Post on 07-Jul-2020
S1
Supporting Information for
Sequential oxonium-olefin-alkyne cyclization for the stereoselective synthesis of octahydro-1H-pyrano[3,4-c]pyridin-5-yl)methanone
derivatives
B. V. Subba Reddy,*† V. Hanuman Reddy,† M. Durgaprasad,† S. Gopal Reddy,† J. K. Lakshmi,§ P. V. Aneesh,§ Y. V. Rami Reddy
†Centre for Semiochemicals, §Centre for Nuclear Magnetic Resonance, CSIR-Indian Institute of Chemical Technology, Hyderabad –500 007, India.
Department of Chemistry, S. V. University, Tirupapti-517502,E-mail: basireddy@iict.res.in; Fax: 0091-40-27160512
Table of Contents
1. Characterization data of products (6a-e) & (8a-n)..........................................S2-11
2. 2D NMR spectra of 8a & 8m ............................................................................S12-24
3. 1H, 13C NMR spectra of (6a-e) & 8(a-n)….......................................................S25-43
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2016
S2
(E)-N-(5-Hydroxypent-2-enyl)-4-nitro-N-(prop-2-ynyl)benzenesulfonamide (6a)
NsN OH
1H NMR (500 MHz, CDCl3) δ 8.36 (d, J = 7.3 Hz, 2H), 8.05 (d, J = 7.1 Hz, 2H), 5.81 – 5.71 (m,
1H), 5.55 – 5.47 (m, 1H), 4.15 (d, J = 6.3 Hz, 2H), 3.84 (d, J = 6.7 Hz, 2H), 3.68 (t, J = 6.3 Hz,
2H), 2.33 (q, J = 6.6 Hz, 2H), 2.04 – 2.01 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 150.10,
144.79, 133.66, 128.94, 125.39, 124.08, 75.89, 74.30, 61.59, 48.55, 35.78, 35.43.
(E)-N-(4-Hydroxybut-2-enyl)-4-nitro-N-(prop-2-ynyl)benzenesulfonamide (6b)
NsNOH
1H NMR (500 MHz, CDCl3) δ 8.35 (d, J = 8.6 Hz, 2H), 8.09 (d, J = 7.8 Hz, 2H), 5.95-5.89 (m,
1H), 5.74 – 5.60 (m, 1H), 4.16 (d, J = 2.2 Hz, 4H), 3.88 (d, J = 6.6 Hz, 2H), 2.24 – 2.09 (m, 1H),
2.09 (t, J = 2.6 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 150.06, 144.57, 135.42, 128.89, 124.08,
123.49, 75.64, 74.46, 62.21, 47.95, 35.84.
(E)-N-(Hept-2-ynyl)-N-(5-hydroxypent-2-enyl)-4-methylbenzenesulfonamide (6c)
TsN OH
1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 6.8 Hz, 2H), 7.28 (d, J = 8.0 Hz, 8H), 5.73 – 5.64 (m,
1H), 5.57 – 5.42 (m, 1H), 4.10 (s, 1H), 4.05 (t, J = 2.2 Hz, 2H), 3.76 (d, J = 6.2 Hz, 2H), 3.65 (t,
J = 9.2 Hz, 2H), 2.42 (s, 3H), 2.33 – 2.25 (m, 2H),1.95 - 1.89 (m, 2H), 1.25 – 1.19 (m, 4H), 0.85
S3
(t, J = 8.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 143.16, 136.15, 132.09, 129.26, 127.75,
126.67, 86.15, 72.42, 61.67, 48.18, 36.32, 35.51, 30.38, 21.78, 21.45, 18.06, 13.47.
(E)-N-(5-Hydroxypent-2-enyl)-4-methyl-N-(3-p-tolylprop-2-ynyl)benzenesulfonamide (6d)
TsN OH
CH3
1H NMR (500 MHz, CDCl3) δ 7.81 (d, J = 6.3 Hz, 1H), 7.77 (d, J = 6.8 Hz, 2H), 7.34 – 7.27 (m,
1H), 7.05 (d, J = 7.9 Hz, 2H), 6.96 (d, J = 8.1 Hz, 2H), 5.76 – 5.71 (m, 1H), 5.60 – 5.50 (m, 1H),
4.29 (s, 2H), 3.85 (d, J = 6.6 Hz, 2H), 3.66 (dd, J = 10.6, 4.2 Hz, 2H), 2.45 – 2.37 (m, 2H), 2.34
(s, 6H); 13C NMR (125 MHz, CDCl3) δ 149.94, 144.83, 139.23, 133.47, 131.10, 129.09, 128.97,
125.68, 123.99, 118.32, 86.45, 80.36, 61.66, 48.84, 48.70, 36.83, 36.72, 35.50, 35.44, 21.50,
21.39.
(E)-N-(5-Hydroxypent-2-enyl)-N-(3-(4-methoxyphenyl)prop-2-ynyl)-4-methylbenzene sulfonamide (6e)
TsN OH
OCH3
1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 7.8 Hz, 2H), 7.25 (d, J = 7.0 Hz, 2H), 7.02 (d, J = 6.8
Hz, 2H), 6.76 (d, J = 7.2 Hz, 2H), 5.76 – 5.70 (, J = 15.2, 6.9 Hz, 1H), 5.55 – 5.50 (m, 1H), 4.27
(s, 2H), 3.84 (d, J = 6.6 Hz, 2H), 3.78 (s, 3H), 3.64 (t, J = 6.4 Hz, 2H), 2.34 (s, 3H), 2.33 – 2.28
(m, 2H), 2.00 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 159.50, 143.34, 135.82, 132.82, 132.44,
129.37, 127.67, 126.30, 114.13, 113.63, 85.46, 80.22, 61.59, 55.19, 48.45, 36.68, 35.46, 21.34.
