derivatives synthesis of octahydro-1H-pyrano[3,4-c]pyridin-5 … · 2016-11-10 · S1 Supporting Information for Sequential oxonium-olefin-alkyne cyclization for the stereoselective

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: [email protected]; 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