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8.26 (d, J¼8.8 Hz, 2H), 7.84 (dt, J¼1.6, 8.0 Hz, 1H), 7.29e7.26 (m,
1H), 7.26 (d, J¼8.8 Hz, 2H), 7.21 (d, J¼8.0 Hz, 1H), 2.34 (s, 3H). MS
m/z 258 ((MþH)þ, 57%), HRMS calcd for C14H12NO4 258.07663
(MþH)þ, found 258.07584.
2H), 4.41 (s, 3H). MS m/z 214 ((MꢁTfOꢁ)þ, 100%), HRMS calcd for
C13H12NO2 214.08680 (MꢁTfOꢁ)þ, found 214.09302.
4.4.2. 2-(4-Methoxycarbonyl-benzoyloxy)-1-methylpyridinium tri-
flate 3b. White solid; 94% yield; mp 132e133 ꢀC; IR (KBr) 3100,
3068, 2959, 1775, 1722, 1711, 1305, 1262 cmꢁ1; 1H NMR (400 MHz,
4.2.5. (E)-Pyridin-2-yl 3-(4-methoxyphenyl)prop-2-enoate 2e. White
crystal: 69% yield. The spectral data were in agreement with those
reported.14d
CDCl3)
d
9.06 (dd, J¼6.4, 2.0 Hz, 1H), 8.55 (dt, J¼8.6, 2.0 Hz, 1H), 8.34
(d, J¼8.8 Hz, 2H), 8.28 (d, J¼8.8 Hz, 2H), 8.02 (d, J¼7.6 Hz, 1H), 7.92
(t, J¼7.2, 1H), 4.47 (s, 3H), 4.01 (s, 3H). MS m/z 272 ((MꢁTfOꢁ)þ,
100%), HRMS calcd for C15H14NO4 272.09228 (MꢁTfOꢁ)þ, found
272.09633.
4.2.6. Preparation of 1-allyl 6-pyridin-2-yl hexanedioate 2f. To
a solution of 1f (102 mg, 0.54 mmol), 2-hydroxypyridine (50.0 mg,
0.54 mmol), and 4-dimethylaminopyridine (6.5 mg, 0.054 mmol) in
dry dichloromethane (1.8 mL) was added 1-ethyl-3-(3-dimethyl-
aminopropyl)carbodiimide hydrochloride (113 mg, 0.59 mmol).
The solution was stirred for 3 h at room temperature under nitro-
gen atmosphere. The reaction mixture was washed with 0.5 N
hydrochloric acid and saturated sodium hydrogen carbonate suc-
cessively. The organic layer was dried over magnesium sulfate and
filtered. The filtrate was concentrated and the residue was purified
by silica gel column chromatography (hexane/ethyl acetate¼2/1) to
give 2f as an oil (77.5 mg, 55%); IR (neat) 2945, 2875, 1732, 1649,
4.4.3. 2-(4-Acetoxy-benzoyloxy)-1-methylpyridiniumtriflate 3d. White
solid; 95% yield; mp 108e109 ꢀC; IR (KBr) 3098, 3080, 1784, 1760,
1277, 1158, 1000 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
9.04 (d, J¼6.0 Hz,
1H), 8.53 (t, J¼7.6 Hz, 1H), 8.30 (d, J¼8.8 Hz, 2H), 7.98 (d, J¼8.8 Hz,
1H), 7.91 (t, J¼6.8 Hz, 1H), 7.38 (d, J¼8.8 Hz, 2H), 4.43 (s, 3H), 2.36
(s, 3H). MS m/z 272 ((MꢁTfOꢁ)þ, 100%), HRMS calcd for C15H14NO4
272.09228 (MꢁTfOꢁ)þ, found 272.08481.
4.5. Examination of the stability of pyridyl ester 2b under
acidic conditions
1610, 1601, 1592, 1469, 1433, 1375, 1123, 994, 926 cmꢁ1
;
1H NMR
8.40 (dd, J¼1.2, 4.8 Hz, 1H), 7.79 (dt,
(400 MHz, CDCl3)
d
To a solution of 2b (19.3 mg, 0.07 mmol) in dry dichloro-
methane, magnesium bromide etherate (30.2 mg, 0.12 mmol) was
added at 0 ꢀC. The solution was stirred at room temperature for 22 h
under nitrogen atmosphere. A saturated sodium hydrogen car-
bonate solution was added to the mixture and the product was
extracted with dichloromethane. The organic layer was dried over
magnesium sulfate and filtered. Concentration of the filtrate
afforded recovered 2b (18.6 mg).