S4
(1-(2-Chlorophenyl)-7-((4-nitrophenyl)sulfonyl)octahydro-1H-pyrano[3,4-c]pyridin-5-yl)(Phenyl)methanone (8a):
1H NMR (400 MHz, CDCl3) δ 7.81(d, J = 8.4 Hz, 2H), 7.73 – 7.64 (m, 2H), 7.62 – 7.51 (m,
3H), 7.51 – 7.41 (m, 3H), 7.38 (t, J = 7.5 Hz, 2H), 7.28 (d, J = 8.9 Hz, 1H), 4.52 (d, J = 10.0 Hz,
1H), 4.19 – 4.10 (m, 2H), 3.73 – 3.62 (m, 1H), 3.49 – 3.42 (m, 1H), 3.27 (dd, J = 13.5, 4.4 Hz,
1H), 3.10 – 2.95 (m, 1H), 2.59 (t, J = 12.0 Hz, 1H), 2.06 – 1.91 (m, 2H), 1.52 – 1.40 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 198.7, 148.0, 137.0, 136.8, 133.4, 133.2, 132.8, 132.0, 131.4,
130.8, 129.4, 129.2, 128.9, 128.8, 128.0, 127.8, 124.0, 68.8, 48.7, 46.9, 43.2, 41.6, 41.0, 29.2; IR
(KBr) 3062, 3010, 2935, 2841, 1753, 1648, 1583, 1512, 1419, 1365, 1298, 1218, 1173, 1136,
1069, 1016, 780 cm-1; HRMS: m/z calcd for C27H25ClN2O6S (M+H)+ 541.1195; found 541.1187
(7-((4-Nitrophenyl)sulfonyl)-1-phenyloctahydro-1H-pyrano[3,4-c]pyridin-5-yl)(phenyl)methanone (8b):
1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 8.5 Hz, 2H), 7.70 (t, J = 6.3 Hz, 1H), 7.63 (t, J = 6.3
Hz, 3H), 7.56 (dt, J = 15.2, 4.4 Hz, 3H), 7.40 – 7.32 (m, 3H), 7.28 (dd, J = 8.7, 3.0 Hz, 2H), 4.14
– 3.96 (m, 3H), 3.66 (td, J = 14.7, 11.3 Hz, 2H), 3.23 (dd, J = 12.9, 2.3 Hz, 1H), 2.95 (t, J = 10.4
Hz, 1H), 2.52 (t, J = 12.3 Hz, 1H), 2.21 – 2.06 (m, 1H), 1.96 – 1.78 (m, 1H), 1.54 – 1.50 (m,
2H); 13C NMR (125 MHz, CDCl3) δ 200.3, 147.9, 138.8, 136.6, 134.0, 133.6, 131.7, 131.6,
130.8, 130.1, 129.0, 128.7, 128.6, 128.4, 126.9, 124.2, 82.3, 68.1, 48.6, 48.1, 46.9, 44.8, 41.5,
30.1; IR (KBr) 3064, 3029, 2922, 2852, 1727, 1674, 1593, 1543, 1450, 1370, 1290, 1218,
1163, 1126, 1084, 1029 cm-1; HRMS: m/z calcd for C27H26N2O6S (M+Na)+ 529.1404; found
529.1441
NsN
O
O
H H
NsN
O
O
Cl
H H
S5
Phenyl(1-(m-tolyl)-7-tosyloctahydro-1H-pyrano[3,4-c]pyridin-5-yl)methanone (8c):
1H NMR (500 MHz, CDCl3) δ 8.04 – 7.95 (m, 2H), 7.68 – 7.61 (m, 1H), 7.53 (t, J = 7.7 Hz, 2H),
7.48 (d, J = 8.2 Hz, 2H), 7.29 (dd, J = 11.6, 7.9 Hz, 3H), 7.19 – 7.11 (m, 2H), 7.04 (d, J = 7.5
Hz, 1H), 4.06 – 3.94 (m, 2H), 3.90 (d, J = 8.6 Hz, 1H), 3.59 (td, J = 14.9, 11.2 Hz, 2H), 3.30 (d,
J = 10.2 Hz, 1H), 2.44 (s, 3H), 2.42 – 2.32 (m, 1H), 2.39 (s, 3H), 2.03 – 1.84 (m, 3H), 1.52 –
1.44 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 200.6, 143.7, 138.8, 138.56, 136.6, 134.3, 133.1,
129.7, 129.5, 129.0, 128.6, 128.3, 127.5, 124.1, 82.8, 68.1, 49.1, 47.7, 47.17, 44.2, 41.6, 30.1,
21.5; IR (KBr) 3025, 2921, 2856, 1730, 1678, 1590, 1478, 1450, 1385, 1285, 1261, 1218,
1165, 1129, 1083, 1045, 995, 971 cm-1; HRMS: m/z calcd for C29H31NO4S(M+Na)+ 512.1866;
found 512.1851
4-(5-Benzoyl-7-((4-nitrophenyl)sulfonyl)octahydro-1H-pyrano[3,4-c]pyridin-1-yl) benzonitrile (8d):
1H NMR (500 MHz, CDCl3) δ 8.02 (t, J = 10.2 Hz, 2H), 7.77 (d, J = 7.8 Hz, 1H), 7.71 – 7.66 (m,
3H), 7.62 (d, J = 8.6 Hz, 3H), 7.54 (t, J = 7.1 Hz, 2H), 7.43 (t, J = 10.7 Hz, 2H), 4.11 – 4.00 (m,
3H), 3.72 – 3.58 (m, 2H), 3.19 (d, J = 6.8 Hz, 1H), 2.90 (t, J = 10.5 Hz, 1H), 2.54 (t, J = 12.3 Hz,
1H), 2.12 (d, J = 9.2 Hz, 1H), 1.87 – 1.80 (m, 1H), 1.57 – 1.49 (m, 2H); 13C NMR (125 MHz,
CDCl3) δ 199.9, 148.0, 144.2, 136.4, 134.2, 133.9, 132.6, 131.7, 131.4, 130.8, 129.1, 128.4,
