Synthesis of extended, π-conjugated isoindolin-1-ones

Article abstract of DOI:10.1021/jo2021345

The synthesis and characterization of extended, conjugated molecules containing isoindolinone units was explored. Nucleophilic cyclizations between an amide and an alkyne were found to be an efficient method of producing the desired isoindolin-1-ones in h

Full text of DOI:10.1021/jo2021345

Note
pubs.acs.org/joc
Synthesis of Extended, π-Conjugated Isoindolin-1-ones
Alex Bubar, Paula Estey, Michael Lawson, and Sara Eisler*
Department of Chemistry, University of New Brunswick, Fredericton, New Brunswick, Canada E3B 5A3
S
* Supporting Information
ABSTRACT: The synthesis and characterization of extended,
conjugated molecules containing isoindolinone units was
explored. Nucleophilic cyclizations between an amide and an
alkyne were found to be an efficient method of producing the
desired isoindolin-1-ones in high yields. A variety of derivatives
were synthesized, demonstrating that a number of structural
alterations could be made while maintaining good regio- and
stereospecificity in the cyclized product.
soindolinone ring systems are frequently observed in natural
products and are integral components of many pharmaceut-
Scheme 1
I
icals.1−4 In fact, while a handful of methods exist for their
formation,5−8 methodology for the synthesis of π-extended
isoindolinone systems are limited in number and applicability
to larger systems.9−11 In addition, little is known about their
electronic properties. Recent work with related structures hints
at the potential utility of these molecular units toward the
formation of organic photovoltaic (OPV) and organic field-
effect transistor (OFET) components.12−14 As we are
interested in the incorporation of isoindolinone units into
conjugated oligomers for the aforementioned applications, a
method for their synthesis is desired that allows for conjugation
length and structural complexity to be varied in a relatively
facile manner. Cyclization reactions are particularly interesting
for the synthesis of nitrogen heterocycles, as evidenced by
several key papers in this field. Larock and co-workers showed
that cyclization of o-(1-alkynyl)benzamides using electrophiles
such as I2 and ICl is an effective strategy to form both 5- and 6-
membered lactams.6,15 Friedel−Crafts acylation of ethynyl
benzamides was found to effectively bring about the formation
of alkylidene isoindolinones in either E or Z configurations.16
Alabugin used base to explore the interplay between 5-exo and
6-endo cyclizations of hydrazides and alkynyl groups in the
formation of N-aminolactams and benzopyridazinones,17 and a
recent discovery of Li and co-workers demonstrates the utility
of I2-induced cyclizations of nitrone-alkynes toward the
formation of simple iodinated isoindolinones.18 We report
herein that intramolecular, nucleophilic cyclizations can be
performed using mild conditions in high yields between an aryl
amide and an adjacent alkynyl moiety to give a variety of π-
extended, isoindolinone containing products that can easily be
envisaged as building blocks for conjugated oligomers.
monomer unit, in 92% yield. While strong bases such as
LHMDS and n-BuLi have been used to induce a similar
cyclization,20 reports of functional group-tolerant conditions
that facilitate this transformation are rare but the group of
Jacobi, in their efforts to synthesize chlorins and corrins, found
that mild base can be an effective method of forming cyclic
enamides.21 Upon treatment with K2CO3 (procedure A),
removal of the trimethylsilyl protective group to give terminal
acetylene 3 and intramolecular cyclization provided lactam 4
quantitatively after 5 days as a result of 5-exo-ring closure, a
structural assignment that was confirmed via the geminal
coupling constant of the vinyl protons.22 Because of the
extended reaction time, the use of tetrabutylammonium
fluoride (TBAF) to initiate cyclization was then explored as
these conditions will remove silyl protective groups and are
compatible with a range of functionality.23 Upon treatment
with TBAF in THF/H2O (procedure B), terminal diyne 3 was
produced directly in 10 min in quantitative yield, although even
Our initial efforts focused on investigating a simple system in
which more than one cyclization could be performed in the
same molecule with a single synthetic operation, Scheme 1.
Diamide 1 is available in a few steps from commercially
available starting material and is easily transformed via a
Sonogashira reaction into diyne 2,19 which serves as a model
Received: October 20, 2011
Published: January 4, 2012
© 2012 American Chemical Society
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after several days of reaction, isoindolinone 4 was not
produced. However, performing the reaction in anhydrous
THF (procedure C) instead of THF/H2O mixtures led
immediately to the production of the desired product 4 as a
stable, crystalline solid. The two methods (B and C) are
conveniently complementary; for some synthetic routes the
isolation of the terminal alkyne 3 is advantageous for
subsequent chain extension reactions but it is often convenient
to have a quick method to form the desired isoindolinone
product. While detailed mechanistic studies are ongoing,
Alabugin’s work and our observations in Scheme 1 indicate
that the first step is likely deprotonation of the amide,17
followed by attack at the triple bond to form the cycle.
