Supporting Information: Ester with Alcohols via …S1 Supporting Information: Manganese-Catalyzed...
Transcript of Supporting Information: Ester with Alcohols via …S1 Supporting Information: Manganese-Catalyzed...
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Supporting Information:
Manganese-Catalyzed Direct C-C Coupling of α-C−H bonds of Amides and
Ester with Alcohols via Hydrogen Autotransfer
Ekambaram Balaraman*a Jagannath Rana,b,c Virendrakumar Gupta*d
a Department of Chemical Sciences, Indian Institute of Science Education and Research –
Tirupati (IISER-T), Tirupati 517507, India.
b Organic Chemistry Division, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi
Bhabha Road, Pune 411008, India.
c Academy of Scientific and Innovative Research (AcSIR), Ghaziabad - 201002, India.
d Polymer Synthesis & Catalysis, Reliance Research & Development Centre, Reliance
Industries Limited, Ghansoli 400701, Navi Mumbai, India.
Table of Content
1. Experimental section S2-S4
2. Mechanistic investigations S4-S8
3. Diversification of C-alkylated amides S8-S9
4. Characterization data of compounds S9-S16
5. Copies of NMR spectra S17-S41
6. HRMS Data S42-S51
Electronic Supplementary Material (ESI) for Dalton Transactions.This journal is © The Royal Society of Chemistry 2019
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1 Experimental Section
1a. General Information
All catalytic experiments were carried out using standard Schlenk techniques. Unless
otherwise stated reaction were conducted in flame-dried glassware under an atmosphere of
nitrogen and commercially obtained reagent were used as received. All solvents were reagent
grade or better. Toluene was refluxed over sodium/benzophenone, followed by distilled under
argon atmosphere and stored over sodium. Chemicals used in catalysis reactions were used
without additional purification. Thin layer chromatography (TLC) was performed using silica
gel precoated aluminium foil which was visualized with visualized with UV light at 254 nm
or under iodine. Column chromatography was performed with SiO2 (Silicycle Siliaflash F60
(230-400 mesh). 1H NMR (500, 200 MHz), 13C NMR (126, 50 MHz) spectra were recorded
on the NMR spectrometer. Deuterated chloroform was used as the solvent, and chemical shift
values (δ) are reported in parts per million relative to the residual signals of this solvent [δ
7.27 for 1H (chloroform-d), δ 77.2 for 13C{1H} (chloroform-d). Abbreviations used in the
NMR follow-up experiments: s, singlet; d, doublet; dd, doublet of doublet; t, triplet; tt, triplet
of triplet; td, triplet of doublet; q, quartet; br, broad; m, multiplet. GC analysis was carried out
using a HP-5 column (30 m, 0.25 mm, 0.25μ). Mass spectra were obtained on a GCMS-QP
5000 instruments with ionization voltages of 70 eV. High resolution mass spectra (HRMS)
were obtained on a High-resolution mass spectra (HRMS) were obtained by fast atom
bombardment (FAB) using a double focusing magnetic sector mass spectrometer and electron
impact (EI) ionization technique (magnetic sector-electric sector double focusing mass
analyzer).
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1b. Complexes used for the present study
In a three-necked round-bottom flask (100 mL) under an argon atmosphere, Mn(CO)5Br (1.0
equivalents) was added in toluene. After that, PNP pincer ligand (1.05 equivalents) was
added drop by drop via syringe at room temperature. After stirring, the reaction mixture was
heated to 100 °C for 20 h. During that time the reaction mixture became an orange solution.
After cooling down to room temperature and removing the solvent at reduced pressure, led to
a yellow solid. Washing this solid with heptane (2 x 10 mL) and drying under high vacuum
provided the corresponding manganese complexes. The synthetic procedure for the complex
was followed from this literature, matches the data with literature value. [M. Peña-López, P.
Piehl, S. Elangovan, H. Neumann, M. Beller, Angew. Chem. Int. Ed. 2016, 55, 14967.]
N PCy2
PCy2
H
MnCO
CO
Br
Ia
N PtBu2
PtBu2
H
MnCO
CO
Br
Ib
N PPh2
PPh2
H
MnCO
CO
Br
Ic
1c. General experimental procedure for Mn-catalyzed C-alkylation of amides
In a 10 mL oven dried sealed tube, alcohol 2 (0.5 mmol, 1 equiv), and amide 1 (1.0 mmol, 2
equiv), manganese complex [Mn]-Ia (0.5 mol%), KOtBu (0.6 mmol, 1.2 equiv) were added
under an argon atmosphere in toluene (1.0 mL). The flask was sealed with a teflon plug under
an argon atmosphere, and the solution stirred at 110 oC for 16 hours. Then the reaction
mixture was cooled to room temperature, and the reaction mixture was quenched with water
(20 mL) and extracted with dichloromethane (2 x 20 mL). The entire organic layer was
combined, washed with brine (20 mL) and then dried over Na2SO4. After concentration under
reduced pressure, residue was purified by 250-400 mesh silica-gel column chromatography
using ethyl acetate/petroleum ether (1:3) to afford the pure product 3.
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1d. General experimental procedure for Mn-catalyzed C-alkylation of tert-butyl acetate
In a 10 mL oven dried sealed tube, alcohol 2 (0.5 mmol, 1 equiv), and tert-butyl acetate 1a’
(1.0 mmol, 2 equiv), manganese complex [Mn]-Ia (0.5 mol%), KOtBu (0.6 mmol, 1.2 equiv)
were added under an argon atmosphere in toluene (1.0 mL). The flask was sealed with a
teflon plug under an argon atmosphere, and the solution stirred at 80 oC for 12 hours. Then
the reaction mixture was cooled to room temperature, and the reaction mixture was quenched
with water (20 mL) and extracted with dichloromethane (2 x 20 mL). The entire organic layer
was combined, washed with brine (20 mL) and then dried over Na2SO4. After concentration
under reduced pressure, residue was purified by 250-400 mesh silica-gel column
chromatography using ethyl acetate/petroleum ether (1:3) to afford the pure product 5.
2. Mechanistic investigations
2a. Detection of H2 gas liberation
The evolution of H2 gas during the alkylation process was qualitatively observed using GC
analysis which reveals the reaction takes place via Mn-catalyzed auto hydrogen transfer
pathway.
OH
O
NMe
Me+ Standard conditions H2
1a 2a
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H2
Figure S1. GC analysis.
2b. Intermediate Determination
An,-unsaturated amide8 was applied under standard catalytic conditions in the presence
of benzyl alcohol 2h as hydrogen donor. The GC analysis of crude mixture showed the
formation of -alkylated amide and the corresponding dehydrogenated product (aldehyde) of
2h which confirmed the formation of enone (8) as a key intermediate in the catalytic process.