127.8, 124.3, 124.0, 118.58, 112.5, 81.5, 68.1, 48.7, 48.0, 46.7, 45.1, 41.3, 29.9; IR (KBr)
3029, 2951, 2891, 2240, 1751, 1675, 1514, 1469, 1380, 1340, 1220, 1168, 1078, 1029, 996, 971
cm-1; HRMS: m/z calcd for C28H25N3O6S (M+Na)+ 554.1356; found 554.1402
NsN
O
O
NCHH
TsN
O
O
H3C
H H
S6
(7-((4-Nitrophenyl)sulfonyl)-1-(2,3,4-trifluorophenyl)octahydro-1H-pyrano[3,4-c]pyridin-5-yl)(phenyl)methanone (8e):
1H NMR (500 MHz, CDCl3) δ 8.07(d, J = 10.5 Hz, 2H), 7.83 – 7.78 (m, 1H), 7.75 – 7.69 (m,
1H), 7.68 – 7.60 (m, 3H), 7.54 (t, J = 7.8 Hz, 2H), 7.32 – 7.27 (m, 1H), 6.96 (t, J = 9.6 Hz, 1H),
4.37 (d, J = 7.8 Hz, 1H), 4.10 – 4.00 (m, 2H), 3.70 – 3.58 (m, 2H), 3.32 (d, J = 9.5 Hz, 1H), 2.92
(t, J = 10.2 Hz, 1H), 2.62 (t, J = 11.8 Hz, 1H), 2.12 (t, J = 11.0 Hz, 1H), 1.79 – 1.72 (m, 1H),
1.56 – 1.47 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 199.9, 148.0, 136.3, 134.1, 133.9, 131.6,
131.3, 130.7, 129.0, 128.4, 124.3, 73.5, 68.2, 48.7, 47.9, 46.3, 45.4, 41.2, 29.8; IR (KBr) 3068,
2922, 2852, 1731, 1675, 1630, 1593, 1545, 1515, 1449, 1428, 1372, 1290, 1246, 1218, 1165,
1089, 1028, 990, 967 cm-1; HRMS: m/z calcd for C27H23F3N2O6S (M+Na)+ 561.1302; found
561.1318
(1-(2-Fluorophenyl)-7-tosyloctahydro-1H-pyrano[3,4-c]pyridin-5-yl)(phenyl)methanone (8f):
TsN
O
O
HH
F
1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 11.2 Hz, 2H), 7.74 (d, J = 7.7 Hz, 1H), 7.65 (t, J = 7.0
Hz, 1H), 7.58 – 7.43 (m, 5H), 7.39 – 7.29 (m, 3H), 7.21 (d, J = 7.4 Hz, 1H), 4.01 (t, J = 9.0 Hz,
2H), 3.91 (d, J = 9.2 Hz, 1H), 3.65 – 3.57 (m, 2H), 3.28 (d, J = 10.6 Hz, 1H), 2.45 (s, 3H), 2.00
(t, J = 10.1 Hz, 2H), 1.95 – 1.78 (m, 2H), 1.54 – 1.47 (m, 2H); 13C NMR (125 MHz, CDCl3) δ
200.5, 141.4, 136.7, 134.1, 133.2, 131.9, 130.4, 130.2, 129.9, 129.1, 128.4, 127.5, 125.6, 82.0,
68.2, 49.1, 47.7, 47.0, 44.4, 41.5, 30.0, 21.6; IR (KBr) 3065, 2928, 2854, 1732, 1668, 1589,
NsN
O
O
FF
FH H
S7
1518, 1450, 1375, 1290, 1251, 1217, 1168, 1089, 970 cm-1; HRMS: m/z calcd for C28H28FNO4S
(M+Na)+ 516.1615; found 516.1620.
(7-((4-Nitrophenyl)sulfonyl)-1-(p-tolyl)octahydro-1H-pyrano[3,4-c]pyridin-5-
yl)(phenyl)methanone (8g):
1H NMR (500 MHz, CDCl3) 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 7.4 Hz, 2H), 7.73 (d, J =
7.9 Hz, 1H), 7.67 (d, J = 7.1 Hz, 1H), 7.65 – 7.57 (m, 3H), 7.53 (t, J = 7.6 Hz, 2H), 7.17 (s, 4H),
4.05 (t, J = 11.2 Hz, 2H), 3.96 (d, J = 9.8 Hz, 1H), 3.65 (td, J = 14.7, 11.3 Hz, 2H), 3.28 (d, J =
6.9 Hz, 1H), 2.95 (t, J = 11.4 Hz, 1H), 2.49 (t, J = 12.3 Hz, 1H), 2.36 (s, 3H), 2.13 – 2.03 (m,
1H), 1.88 – 1.80 (m, 1H), 1.53 – 1.46 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 200.4, 147.9,
138.3, 136.5, 135.8, 134.0, 133.6, 131.7, 131.6, 130.8, 129.4, 129.03, 128.4, 126.8, 124.2, 82.1,
68.0, 48.6, 48.0, 46.9, 44.7, 41.6, 30.1, 21.2; IR (KBr) 3025, 2921, 2851, 2312, 1736, 1675,
1593, 1545, 1450, 1371, 1218, 1165, 1085, 1029, 989, 966 cm-1; HRMS: m/z calcd for
C28H28N2O6S (M+Na)+ 543.1560; found 543.1573
(1-(3-Methoxyphenyl)-7-((4-nitrophenyl)sulfonyl)octahydro-1H-pyrano[3,4-c]pyridin-5-yl)(phenyl)methanone (8h):
1H NMR (500 MHz, CDCl3) δ 8.02 (d, J = 9.5 Hz, 2H), 7.74 – 7.71 (m, 1H), 7.71 – 7.66 (m,
1H), 7.66 – 7.61 (m, 2H), 7.59 (t, J = 7.7 Hz, 1H), 7.53 (t, J = 7.7 Hz, 2H), 7.30 – 7.26 (m, 1H),