Protonation of the resulting anion then leads to the product.
The addition of water, as in procedure B, serves to decrease the
basicity of the fluoride anion, thereby disfavoring the
deprotonation and therefore the cyclization.24 Encouraged by
these early results, we set out to explore the scope of this
approach toward the formation of more extended π-systems.25
A small series of diynes was therefore synthesized in an
analogous manner to compound 2, via a Sonogashira reaction
between either dibromide 1 and various terminal alkynes, or
diyne 3 and an aryl halide, Scheme 2. We initially extended the
Intrigued by the disparity in product ratios between 6c and
6d, compounds 7 and 8 were synthesized via a Sonogashira
reaction between N-butyl-2-iodobenzamide and the corre-
sponding terminal acetylene29 to determine the generality of
this observation, Scheme 3.
Scheme 3
Cyclizations of these monoynes 7 and 8 were carried out
with 1.2 equiv of TBAF. The para- derivative 7 gave a mixture
of two isomers, Z-9 and E-9 in a ratio of 1:2, quite dissimilar to
the ratio of products found for the cyclization of compound 5c.
However, cyclization of the meta- derivative 8, again gave only
one product, Z-10, in excellent yield. While derivatives Z-9 and
E-9 possess different Rf values on silica, their isomerization in
the presence of mild acid prevented isolation via flash
chromatography and were therefore characterized as a mixture.
At this point, we decided to open up the structural
possibilities by attempting cyclization with a butadiyne unit
instead of an ethynyl unit, Scheme 4. To the best of our
Scheme 2
Scheme 4
conjugation length by appending a simple phenyl group on the
alkyne, diyne 5a. Compound 5a was subsequently cyclized
using TBAF to give Z,Z-6a as the sole product in 95% yield.26
Substitution of the pendant aryl rings with methoxy groups in
the 3,4,5-positions, as for 5b, again did not hinder the reaction
and derivative Z,Z-6b was isolated in 79% yield with ≤10% of
other isomers produced. The conjugated structure was further
extended by the placement of a silyl protected alkynyl moiety in
either the para- and meta-positions of the phenyl ring,
compounds 5c and 5d, respectively. Surprisingly, when diyne
5c was exposed to the standard cyclization conditions, three
products were produced as an inseparable mixture in a
combined yield of 77%. NOE spectroscopy identified the
products as the ZZ/ZE/EE-isomers of 6c isolated in a 10:8:1
ratio.27,28 Conversely, when meta-substituted 5d was subjected
to the same cyclization conditions, only the isoindolinone Z,Z-
6d was produced as the main product, with <5% of other
isomers being formed.
knowledge, anionic cyclizations between an amide and a
butadiyne moiety have never been attempted. For amide 12,
the butadiyne was put into place via removal of the TMS group
on 11 with TBAF in THF/H2O, followed by oxidative coupling
with excess trimethylsilylacetylene (TMSA) to give the
protected butadiyne 12 in 65% yield.30 The standard cyclization
conditions were then applied to give a mixture of vinylic
products 13 in a 5:1 ratio. The two peaks that appear in the
vinylic region of the 1H NMR spectrum of 13 are both coupled
to the terminal acetylene proton, with J = 3 Hz, corresponding
to a four-bond coupling, confirming the formation of a 5-
membered ring. A NOESY experiment revealed that the main
product was Z-13 due to the presence of through-space
coupling between the vinyl and aromatic protons. NOESY
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Scheme 5
correlations between the vinyl proton and the butyl group
confirmed the identity of the minor isomer as E-13.
20, and 21 are particularly suitable for our continuing interest
in isoindolinone-containing oligomers. Treatment with acid
seems like a particularly reasonable method,35 as putting the
crude reaction mixture through a mildly acidic silica plug caused
the isomer ratios for 20 and 21 to change in favor of the Z,Z
and Z,E isomers and experiments involving acid-induced
isomerization will be performed in the future.36
In conclusion, we have synthesized a number of
isoindolinone derivatives with extended π-conjugation using
5-exo ring closures. While products can generally be isolated in
excellent yields as stable crystalline solids, isomer formation is
very sensitive to structure.
