E
H. Abdellaoui et al.
Paper
Synthesis
CHCO), 2.52–2.39 (m, 1 H in CH2CO), 2.33–2.17 (m, 1 H in CH2CS),
2.03–1.92 (m, 1 H in CH2CO), 1.87–1.69 (m, 1 H in CH2CS), 1.41 (t, J =
7.1 Hz, 3 H, CH3).
13C NMR (101 MHz, CDCl3): δ = 213.0 (212.6), 178.6, 156.5, 136.3,
128.5, 128.1, 128.0, 70.4 (70.6), 66.4 (66.9), 50.0 (49.8), 44.8, 43.7,
37.2, 31.9 (32.3), 29.3, 13.7.
IR (KBr): 3344, 2939, 1715, 1611, 1521, 1451, 1363, 1224, 1052 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.85 (d, J = 8.2 Hz, 2 H, ArH), 7.31 (br s,
5 H, ArH), 7.24 (d, J = 8.2 Hz, 2 H, ArH), 5.22 (s, 1 H, NH), 5.10 (s, 2 H,
CH2), 4.60 (q, J = 6.8 Hz, 2 H, CH2), 3.97–3.89 (m, 1 H, CH), 3.61–3.53
(m, 1 H in CH2), 3.56–3.47 (m, 1 H in CH2), 3.13 (t, J = 6.8 Hz, 2 H, CH2),
2.40 (s, 3 H, CH3), 2.28–2.17 (m, 1 H in CH2), 2.03–1.96 (m, 1 H in CH2),
1.39 (t, J = 7.1 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 213.2, 198.6, 156.5, 144.0, 136.4,
134.2, 129.3, 128.5, 128.2, 128.15, 128.10, 70.3, 66.9, 51.1, 44.4, 35.5,
25.5, 21.7, 13.7.
HRMS (ESI): m/z calcd for C18H24NO5S2+: 398.1090 [M + H]+; found:
398.1056.
Diethyl 2-[3-Benzyloxycarbonylamino-2-(ethoxycarbono-
thioyl)thiopropyl]malonate (3e)
HRMS (ESI): m/z calcd for C23H28NO4S2+: 446.1454 [M + H]+; found:
446.1462.
Yellow oil; yield: 1.342 g (95%, 3 mmol scale).
IR (KBr): 3367, 2979, 1711, 1610, 1540, 1450, 1221, 1052 cm–1
.
Benzyl [5-(4-Chlorophenyl)-2-(ethoxycarbonothioyl)thio-5-oxo-
pentyl]carbamate (3i)
1H NMR (400 MHz, CDCl3): δ = 7.31 (br s, 5 H, ArH), 5.14 (s, 1 H, NH),
5.10 (s, 2 H, OCH2), 4.62 (q, J = 7.0 Hz, 2 H, CH2O), 4.20 (q, J = 7.0 Hz, 2
H, CH2O), 4.19 (q, J = 7.0 Hz, 2 H, CH2O), 3.96–3.84 (m, 1 H, CH), 3.70–
3.59 (m, 1 H, CHCO), 3.58–3.46 (m, 2 H, CH2), 2.47–2.35 (m, 1 H in
CH2), 2.16–2.05 (m, 1 H in CH2), 1.40 (t, J = 7.0 Hz, 3 H, CH3), 1.26 (t, J =
7.1 Hz, 6 H, 2 × CH3).
13C NMR (101 MHz, CDCl3): δ = 212.8, 169.0, 168.8, 156.5, 136.5,
128.6, 128.23, 128.17, 70.6, 67.0, 61.9, 61.8, 49.8, 49.6, 44.6, 30.3,
14.15, 14.12, 13.8.
Yellow oil; yield: 1.102 g (79%, 3 mmol scale).
IR (KBr): 3347, 2928, 1713, 1590, 1489, 1361, 1223, 1049 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.88 (d, J = 8.4 Hz, 2 H, ArH), 7.43 (d, J =
8.4 Hz, 2 H, ArH), 7.32 (br s, 5 H, ArH), 5.21 (s, 1 H, NH), 5.10 (s, 2 H,
CH2), 4.60 (q, J = 7.0 Hz, 2 H), 3.98–3.89 (m, 1 H, CH), 3.67–3.55 (m, 1
H in CH2), 3.54–3.43 (m, 1 H in CH2), 3.14 (t, J = 6.8 Hz, 2 H, CH2),
2.28–2.19 (m, 1 H in CH2), 2.03–1.96 (m, 1 H in CH2), 1.39 (t, J = 6.8 Hz,
3 H).
13C NMR (101 MHz, CDCl3): δ = 213.1, 197.7, 156.5, 139.7, 136.4,
135.0, 129.5, 129.0, 128.5, 128.2, 128.1, 70.4, 66.9, 51.1, 44.4, 35.6,
25.4, 13.7.
HRMS (ESI): m/z calcd for C21H30NO7S2+: 472.1458 [M + H]+; found:
472.1434.
Benzyl [2-(Ethoxycarbonothioyl)thio-5-oxohexyl]carbamate (3f)
HRMS (ESI): m/z calcd for C22H25ClNO4S2+: 466.0908 [M + H]+; found:
Yellow oil; yield: 0.94 g (85%, 3 mmol scale).
466.0915.