NsN
O
O
H H
NsN
O
O
H3CO
H H
S8
6.90 – 6.82 (m, 3H), 4.11 – 4.00 (m, 2H), 3.98 (d, J = 9.5 Hz, 1H), 3.83 (s, 3H), 3.72 – 3.59 (m,
2H), 3.31 – 3.23 (m, 1H), 2.96 (t, J = 13.0 Hz, 1H), 2.58 – 2.46 (m, 1H), 2.12 – 2.06 (m, 1H),
1.86 – 1.79 (m, 1H), 1.54 – 1.40 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 200.3, 159.9, 147.8,
140.3, 136.5, 134.0, 133.6, 131.7, 131.6, 130.8, 129.7, 129.0, 128.3, 124.20, 119.4, 114.5, 112.0,
82.2, 68.0, 55.2, 48.5, 48.0, 46.8, 44.7, 41.5, 30.0; IR (KBr) 3012, 2923, 2852, 1731, 1673,
1592, 1489, 1453, 1453, 1370, 1288, 1265, 1215, 1161, 1082, 1041, 990 cm-1; HRMS: m/z calcd
for C28H28N2O7S (M+Na)+ 559.1509; found 559.1521
(1-(4-Methoxy-3-methylphenyl)-7-((4-nitrophenyl)sulfonyl)octahydro-1H-pyrano[3,4-c]pyridin-5-yl)(phenyl)methanone (8i):
1H NMR (500 MHz, CDCl3) δ 8.34 (d, J = 11.8 Hz, 2H), 7.99 (d, J = 11.2 Hz, 2H), 7.80 (d, J
=11.6 Hz, 2H), 7.67 (t , J = 7.4 Hz, 1H), 7.55 (t, J = 7.8 Hz, 2H), 7.07 (dd, J = 13.6, 5.4 Hz, 2H),
6.84 (t, J = 7.1 Hz, 1H), 4.01 (d, J = 8.6 Hz, 2H), 3.87 (s, 3H), 3.65 (td, J = 10.9, 3.9 Hz, 1H),
3.59 – 3.51 (m, 1H), 3.37 (d, J = 10.0 Hz, 1H), 2.55 (t, J = 11.6 Hz, 1H), 2.25 (s, 3H), 2.07 –
1.85 (m, 4H), 1.51 – 1.46 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 200.2, 158.0, 150.2, 142.4,
136.5, 134.2, 130.3, 129.1, 128.5, 128.3, 127.3, 125.5, 124.4, 109.9, 82.1, 68.0, 55.3, 49.0, 47.7,
47.2, 44.3, 41.8, 30.1, 16.4; IR (KBr) 3075, 3015, 2928, 2845, 1727, 1664, 1593, 1543, 1451,
1365, 1281, 1210, 1160, 1126, 1091, 1020, 975 cm-1; HRMS: m/z calcd for C29H30N2O7S
(M+H)+ 551.1846; found 551.1815
(1-([1,1'-Biphenyl]-4-yl)-7-((4-nitrophenyl)sulfonyl)octahydro-1H-pyrano[3,4-c]pyridin-5-
yl)(phenyl)methanone (8j):
NsN
O
O
H3C
H3COH H
NsN
O
O
HH
S9
1H NMR (500 MHz, CDCl3) δ 8.34 (d, J = 11.8 Hz, 2H), 8.04 – 7.98 (m, 2H), 7.83 – 7.78 (m,
2H), 7.70 – 7.61 (m, 5H), 7.56 (t, J = 7.8 Hz, 2H), 7.47 (t, J = 7.6 Hz, 2H), 7.38 (dd, J = 7.7, 5.3
Hz, 3H), 4.03 - 3.80 (m, 3H), 3.72 – 3.56 (m, 2H), 3.41 (d, J = 9.9 Hz, 1H), 2.57 (t, J = 11.6 Hz,
1H), 2.19 – 1.91 (m, 3H), 1.38 – 1.25 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 200.1, 150.2,
142.3, 141.7, 140.5, 137.6, 136.4, 134.2, 129.1, 128.8, 128.5, 128.3, 127.6, 127.5, 127.4, 127.5,
124.4, 82.2, 68.1, 49.0, 47.7, 47.1, 44.4, 41.7, 30.0; IR (KBr) 3085, 3026, 2945, 2872, 1787,
1692, 1583, 1503, 1465, 1370, 1290, 1210, 1175, 1106, 1091, 1014, 985 cm-1; HRMS: m/z calcd
for C33H30N2O6S (M+Na)+ 605.1680; found 605.1717
(1-Heptyl-7-((4-nitrophenyl)sulfonyl)octahydro-1H-pyrano[3,4-c]pyridin-5-yl)(phenyl) methanone (8k):
1H NMR (400 MHz, CDCl3) δ 8.30 – 8.25 (m, 2H), 7.90 – 7.84 (m, 2H), 7.77 (d, J = 8.3 Hz,
2H), 7.60 – 7.53 (m, 1H), 7.44 (dd, J = 10.6, 4.8 Hz, 2H), 4.06 – 3.94 (m, 2H), 3.89 (d, J = 9.7
Hz, 1H), 3.64 (d, J = 4.1 Hz, 1H), 3.39 (t, J = 11.9 Hz, 1H), 3.02 – 2.81 (m, 2H), 2.54 - 2.40 (m,
1H), 2.20 (t, J = 11.6 Hz, 1H), 1.88 – 1.73 (m, 2H), 1.40 – 1.20 (m, 13H), 0.89 (t, J = 6.7 Hz,
3H); 13C NMR (125 MHz, CDCl3) δ 198.4, 150.0, 143.6, 136.5, 133.2, 128.7, 128.6, 127.9,
124.1, 79.9, 68.0, 48.2, 47.0, 42.9, 41.3, 38.3, 32.8, 31.8, 30.9, 29.3, 29.3, 25.0, 22.6, 14.0; IR
(KBr) 3060, 3015, 2912, 2862, 1749, 1654, 1581, 1535, 1450, 1381, 1290, 1216, 1173, 1120,
