High-Load, Oligomeric Dichlorotriazine
oligometric reagent. After successful precipitation, the crude mixture
was filtered through a SiO2 SPE, yielding the desired products
5-13.
Experimental Section
exo-Norborenyl Alcohol 2. Into a flame-dried flask fitted with
a Dean-Stark apparatus under Ar was added exocarbic anhydride
1 (1 g, 6.10 mmol). After addition of dry toluene (8.7 mL) and
stirring for 5 min at rt, ethanolamine (0.75 mL, 12.2 mmol) was
added. The reaction was heated at reflux for 14 h, then upon
completion (monitoring via TLC) cooled to rt and concentrated
under reduced pressure. The resulting crude solid was dissolved in
DCM (20 mL), filtered through a silica plug, and concentrated to
give 1.12 g (89% yield) of 2 as a white solid. Mp 90-92 °C; FTIR
General Procedure C for the Amide Coupling of Simple
Acids and Amines Utilizing ODCT50 4/16. A 1 dram vial equipped
with a stir bar was charged with ODCT50 4/16 (0.328 mmol, 2.0
equiv), CH2Cl2 (0.075 M), acid (0.164 mmol, 1 equiv), and NMM
(0.492 mmol, 3 equiv). After the mixture was stirred for 10 min,
amine (0.328 mmol, 2 equiv) was added and the reaction was stirred
for 2 h. Silica was added to the reaction mixture, the solvent was
removed under reduced pressure, and the resulting powder was
loaded onto a silica SPE and eluted with solvent (1:1 EtOAc:hexane)
to yeild the desired products 5-13 in high purity.
General Procedure D for the Amide Coupling of Simple
Acids and Amines. A vial equipped with a stir bar was charged
with DCT monomer 3 (0.328 mmol, 2.0 equiv), dry CH2Cl2 (0.075
M), acid (0.164 mmol, 1 equiv), and NMM (0.492 mmol, 3 equiv).
After the mixture was stirred for 10 min, amine (0.328 mmol, 2
equiv) was added to the crude mixture and the reaction was stirred
at rt for 2 h. After the stated time, cat-B (2 mol %) was added to
the crude mixture, which was heated at reflux for 1 h. After such
time, the reaction was cooled to rt, quenched via the addition of
ethyl vinyl ether (50 µL), and stirred for 15 min. The spent oligomer
was precipitated by the slow addition of the crude mixture to a
stirring solution of Et2O (5 mL) and filtered through a silica SPE
with solvent (1:1 EtOAc:hexane) to afford the desired products
5-13 in good purity.
DCT Norborenyl Monomer 15. Into a flame-dried flask under
Ar, a solution of TCT (1.55 g, 8.4 mmol) in dry THF (10.0 mL)
was cooled to 0 °C and stirred for 15 min. After such time, 2,4,6-
collidine (2.12 mL, 16.0 mmol) was added, followed by the slow
addition of alcohol 14 (1.0 g, 8.0 mmol). After being stirred for an
additional 15 min at 0 °C, the reaction was warmed to rt and stirred
for 10 h. Purification of the crude reaction mixture entailed in situ
concentration followed by flash chromatography (6:4 EtOAc:
hexane) to give 1.86 g (83% yield) of 15 (2:1 mixture of
diastereoisomers) as a brown viscous oil. FTIR (neat) 1769, 1695,
1550, 1510, 1248 cm -1; [major isomer] 1H NMR (500 MHz,
CDCl3) δ 6.21 (dd, J ) 5.7, 3.1 Hz, 1H), 5.97 (dd, J ) 5.7, 2.9
Hz, 1H), 4.26 (dd, J ) 10.5, 6.6 Hz, 1H), 4.06 (dd, J ) 10.4, 9.7
Hz, 1H), 2.99 (s, 1H), 2.87 (s, 1H), 1.92 (ddd, J ) 11.9, 9.3, 3.8
Hz, 2H), 1.50 (dd, J ) 8.3, 2.1 Hz, 1H), 1.30 (d, J ) 8.3 Hz, 1H),
0.64 (ddd, J ) 11.8, 4.4, 2.6 Hz, 1H); [minor] 1H NMR (500 MHz,
CDCl3) δ 6.11 (t, J ) 1.8 Hz, 2H), 4.56 (dd, J ) 10.6, 6.4 Hz,
1H), 4.36 (dd, J ) 10.6, 9.4 Hz, 1H), 2.89 (s, 1H), 2.83 (d, J ) 1.5
Hz, 1H), 1.92 (ddd, J ) 11.9, 9.3, 3.8 Hz, 2H), 1.42-1.37 (m,
1H), 1.37-1.32 (m, 1H), 1.24 (ddd, J ) 11.9, 4.5, 3.5 Hz, 1H);
13C NMR (126 MHz, CDCl3) δ 172.4, 170.9, 138.1, 137.0, 136.0,
131.9, 74.4, 73.8, 49.4, 44.9, 43.7, 43.5, 42.1, 41.6, 37.7, 37.4, 29.3,
28.7; HRMS calcd for C11H11Cl2N3ONa (M + Na)+ 294.0177,
found 294.0182 (TOF MS ES+).
(neat) 3442, 2945, 1766, 1696, 1174 cm-1; H NMR (500 MHz,
1
CDCl3) δ 6.11 (t, J ) 1.8 Hz, 2H), 3.63 (t, J ) 4.9 Hz, 2H), 3.55
(t, J ) 5.5 Hz, 2H), 3.39 (m, 2H), 3.29 (dd, J ) 2.9, 1.5 Hz, 2H),
1.74 (t, J ) 1.6 Hz, 1H), 1.72 (t, J ) 1.6 Hz, 1H), 1.56 (m, 1H),
1.53 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 178.4, 134.4, 60.8,
52.2, 45.8, 44.9, 41.2; HRMS calcd for C11H13NO3Na (M + Na)+
230.0793, found 230.0786 (TOF MS ES+).