J¼1.2, 8.0 Hz, 1H), 7.23 (ddd, J¼1.2, 4.8, 8.0 Hz, 1H), 7.07 (d, J¼8.0 Hz,
1H), 5.89e5.93 (m, 1H), 5.32 (dt, J¼1.2, 17.6 Hz, 1H), 5.24 (dd, J¼1.2,
10.4, 1H), 4.59 (d, J¼7.2 Hz, 2H), 2.65 (t, J¼7.2 Hz, 2H), 2.38e2.43
(m, 2H), 1.77e1.82 (m, 4H). MS m/z 264 ((MþH)þ, 100%), 191
(64), HRMS calcd for C14H18NO4 264.12358 (MþH)þ, found
264.11909.
4.3. General procedure for the deprotection with MeI
4.6. Examination of the stability of pyridyl ester 2c under
acidic conditions
A mixture of pyridyl ester and methyl iodide (4.3 mL for 1 mmol)
was heated in a sealed tube at 100 ꢀC for 6 h. After cooling to room
temperature, excess methyl iodide was evaporated. Tetrahydrofu-
ran (4.3 mL for 1 mmol) and water (1.4 mL for 1 mmol) were added
to the residue, and the solution was stirred at room temperature for
16 h. Evaporation of the solvent and purification by general method
gave carboxylic acid.
Trifluoroacetic acid (40
ml, 0.53 mmol) was added to a solution of
2c (6.8 mg, 0.02 mmol) in dry dichloromethane (160
ml). After
stirring for 30 min at room temperature under nitrogen atmo-
sphere, the reaction mixture was quenched by triethylamine. The
solution was extracted with dichloromethane and washed with
saturated sodium hydrogen carbonate and brine successively.
Evaporation of the solvent afforded recovered 2c (6.4 mg).
4.4. General procedure for the synthesis of pyridinium salt
3aef with MeOTf and their hydrolysis
4.7. General procedure for conversion of pyridinium salt 3b
To an ice-cooled solution of 2aef in dry toluene (1.4 mL for
1 mmol) was added methyl trifluoromethanesulfonate (1.1 equiv).
The mixture was stirred at room temperature. Pyridinium salts 3a,
3b, and 3d were precipitated as white solids within a few minutes,
which were corrected by filtration. The solid was dissolved in
a 2.5:1 mixture of THF/H2O in the presence of Et3N (2 equiv) and
the solution was stirred for 5 min at room temperature. After
the solvent was removed, 10% citric acid solution was added to the
residue, which was extracted with chloroform three times. The
combined organic layer was dried over anhydrous MgSO4 and
concentrated to give a crude product. This was purified by pre-
parative TLC using a 1:1 mixture of ethyl acetate and dichloro-
methane as an eluent solvent to give a pure carboxylic acid. On the
other hand, 3c, 3e, and 3f were hydrolyzed without isolation to give
corresponding carboxylic acids, which were purified as described
above. The isolated yields and NMR yields are listed in Table 2.
into amides 4e7
To a solution of 3b in dry tetrahydrofuran was added amine at
room temperature. The solution was stirred for 5 min, and the
solvent was evaporated to give a crude product, which was purified
by preparative TLC to give a pure amide. The isolated yields and
NMR yields are listed in Table 3.
4.7.1. Conversion of pyridinium salt 3b into amides 4. To a solution
of 3b (14.4 mg, 0.035 mmol) in dry tetrahydrofuran (0.35 mL) was
introduced gaseous methylamine, which was generated from 40%
MeNH2 solution by heating at 60 ꢀC, by bubbling at room temper-
ature. The solution was stirred for 5 min and the solvent was
evaporated to give a crude product, which was purified by pre-
parative TLC using a 1:1 mixture of ethyl acetate and dichloro-
methane as an eluent solvent to give pure amide 4 (6.3 mg, 94%).
4.4.1. 2-Benzoyloxy-1-methylpyridinium triflate 3a. White solid;
98% yield; mp 84e85 ꢀC; IR (KBr) 3107, 3073, 1778, 192, 1262, 1227,
4.7.2. Conversion of pyridinium salt 3b into amide 5. To a solution of
3b (14.3 mg, 0.034 mmol) in dry tetrahydrofuran (0.35 mL) was
introduced gaseous dimethylamine, which was generated from
Me2NH solution by heating at 60 ꢀC, by bubbling at room temper-
ature. The solution was stirred for 5 min and the solvent was
1159, 700 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
9.05 (d, J¼6.4 Hz, 1H),
8.55 (t, J¼7.6 Hz, 1H), 8.25 (d, J¼7.2 Hz, 2H), 7.99 (d, J¼8.4 Hz,
1H), 7.92 (t, J¼6.8 Hz, 1H), 7.80 (t, J¼7.2 Hz, 1H), 7.62 (t, J¼7.8 Hz,