1061, 1019, 973 960 cm-1; HRMS: m/z calcd for C28H36N2O6S (M+H)+ 529.2367; found
529.2347
(7-((4-Nitrophenyl)sulfonyl)-1-pentyloctahydro-1H-pyrano[3,4-c]pyridin-5-yl)(phenyl)
methanone (8l):
NsN
O
O
HH
NsN
O
O
H H
S10
1H NMR (400 MHz, CDCl3) δ 8.29 (d, J = 10.0 Hz, 2H), 7.85 (d, J = 11.4 Hz, 2H), 7.78 (d, J =
9.6 Hz, 2H), 7.61 – 7.50 (m, 1H), 7.44 (dd, J = 10.6, 4.8 Hz, 2H), 4.05 – 3.95 (m, 2H), 3.92 (d, J
= 9.8 Hz, 1H), 3.64 (d, J = 4.2 Hz, 1H), 3.39 (t, J = 8.5 Hz, 1H), 2.97 (d, J = 8.8 Hz, 1H), 2.92 –
2.83 (m, 1H), 2.60 – 2.42 (m, 1H), 2.19 (t, J = 10.0 Hz, 1H), 1.85 – 1.70 (m, 1H), 1.52 – 1.46 (m,
2H), 1.37 – 1.25 (m, 8H), 0.90 (t, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 198.4, 150.0,
143.6, 136.5, 133.2, 128.7, 128.6, 127.9, 124.1, 79.9, 68.0, 48.2, 47.0, 42.9, 41.3, 38.2, 32.7,
31.9, 29.3, 24.6, 22.6, 14.0; IR (KBr) 3055, 3016, 2938, 2352, 1748, 1684, 1595, 1519, 1460,
1386, 1295, 1209, 1175, 1106, 1086, 1016, 975, 962 cm-1; HRMS: m/z calcd for C26H32N2O6S
(M+H)+ 501.2054; found 501.2024
1-(4-Chlorophenyl)-7-tosyloctahydro-1H-pyrano[3,4-c]pyridin-5-yl)(p-tolyl)methanone
(8m)
TsN
O
O
H H
CH3
Cl
1H NMR (500 MHz, CDCl3) δ 7.89 (d, J = 8.2 Hz, 2H), 7.48 (d, J = 9.4 Hz, 2H), 7.37 (d, J = 7.8
Hz, 2H), 7.34 – 7.27 (m, 4H), 7.25 – 7.22 (m, 2H), 4.04 – 3.98 (m, 1H), 3.97 – 3.90 (m, 2H),
3.63 – 3.51 (m, 2H), 3.25 (d, J = 10.5 Hz, 1H), 2.46 (s, 3H), 2.45 (s, 3H), 2.37 – 2.31 (m, 1H),
1.96 (t, J = 14.4 Hz, 1H), 1.91 – 1.84 (m, 2H), 1.50 – 1.43 (m, 2H); 13C NMR (125 MHz, CDCl3)
δ 200.06, 145.27, 143.92, 137.63, 134.46, 134.11, 133.04, 129.84, 129.78, 129.10, 128.54,
128.38, 127.54, 81.96, 68.18, 49.15, 47.57, 44.56, 41.53, 30.03, 29.73, 21.78, 21.59.
S11
(4-Methoxyphenyl)-(1-phenyl-7-tosyloctahydro-1H-pyrano[3,4-c]pyridin-5-yl)methanone
(8n)
TsN
O
O
HH
OCH3
1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.2 Hz, 1H), 7.63 (d, J = 7.5 Hz, 2H), 7.49 (d, J = 7.8
Hz, 3H), 7.39 (dd, J = 14.1, 7.1 Hz, 2H), 7.34 – 7.26 (m, 3H), 7.02 – 6.97 (m, 1H), 6.80 – 6.73
(m, 1H), 4.38 (d, J = 9.8 Hz, 1H), 4.31 – 4.23 (m, 2H), 4.19 (d, J = 11.2 Hz, 1H), 4.01 – 3.92 (m,
1H), 3.83 (d, J = 10.0 Hz, 1H), 3.77 – 3.70 (m, 3H), 3.45 (d, J = 6.5 Hz, 1H), 2.99 (d, J = 8.0 Hz,
1H), 2.53 (dd, J = 11.4, 3.0 Hz, 1H), 2.39 (d, J = 3.5 Hz, 3H), 2.12 – 2.08 (m, 2H), 1.54 (d, J =
11.6 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 207.27, 171.11, 158.19, 149.56, 143.63, 140.04,
138.57, 136.04, 134.61, 133.71, 130.16, 129.68, 128.47, 127.55, 126.09, 120.21, 111.87, 110.64,
101.21, 77.84, 67.03, 60.44, 55.82, 55.48, 45.10, 39.22, 30.97, 21.50, 14.18.
S12
NMR spectroscopic data:
1D (1H, 1H-1H Homo-nuclear Decoupling and 13C) and 2D (DQCOSY, NOESY, TOCSY and
HSQC) NMR spectra of 8a dissolved in CDCl3, are recorded at 298 K on a Bruker Avance 700
MHz and 600 MHz (13C at 150 MHz) spectrometers Chemical shifts () are reported in ppm and
tetra methyl silane (TMS) δ=0.00 ppm for 1H (CDCl3 δ=77.00 ppm for 13C) is used as the
internal standard. Coupling constants (J) are reported in hertz (Hz). The following abbreviations
are used to designate the multiplicities: d=doublet, ddd= doublet of doublet of doublet, tdd=
triplet of doublet of doublet, td=triplet of doublet, q=quartet, m=multiplet.
