Page 7 of 16
The Journal of Organic Chemistry
18.2, 14.2, –5.5, –5.7; IR (neat, cm-1) = 3103, 2954, 2931, 2856,
experimental procedure of 4aa with 4-bromo-3-butyn-1-ol and
1
2
3
2e (143 mg, 0.38 mmol), 4ea (173 mg, 90%) was obtained as
1736, 1554, 1538, 1350, 1245, 1155, 1079, 1046; HRMS (FAB)
calcd for C21H31BrN3O9SSi: 608.0734 ([M+H]+), found
608.0744.
light yellow oil; Rf = 0.40 (hexane/EtOAc, 3:1); [α]D20 = +6.7 (c
1
= 0.5, CHCl3); H NMR (500 MHz, CDCl3) δ = 8.48 (dd, J =
8.7, 2.2 Hz, 1H), 8.38 (d, J = 2.1 Hz, 1H), 8.26 (d, J = 8.7 Hz,
1H), 4.63 (q, J = 7.4 Hz, 1H), 3.63 (ddd, J = 15.4, 10.2, 5.2 Hz,
1H), 3.22 (ddd, J = 15.6, 9.9, 5.8 Hz, 1H), 2.70 (qd, J = 16.3,
5.3 Hz, 1H), 2.53 (qd, J = 16.5, 5.5 Hz, 1H), 1.52 (d, J = 7.4 Hz,
3H), 1.33 (s, 9H); 13C{1H} NMR (125 MHz, CDCl3) δ = 169.7,
149.6, 148.0, 138.1, 132.6, 126.0, 119.5, 82.8, 76.3, 57.3, 45.1,
41.3, 27.7 (3C), 22.3, 17.0; IR (neat, cm-1) = 3102, 2980, 1729,
1554, 1537, 1364, 1349, 1301, 1245, 1072; HRMS (FAB) calcd
for C17H21BrN3O8S: 506.0233 ([M+H]+), found 506.0221.
4
5
6
7
8
9
Methyl
N-(4-bromobut-3-yn-1-yl)-O-(tert-
butyldimethylsilyl)-N-((2,4-dinitrophenyl)sulfonyl)-L-
homoserinate (4ka). Following the same experimental
procedure of 4aa with 4-bromo-3-butyn-1-ol and 2k (640 mg,
1.34 mmol), 4ka (700 mg, 86%) was obtained as light yellow
20
oil; Rf = 0.50 (hexane/EtOAc, 3:1); [α]D = +6.8 (c = 0.5,
CHCl3); 1H NMR (400 MHz, CDCl3) δ = 8.47 (dd, J = 8.7, 2.3
Hz, 1H), 8.40 (d, J = 2.1 Hz, 1H), 8.30 (d, J = 8.7 Hz, 1H), 4.83
(dd, J = 8.8, 5.3 Hz, 1H), 3.72 (q, J = 3.9 Hz, 2H), 3.66–3.61
(m, 1H), 3.59 (s, 3H), 3.28 (ddd, J = 15.6, 9.5, 6.1 Hz, 1H), 2.74
(ddd, J = 15.8, 10.5, 6.2 Hz, 1H), 2.53 (qd, J = 16.5, 9.9, 6.4 Hz,
1H), 2.31–2.23 (m, 1H), 1.96–1.87 (m, 1H), 0.87 (s, 9H), 0.05
(d, J = 1.4 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ = 171.1,
149.7, 148.2, 137.6, 132.8, 125.8, 119.5, 76.3, 58.8, 58.3, 52.6,
45.9, 41.3, 33.4, 25.8 (3C), 21.9, 18.2, –5.5, –5.6; IR (neat, cm-
1) = 3105, 2954, 2931, 2858, 1741, 1555, 1539, 1351, 1253,
1170, 1149, 1104; HRMS (FAB) calcd for C21H31BrN3O9SSi:
608.0734 ([M+H]+), found 608.0729.