IR (KBr): 3338, 2926, 1715, 1605, 1520, 1222, 1051 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.31 (br s, 5 H, ArH), 5.18 (s, 1 H, NH),
5.10 (s, 2 H, CH2), 4.62 (q, J = 7.1 Hz, 2 H, CH2), 3.87–3.78 (m, 1 H, CH),
3.62–3.49 (m, 1 H in CH2), 3.47–3.35 (m, 1 H in CH2), 2.63 (t, J = 7.2 Hz,
2 H, CH2), 2.13 (s, 3 H, CH3), 2.10–2.00 (m, 1 H in CH2), 1.87–1.75 (m, 1
H in CH2), 1.41 (t, J = 7.1 Hz, 3 H, CH3).
Benzyl [5-(4-Bromophenyl)-2-(ethoxycarbonothioyl)thio-5-oxo-
pentyl]carbamate (3j)
Yellow oil; yield: 1.36 g (89%, 3 mmol scale).
IR (KBr): 3346, 2935, 1690, 1586, 1519, 1451, 1224, 1050 cm–1
.
13C NMR (101 MHz, CDCl3): δ = 213.3, 207.5, 156.5, 136.4, 128.5,
128.2, 128.1, 70.4, 66.9, 51.0, 44.3, 40.5, 30.0, 24.9, 13.7.
HRMS (ESI): m/z calcd for C17H24NO4S2+: 370.1141 [M + H]+; found:
370.1131.
1H NMR (400 MHz, CDCl3): δ = 7.81 (d, J = 8.4 Hz, 2 H, ArH), 7.59 (d, J =
8.4 Hz, 2 H, ArH), 7.32 (br s, 5 H, ArH), 5.19 (s, 1 H, NH), 5.10 (s, 2 H,
CH2), 4.60 (q, J = 6.8 Hz, 2 H, CH2), 3.98–3.89 (m, 1 H, CH), 3.65–3.55
(m, 1 H in CH2), 3.55–3.44 (m, 1 H in CH2), 3.15 (t, J = 6.8 Hz, 2 H, CH2),
2.27–2.18 (m, 1 H in CH2), 20.3–1.94 (m, 1 H in CH2), 1.39 (t, J = 6.8 Hz,
3 H, CH3).
13C NMR (101 MHz, CDCl3): δ = 213.1, 197.9, 156.5, 136.4, 135.4,
132.0, 129.6, 128.6, 128.4, 128.2, 128.1, 70.4, 66.9, 51.1, 44.4, 35.6,
25.4, 13.7.
Benzyl [2-(Ethoxycarbonothioyl)thio-5-oxo-5-phenylpentyl]car-
bamate (3g)
Yellow oil; yield: 1.19 g (92%, 3 mmol scale).
IR (KBr): 3336, 2935, 1686, 1599, 1520, 1370, 1182, 1005 cm–1
.
HRMS (ESI): m/z calcd for C22H25BrNO4S2+: 510.0403 [M + H]+; found:
510.0412.
1H NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 7.5 Hz, 2 H, ArH), 7.56 (t, J =
7.4 Hz, 1 H, ArH), 7.45 (t, J = 7.6 Hz, 2 H, ArH), 7.35–7.26 (m, 5 H, ArH),
5.23 (s, 1 H, NH), 5.10 (s, 2 H, CH2O), 4.60 (q, J = 6.8 Hz, 2 H, CH2),
4.00–3.95 (m, 1 H, CH), 3.68–3.53 (m, 1 H in CH2), 3.52–3.47 (m, 1 H
in CH2), 3.18 (t, J = 7.2 Hz, 2 H, CH2), 2.30–2.23 (m, 1 H in CH2), 2.04–
1.96 (m, 1 H in CH2), 1.38 (t, J = 7.1 Hz, 3 H, CH3).
13C NMR (101 MHz, CDCl3): δ = 213.1, 198.9, 156.4, 136.6, 136.3,
133.1, 128.6, 128.5, 128.1, 128.02, 127.99, 70.3, 66.8, 51.0, 44.3, 35.5,
25.4, 13.6.
N-Cbz-2-aminoalkanesulfonyl Chlorides 4; General Procedure22
To a mixture of xanthate 3 (1.4 mmol) and H2O (0.13 mL, 7 mmol) in
MeCN (2 mL) at 0 °C was added dropwise t-BuOCl (0.79 mL, 7 mmol).
The reaction mixture was stirred at 0 °C for 15 min. The mixture was
extracted with CH2Cl2 (3 × 4 mL). The combined organic phases were
washed with H2O (5 mL) and then dried (Na2SO4). After filtration and
removal of the solvent in vaccum, the residue was chromatographied
on silica gel [PE (60–90 °C)/EtOAc = 5:1, v/v] to afford the desired sul-
fonyl chloride 4.
HRMS (ESI): m/z calcd for C22H26NO4S2+: 432.1298 [M + H]+; found:
432.1295.
Benzyl [2-(Ethoxycarbonothioyl)thio-5-oxo-5-(4-methylphe-
nyl)pentyl]carbamate (3h)
Ethyl 5-Benzyloxycarbonylamino-4-chlorosulfonylpentanoate
(4a)
Yellow oil; yield: 1.135 g (85%, 3 mmol scale).
Yellow oil; yield: 449 mg (85%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G