DCT Norborenyl Monomer 3. Into a flame dried flask under
Ar was added TCT (1.78 g, 9.7 mmol). This was dissolved in dry
THF (12 mL) and the solution was cooled to 0 °C and stirred for
15 min. After such time, 2,4,6-colidine (2.53 mL, 19.2 mmol) was
added followed by addition of 2 (2.0 g, 9.6 mmol). Upon stirring
for an additional 15 min at 0 °C, the reaction was warmed to rt
and stirred for 10 h. The reaction was then concentrated in situ
and purified by flash chromatography (6:4 hexane:EtOAc) to afford
2.59 g (79% yield) of the 3 as a light brown solid. FTIR (neat)
1770, 1699, 1549, 1514, 1255 cm -1; 1H NMR (500 MHz, CDCl3)
δ 6.11 (t, J ) 1.8 Hz, 2H), 4.52 (t, J ) 3.3 Hz, 2H), 3.78 (t, J )
5.5 Hz, 2H), 3.38 (m, 2H), 3.28 (dd, J ) 2.9, 1.5 Hz, 2H), 1.73 (t,
J ) 1.6 Hz, 1H), 1.72 (t, J ) 1.6 Hz, 1H), 1.54 (m, 1H), 1.52 (m,
1H); 13C NMR (125 MHz, CDCl3) δ177.4, 172.5, 170.7, 134.3,
65.9, 56.0, 45.9, 45.0, 36.2; HRMS calcd for C14H12Cl2N4O3Na
(M + Na)+ 377.0184, found 377.0186 (TOF MS ES+).
General Procedure for the Polymerization of DCT
Norborenyl Monomer 3 to Generate 4. Norbornenyl monomer 3
(0.5 g, 1.41 mmol) was dissolved in degassed CH2Cl2 (0.085 M,
16.6 mL), to which cat-B (23.9 mg, 28 µmol) was added, and the
reaction was refluxed for 2 h under Ar. After such time, the reaction
was cooled to rt, ethyl vinyl ether (0.05 mL) was added, and the
reaction was stirred for 15 min. The crude reaction mixture was
concentrated and precipitated by dropwise addition to a stirring
solution of Et2O (100 mL). The resulting precipitate was filtered,
washed with Et2O, and dried under vacuum to produce 0.49 g (98%
yield) of 4 as a light brown, free-flowing solid.
The following represents general experimental procedures for
the implementation of the titled oligomer reagents in synthetic
transformations. Specific experimental details and characterization
data for the aforementioned compounds and other new compounds
can be found in the Supporting Information.
General Procedure for the Polymerization of DCT
Norborenyl Monomer 15 to Generate 16. Norbornenyl monomer
15 (1.67 g, 6.14 mmol) was dissolved in degassed CH2Cl2 (0.085
M, 72.2 mL), to which cat-A (0.104 g, 0.123 mmol) was added.
The reaction refluxed for 2 h and subsequently cooled to rt, upon
which time the reaction was quenched by the addition of ethyl vinyl
ether (0.1 mL). After being stirred for 15 min, the crude mixture
was concentrated and precipitated via dropwise addition to a stirring
solution of hexane (200 mL). The resulting precipitate was filtered,
washed with hexanes, and dried under vacuum to produce 1.63 g
(98% yield) of 16 as a light brown, free-flowing solid.
General Procedure E for the Swern Oxidation of Simple
Primary Alcohols Utilizing 1GODCT50 16. To a stirring solution
of 1GODCT50 16 (0.246, 1.5 equiv) in dry THF (1 mL) at -30 °C
was added DMSO (0.984 mmol, 6 equiv) slowly under Ar. After
being stirred for 30 min, a solution of alcohol (0.164 mmol, 1 equiv)
in dry THF (0.5 mL) was slowly added maintaining the reaction
temperature at -30 °C. After the mixture was stirred for 30 min,
General Procedure A for the Scavenging of Amines or
Alcohols ODCT50 4/16 or Monomer 3/15. A vial equipped with
a stir bar was charged with amine/alcohol (0.246 mmol, 1.5 equiv),
Et3N, and CH2Cl2 (0.075 M). After the mixture was stirred for 5
min, acid chloride (0.164 mmol, 1 equiv) was added and the reaction
was stirred for 1 h at rt. After the stated time, ODCT50 4/16 or
monomer 3/15 (0.328 mmol, 2.0 equiv) was added and the crude
reaction was stirred for an additional 2 h. This was monitored by
1H NMR and GC when monomer 3 was applied.
General Procedure B for the Amide Coupling of Simple
Acids and Amines Utilizing ODCT50 4/16. A vial equipped with
a stir bar was charged with ODCT50 4/16 (0.328 mmol, 2.0 equiv),
CH2Cl2 (0.075 M), acid (0.164 mmol, 1 equiv), and NMM (0.492
mmol, 3 equiv). After the mixture was stirred for 10 min, amine
(0.328 mmol, 2 equiv) was added and the reaction was stirred at rt
for 2 h. After such time, the crude mixture was added dropwise to
a stirring solution of dry Et2O (10 mL), precipitating the spent
J. Org. Chem. Vol. 73, No. 22, 2008 8789