The structure of 8a is unambiguously conformed by the incisive NMR studies such as 2D-
NOESY, and J-coupling analysis.
Table 1. 1H NMR chemical shift (ppm) and coupling constant (Hz) values of compound-8a in CDCl3 (298 K, 700 MHz):
Proton (δ) ppm multiplicity Coupling constant
(J) values (Hz)
2-H(a) 3.66 td 2J2-H(a)/2-H(b) = 12.3
3J2-H(a)/3-H(a) = 12.1
3J2-H(a)/3-H(b) = 3.5
2-H(b) 4.13 ddd 2J2-H(b)/2-H(a) = 12.3
3J2-H(b)/3-H(a) = 4.8
3J2-H(b)/3-H(b) = 1.9
3-H(a) 2.03 m 2J3-H(a)/3-H(b) = 12.8
3J3-H(a)/2-H(a) = 12.1
S13
3J3-H(a)/10-H = 12.0
3J3-H(a)/2-H(b) = 4.8
3-H(b) 1.48 m 2J3-H(b)/3-H(a) = 12.8
3J3-H(b)/2-H(a) = 3.5
3J3-H(b)/2-H(b) = 1.9
3J3-H(b)/10-H = 1.5
4-H 3.76 m 3J4-H/5-H(a) = 4.4
3J4-H/10-H = 4.2
3J4-H/5-H(b) = 1.8
5-H(a) 3.27 dd 2J5-H(a)/5-H(b) = 12.8
3J5-H(a)/4-H = 4.4
5-H(b) 4.15 dt 2J5-H(b)/5-H(a) = 12.8
3J5-H(b)/4-H = 1.8
7-H(a) 2.58 t 2J7-H(a)/7-H(b) = 12.2
3J7-H(a)/9-H = 12.0
7-H(b) 3.45 ddd 2J7-H(b)/7-H(a) = 12.2
3J7-H(b)/9-H = 4.4
8-H 4.52 d 3J8-H/9-H = 9.9
S14
9-H 3.03 m 3J9-H/7-H(a) = 12.0
3J9-H/10-H = 12.5
3J9-H/8-H = 9.9
3J9-H/7-H(b) = 4.4
10-H 1.93 m 3J10-H/9-H = 12.5
3J10-H/3-H(a) = 12.0
3J10-H/4-H = 4.2
3J10-H/3-H(b) = 1.5
S15
Figure 2. 1H NMR spectrum of 8a with chemical shift assignments (CDCl3, 298 K, AVANCE 600 MHz)
S16
Figure 2. 1H NMR spectrum of 8a (CDCl3, 298 K, AVANCE 600 MHz)
Figure 3. 13C NMR spectrum of 8a (CDCl3, 298 K, AVANCE 150 MHz)
S17
Figure 4. DQFCOSY spectrum of 8a (CDCl3, 298 K, AVANCE 600 MHz)
Figure 5. TOCSY spectrum of 8a (CDCl3, 298 K, AVANCE 600 MHz)
S18
Figure 6. NOESY spectrum of 8a (CDCl3, 298 K, AVANCE 600 MHz)
S19
Figure 7. HSQC spectrum of 8a (CDCl3, 298 K, AVANCE 600 MHz)
S20
Figure 1. 1H NMR spectrum of 8m (CDCl3, 298 K, AVANCE 500 MHz)
Figure 2. 13C NMR spectrum of 8m (CDCl3, 298 K, AVANCE 125 MHz)
S21
Figure 3. Expanded region of DQFCOSY spectrum of 8m (CDCl3, 298 K, AVANCE 500 MHz)
S22
Figure 4. Expanded region of TOCSY spectrum of 8m (CDCl3, 298 K, AVANCE 500 MHz)
S23
Figure 5. Expanded region of TOCSY spectrum of 8m (CDCl3, 298 K, AVANCE 500 MHz)
S24
Figure 6. HSQC spectrum of 8m (CDCl3, 298 K, AVANCE 500 MHz)
S25
1H NMR Spectra of compound 6a (500 MHz, CDCl3)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
0.84
2.08
2.012.01
2.07
1.00
1.03
1.84
1.84
13C NMR Spectra of compound 6a (100 MHz, CDCl3)
0102030405060708090100110120130140150f1 (ppm)
35.4
335
.78
48.5
5
61.5
9
74.3
075
.89
76.6
877
.00
77.3
2
124.
0812
5.39
128.
9413
3.66
144.
79
150.
10
NsN OH
NsN OH
S26
1H NMR Spectra of compound 6b (500 MHz, CDCl3)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)
1.13
1.04
2.16
4.35
1.02
1.04
2.03
2.00
13C NMR Spectra of compound 6b (125 MHz, CDCl3)
0102030405060708090100110120130140150f1 (ppm)
35.8
4
47.9
5
62.2
1
74.4
675
.64
76.7
577
.00
77.2
5
123.
4912
4.08
128.
89
135.
42
144.
57
150.
06
NsNOH
NsNOH
S27
1H NMR Spectra of compound 6c (400 MHz, CDCl3)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
3.11
4.06
2.40
2.13
3.38
1.81
1.82
1.81
1.02
0.91
1.22
2.45
2.27
13C NMR Spectra of compound 6c (100 MHz, CDCl3)
-505101520253035404550556065707580859095105115125135145f1 (ppm)
13.4
7
18.0
621
.45
21.7
8
30.3
8
35.5
136
.32
48.1
8
61.6
7
72.4
276
.68
77.0
077
.32
86.1
5
126.
6712
7.75
129.
2613
2.09
136.
15
143.