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14
15
16
17
18
19
20
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25
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Ethyl
N-(4-bromobut-3-yn-1-yl)-N-((2,4-
dinitrophenyl)sulfonyl)-L-valinate (4ha). Following the same
experimental procedure of 4aa with 4-bromo-3-butyn-1-ol and
2h (300 mg, 0.80 mmol), 4ha (347 mg, 86%) was obtained as
light yellow oil; Rf = 0.50 (hexane/EtOAc, 5:1); [α]D20 = –29.5
(c = 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ = 8.47 (dd, J =
8.7, 2.2 Hz, 1H), 8.40 (d, J = 2.1 Hz, 1H), 8.25 (d, J = 8.7 Hz,
1H), 4.13 (d, J = 9.8 Hz, 1H), 4.10–4.00 (m, 2H), 3.65–3.55 (m,
2H), 2.75 (ddd, J = 16.5, 9.8, 6.3 Hz, 1H), 2.53 (ddd, J = 16.2,
9.8, 6.3 Hz, 1H), 2.23–2.17 (m, 1H), 1.15 (t, J = 7.1 Hz, 3H),
0.99 (dd, J = 6.6, 3.8 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3)
δ = 169.7, 149.7, 148.2, 137.9, 132.9, 125.8, 119.5, 76.2, 66.7,
61.5, 44.9, 41.1, 29.0, 21.7, 19.7, 19.4, 14.0; IR (neat, cm-1) =
3103, 2972, 1732, 1554, 1538, 1365, 1349, 1167, 1146, 1108,
1022; HRMS (FAB) C17H21BrN3O8S: 506.0233 ([M+H]+),
found 506.0231.
Methyl
N-(4-bromobut-3-yn-1-yl)-N-((2,4-
dinitrophenyl)sulfonyl)-L-methioninate (4la). Following the
same experimental procedure of 4aa with 4-bromo-3-butyn-1-
ol and 2l (435 mg, 1.11 mmol), 4la (475 mg, 82%) was obtained
as light yellow oil; Rf = 0.60 (hexane/EtOAc, 2:1); [α]D
20
=
1
+20.2 (c = 0.5, CHCl3); H NMR (400 MHz, CDCl3) δ = 8.50
(dd, J = 8.7, 2.3 Hz, 1H), 8.41 (d, J = 2.2 Hz, 1H), 8.28 (d, J =
8.8 Hz, 1H), 4.80 (dd, J = 9.6, 4.8 Hz, 1H), 3.66–3.59 (m, 1H),
3.60 (s, 3H), 3.26 (ddd, J = 15.6, 9.6, 6.0 Hz, 1H), 2.77 (ddd, J
= 15.8, 10.5, 6.1 Hz, 1H), 2.68–2.50 (m, 3H), 2.38–2.30 (m, 1H),
2.11 (s, 3H), 2.03–1.94 (m, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ = 170.5, 149.8, 148.1, 137.3, 132.9, 125.9, 119.6,
76.1, 60.3, 52.8, 45.8, 41.6, 30.6, 29.6, 22.0, 15.4; IR (neat, cm-
1) = 3101, 2953, 2919, 1739, 1553, 1538, 1364, 1350, 1163,
1107; HRMS (FAB) calcd for C16H19BrN3O8S2: 523.9797
([M+H]+), found 523.9792.
Ethyl
N-(4-bromobut-3-yn-1-yl)-N-((2,4-
dinitrophenyl)sulfonyl)-L-phenylalaninate (4ia). Following
the same experimental procedure of 4aa with 4-bromo-3-butyn-
1-ol and 2i (416 mg, 0.98 mmol), 4ia (440 mg, 81%) was
obtained as light yellow oil; Rf = 0.50 (hexane/EtOAc, 3:1);
[α]D20 = –4.0 (c = 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ =
8.35 (d, J = 2.0 Hz, 1H), 8.33 (dd, J = 8.6, 2.2 Hz, 1H), 7.99 (d,
J = 8.5 Hz, 1H), 7.27–7.20 (m, 5H), 4.92 (q, J = 5.2 Hz, 1H),
4.09–4.03 (m, 2H), 3.64 (ddd, J = 15.5, 10.0, 5.6 Hz, 1H), 3.48–
3.42 (m, 2H), 3.03 (dd, J = 14.7, 9.1 Hz, 1H), 2.65 (qd, J = 16.5,
5.4 Hz, 1H), 2.45 (qd, J = 16.4, 5.4 Hz, 1H), 1.14 (t, J = 7.2 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ = 169.8, 149.5, 148.0,
137.7, 135.6, 132.4, 128.8 (2C), 128.7 (2C), 127.2, 125.9, 119.5,
76.3, 62.0, 61.9, 45.1, 41.3, 36.1, 21.5, 13.9; IR (neat, cm-1) =
3102, 2984, 1737, 1555, 1368, 1352, 1167, 1107, 1021; HRMS
(FAB) calcd for C21H21BrN3O8S: 554.0233 ([M+H]+), found
554.0230.