The more extended tetrayne system 14 was then synthesized
to determine if more than one butadiyne cyclization could be
performed in a single step. From diyne 2, compound 14 was
synthesized in 31% yield in an analogous manner to diyne 12,
via removal of the silyl group followed by oxidative coupling
with excess trimethylsilylacetylene. Cyclization was induced
with 2 equiv of TBAF. Again, the reaction proceeded in
excellent yields to give a mixture of mainly two products as an
inseparable mixture, which a NOESY experiment revealed to be
isoindolinone 15 with a 19:1 Z,Z to E,Z ratio.31 As diene 15
proved to be unstable, complicating purification and character-
ization, future studies will focus on discovering how to stabilize
the conjugated core and producing this compound as a single
isomer.32
Our initial success with the formation of these isoindolinone
derivatives led us to further test the capabilities of this
cyclization toward the formation of other extended networks
with novel conjugation pathways. In addition, the results we
have presented so far indicate that isomer formation is highly
dependent on structure. The diyne 16 was therefore designed
and synthesized through deprotection and an oxidative
coupling reaction of amide 11,33 Scheme 5. Cyclization of 16
proceeded smoothly in high yield to provide conjugated diene
17 as a mixture of three isomers of the five-membered ring
lactam, ZZ/ZE/EE, in a 1.3:2.0:1.2 ratio.34 This experiment is
the first example in this study where almost no Z/E selectivity is
observed, with each individual cyclization in 16 proceeding
close to 50% Z and 50% E. Intrigued by this incongruent result,
an aryl group was inserted to provide diynes 18 and 19 to
determine if the cyclizations in these systems generally proceed
with less selectivity than the examples in Schemes 1−4. Upon
cyclization of the derivative with a simple thiophene group, 20,
the Z,Z, Z,E, and E,E isomers were formed in a 1:15:44 ratio.
Similar mixtures were produced with methoxy-substituted 21,
with a ZZ/ZE/EE ratio of 1.3:7.0:10. In both cases, the E,E
isomers are greatly favored, indicating how different these
derivatives behave under our cyclization reaction conditions.
Future studies will focus on determining how to influence the
isomer ratio in a controlled manner as the diene motifs in 17,
EXPERIMENTAL SECTION
■
Procedure A: General Deprotection. Arylsilylacetylene was
dissolved in 10:5:1 THF/MeOH/H2O. 1.2 equiv of K2CO3 per equiv
of silyl group was added and the solution stirred for 30−90 min at rt.
NH4Clsatd was added, the solution extracted with Et2O, dried over
MgSO4, and filtered, and solvent removed.
Procedure B: General Deprotection. Arylsilylacetylene was
dissolved in 20:1 THF/H2O and cooled to 0 °C. 1.2 equiv of
tetrabutylammonium fluoride (TBAF) per equiv of silyl group was
added and the solution stirred for 5−10 min at 0 °C. NH4Clsatd was
added, the solution extracted with Et2O, dried over MgSO4, and
filtered, and solvent removed.
Procedure C: General Cyclization. Arylamide was dissolved in
anhydrous THF and cooled to 0 °C. 1−1.5 equiv of TBAF per equiv
of amide was added and the solution stirred for 5−10 min. NH4Clsatd
was added, the solution extracted with Et2O, dried over MgSO4, and
filtered, and solvent removed. The product was purified by flash
chromatography (SiO2) or recrystallization.
Procedure D: General Sonogashira. Under N2, 1 equiv of aryl
halide was dissolved in 25:1 anhyd THF/triethylamine (TEA), and the
solution was degassed with N2. 1−3 equiv of alkyne per equiv of alkyl
halide was added, followed by 2.5−6 mol % of CuI and 2.5−5 mol %
of Pd(PPh3)2Cl2. The solution was heated to 70 °C until TLC
indicated complete reaction. NH4Clsatd was added, the solution
extracted with Et2O, dried over MgSO4, and filtered, and solvent
removed. The product was purified by flash chromatography (SiO2).
Procedure E. Deprotected alkyne was dissolved in CH2Cl2. 15
equiv of trimethylsilylacetylene per alkyne was added followed by a
solution of 2:2.5 equiv of CuI/TMEDA in CH2Cl2. The solution was
stirred for 2−3 h at rt. NH4Clsatd was added, the mixture extracted with
Et2O, dried over MgSO4, and filtered, and solvent removed. The
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product was purified by flash chromatography (SiO2) using 1:1
hexanes/EtOAc.
106.3, 96.7, 94.0, 87.9, 40.2, 31.8, 20.3, 18.8, 13.9, 11.4; IR (film, KBr)
3250, 2958, 2154, 1640 cm−1; HRMS (APCI) calcd for C54H73N2O2Si2
[M + H]+ 837.5205, found 837.5213.