16
TsN OH
TsN OH
S28
1H NMR Spectra of compound 6d (500 MHz, CDCl3)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
6.66
1.82
2.14
2.01
2.00
1.04
1.24
1.93
1.99
1.20
1.99
1.02
13C NMR Spectra of compound 6d (125 MHz, CDCl3)
0102030405060708090100110120130140150f1 (ppm)
21.3
921
.50
35.4
435
.50
36.7
236
.83
48.7
048
.84
61.6
6
76.7
577
.00
77.2
580
.36
86.4
5
118.
32
123.
9912
5.68
128.
9712
9.09
131.
1013
3.47
139.
23
144.
83
149.
94
TsN OH
CH3
TsN OH
CH3
S29
1H NMR Spectra of compound 6e (400 MHz, CDCl3)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
0.98
1.81
3.26
2.04
2.97
2.06
2.00
1.02
1.02
2.05
2.01
2.02
2.00
13C NMR Spectra of compound 6e (100 MHz, CDCl3)
0102030405060708090100110120130140150160f1 (ppm)
21.3
4
35.4
636
.68
48.4
5
55.1
9
61.5
9
76.6
877
.00
77.3
280
.22
85.4
6
113.
6311
4.13
126.
3012
7.67
129.
3713
2.44
132.
8213
5.82
143.
34
159.
50
TsN OH
OCH3
TsN OH
OCH3
S30
1H NMR Spectra of compound 8a (500 MHz, CDCl3)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
2.14
2.12
1.08
1.04
1.06
1.03
1.14
2.12
0.99
1.15
2.02
2.92
3.44
2.25
2.00
13C NMR Spectra of compound 8a (125 MHz, CDCl3)
0102030405060708090100110120130140150160170180190200f1 (ppm)
29.2
1
41.0
341
.64
43.2
546
.93
48.7
4
68.8
2
76.7
977
.04
77.3
0
124.
0512
7.85
128.
0512
8.85
128.
9812
9.21
129.
4813
0.81
131.
4213
2.05
132.
8313
3.26
133.
4013
6.84
137.
0314
8.03
198.
74
NsN
O
O
Cl
H H
NsN
O
O
Cl
H H
S31
1H NMR Spectra of compound 8b (400 MHz, CDCl3)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
2.35
1.11
1.18
1.00
1.01
1.04
2.00
3.07
2.13
3.26
2.84
3.01
1.38
1.91
13C NMR Spectra of compound 8b (125 MHz, CDCl3)
0102030405060708090100110120130140150160170180190200f1 (ppm)
30.1
3
41.5
844
.85
46.9
148
.10
48.6
4
68.1
1
76.7
577
.00
77.2
582
.35
124.
2412
6.99
128.
4112
8.66
128.
7712
9.04
130.
1313
0.86
131.
6613
1.77
133.
6513
4.02
136.
6113
8.87
147.
93
200.
37
NsN
O
O
H H
NsN
O
O
H H
S32
1H NMR Spectra of compound 8c (500 MHz, CDCl3)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
1.94
2.94
3.034.28
1.07
2.11
1.002.09
1.041.071.083.002.011.981.00
1.96
13C NMR Spectra of compound 8c (125 MHz, CDCl3)
0102030405060708090100110120130140150160170180190200f1 (ppm)
21.5
3
30.1
0
41.6
844
.23
47.1
747
.76
49.1
2
68.1
1
76.7
577
.00
77.2
5
82.8
1
124.
1712
7.51
128.
3312
8.61
129.
0312
9.55
129.
7713
3.19
134.
0313
6.60
138.
5613
8.83
143.
79
200.
63
TsN
O
O
H3C
H H
TsN
O
O
H3C
H H
S33
1H NMR Spectra of compound 8d (400 MHz, CDCl3)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
2.27
1.31
1.19
1.07
1.17
1.15
2.18
3.25
2.492.343.243.381.372.00
13C NMR Spectra of compound 8d (125 MHz, CDCl3)
0102030405060708090100110120130140150160170180190200f1 (ppm)
29.9
5
41.3
545
.12
46.7
348
.04
48.7
7
68.1
5
76.7
977
.04
77.3
081
.53
112.
53
118.
5812
4.35
127.
8212
8.43
129.
1413
0.85
131.
7613
2.60
133.
9513
4.20
144.
22
148.
01
199.
97
NsN
O
O
NCHH
NsN
O
O
NCHH
S34
1H NMR Spectra of compound 8e (500 MHz, CDCl3)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
2.10
1.37
0.97
1.02
1.02
1.06
2.06
2.08
1.10
1.16
1.012.043.141.241.032.00
13C NMR Spectra of compound 8e (100 MHz, CDCl3)
0102030405060708090100110120130140150160170180190200f1 (ppm)
29.8
5
41.2
745
.40
46.3
347
.94
48.7
7
68.2
1
73.5
276
.68
77.0
077
.32
124.
3112
8.40
129.
0913
0.70
131.
3913
1.68
133.
9213
4.15
136.
38
148.
05
199.
94
NsN
O
O
FF
FH H
NsN
O
O
FF
FH H
S35
1H NMR Spectra of compound 8f (400 MHz, CDCl3)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
1.96
2.291.73
3.11
0.84
1.88
0.901.71
1.173.085.210.900.742.14
13C NMR Spectra of compound 8f (125 MHz, CDCl3)
0102030405060708090100110120130140150160170180190200f1 (ppm)
21.6
4
30.0
3
41.5
544
.45
47.0
547
.72
49.1
4
68.2
0
76.8
377
.08
77.3
382
.03
125.
6212
7.58
128.
4212
9.15
129.
9413
0.24
130.
4513
1.93
133.
2713
4.19
136.
7114
1.40
200.