H
O
N Me
Me+
KOtBu (1.5 eq) N
OMe
Me
O
N
OMe
Me[Mn]-1a (0.5 mol%)
KOtBu (1.2 eq.)Toluene, 110 oC
N
OMe
Me
Cl Cl
Cl Cl
8
8 3h
1a (90%)THF, rt
+
O
H
Cl
2h (2 equiv)
(a)
(b)
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2c. Deuterium experiment
a) To a 15 mL clean and oven-dried screw cap reaction tube, 1a or 8 (1.0 mmol) and 2h-
[d] (96%) (0.5 mmol) were added under standard reaction conditions. Then the reaction was
performed under standard condition for 16 h. The percentage of deuterium incorporation in
the product was calculated based on HRMS analysis.
OH/D
DD
Cl
+ standard condtions N
OMe
MeCl
D/H
3h-d13h-d2
D/H = 46%D/D = 54%
1a or 8
2h-[d]
D D/H
J-92 #288 RT: 1.28 AV: 1 NL: 3.31E7T: FTMS + p ESI Full ms [100.0000-1500.0000]
210.0 210.5 211.0 211.5 212.0 212.5 213.0 213.5 214.0 214.5 215.0 215.5m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
211.0740R=77006
C 11 H12 2H O N Cl = 211.0743-1.3012 ppm
214.0959R=77006
C 11 H13 2H2 O N Cl = 214.0962-1.4963 ppm
213.0896R=77302
C 11 H12 2H2 O N Cl = 213.08845.5729 ppm
215.0866R=76502212.0648
R=76202
214.9171R=75702
210.9890R=60600
D
N
O
Cl
D
N
O
ClD
Figure S2. HRMS data for deuterium incorporation.
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2d. Parallel and competition experiments
To a 15 mL clean and oven-dried screw cap reaction tube, 1a (1.0 mmol) and 2h (0.5 mmol),
2h-[d] (96%) (0.5 mmol) were added under standard reaction conditions. Then the reaction
was carried out for 16 h. The percentage of deuterium incorporation in the product was
calculated based on HRMS analysis.
OH/D
DD
Cl
+standard condtions
D
N
OMe
MeCl
N
OMe
MeCl
3h-d1
3h
D/H = 35%
H/H = 65%1a
2h-[d]
+
OH
HH
Cl 2h
J-93 #275 RT: 1.22 AV: 1 NL: 4.10E8T: FTMS + p ESI Full ms [100.0000-1500.0000]
211 212 213 214 215 216 217 218 219 220 221 222 223 224m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
212.0827R=78002
C 11 H15 O N Cl = 212.0837-4.4815 ppm
213.0889R=75206
214.0803R=77402
215.0869R=74502
216.0929R=72200
219.1741R=73607
220.9344R=71502
220.1122R=70602
211.1596R=56900
217.0962R=59600
218.1177R=37100
N
OMe
MeCl
N
OMe
MeCl
D
Figure S3. HRMS data for deuterium incorporation.
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2e. Homogeneous nature of Mn-catalysis
In a 10 mL oven dried sealed tube, 2b (0.5 mmol, 1 equiv), 1a (1.0 mmol, 2 equiv),
manganese complex [Mn]-Ia (0.5 mol%), KOtBu (0.6 mmol, 1.2 equiv), and Hg (1 drop)
were added under an argon atmosphere in toluene (1.0 mL). The flask was sealed with a
teflon plug under an argon atmosphere, and the solution stirred at 110 oC for 16 hours. Then
the reaction mixture was cooled to room temperature, and the reaction mixture was quenched
with water (20 mL) and extracted with dichloromethane (2 x 20 mL). The entire organic layer
was combined, washed with brine (20 mL) and then dried over Na2SO4. After concentration
under reduced pressure, residue was purified by 250-400 mesh silica-gel column
chromatography using ethyl acetate/petroleum ether (1:3) to afford C-alkylated amide (3b) in
71% isolated yield.
3. Diversification of C-alkylated amides
N
OMe
Me
i. Bu3SnLi, THF, rt
ii. H2O, rtH
O
OHi. SmI2-Et3N-H2O
THF, rt
3a
6 (52%)
7 (75%)
3.1. α-alkylated amide to aldehyde
To a 15 mL clean, oven-dried screw cap reaction tube was added 3a (0.1 mmol) and Bu3SnLi
(320 mol%) in THF under argon atmosphere at 0oC. Then the reaction was stirring at room
temperature for 48 h. After that the reaction mixture was quenched with water and extracted
with dichloromethane (3 x 5 mL). The resultant organic layer was dried over anhydrous
Na2SO4 and the solvent was evaporated under reduced pressure. The crude mixture was
purified by silica gel column chromatography (230-400 mesh size) using petroleum-
ether/ethyl acetate as an eluting system.
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3.2. α-alkylated amide to alcohol
To a 15 mL clean, oven-dried screw cap reaction tube was added 3a (0.1 mmol) and
samarium(II) iodide (THF solution, 8 equiv) followed by Et3N (72 equiv) and H2O (72 equiv)
under argon atmosphere, resulted the formation of a dark brown color of the SmI2-Et3N-H2O
complex. Then the reaction mixture was stirred for 24 h at room temperature. After the
completion of reaction the reaction mixture was diluted with CH2Cl2 and NaOH (1N)
solution. The aqueous layer was extracted with CH2Cl2 (3 x 30 mL) and the combined
organic layers were dried over Na2SO4, and concentrated. The crude mixture was purified by
silica gel column chromatography (230-400 mesh size) using petroleum-ether/ethyl acetate as
an eluting system.
4. Characterization Data of Compounds
N,N-dimethyl-3-phenylpropanamide (3a)
The general procedure was followed to afford the title compound as colourless liquid,
isolated yield: 82%, 72 mg; 1H NMR (200 MHz, CDCl3) δ 7.39-7.33 (m, 2H), 7.31-7.25 (m,
3H), 3.07-2.98 (m, 8H), 2.69 (t, J = 6.7 Hz, 2H); 13C NMR (50 MHz, CDCl3) δ 172.1, 141.4,
128.4, 128.3, 126.0, 37.0, 35.3,35.2, 31.3. HRMS (EI) m/z Calcd for C11H16NO [M+H]+:
178.1226; Found: 178.1233.
N,N-dimethyl-3-(p-tolyl)propanamide (3b)
The general procedure was followed to afford the title compound as colourless oil, isolated
yield: 85%, 81 mg; 1H NMR (200 MHz, CDCl3) δ 7.22-7.03 (m, 4H), 3.04-2.86 (m, 8H), 2.60
(t, J = 6.7 Hz, 2H), 2.33(s, 3H); 13C NMR (50 MHz, CDCl3) δ 172.3, 138.4, 135.5, 129.0,
128.2, 37.1, 35.4 (2), 30.9, 20.9; HRMS (EI) m/z Calcd for C12H18NO [M+H]+: 192.1383;
Found: 192.1384.