N1,N3-Dibutyl-4,6-dibromoisophthalamide (1). 4,6-Dibromoi-
sophthalic acid37 (757 mg, 2.34 mmol) was dissolved in 20 mL of
benzene and SOCl2 (8.50 mL, 117 mmol). After 5 h of reflux, solvent
was removed and 10 mL DCM was added, followed by pyridine (0.50
mL, 6.2 mmol) and n-butylamine (0.68 mL, 6.9 mmol). The solution
was stirred at rt for 18 h, concentrated under reduced pressure,
followed by addition of water and extraction using Et2O. The product
was purified by elution through a silica plug (2:1 DCM/EtOAc): yield
N1,N3-Dibutyl-4,6-bis[3-((trimethylsilyl)ethynylphenyl)-
ethynyl]isophthalamide (5d). Prepared by procedure D using 3
and 3-trimethylsilylethynyl-1-iodobenzene:39 yield 40%; orange solid;
mp 143−146 °C; 1H NMR (300 MHz, CDCl3) δ 8.44 (d, J = 0.6 Hz,
1H), 7.80 (d, J = 0.6 Hz, 1H), 7.65 (td, J = 0.6, 1.5 Hz, 2H), 7.48 (tt, J
= 1.2, 7.5 Hz, 4H), 7.33 (td, J = 0.6, 7.8 Hz, 2H), 6.89 (br t, 2H), 3.51
(dt, J = 5.7, 6.9 Hz, 4H), 1.61 (m, 4H), 1.41 (m, 4H), 0.91 (t, J = 7.2
Hz, 6H), 0.26 (s, 18H); 13C NMR (100 MHz, CDCl3) 165.6, 138.3,
136.7, 135.2, 132.8, 131.6, 130.5, 128.7, 124.1, 122.2, 121.8, 103.7,
96.2, 95.8, 86.8, 40.2, 31.9, 20.4, 13.9, 0.01; IR (film, KBr) 3254, 2957,
2160, 1640, 1250 cm−1; HRMS (ESI) calcd for C42H49N2O2Si2 [M +
H]+ 669.3333, found 669.3339.
1
853 mg (84%); white solid; mp 174−176 °C; H NMR (300 MHz,
CDCl3) δ 7.84 (s, 1H), 7.63 (s, 1H), 6.00 (br t, 2H), 3.45 (dt, J = 4.2,
5.4 Hz, 4H), 1.61 (m, 4H), 1.42 (m, 4H), 0.96 (t, J = 5.4 Hz, 6H); 13C
NMR (100 MHz, CDCl3) 166.2, 137.5, 137.3, 129.6, 121.2, 40.1, 31.5,
20.3, 13.9; IR (film, KBr) 3248, 2958, 1643, 1301 cm−1; HRMS (ESI)
calcd for C16H22Br2N2O2Na [M + Na]+ 454.9940, found 454.9942.
N1,N3-Dibutyl-4,6-bis[(trimethylsilyl)ethynyl]isophthalamide
(2). Prepared by procedure D using 1 and trimethylsilylacetylene:
(3Z,5Z)-3, 5-Dibenzylidene-2,6-dibutyl-2, 3, 5, 6-
tetrahydropyrrolo[3,4-f ]isoindole-1,7-dione (6a). Prepared by
procedure C using 5a: yellow oil; 1H NMR (300 MHz, CDCl3) δ 8.31
(d, J = 0.9 Hz, 1H), 8.08 (d, J = 1.2 Hz, 1H), 7.39 (m, 10H), 6.93 (s,
2H), 3.68 (m, 4H), 1.21 (m, 4H), 0.86 (m, 4H), 0.62 (t, J = 7.2 Hz,
6H); 13C NMR (75 MHz, CDCl3) 167.7, 141.7, 134.7, 134.6, 129.6,
129.4, 128.3, 128.0, 118.9, 110.4, 108.0, 41.6, 30.3, 19.8, 13.6; IR (film,
KBr) 2958, 1716, 1683, 1064 cm−1; HRMS (ASAP) calcd for
C32H33N2O2 [M + H]+ 477.2542, found 477.2540.
