 H), 1.43 (s, 9 H).
13C NMR (CDCl3, 62.8 MHz): = 172.6, 171.7, 170.8, 170.63,
170.56, 169.3, 155.6, 135.3, 128.5, 128.3, 127.9, 83.4, 79.8, 75.7,
73.4, 68.6, 67.0, 62.1, 53.8, 52.4, 48.1, 32.5, 28.2, 26.2, 23.1, 20.61,
20.56, 20.5, 17.5.
Phenyl 2-Acetamido-4,6-O-benzylidene-3-O-(N-tert-butoxycar-
bonyl-O-tert-butyl-L-threonyl)-2-deoxy-1-thio- -D-glucopyra-
noside (14)
[ ]D –47.2 (c = 1.0 CHCl3).
1H NMR (CDCl3, 250 MHz): = 7.50 (m, 2 H), 7.38 (m, 2 H), 7.29
(m, 6 H), 6.55 (d, J = 6.5 Hz, 1 H), 6.00 (d, J = 10.3 Hz, 1 H), 5.86
(t like, J = 9.2 Hz, 1 H), 5.48 (s, 1 H), 5.36 (d, J = 8.4 Hz, 1 H), 4.36
(d like, J = 8.6 Hz, 1 H), 4.15 (m, 1 H), 4.00 (dd, J = 8.3, 1.9 Hz, 1
H), 3.82–3.68 (m, 3 H), 2.97 (m, 1 H), 1.96 (s, 3 H), 1.46 (s, 9 H),
1.18 (d, J = 6.2 Hz, 3 H), 0.81 (s, 9 H).
MALDI-MS: m/z = 764.8 [MK+].
13C NMR (CDCl3, 62.8 MHz): = 171.4, 171.3, 157.1, 136.9,
132.6, 132.5, 129.2, 129.0, 128.0, 127.8, 126.7, 102.2, 85.4, 80.2,
78.9, 74.2, 72.2, 70.4, 68.7, 66.5, 60.5, 57.6, 28.4, 28.0, 23.4, 21.0.
N-Acetyl-N -(tert-butoxycarbonyl)hexane-1,6-diamine (10)9
1H NMR (CDCl3, 250 MHz): = 5.90 (br s, 1 H), 4.62 (br s, 1 H),
3.23 (q, J = 6.6 Hz, 2 H), 3.11 (m, 2 H), 1.99 (s, 3 H), 1.44 (s, 9 H),
1.42 (m, 8 H).
MALDI-MS: m/z = 680.0 [MNa+], 695.9 [MK+].
13C NMR (CDCl3, 62.8 MHz): = 170.1, 156.1, 78.8, 40.1, 39.2,
29.9, 29.4, 28.4, 26.1, 26.0, 23.3.
Anal. Calcd for C34H46N2O9S (658.8): C, 61.99; H, 7.04; N, 4.25.
Found: C, 62.16; H, 7.33; N, 4.05.
MALDI-MS: m/z = 296.9 [MK+].
Acknowledgment
This work was supported by the Deutsche Forschungsgemeinschaft
and the Fonds der Chemischen Industrie.
Synthesis 2003, No. 8, 1262–1266 ISSN 1234-567-89 © Thieme Stuttgart · New York

1266
X. Zhu, R. R. Schmidt
PAPER
(3) Dong, Q.; Anderson, C. E.; Ciufolini, M. A. Tetrahedron
Lett. 1995, 36, 5681; and references cited therein.
(4) Woodward, R. B.; Heusler, K.; Gosteli, J.; Naegeli, P.;
Oppolzer, W.; Ramage, R.; Ranganathan, S.; Vorbrüggen,
H. J. Am. Chem. Soc. 1966, 88, 852.
(5) Just, G.; Grozinger, K. Synthesis 1976, 457.
(6) Castro-Palomino, J. C. Ph.D. Thesis; University of
Konstanz: Germany, 1998.
(7) For examples, see: (a) Hale, K. J.; Cai, J. Chem. Commun.
1997, 2319. (b) Hancock, G.; Galpin, I. J.; Morgan, B. A.
Tetrahedron Lett. 1982, 23, 249.
References
(1) (a) Green, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd ed.; Wiley: New York, 1991, 42.
(b) Kocienski, P. J. Protecting Groups; Georg Thieme
Verlag: Stuttgart, 1994.
(2) For some recent examples of the use of the N-Troc group as
protecting group in the synthesis of amino sugar derivatives:
(a) Dullenkopf, W.; Castro-Palomino, J. C.; Manzoni, L.;
Schmidt, R. R. Carbohydr. Res. 1996, 296, 135. (b) Saha,
U. K.; Schmidt, R. R. J. Chem. Soc., Perkin Trans 1 1997,
1855. (c) Fukase, K.; Fukase, Y.; Oikawa, M.; Liu, W.;
Suda, Y.; Kusumoto, S. Tetrahedron 1998, 54, 4033.
(d) Ellervik, U.; Magnusson, G. Tetrahedron Lett. 1997, 38,
1627; and references cited therein. (e) Mitchell, S. A.; Pratt,
M. R.; Hruby, V. J.; Polt, R. J. Org. Chem. 2001, 61, 2327.
(f) Mong, K. T.; Wong, C. H. Angew. Chem. Int. Ed. 2002,
41, 4087; Angew. Chem. 2002, 114, 4261.
(8) Nigam, S. C.; Mann, A.; Taddei, M.; Wermuth, C. G. Synth.
Commun. 1989, 19, 3139.
(9) Kovács, L.; Hesse, M. Helv. Chim. Acta. 1992, 75, 1909.
(10) Luebke, K.; Schroeder, E. Liebigs Ann. Chem. 1966, 692,
237.
Synthesis 2003, No. 8, 1262–1266 ISSN 1234-567-89 © Thieme Stuttgart · New York