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N,N-dimethyl-3-(m-tolyl)propanamide (3c)
The general procedure was followed to afford the title compound as colourless oil, isolated
yield: 78%, 74 mg; 1H NMR (200 MHz, CDCl3) δ = 7.18 (t, J = 8.1 Hz, 1H), 7.04-7.01 (m,
3H), 2.95-2.90 (m, 8H), 2.61 (t, J = 7.3 Hz, 2H), 2.34 (s, 3H); 13C NMR (50 MHz, CDCl3) δ
= 172.2, 141.3, 137.9, 129.1, 128.3, 126.7, 125.3, 37.1, 35.3, 35.3, 31.2, 21.3; HRMS (EI):
m/z Calcd for C12H18NO [M+H]+: 192.1383; Found: 192.1384.
N,N-dimethyl-3-(o-tolyl)propanamide (3d)
The general procedure was followed to afford the title compound as colourless oil, isolated
yield: 70%, 67 mg; 1H NMR (500 MHz, CDCl3) δ 7.20-7.07 (m, 4H), 3.00-2.90 (m, 8H), 2.57
(t, J = 6.7 Hz, 2H), 2.34(s, 3H); 13C NMR (126 MHz, CDCl3) δ 172.3, 139.5, 135.9, 130.2,
128.7, 126.2, 126.0, 37.1, 35.4, 33.8, 28.7, 19.3; HRMS (EI): m/z Calcd for C12H18NO
[M+H]+: 192.1383; Found: 192.1384.
3-(4-methoxyphenyl)-N,N-dimethylpropanamide (3e)
The general procedure was followed to afford the title compound as colourless oil, isolated
yield: 88%, 91 mg; 1H NMR (200 MHz, CDCl3) δ 7.20-7.06 (td, J = 8.6, 2.1 Hz, 2H), 6.89-
6.76 (td, J = 8.6, 2.1 Hz, 2H), 3.78 (s, 3H), 2.98-2.84 (m, 8H), 2.58 (t, J = 6.6 Hz, 2H); 13C
NMR(50 MHz, CDCl3) δ 172.2, 157.8, 133.4, 129.2, 113.7, 55.1, 37.0, 35.4, 35.3, 30.3;
HRMS (EI): m/z Calcd for C12H18NO2[M+H]+: 208.1332; Found: 208.1331.
3-(3-methoxyphenyl)-N,N-dimethylpropanamide (3f)
The general procedure was followed to afford the title compound as colorless oil, isolated
yield: 72%, 74mg; 1H NMR (200 MHz, CDCl3) δ 7.23-7.03 (m, 1H), 6.84-6.58 (m, 3H), 3.71
(s, 3H), 3.04-2.72 (m, 8H), 2.53 (t, J = 6.7 Hz, 2H); 13C NMR (50 MHz, CDCl3) δ 172.3,
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159.6, 143.0, 129.4, 120.7, 114.1, 111.3, 55.1, 37.1, 35.4, 35.1, 31.3; HRMS (EI): m/z Calcd
for C12H18NO2[M+H]+: 208.1332; Found: 208.1331.
N,N-dimethyl-3-(4-(methylthio)phenyl)propanamide (3g)
The general procedure was followed to afford the title compound as colourless sticky liquid,
isolated yield: 78%, 87 mg; 1HNMR (200 MHz, CDCl3) δ = 7.23-7.12 (m, 4H), 2.97-2.89 (m,
8H), 2.59 (t, J = 8.3 Hz, 2H), 2.46 (s, 3H); 13CNMR (50 MHz, CDCl3) δ = 172.2, 138.5,
135.7, 128.9, 127.1, 37.2, 35.5, 35.1, 30.7, 16.2. HRMS(EI): m/z Calcd for C12H17NOS
[M+H]+: 224.1031; Found: 224.1029.
3-(4-chlorophenyl)-N,N-dimethylpropanamide (3h)
The general procedure was followed to afford the title compound as colourless oil, isolated
yield: 65%, 68 mg; 1H NMR (500 MHz, CDCl3) δ 7.38-7.34 (m, 2H), 7.31-7.28 (m, 2H),
3.06-2.97 (m, 8H), 2.69 (t, J = 6.6 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 172.2, 141.5,
128.5, 128.4, 126.1, 37.2, 35.4, 35.3, 33.4; HRMS (EI): m/z Calcd for C11H15NOCl [M+H]+:
212.0837; Found: 212.0837.
3-(4-fluorophenyl)-N,N-dimethylpropanamide (3i)
The general procedure was followed to afford the title compound as colourless sticky liquid.
Yield: 62%, 60 mg; 1HNMR (500 MHz, CDCl3) δ = 7.19-7.16 (m, 2H), 6.96 (t, J = 8.8 Hz,
2H), 2.96-2.91 (m, 8H), 2.59 (t, J = 8.0 Hz, 2H); 13CNMR (126 MHz, CDCl3) δ = 172.0,
162.3, 160.4, 137.0, 129.7, 128.4, 126.1, 115.2, 115.0, 37.1, 35.4, 35.2, 30.5.
3-(3,4-dimethoxyphenyl)-N,N-dimethylpropanamide (3j)
The general procedure was followed to afford the title compound as a colorless oil, isolated
yield: 80%, 95 mg; 1H NMR (500 MHz, CDCl3) δ 6.81-6.71 (m, 3H), 3.86 (s, 3H), 3.84 (s,
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3H), 2.96-2.84 (m, 8H), 2.59 (t, J = 6.8 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 172.2,
148.7, 147.2, 134.0, 120.0, 111.7, 111.1, 55.8, 55.7, 37.1, 35.4, 35.3, 30.9; HRMS (EI): m/z
Calcd for C13H20NO3 [M+H]+: 238.1438; Found: 238.1439.
N,N-dimethyl-3-(naphthalen-2-yl)propanamide (3k)
The general procedure was followed to afford the title compound as colourless oil, isolated
yield: 76%, 86 mg; 1H NMR (500 MHz, CDCl3) δ 7.84-7.76 (m, 3H), 7.67 (m, 1H), 7.49-7.41
(m, 2H), 7.40-7.35 (m, 1H), 3.15 (t, J = 8.4 Hz, 2H), 2.97 (s, 3H), 2.94 (s, 3H), 2.71 (t, J =
7.4Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 172.1, 138.9, 133.6, 132.0, 127.9, 127.6, 127.4,
127.2, 126.4, 125.9, 125.2, 37.2, 35.4, 35.2, 31.5; HRMS (EI): m/z Calcd for C15H18NO
[M+H]+: 228.1383; Found: 228.1384.