(3Z,5Z)-2,6-Dibutyl-3,5-bis(3,4,5-trimethoxybenzylidene)-
2,3,5,6-tetrahydropyrrolo[3,4-f ]isoindole-1,7-dione (6b). Pre-
pared by procedure C using 5b: yellow solid; mp 79−82 °C; 1H NMR
(300 MHz, CDCl3) δ 8.31 (d, J = 0.6 Hz, 1H), 8.04 (d, J = 0.9 Hz,
1H), 6.87 (s, 2H), 6.59 (d, J = 0.0.6 Hz, 4H), 3.89 (d, J = 0.8 Hz,
18H), 3.74 (m, 4H), 1.31 (m, 4H), 0.96 (m, 4H), 0.68 (t, J = 7.2 Hz,
6H); 13C NMR (75 MHz, CDCl3) 167.7, 153.2, 141.7, 138.1, 134.6,
130.1, 129.4, 119.0, 110.2, 107.9, 106.9, 61.2, 56.4, 41.8, 30.6, 19.9,
13.7; IR (film, KBr) 2957, 1712, 1126 cm−1; HRMS (ESI) calcd
C38H44N2O8Na [M + Na]+ 679.2990, found 679.3002.
1
orange solid; mp 198−201 °C; H NMR (300 MHz, CDCl3) δ 8.58
(s, 1H), 7.68 (s, 1H), 7.27 (br, 2H), 3.48 (dt, J = 4.2, 5.4 Hz, 4H), 1.61
(m, 4H), 1.42 (m, 4H), 0.96 (t, J = 5.4 Hz, 6H), 0.28 (s, 18H); 13C
NMR (75 MHz, CDCl3) 164.9, 139.4, 136.3, 131.5, 121.5, 104.0,
101.9, 40.2, 31.8, 20.5, 13.9, 0.2; IR (film, KBr) 3245, 2960, 2160,
1639, 1249 cm−1; HRMS (ESI) calcd for C26H40N2O2Si2Na [M +
Na]+ 491.2541, found 491.2529.
N1,N3-Dibutyl-4,6-diethynylisophthalamide (3). Prepared by
procedure A or B using 2: orange solid; mp 93−96 °C; 1H NMR (300
MHz, CDCl3) δ 8.28 (d, J = 0.6 Hz, 1H), 7.72 (s, 1H), 6.90 (br t, 2H),
3.53 (s, 2H), 3.46 (dt, J = 5.7, 6.9 Hz, 4H), 1.60 (m, 4H), 1.42 (m,
4H), 0.95 (t, J = 7.2 Hz, 6H); 13C NMR (75 MHz, CDCl3) 165.2,
139.6, 137.8, 130.1, 120.8, 85.3, 80.6, 40.1, 31.5, 20.3, 13.9; IR (film,
KBr) 3296, 2960, 2105, 1665, 1066 cm−1; HRMS (ESI) calcd for
C20H24N2O2Na [M + Na]+ 347.1730, found 347.1731.
2,6-Dibutyl-3,5-dimethylene-2,3,5,6-tetrahydropyrrolo[3,4-
(3Z,5Z)-2,6-Dibutyl-3,5-bis(4-ethynylbenzylidene)-2,3,5,6-
f]isoindole-1,7-dione (4). Prepared by procedure C using 2: orange-
tetrahydropyrrolo[3,4-f ]isoindole-1,7-dione (Z,Z-6c, Z,E-6c,
1
yellow solid; mp 116−119 °C; H NMR (400 MHz, CDCl3) δ 8.23
1
and E,E-6c). Prepared by procedure C using 5c: yellow solid; H
(d, J = 0.8 Hz, 1H), 7.92 (d, J = 0.8 Hz, 1H), 5.32 (d, J = 2.8 Hz, 2H),
4.97 (d, J = 2.8 Hz, 2H), 3.79 (t, J = 7.2 Hz, 4H), 1.67 (m, 4H), 1.39
(m, 4H), 0.96 (t, J = 7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3)
166.0, 141.5, 139.7, 130.8, 118.5, 111.5, 90.3, 39.6, 30.4, 20.4, 13.9; IR
(film, KBr) 2959, 1699, 1639, 1393 cm−1; HRMS (ASAP) calcd for
C20H25N2O2 [M + H]+ 325.1916, found 325.1913.