Dimethyl
N-(4-bromobut-3-yn-1-yl)-N-((2,4-
dinitrophenyl)sulfonyl)-D-glutamate (4ma). Following the
same experimental procedure of 4aa with 4-bromo-3-butyn-1-
ol and 2m (455 mg, 1.12 mmol), 4ma (518 mg, 86%) was
obtained as light yellow oil; Rf = 0.50 (hexane/EtOAc, 2:1);
[α]D20 = –7.3 (c = 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ =
8.49 (dd, J = 8.7, 2.2 Hz, 1H), 8.40 (d, J = 2.1 Hz, 1H), 8.26 (d,
J = 8.7 Hz, 1H), 4.69 (dd, J = 10.3, 4.5 Hz, 1H), 3.69 (s, 3H),
3.67–3.61 (m, 1H), 3.60 (s, 3H), 3.22 (ddd, J = 15.6, 9.4, 6.3
Hz, 1H), 2.75 (ddd, J = 16.2, 10.0, 5.7 Hz, 1H), 2.59–2.42 (m,
4H), 2.02–1.95 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ =
172.6, 170.2, 149.8, 148.2, 137.3, 132.9, 125.9, 119.6, 76.1,
60.8, 52.8, 52.0, 45.8, 41.6, 30.2, 25.1, 22.0; IR (neat, cm-1) =
3102, 2954, 1737, 1554, 1540, 1368, 1353, 1166, 1108; HRMS
(FAB) calcd for C17H19N3O10SBr: 535.9975 ([M+H]+), found
535.9973.
Ethyl
N-(4-bromobut-3-yn-1-yl)-O-(tert-
butyldimethylsilyl)-N-((2,4-dinitrophenyl)sulfonyl)serinate
(4ja). Following the same experimental procedure of 4aa with
4-bromo-3-butyn-1-ol and 2j (639 mg, 1.34 mmol), 4ja (699
mg, 86%) was obtained as light yellow oil; Rf = 0.60
(hexane/EtOAc, 3:1); [α]D20 = +47.6 (c = 0.5, CHCl3); 1H NMR
(400 MHz, CDCl3) δ = 8.49 (dd, J = 8.6, 2.2 Hz, 1H), 8.38 (d,
J = 2.0 Hz, 1H), 8.30 (d, J = 8.8 Hz, 1H), 4.71 (dd, J = 5.0, 1.8
Hz, 1H), 4.29 (dd, J = 11.4, 5.0 Hz, 1H), 4.17–4.08 (m, 1H),
4.03–3.95 (m, 2H), 3.68–3.53 (m, 2H), 2.80 (ddd, J = 16.2, 10.9,
5.5 Hz, 1H), 2.62 (ddd, J = 16.4, 10.9, 5.5 Hz, 1H), 1.20 (t, J =
7.2 Hz, 3H), 0.85 (s, 9H), 0.07 (d, J = 11.2 Hz, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ = 168.9, 149.8, 148.2, 137.7, 132.8,
126.2, 119.8, 76.8, 63.8, 62.8, 62.2, 46.9, 41.1, 25.8 (3C), 22.5,
General Procedure for the Synthesis of MOC Substrates
(1, 5a, 5c', and 5c–5e). To a solution of 4aa (273 mg, 0.57
mmol) and thioglycolic acid (79.6 μL, 1.14 mmol, 2.00 equiv)
in DCM (10 mL), triethylamine (241 μL, 1.72 mmol, 3.00 equiv)
in DCM (4 mL) was added dropwise at room temperature under
an inert atmosphere. The reaction was stirred until judged to be
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