N,N-dimethyloctanamide (3l)
The general procedure was followed to afford the title compound as colourless oil, isolated
yield: 56%, 48 mg; 1H NMR (200 MHz, CDCl3) δ 2.98 (s, 3H), 2.91 (s, 3H), 2.28 (t, J = 7.1
Hz, 2H), 1.69-1.48 (m, 2H), 1.32-1.19 (m, 8H), 0.89-0.80 (m, 3H); 13C NMR (50 MHz,
CDCl3) δ 173.3, 37.2, 35.2, 33.4, 31.6, 29.4, 29.0, 25.1, 22.5, 13.9; HRMS (EI): m/z Calcd
for C10H22NO [M+H]+: 172.1696; Found: 172.1697.
3-cyclopropyl-N,N-dimethylpropanamide (3m)
The general procedure was followed to afford the title compound as a colorless oil, isolated
yield: 52%, 37 mg; 1H NMR (500 MHz, CDCl3) δ 3.03 (s, 3H), 2.94 (s, 3H), 2.42 (t, J = 7.4
Hz, 2H), 1.52 (q, J = 7.6 Hz, 2H), 0.73 (m, 1H), 0.48-0.34 (m, 2H), 0.10-0.02 (m, 2H); 13C
NMR (126 MHz, CDCl3) δ 173.1, 37.3, 35.3, 33.3, 30.4, 10.7, 4.5; HRMS (EI): m/z Calcd
for C8H16NO [M+H]+: 142.1226; Found: 142.1228.
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3-(furan-2-yl)-N,N-dimethylpropanamide (3n)
The general procedure was followed to afford the title compound as colourless oil, isolated
yield: 75%, 62 mg; 1H NMR (500 MHz, CDCl3) δ 7.31 (m, 1H), 6.30-6.25 (m, 1H), 6.06-6.00
(m, 1H), 3.02-2.94 (m, 8H), 2.66 (t, J = 8.7 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 171.8,
154.9, 140.9, 110.2, 105.2, 37.1, 35.4, 31.8, 23.7; HRMS (EI): m/z Calcd for C9H14O2N
[M+H]+: 168.1019; Found: 168.1027.
1-(pyrrolidin-1-yl)-3-(p-tolyl)propan-1-one (4a)
The general procedure was followed to afford the title compound as colourless oil, isolated
yield: 65%, 70 mg; 1H NMR (500 MHz, CDCl3) δ 7.11 (s, 4H), 3.67-3.57 (m, 4H), 3.52 (t, J
= 5.0 Hz, 2H), 3.36 (t, J = 4.4 Hz, 2H), 2.94 (t, J = 8.2 Hz, 2H), 2.60 (t, J = 7.6 Hz, 2H), 2.32
(s, 3H); 13C NMR (126 MHz, CDCl3) δ 170.9, 137.9, 135.7, 129.2, 128.3, 66.8, 66.4, 45.9,
41.9, 34.9, 30.9, 20.9; HRMS (EI): m/z Calcd for C14H20NO [M+H]+: 218.1539; Found:
218.1545.
1-(piperidin-1-yl)-3-(p-tolyl)propan-1-one (4b)
The general procedure was followed to afford the title compound as colourless oil, isolated
yield: 74%, 85 mg; 1H NMR (500 MHz, CDCl3) δ 7.16-7.06 (m, 4H), 3.56 (t, J = 6.7 Hz,
2H), 3.35 (t, J = 5.7 Hz, 2H), 2.93 (t, J = 8.3 Hz, 2H), 2.60 (t, J = 7.7 Hz, 2H), 2.32 (s, 3H),
1.65-1.58 (m, 2H), 1.56-1.45 (m, 4H); 13C NMR (126 MHz, CDCl3) δ 170.5, 138.4, 135.5,
129.1, 128.3, 46.6, 42.7, 35.4, 31.1, 26.4, 25.5, 24.5, 20.9; HRMS (EI): m/z Calcd for
C15H22NO [M+H]+: 232.1696; Found: 232.1697.
1-morpholino-3-(p-tolyl)propan-1-one (4c)
The general procedure was followed to afford the title compound as colourless oil, isolated
yield: 54%, 69 mg; 1H NMR (500 MHz, CDCl3) δ 7.13-7.09 (m, 4H), 3.47 (t, J = 6.7 Hz,
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2H), 3.30 (t, J = 6.9 Hz, 2H), 2.95 (t, J = 8.5 Hz, 2H), 2.54 (t, J = 8.5 Hz, 2H), 2.32 (s, 3H),
1.89 (m, 2H), 1.82 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 170.9, 138.4, 135.5, 129.0, 128.3,
46.5, 45.6, 36.9, 30.7, 26.0, 24.3, 20.9. HRMS (EI): m/z Calcd for C14H19NO2Na [M+Na]+:
256.1308; Found:256.1306.
N-methyl-N-phenyl-3-p-tolylpropanamide (4d)
The general procedure was followed to afford the title compound as colourless oil, isolated
yield: 72%, 91 mg; 1HNMR (200 MHz, CDCl3) δ = 7.38-7.33 (m, 3H), 7.07-6.94 (m, 5H),
3.26 (s, 3H), 2.88 (t, J = 8.2 Hz, 2H), 2.36 (t, J = 7.9 Hz, 2H), 2.30 (s, 3H). 13CNMR (50
MHz, CDCl3) δ = 172.3, 143.9, 138.1, 135.4, 129.7, 128.9, 128.2, 127.7, 127.3, 37.3, 36.1,
31.3, 20.9. HRMS(EI): m/z Calcd for C17H19NO [M+H]+: 254.1467; Found: 254.1466.
1-methyl-3-(4-methylbenzyl)piperidin-2-one (4e)
The general procedure was followed to afford the title compound as colourless oil, isolated
yield: 48%, 52mg; 1H NMR (500 MHz, CDCl3) δ 7.15-7.04 (m, 4H), 3.49-3.33 (m, 1H),
3.31-3.13 (m, 2H), 2.95 (s, 3H), 2.68-2.45 (m, 2H), 2.31(s, 3H), 1.90-1.57 (m, 3H), 1.53-1.36
(m, 1H); 13C NMR (126 MHz, CDCl3) δ 172.0, 137.0, 135.4, 129.0, 128.9, 50.1, 43.3, 37.3,
34.9, 25.7, 21.3, 20.9; HRMS (EI): m/z Calcd for C14H20NO [M+H]+: 218.1539; Found:
218.1545.
3-(4-methylbenzyl)piperidin-2-one (4f)
The general procedure was followed to afford the title compound as colourless oil. Here we
got N-alkylation product rather than C-alkylation product. Isolated yield: 35%, 36 mg; 1H
NMR (200 MHz, CDCl3) δ = 7.18-7.09 (m, 4H), 4.56 (s, 2H), 3.18 (t, J = 4.4 Hz, 2H), 2.46
(t, J = 6.3 Hz, 2H), 2.33 (s, 3H), 1.78-1.75 (m, 4H); 13C NMR (50 MHz, CDCl3) δ = 169.7,
S15
136.9, 134.2, 129.2, 128.0, 49.7, 47.0, 32.3, 23.1, 21.3, 21.0; HRMS (EI): m/z Calcd for
C13H18NO [M+H]+: 204.1383; Found: 204.1386.
tert-butyl 3-(4-methoxyphenyl)propanoate (5a)
The general procedure was followed to afford the title compound as colorless sticky liquid.