NMR (400 MHz, CDCl3) Z,Z-6c: δ 8.31 (d, J = 0.8 Hz, 1H), 8.07 (d,
J = 0.8 Hz, 1H), 7.54 (d, J = 8.0 Hz, 4H), 7.34 (d, J = 8.0 Hz, 4H),
6.86 (s, 2H), 3.70 (m, 4H), 3.17 (s, 2H), 0.65 (t, J = 7.6 Hz, 6H); Z,E-
6c: δ 8.29 (d, J = 0.8 Hz, 1H), 7.63 (d, J = 0.8 Hz, 1H), 7.60 (d, J = 8.4
Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.27 (d, J
= 8.0 Hz, 2H), 6.58 (s, 1H), 6.30 (s, 1H), 3.91 (t, J = 7.6 Hz, 2H), 3.63
(m, 2H), 3.17 (s, 1H), 3.16 (s, 1H), 0.62 (t, J = 7.2 Hz, 3H); E,E-6c: δ
8.28 (d, J = 0.8 Hz, 1H), 7.88 (d, J = 0.8 Hz, 1H), 7.32 (d, J = 8.0 Hz,
4H), 7.16 (d, J = 8.0 Hz, 4H), 6.39 (s, 2H), 3.84 (t, J = 7.2 Hz, 4H),
3.23 (s, 2H); overlapping signals: 1.73 (m), 1.44 (m), 1.17 (m), 1.00
(m), 0.89 (m) (33 protons); 13C NMR (75 MHz, CDCl3) Z,Z-6c: δ
167.7, 141.7, 135.3, 135.2, 132.0, 129.6, 121.8, 119.2, 110.6, 107.0,
83.3, 78.5, 41.6, 30.2, 19.8, 13.6; one signal missing. Z,E-6c: δ 167.5,
165.5, 141.0, 138.1, 136.5, 135.8, 135.2, 135.0, 132.6, 131.9, 129.9,
129.7, 129.5, 129.5, 129.2, 122.1, 121.7, 118.9, 114.2, 110.7, 107.0,
83.3, 78.7, 78.5, 41.6, 39.8, 30.5, 30.2, 20.5, 19.7, 14.0, 13.6; E,E-6c:
two very small signals assigned to this isomer: δ 132.7 and 131.6; IR
(film, KBr) 3296, 3239, 2959, 1712 cm−1; HRMS (ESI) calcd for
C36H32N2O2Na [M + Na]+ 547.2356, found 547.2314.
N1,N3-Dibutyl-4,6-bis(phenylethynyl)isophthalamide (5a).
Prepared by procedure D using 1 and phenylacetylene: yield 99%;
1
brown solid; mp 137−140 °C; H NMR (300 MHz, CDCl3) δ 8.48
(d, J = 0.6 Hz, 1H), 7.83 (d, J = 0.3 Hz, 1H), 7.54 (m, 4H), 7.41 (m,
6H), 7.02 (br t, 2H), 3.51 (dt, J = 5.7, 7.2 Hz, 4H), 1.59 (m, 4H), 1.39
(m, 4H), 0.88 (t, J = 7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3)
165.6, 138.2, 136.3, 131.8, 130.8, 129.6, 128.8, 122.0, 97.3, 86.4, 40.2,
31.8, 20.4, 13.9 (one carbon signal missing); IR (film, KBr) 3399,
2961, 1643, 1261 cm−1; HRMS (ASAP) calcd for C32H33N2O2 [M +
H]+ 477.2542, found 477.2523.
N1,N3-Dibutyl-4,6-bis[(3,4,5-trimethoxyphenyl)ethynyl]-
isophthalamide (5b). Prepared by procedure D using 1 and 1-
ethynyl-3,4,5-trimethoxybenzene:38 yield 39%; yellow solid; mp 200−
1
202 °C; H NMR (400 MHz, CDCl3) δ 8.45 (s, 1H), 7.82 (s, 1H),
(3Z,5Z)-2,6-Dibutyl-3,5-bis(3-ethynylbenzylidene)-2,3,5,6-
7.00 (br t, 2H), 6.76 (s, 4H), 3.89 (s, 6H), 3.88 (s, 12H), 3.51 (dt, J =
4.5, 5.4 Hz, 4H), 1.61 (m, 4H), 1.41 (m, 4H), 0.89 (t, J = 5.7 Hz, 6H);
13C NMR (100 MHz, CDCl3) 165.6, 153.4, 140.1, 138.1, 136.1, 130.7,
tetrahydropyrrolo[3,4-f ]isoindole-1,7-dione (6d). Prepared by
1
procedure C using 5d: orange solid; mp 90−93 °C; H NMR (400
MHz, CDCl3) δ 8.31 (s, 1H), 8.06 (s, 1H), 7.50 (m, 4H), 7.38 (m,
4H), 6.85 (s, 2H), 3.65 (m, 4H), 3.13 (s, 2H), 1.24 (m, 4H), 0.92 (m,
4H), 0.66 (t, J = 7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3) 167.6,
141.6, 135.2, 135.0, 133.0, 131.6, 130.0, 129.6, 128.4, 122.4, 119.1,
110.6, 106.6, 83.0, 78.2, 41.7, 30.3, 19.8, 13.6; IR (film, KBr) 3296,
2958, 1712, 1397 cm−1; HRMS (ESI) calcd for C36H33N2O2 [M + H]+
525.2542, found 525.2545.
