LETTER
Dehydrosulfurizing Agent for the Synthesis of Nb-Fmoc-Amino Alkyl Isonitriles
1099
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(47) The two dipeptide thioformamides were synthesized in to
verify the optical purity of Nb-Fmoc-amino alkyl thiofor
mamides 1. For this, 1b was treated with 20% Et2NH in
CH2Cl2 to deprotect the Fmoc group. The resulting amino-
free Nb-(1-amino alanine)-thioformamide was coupled both
D and L isomers of Fmoc-Phg-OH using EDC/separately to
obtain 1k and 1l. The 1H NMR spectra of both Fmoc-L-Phg-
Ala-Y[CH2NHCHS]andFmoc-D-Phg-Ala-Y[CH2NHCHS]
showed distinct methyl group doublets at d = 1.13, 1.14 ppm
and d = 1.21, 1.23, respectively. However, the mixture of
epimers prepared by coupling amino-free Nb-(1-amino
alanine)-thioformamide with epimeric mixture of Fmoc
(L/D)-Phg-OH had two separate doublets corresponding to
each diastereomer. This clearly confirmed the optical purity
of thioformamides.
(48) The mechanism of the dehydrosulforization of
thioformamides using CNBr is given in Scheme 3.
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H
N
H
N
H
N
H
H
H
•
R
R
R
CNBr
•
S
S
S
CN
CN
(25) Xu, P.; Zhang, T.; Wang, W.; Zou, X.; Zhang, X.; Fu, Y.
Synthesis 2003, 1171.
NMM
N+
H
R
N+ C–
R
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102, 2536.
Scheme 3
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(49) Typical Experimental Procedure for 1a–j
To a stirred solution of Nb-Fmoc amino alkyl formamide 5
(1 mmol) in THF (5 mL), P2S5 (0.7 mmol) was added. The
reaction mixture was subjected to ultrasonication for 15 min.
After the completion of reaction (TLC), the solvent was
evaporated in vacuo, and the crude was purified by a flash
chromatography to obtain the thioformamides as solids.
(50) Selected Spectroscopic Data.
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Compound 1b: 1H NMR (400 MHz, CDCl3): d = 1.30 (d, 3
H, J = 6.53 Hz), 2.65 (d, 2 H), 3.90 (m, 1 H), 4.20 (t, 1 H,
J = 13.04 Hz), 4.41 (d, 2 H, J = 6.62 Hz), 5.01 (br, 1 H), 7.31
(t, 2 H, J = 14.79 Hz), 7.39 (t, 2 H, J = 14.69 Hz), 7.57 (d, 2
H, J = 7.21 Hz), 7.76 (d, 2 H, J = 7.48 Hz), 8.20 (s, 1 H). 13
NMR (100 MHz, CDCl3): d = 17.44, 46.83, 47.18, 56.18,
66.83, 122.24, 124.93, 127.08, 128.17, 141.34, 143.66,
155.77, 139.31.
C
Compound 1j: 1H NMR (400 MHz, CDCl3): d = 2.39–2.65
(m, 2 H), 3.12–3.51 (m, 2 H), 3.1 (m, 1 H), 4.10 (t, 1 H,
J = 6.90 Hz), 4.12 (d, 2 H, J = 7.2 Hz), 4.74 (s, 2 H), 5.56 (br,
1 H), 7.15–7.80 (m, 13 H), 8.25 (s, 1 H). 13C NMR (100
MHz, CDCl3; CCl4): d = 36.91, 43.06, 46.82, 51.89, 65.83,
69.82, 119.15, 124.90, 126.25, 127.53, 128.12, 128.24,
141.67, 143.53, 143.81, 156.38, 139.22, 171.58.
Compound 1k: 1H NMR (400 MHz, CDCl3): d = 1.14 (d, 3
Synlett 2010, No. 7, 1096–1100 © Thieme Stuttgart · New York