Isolated yield: 72%, 85 mg; 1HNMR (200 MHz, CDCl3) δ = 7.13 (d, J = 8.5 Hz, 2H), 6.83 (d,
J = 8.7 Hz, 2H), 3.79 (s, 3H), 2.86 (t, J = 8.1 Hz, 2H), 2.51 (t, J = 7.3 Hz, 2H), 1.43 (s, 9H);
13CNMR (50 MHz, CDCl3) δ = 172.4, 157.9, 132.8, 129.2, 113.8, 80.2, 55.2, 37.4, 30.2, 28.1.
(Known compound: Deibl, N.; Kempe, R. J. Am. Chem. Soc. 2016, 138, 10786-10789).
tert-butyl 3-p-tolylpropanoate (5b)
The general procedure was followed to afford the title compound as colorless sticky liquid.
Isolated yield: 65%, 71 mg; 1HNMR (400 MHz, CDCl3) δ = 7.12-7.10 (m, 4H), 2.90 (t, J =
7.9 Hz, 2H), 2.54 (t, J = 7.9 Hz, 2H), 2.34 (s, 3H), 1.45 (s, 9H); 13CNMR (100 MHz, CDCl3)
δ = 172.3, 137.7, 135.5, 129.0, 128.1, 80.2, 37.2, 30.7, 28.0, 20.9. (Known compound: Deibl,
N.; Kempe, R. J. Am. Chem. Soc. 2016, 138, 10786-10789).
tert-butyl 3-o-tolylpropanoate (5c)
The general procedure was followed to afford the title compound as colorless sticky liquid.
Isolated yield: 54%, 59 mg; 1HNMR (400 MHz, CDCl3) δ = 7.16-7.14 (m, 4H), 2.91 (t, J =
7.9 Hz, 2H), 2.51 (t, J = 8.5 Hz, 2H), 2.34 (s, 3H), 1.45 (s, 9H); 13CNMR (100 MHz, CDCl3)
δ = 172.4, 138.9, 135.9, 130.2, 128.5, 126.2, 125.9, 80.3, 35.7, 28.4, 28.1, 19.3. (Known
compound: Deibl, N.; Kempe, R. J. Am. Chem. Soc. 2016, 138, 10786-10789).
S16
3-phenylpropanal (6)
Colourless liquid, 35 mg, 52% yield; 1H NMR (500 MHz, CDCl3) δ 9.89 (s, 1H), 7.41-7.33
(m, 2H), 7.30-7.24 (m, 3H), 3.04 (t, J = 6.4 Hz, 2H), 2.85 (t, J = 7.4 Hz, 2H); 13C NMR (126
MHz, CDCl3) δ 200.8, 139.5, 127.8, 127.5, 125.5, 44.5, 27.3; HRMS (EI) m/z Calcd for
C9H10ONa [M+Na]+: 157.0624; Found: 157.0626.
3-phenylpropan-1-ol (7)
Colouless liquid, 51 mg, 75% yield; 1H NMR (500 MHz, CDCl3) δ 7.42-7.34 (m, 2H), 7.33-
7.22 (m, 3H), 3.73 (t, J = 6.4 Hz, 2H), 2.79 (t, J = 7.4 Hz, 2H), 2.42 (brs, 1H), 1.97 (p, J = 6.7
Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 141.7, 128.3, 128.2, 125.7, 61.9, 34.1, 31.9; HRMS
(EI) m/z Calcd for C9H12ONa [M+Na]+: 159.0780; Found: 159.0783.
S17
5. Copy of 1H & 13C NMR
10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.028.012.972.04
7.38
7.36
7.34
7.30
7.29
7.27
3.06
3.04
3.02
2.99
2.70
2.69
2.67
1H-NMR of 3a
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
172.
09
141.
37
128.
3112
5.97
77.2
677
.00
76.7
4
37.0
435
.31
35.1
931
.26
13C-NMR of 3a
N
OMe
Me
N
OMe
Me
S18
10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.062.108.004.01
7.12
2.98
2.98
2.96
2.94
2.90
2.64
2.61
2.60
2.56
2.33
1H-NMR of 3b
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
172.
26
138.
3613
5.53
129.
0912
8.25
77.6
377
.00
76.3
7
37.1
235
.45
35.3
830
.88
20.9
6
13C-NMR of 3b
Me
N
OMe
Me
Me
N
OMe
Me
S19
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
3.002.087.652.840.97
7.23
7.18
7.15
7.04
7.01
2.96
2.94
2.90
2.65
2.61
2.57
2.34
1H-NMR of 3c
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
172.
25
141.
3213
7.93
129.
1312
8.28
126.
7412
5.30
77.6
377
.00
76.3
6
37.0
935
.28
31.2
2
21.2
9
13C-NMR of 3c
N
O
N
O
S20
9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.072.008.063.99
7.27
7.17
7.16
7.15
7.14
7.13
2.99
2.97
2.95
2.94
2.59
2.57
2.56
2.34
1H-NMR of 3d
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
172.
29
139.
5413
5.95
130.
2412
8.74
126.
2312
6.06
77.2
577
.00
76.7
4
37.1
035
.40
33.8
9
28.6
7
19.2
5
13C-NMR of 3d
N
OMe
Me
Me
N
OMe
Me
Me
S21
10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.007.953.002.001.98
7.17
7.16
7.13
7.12
6.85
6.84
6.82
6.81
3.78
2.94
2.93
2.91
2.91
2.90
2.87
2.62
2.58
2.54
1H-NMR of 3e
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
172.
16
157.
83
133.
3812
9.21
113.
72
77.6
477
.00
76.3
7
55.1
1
37.0
435
.39
35.2
630
.35
13C-NMR of 3e
N
OMe
MeMeO
N
OMe
MeMeO
S22
10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
1.968.063.003.121.15
7.17
7.13
7.09
6.75
6.72
6.69
6.65
6.64
3.71
2.88
2.86
2.82
2.57
2.53
2.50
1H-NMR of 3f
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
172.
26
159.
61
142.
97
129.
35
120.
67
114.
0811
1.32
77.6
377
.00
76.3
6
55.0
5
37.1
235
.40
35.0
931
.34
13C-NMR of 3f
N
OMe
Me
OMe
N
OMe
Me
OMe
S23
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
3.422.168.004.36
7.23
7.18
7.17
7.12
2.97
2.95
2.93
2.89
2.63
2.59
2.56
2.46
1H-NMR of 3g
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
172.