122.1, 116.8, 109.1, 97.4, 85.5, 61.2, 56.4, 40.2, 31.8, 20.4, 13.9; IR
(film, KBr) 3243, 2957, 1632, 1238 cm−1; HRMS (ESI) calcd for
C38H44N2O8Na [M + Na]+ 679.2990, found 679.2979.
N1,N3-Dibutyl-4,6-bis[4-((triisopropylsilyl)ethynyl)phenyl]-
isophthalamide (5c). Prepared by procedure D using 1 and 4-
triisopropylsilylethynyl-1-ethynylbenzene:30 yield 51%; yellow solid;
1
mp 200 °C dec; H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 2.4 Hz,
N-Butyl-2[(4-((triisopropylsilyl)ethynyl)phenyl)ethynyl]-
benzamide (7). Prepared by procedure D using N-butyl-2-
iodobenzamide40 and 4-triisopropylsilylethynyl-1-ethynylbenzene:30
yield 63%; yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.03 (m,
1H), 7.59 (m, 1H), 7.47 (m, 6H), 7.18 (br t, 1H), 3.51 (dt, J = 7.2, 5.6
1H), 7.79 (d, J = 1.6 Hz, 1H), 7.49 (d, J = 8.0 Hz, 4H), 7.45 (d, J = 8.0
Hz, 4H), 7.00 (br t, 2H), 3.48 (q, J = 6.4 Hz, 4H), 1.58 (m, 4H), 1.39
(m, 4H), 1.14 (s, 42H), 0.89 (t, J = 7.2 Hz, 6H); 13C NMR (100 MHz,
CDCl3) 165.6, 138.2, 136.5, 132.3, 131.6, 130.5, 124.7, 121.8, 121.6,
1575
dx.doi.org/10.1021/jo2021345 | J. Org. Chem. 2012, 77, 1572−1578

The Journal of Organic Chemistry
Note
Hz, 2H), 1.58 (m, 2H), 1.40 (m, 2H), 1.14 (s, 21H), 0.88 (t, J = 7.2
Hz); 13C NMR (75 MHz, CDCl3) 166.5, 136.3, 133.6, 132.3, 131.4,
130.5, 130.1, 129.2, 124.4, 122.1, 119.4, 106.4, 95.0, 93.7, 89.4, 40.1,
31.8, 20.4, 18.8, 13.9, 11.4; IR (film, KBr) 2865, 2153, 1652, 1464
cm−1; HRMS (ESI) calcd for C30H39NOSiNa [M + Na]+ 480.2693,
found 480.2677.
N-Butyl-2[3-((triisopropylsilyl)ethynyl)phenyl)ethynyl]-
benzamide (8). Prepared by procedure D using N-butyl-2-
iodobenzamide40 and 3-triisopropylsilylethynyl-1-ethynylbenzene:30
yield 98%; yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.03 (m,
1H), 7.62 (t, J = 1.2 Hz, 1H), 7.59 (m, 1H), 7.47 (m, 4H), 7.33 (t, J =
8.0 Hz, 1H), 7.22 (br t, 1H), 3.51 (dt, J = 7.2, 5.6, 2H), 1.59 (m, 2H),
1.40 (m, 2H), 1.14 (s, 21H), 0.88 (t, J = 7.6 Hz, 3H); 13C NMR (100
MHz, CDCl3) 166.5, 136.3, 135.0, 133.6, 132.6, 131.3, 130.5, 130.1,
129.2, 128.7, 124.3, 122.5, 119.3, 105.8, 94.5, 92.2, 88.2, 40.1, 31.8,
20.4, 18.8, 13.9, 11.4; IR (film, KBr) 2941, 2162, 1652, 1464 cm−1;
HRMS (ASAP) calcd for C30H40NOSi [M + H]+ 458.2879, found
458.2871.
2-Butyl-3-(4-ethynylbenzilidene)isoindolin-1-one (Z-9, E-9).