52
TsN
O
O
HH
F
TsN
O
O
HH
F
S36
1H NMR Spectra of compound 8g (500 MHz, CDCl3)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
2.35
1.26
1.28
3.041.09
1.05
1.09
2.20
1.212.25
4.37
2.182.901.321.01
2.00
13C NMR Spectra of compound 8g (100 MHz, CDCl3)
0102030405060708090100110120130140150160170180190200f1 (ppm)
21.2
6
30.1
3
41.6
444
.71
46.9
848
.04
48.6
6
68.0
8
76.6
877
.00
77.3
282
.15
124.
2312
6.89
128.
4112
9.03
129.
4513
0.85
131.
6413
1.72
133.
6613
4.03
135.
8313
6.59
138.
3314
7.94
200.
45
NsN
O
O
H H
NsN
O
O
H H
S37
1H NMR Spectra of compound 8h (500 MHz, CDCl3)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
2.56
0.92
0.99
1.09
1.01
1.04
2.05
3.00
1.05
2.05
3.17
1.39
2.00
1.12
1.98
1.03
0.94
1.90
13C NMR Spectra of compound 8h (125 MHz, CDCl3)
0102030405060708090100110120130140150160170180190200f1 (ppm)
30.1
41.5
44.7
46.9
48.1
48.6
55.2
68.1
76.7
77.0
77.3
82.2
112.
011
4.6
119.
512
4.2
128.
412
9.0
129.
713
0.8
131.
713
1.7
133.
713
4.0
136.
614
0.3
147.
9
159.
9
200.
4
NsN
O
O
H3CO
H H
NsN
O
O
H3CO
H H
S38
1H NMR Spectra of compound 8i (500 MHz, CDCl3)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
2.15
3.12
3.33
1.00
1.041.051.054.452.10
1.08
2.10
2.071.041.992.04
2.00
13C NMR Spectra of compound 8i (100 MHz, CDCl3)
0102030405060708090100110120130140150160170180190200f1 (ppm)
16.4
30.1
41.9
44.3
47.2
47.7
49.0
55.4
68.0
76.7
77.0
77.3
82.2
110.
0
124.
412
5.6
127.
312
8.3
128.
612
9.1
130.
313
4.2
136.
514
2.4
150.
2
158.
1
200.
3
NsN
O
O
H3C
H3COH H
NsN
O
O
H3C
H3COH H
S39
1H NMR Spectra of compound 8j (500 MHz, CDCl3)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)
1.92
2.85
1.07
1.08
2.09
3.18
3.022.282.285.191.972.00
1.88
13C NMR Spectra of compound 8j (100 MHz, CDCl3)
0102030405060708090100110120130140150160170180190200f1 (ppm)
30.1
41.8
44.5
47.1
47.7
49.0
68.1
76.7
77.0
77.3
82.2
124.
512
7.2
127.
412
7.5
127.
712
8.4
128.
612
8.8
129.
113
4.2
136.
513
7.7
140.
614
1.7
142.
415
0.2
200.
2
NsN
O
O
HH
NsN
O
O
HH
S40
1H NMR Spectra of compound 8k (400 MHz, CDCl3)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
3.43
13.00
1.54
0.96
0.97
1.83
1.000.951.091.85
1.720.921.661.67
1.59
13C NMR Spectra of compound 8k (125 MHz, CDCl3)
0102030405060708090100110120130140150160170180190200f1 (ppm)
14.1
22.6
25.0
29.3
29.4
30.9
31.8
32.8
38.3
41.4
43.0
47.0
48.3
68.0
76.7
77.0
77.3
80.0
124.
212
7.9
128.
712
8.8
133.
313
6.6
143.
6
150.
0
198.
4
NsN
O
O
HH
NsN
O
O
HH
S41
1H NMR Spectra of compound 8l (400 MHz, CDCl3)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
3.18
8.052.29
1.15
1.05
1.09
1.061.01
1.121.001.102.13
1.961.141.981.90
1.99
13C NMR Spectra of compound 8l (125 MHz, CDCl3)
0102030405060708090100110120130140150160170180190200f1 (ppm)
14.1
22.6
24.7
29.3
32.0
32.8
38.3
41.3
43.0
47.0
48.3
68.0
76.7
77.0
77.3
80.0
124.
212
7.9
128.
712
8.8
133.
313
6.6
143.
6
150.
0
198.
5
NsN
O
O
H H
NsN
O
O
H H
S42
1H NMR Spectra of compound 8m (500 MHz, CDCl3)
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
2.35
2.10
1.10
1.28
6.27
1.01
2.17
2.09
1.09
2.27
4.39
2.13
2.02
2.00
13C NMR Spectra of compound 8m (125 MHz, CDCl3)
0102030405060708090100110120130140150160170180190200210f1 (ppm)
21.5
921
.78
29.7
330
.03
41.5
344
.56
47.5
749
.15
68.1
8
76.7
977
.05
77.3
081
.96
127.
5412
8.38
128.
5412
9.10
129.
7812
9.84
133.
0413
4.11
134.
4613
7.63
143.
9214
5.27
200.
06
TsN
O
O
H H
CH3
Cl
TsN
O
O
H H
CH3
Cl
S43
1H NMR Spectra of compound 8n (400 MHz, CDCl3)
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
1.36
2.33
3.01
1.23
1.19
1.00
3.06
0.74
1.08
1.12
2.17
0.93
1.15
1.46
3.32
2.59
3.56
2.26
1.33
13C NMR Spectra of compound 8n (150 MHz, CDCl3)
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
14.1
8
21.5
0
30.9
7
39.2
2
45.1
0
55.4
855
.82
60.4
467
.03
76.7
977
.00
77.2
177
.84
101.
21
110.
6411
1.87
120.
2112
6.09
127.
5512
8.47
129.
6813
0.16
133.
7113
4.61
138.
5714
3.63
149.
56
158.
19
171.
11
207.
27
TsN
O
O
HH
OCH3
TsN
O
O
HH
OCH3