20
138.
5013
5.69
128.
9512
7.14
77.6
377
.00
76.3
6
37.1
735
.46
35.1
430
.75
16.2
3
13C-NMR of 3g
N
O
MeS
N
O
MeS
S24
9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.008.362.222.00
7.37
7.36
7.34
7.30
7.29
7.27
3.06
3.04
3.02
3.00
2.70
2.69
2.67
1H-NMR of 3h
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
172.
23
141.
51
128.
4712
6.10
77.3
077
.04
76.7
9
37.1
735
.45
35.3
231
.39
13C-NMR of 3h
N
OMe
MeCl
N
OMe
MeCl
S25
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
1.978.401.862.00
7.27
7.19
7.18
7.17
7.16
6.98
6.96
6.95
2.96
2.95
2.95
2.93
2.91
2.61
2.59
2.58
1H-NMR of 3i
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
172.
01
162.
3416
0.40
137.
05
129.
7512
8.42
128.
3812
6.05
115.
2111
5.04
77.2
577
.00
76.7
4
37.1
235
.43
35.1
930
.46
13C-NMR of 3i
N
O
F
N
O
F
S26
10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.108.323.053.002.99
6.79
6.77
6.75
6.75
3.86
3.84
2.94
2.92
2.90
2.89
2.60
2.59
2.57
1H-NMR of 3j
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
172.
17
148.
7314
7.25
134.
03
120.
07
111.
7011
1.14
77.2
677
.00
76.7
4
55.8
155
.74
37.1
235
.45
35.3
430
.95
13C-NMR of 3j
N
OMe
MeMeO
OMe
N
OMe
MeMeO
OMe
S27
8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
2.003.052.952.070.961.950.993.00
7.82
7.81
7.79
7.78
7.67
7.46
7.45
7.44
7.39
7.37
7.27
3.16
3.15
3.13
2.97
2.94
2.73
2.71
2.70
1H-NMR of 3k
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
172.
12
138.
9813
3.58
132.
0512
7.98
127.
5712
7.41
127.
1812
6.44
125.
9412
5.24
77.2
677
.00
76.7
5
37.1
535
.43
35.1
731
.48
13C-NMR of 3k
N
OMe
Me
N
OMe
Me
S28
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
3.078.072.182.002.863.04
7.27
2.98
2.91
2.31
2.28
2.24
1.63
1.59
1.59
1.29
1.28
1.26
1.25
1.25
1.24
0.88
0.87
0.85
0.81
1H-NMR of 3l
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
173.
33
77.6
477
.00
76.3
7
37.2
335
.25
33.3
531
.64
29.3
929
.04
25.1
222
.54
13.9
9
13C-NMR of 3l
N
OMe
Me
N
OMe
Me
S29
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
1.992.111.072.212.003.022.91
7.27
7.27
3.03
2.94
2.46
2.42
2.38
1.58
1.55
1.51
1.47
0.77
0.73
0.45
0.44
0.44
0.41
0.40
0.07
0.06
0.06
1H-NMR of 3m
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
173.
08
77.2
576
.99
76.7
4
37.2
935
.32
33.3
430
.36
10.6
8
4.46
13C-NMR of 3m
N
OMe
Me
N
OMe
Me
S30
8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
2.138.411.001.001.01
7.31
7.27
6.29
6.28
6.28
6.03
6.03
6.03
3.01
2.99
2.98
2.96
2.67
2.66
2.64
1H-NMR of 3n
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
171.
78
154.
97
140.
97
110.
22
105.
23
77.2
577
.00
76.7
4
37.0
935
.45
31.7
9
23.6
9
13C-NMR of 3n
N
OMe
MeO
N
OMe
MeO
S31
8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
3.002.011.991.961.993.973.89
7.27
7.11
3.64
3.63
3.63
3.62
3.52
3.52
3.37
3.36
2.96
2.94
2.93
2.61
2.60
2.58
2.32
1H-NMR of 4a
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
170.
93
137.
9013
5.73
129.
1612
8.28
77.2
677
.00
76.7
5
66.8
266
.42
45.9
241
.88
34.9
330
.99
20.9
6
13C-NMR of 4a
N
O
N
O
S32
8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
4.022.293.011.972.002.022.083.90
7.27
7.13
7.12
7.11
7.09
3.58
3.56
3.55
3.36
3.35
3.33
2.95
2.93
2.91
2.62
2.60
2.59
2.32
1.62
1.61
1.54
1.53
1.49
1.49
1.48
1H-NMR of 4b
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
170.
50
138.
3713
5.53
129.
1112
8.26
77.2
677
.00
76.7
5
46.5
842
.67
35.3
631
.13
26.3
725
.52
24.5
220
.97
13C-NMR of 4b
N
O
N
O
S33
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
2.292.153.001.992.012.011.983.88
7.13
7.12
7.10
7.09
3.48
3.47
3.45
3.31
3.30
3.29
2.96
2.95
2.93
2.56
2.54
2.53
2.32
1.90
1.89
1.88
1.84
1.82
1H-NMR of 4c
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
170.
86
138.
3713
5.48
129.
0512
8.26
77.2
577
.00
76.7
4
46.5
145
.59
36.8
8
30.7
026
.01
24.3
320
.94
13C-NMR of 4c
N
O
O
N
O
O
S34
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
3.112.112.023.005.932.92
7.38
7.37
7.36
7.34
7.33
7.27
7.07
7.03
6.98
6.94
3.26
2.92
2.88
2.84
2.40
2.36
2.32
2.30
1H NMR of 4d
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
172.
28
143.
9913
8.13
135.
4212
9.66
128.
9612
8.23
127.
6812
7.25
77.6
477
.00
76.3
7
37.3
136
.13
31.2
6
20.9
2
13C NMR of 4d
N
OPh
N
OPh
S35
9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
1.032.061.053.061.021.003.002.021.034.17
7.27
7.09
7.07
3.41
3.40
3.38
3.38
3.26
3.25
3.24
3.23
2.95
2.61
2.59
2.57
2.31
1.70
1.69
1.45
1.44
1H-NMR of 4e
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
172.
01
137.
0213
5.43
129.
0312
8.92
77.6
377
.00
76.3
7
50.0
9
43.3
1
37.3
134
.89
25.6
721
.35
20.9
3
13C-NMR of 4e
NMe
O Me
NMe
O Me
S36
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)
3.923.141.971.981.954.00
7.18
7.14
7.09
4.56
3.21
3.18
3.16
3.15
2.49
2.48
2.46
2.43
2.33
1.78
1.77
1.75
1H-NMR of 4f
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
169.
74
136.
8713
4.18
129.
1512
8.04
77.6
377
.00
76.3
7
49.7
247
.04
32.3
5
23.1
021
.32
21.0
3
13C-NMR of 4f
N
O
N
O
S37
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
9.021.991.983.001.971.95
7.27
7.15
7.10
6.85
6.84
6.82
6.81
3.79
2.90
2.86
2.82
2.55
2.51
2.47
1.43
1H-NMR of 5a
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
172.
35
157.
93
132.
8412
9.22
113.
76
80.2
477
.63
77.0
076
.37
55.2
1
37.3
6
30.2
428
.05
13C-NMR of 5a
O
OtBu
OMe
O
OtBu
OMe
S38
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
8.853.091.961.984.00
7.11
7.10
2.91
2.90
2.88
2.56
2.54
2.52
2.34
1.45
1H-NMR of 5b
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
172.
32
137.
6613
5.49
129.
0212
8.40
128.
13
80.2
277
.32
77.0
076
.69
37.1
9
30.6
628
.03
20.9
5
13C-NMR of 5b
O
OtBu
O
OtBu
S39
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)
8.833.251.952.004.09
7.15
7.15
7.14
2.93
2.91
2.89
2.53
2.52
2.51
2.49
2.34
1.45
1H-NMR of 5c
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
172.
43
138.
8613
5.97
130.
1712
8.48
126.
2312
5.98
80.3
477
.32
77.0
076
.69
35.7
128
.41
28.0
6
19.2
6
13C-NMR of 5c
O
OtBu
O
OtBu
S40
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.001.993.032.020.99
9.89
7.38
7.37
7.29
3.04
2.85
1H-NMR of 6
220 200 180 160 140 120 100 80 60 40 20 0 -20Chemical Shift (ppm)
200.
79
139.
54
127.
8112
7.51
125.
51
77.2
577
.00
76.7
4
44.4
8
27.3
2
13C-NMR of 6
H
O
H
O
S41
9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.020.972.002.002.881.87
7.39
7.38
7.36
7.30
7.28
7.27
3.75
3.73
3.72
2.80
2.79
2.77
2.42
2.00
1.99
1.97
1.96
1.94
1H-NMR of 7
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
141.
75
128.
2712
5.72
77.2
677
.00
76.7
4
61.9
6
34.0
631
.95
13C-NMR of 7
OH
OH
S42
6. HRMS Data
AM-1 #116 RT: 0.51 AV: 1 NL: 5.36E6T: FTMS + p ESI Full ms [100.00-1500.00]
177.95 178.00 178.05 178.10 178.15 178.20 178.25m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
178.1233R=70600
C 11 H16 O N = 178.12263.9080 ppm
HRMS Data of 3a
AM-3 #117 RT: 0.52 AV: 1 NL: 6.88E9T: FTMS + p ESI Full ms [100.00-1500.00]
150 160 170 180 190 200 210 220 230 240 250 260m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
192.1384R=81107
C 12 H18 O N = 192.13830.6336 ppm
214.1208R=77207
C 12 H17 O N Na = 214.12022.8685 ppm
256.1308R=70507
234.1489R=73107
178.1229R=79502
C 11 H16 O N = 178.12261.2524 ppm
219.1571R=73502
241.1391R=68602 248.0752
R=64100152.3460R=62600
162.0868R=72100
HRMS Data of 3b
N
O
3a
N
O
3b
S43
AM-3 #117 RT: 0.52 AV: 1 NL: 6.88E9T: FTMS + p ESI Full ms [100.00-1500.00]
150 160 170 180 190 200 210 220 230 240 250 260m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
192.1384R=81107
C 12 H18 O N = 192.13830.6336 ppm
214.1208R=77207
C 12 H17 O N Na = 214.12022.8685 ppm
256.1308R=70507
234.1489R=73107
178.1229R=79502
C 11 H16 O N = 178.12261.2524 ppm
219.1571R=73502
241.1391R=68602 248.0752
R=64100152.3460R=62600
162.0868R=72100
HRMS Data of 3c
AM-3 #117 RT: 0.52 AV: 1 NL: 6.88E9T: FTMS + p ESI Full ms [100.00-1500.00]
150 160 170 180 190 200 210 220 230 240 250 260m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
192.1384R=81107
C 12 H18 O N = 192.13830.6336 ppm
214.1208R=77207
C 12 H17 O N Na = 214.12022.8685 ppm
256.1308R=70507
234.1489R=73107
178.1229R=79502
C 11 H16 O N = 178.12261.2524 ppm
219.1571R=73502
241.1391R=68602 248.0752
R=64100152.3460R=62600
162.0868R=72100
HRMS Data of 3d
N
O
3c
N
O
3d
S44
AM-5 #114 RT: 0.51 AV: 1 NL: 4.58E9T: FTMS + p ESI Full ms [100.00-1500.00]
198 200 202 204 206 208 210 212 214 216 218 220 222m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
208.1331R=78407
C 12 H18 O2 N = 208.1332-0.4945 ppm
209.1358R=77902
206.1178R=77002
C 12 H16 O2 N = 206.11761.3989 ppm
210.1398R=57302
215.0908R=60900
C 11 H14 O2 N Na = 215.0917-4.0442 ppm
HRMS Data of 3e
AM-5 #114 RT: 0.51 AV: 1 NL: 4.58E9T: FTMS + p ESI Full ms [100.00-1500.00]
198 200 202 204 206 208 210 212 214 216 218 220 222m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e Ab
unda
nce
208.1331R=78407
C 12 H18 O2 N = 208.1332-0.4945 ppm
209.1358R=77902
206.1178R=77002
C 12 H16 O2 N = 206.11761.3989 ppm
210.1398R=57302
215.0908R=60900
C 11 H14 O2 N Na = 215.0917-4.0442 ppm
HRMS Data of 3f
N
OMe
MeMeO
3e
N
OMe
Me3f
MeO
S45
AM-8 #108 RT: 0.48 AV: 1 NL: 2.84E7T: FTMS + p ESI Full ms [100.00-1500.00]
211.75 211.80 211.85 211.90 211.95 212.00 212.05 212.10 212.15m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
212.0837R=74106
C 11 H15 O N Cl = 212.08370.1231 ppm
212.1046R=70702
HRMS Data of 3h
AM-9 #101 RT: 0.45 AV: 1 NL: 7.13E9T: FTMS + p ESI Full ms [100.00-1500.00]
160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
238.1439R=72207
C 13 H20 O3 N = 238.14380.6336 ppm
260.1258R=69207
C 13 H19 O3 N Na = 260.12570.4202 ppm
224.1283R=73907
C 12 H18 O3 N = 224.12810.8532 ppm
191.0704R=79707
C 12 H10 N Na = 191.0705-0.5811 ppm
257.1175R=67307
262.1315R=59100
288.1571R=63302
165.0911R=80907
C 10 H13 O2 = 165.09100.8150 ppm
276.0997R=63107
302.1366R=55702
316.1542R=53300
HRMS Data of 3j
N
OMe
MeCl 3h
N
OMe
MeMeO
OMe 3i
S46
AM-13 #119 RT: 0.53 AV: 1 NL: 6.43E9T: FTMS + p ESI Full ms [100.00-1500.00]
180 190 200 210 220 230 240 250 260 270 280m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
228.1384R=73707
C 15 H18 O N = 228.13830.2661 ppm
250.1203R=70603
C 15 H17 O N Na = 250.12020.3814 ppm
200.1072R=76407
C 13 H14 O N = 200.10701.1638 ppm
276.1360R=64307
234.1462R=67307
266.0944R=64602
242.1543R=65200
HRMS Data of 3k
AM-6 #122 RT: 0.54 AV: 1 NL: 1.15E10T: FTMS + p ESI Full ms [100.00-1500.00]
120 125 130 135 140 145 150 155 160 165 170 175 180 185 190 195 200 205 210 215m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e Ab
unda
nce
172.1697R=84607
C 10 H22 O N = 172.16960.7705 ppm
194.1517R=79407
C 10 H21 O N Na = 194.15150.9406 ppm
214.1803R=76407
178.1227R=82507
200.1047R=72802
208.0968R=69502
184.1694R=68302
151.0390R=83000
C 9 H6 N Na = 151.0392-1.7166 ppm
130.1229R=89100
C 7 H16 O N = 130.12261.7145 ppm
HRMS Data of 3l
N
OMe
Me
3k
N
OMe
Me3l
S47
AM-7 #105 RT: 0.47 AV: 1 NL: 3.68E9T: FTMS + p ESI Full ms [100.00-1500.00]
120 130 140 150 160 170 180 190 200 210 220 230m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
142.1228R=93307
C 8 H16 O N = 142.12260.9255 ppm
164.1047R=87707
C 8 H15 O N Na = 164.10460.7340 ppm
206.1153R=78407
184.1333R=82807130.0865
R=98707224.1282R=73407
194.1541R=79707
168.1384R=84507
214.1200R=69307
154.1228R=85802
HRMS Data of 3m
AM-14 #148 RT: 0.66 AV: 1 NL: 4.93E8T: FTMS + p ESI Full ms [100.00-1500.00]
100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e Ab
unda
nce
168.1027R=87307
C 9 H14 O2 N = 168.10194.8598 ppm
190.0849R=82707
301.1423R=64507214.1212
R=77107 357.1800R=59507
149.0241R=92307
252.0555R=70607
232.0955R=74507 386.2318
R=56807204.1393R=78107
270.0660R=66202 327.1582
R=57807
HRMS Data of 3n
N
OMe
Me3m
N
OMe
MeO3n
S48
AM-15 #135 RT: 0.60 AV: 1 NL: 9.84E9T: FTMS + p ESI Full ms [100.00-1500.00]
100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 420 440 460m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
218.1545R=76707
C 14 H20 O N = 218.15392.7513 ppm
240.1364R=72907
457.2836R=52807
435.3017R=53607
360.1941R=58307
310.1344R=62407
136.0761R=92907
C 8 H10 O N = 136.07573.0890 ppm
256.1103R=68007
402.2052R=34800
HRMS Data of 4a
AM-12 #124 RT: 0.55 AV: 1 NL: 1.02E10T: FTMS + p ESI Full ms [100.00-1500.00]
170 180 190 200 210 220 230 240 250 260 270 280 290m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
232.1697R=73107
C 15 H22 O N = 232.16960.6371 ppm
254.1515R=70507
C 15 H21 O N Na = 254.1515-0.0020 ppm
172.1696R=84607
C 10 H22 O N = 172.16960.3273 ppm
234.1755R=70002
256.1579R=64402
251.1431R=68007
270.1252R=64607
290.1514R=58607
214.1805R=65100
197.1651R=62800
226.9516R=63500
HRMS Data of 4b
N
O
Me4a
N
O
Me4b
S49
AS-31 #263 RT: 1.17 AV: 1 NL: 2.16E6T: FTMS + p ESI Full ms [100.0000-1500.0000]
254.0 254.2 254.4 254.6 254.8 255.0 255.2 255.4 255.6 255.8 256.0 256.2 256.4 256.6 256.8 257.0 257.2m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
256.1306R=66107
C 14 H19 O2 N Na = 256.1308-0.7216 ppm
254.1143R=63702
C 14 H17 O2 N Na = 254.1152-3.1507 ppm
257.1077R=60500
255.0934R=59600
HRMS Data of 4c
AM-15 #135 RT: 0.60 AV: 1 NL: 9.84E9T: FTMS + p ESI Full ms [100.00-1500.00]
100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 420 440 460m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
218.1545R=76707
C 14 H20 O N = 218.15392.7513 ppm
240.1364R=72907
457.2836R=52807
435.3017R=53607
360.1941R=58307
310.1344R=62407
136.0761R=92907
C 8 H10 O N = 136.07573.0890 ppm
256.1103R=68007
402.2052R=34800
HRMS Data of 4e
N
O
OMe
4c
NMe
O Me
4e
S50
AM-23 #107 RT: 0.48 AV: 1 NL: 6.60E9T: FTMS + p ESI Full ms [100.00-1500.00]
160 180 200 220 240 260 280 300 320 340 360 380m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
204.1386R=79107
C 13 H18 O N = 204.13831.5681 ppm
226.1206R=75103
C 13 H17 O N Na = 226.12021.7040 ppm
242.1154R=72607 323.6699
R=60407272.1261R=67607
288.0911R=61902
174.1282R=72600
C 12 H16 N = 174.12772.5714 ppm
340.6730R=51400
356.0792R=37300
307.1786R=45200
HRMS Data of 4f
AM-21 #100 RT: 0.45 AV: 1 NL: 5.85E6T: FTMS + p ESI Full ms [100.00-1500.00]
155.6 155.8 156.0 156.2 156.4 156.6 156.8 157.0 157.2 157.4 157.6 157.8 158.0m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
157.0626R=88802
C 9 H10 O Na = 157.06241.2103 ppm
158.0966R=86902
HRMS Data of 6
N
Me4fO
H
O
6
S51
AM-20 #107 RT: 0.48 AV: 1 NL: 8.85E7T: FTMS + p ESI Full ms [100.00-1500.00]
148 150 152 154 156 158 160 162 164 166 168 170 172 174m/z
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
Rel
ativ
e A
bund
ance
159.0783R=90007
C 9 H12 O Na = 159.07801.5170 ppm
173.0576R=85107
149.0236R=90602 151.0756
R=90207156.0811R=84707
153.1276R=85202
167.0947R=80802
163.0756R=74900
171.1495R=71600
150.0269R=81300
158.0968R=85400
169.0832R=54800
HRMS Data of 7
OH
7