Prepared by procedure C using 7. Crude ratio 1:2 of Z:E, but after
silica plug the ratios changed to 1:0.4 of Z:E: yellow oil; 1H NMR (300
MHz, CDCl3) Z-9: δ 7.85 (dt, J = 7.5, 0.9 Hz, 1H), 7.73 (d, J = 7.5 Hz,
1H), 7.61 (dd, J = 7.8, 1.2 Hz, 1H), 7.51 (m, 3H), 7.33 (m, 2H), 6.71
(s, 1H), 3.66 (t, J = 7.5 Hz, 2H), 3.15 (s, 1H), 1.19 (m, 2H), 0.89 (m,
2H), 0.64 (t, J = 7.2 Hz, 3H); E-9: δ 7.83 (dt, J = 7.5, 0.9 Hz, 1H),
7.65 (d, J = 8.4 Hz, 2H), 7.43 (m, 3H), 7.33 (m, 2H), 6.47 (s, 1H),
3.88 (t, J = 7.5 Hz, 2H), 3.17 (s, 1H), 1.73 (m, 2H), 1.45 (m, 2H),
0.99 (t, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) 168.9, 166.7,
138.4, 137.0, 136.2, 135.9, 135.5, 134.9, 132.5, 132.1, 131.9, 131.6,
129.8, 129.7, 129.6, 129.3, 128.6, 123.5, 123.4, 123.2, 121.6, 121.4,
119.4, 109.2, 105.5, 83.5, 83.5, 78.3, 78.2, 41.3, 39.4, 30.6, 30.3, 20.5,
19.8, 14.0, 13.7; IR (film, KBr) 3293, 2921, 2359, 1701, 1094 cm−1;
HRMS (ASAP) calcd for C21H20NO [M + H]+ 302.1545, found
302.1544.
2H), 5.42 (d, J = 2.8 Hz, 1H), 3.76 (m, 2H), 3.52 (d, J = 2.8 Hz, 1H),
1.64 (m, 2H), 0.96 (t, J = 7.6 Hz, 3H), one buried signal for E isomer
in alkyl region; 13C NMR (75 MHz, CDCl3) Z-13: δ 167.6, 143.6,
136.7, 132.1, 130.1, 128.2, 123.5, 119.2, 84.8, 83.0, 79.7, 40.7, 32.0,
19.9, 14.1; E-13: δ 166.4, 145.3, 134.9, 132.5, 130.3, 129.6, 123.9,
123.3, 85.8, 85.4, 80.7, 39.3, 30.4, 20.3, 13.9; IR (film, KBr) 2959,
1709, 1636, 1074 cm−1; HRMS (ESI) calcd for C15H15NONa [M +
Na]+ 248.1046, found 248.1040.
N1,N3-Dibutyl-4,6-bis((trimethylsilyl)buta-1,3-diynyl)-
benzamide (14). Prepared first by procedure B using 2, followed by
1
procedure E: orange solid; mp 166−168 °C; H NMR (400 MHz,
CDCl3) δ 8.24 (s, 1H), 7.69 (s, 1H), 6.65 (br t, 2H), 3.48 (dt, J = 6.8,
5.6 Hz, 4H), 1.62 (m, 4H), 1.45 (m, 4H), 0.98 (t, J = 7.2 Hz, 6H),
0.24 (s, 18 H); 13C NMR (100 MHz, CDCl3) δ 164.9, 140.2, 138.7,
130.4, 120.7, 95.4, 86.7, 81.9, 72.3, 40.2, 31.5, 20.4, 14.0, −0.4; IR
(film, KBr) 3249, 2959, 2211, 2103, 1641, 1250 cm−1; HRMS (ESI)
calcd for C30H40N2O2Si2Na [M + Na]+ 539.2521, found 539.2506.
N2 ,N6 -Dibutyl-3,5-di(prop-2-ynylidene)-2,3,5,6-
tetrahydropyrrolo[3,4-f ]isoindole-1,7-dione (Z,Z-15, Z,E-15).
1
Prepared by procedure C using 14: dark red solid; H NMR (300
MHz, CDCl3) Z,Z-15: δ 8.25 (d, J = 0.9 Hz, 1H), 7.80 (d, J = 0.9 Hz,
1H), 5.74 (d, J = 3.0 Hz, 2H), 4.21 (m, 4H), 3.44 (d, J = 3.0 Hz, 2H),
1.75 (m, 4H), 1.40 (m, 4H), 0.96 (t, J = 7.5 Hz, 6H); Z,E-15: 8.85 (d,
J = 1.2 Hz, 1H), 8.26 (d, J = 0.9 Hz, 1H), 5.52 (d, J = 3.0 Hz, 1H),
3.72 (t, 7.5 Hz, 4H), 3.66 (d, J = 3.0 Hz, 1H); five signals for isomer
Z,E are buried (1 alkynyl, 1 alkenyl, 3 alkyl); 13C NMR (100 MHz,
CDCl3) Z,Z-15: δ 166.2, 142.8, 140.1, 129.7, 119.2, 110.1, 86.3, 84.9,
79.3, 41.1, 32.0, 20.0, 14.0; IR (film, KBr) 2959, 1709, 1622, 1259
cm−1.41
N,N′-Dibutyl-2,2′-(buta-1,3-diyne-1,4-diyl)bisbenzamide
(16). Prepared by procedure B using 11 to form N-butyl-2-
ethynylbenzamide (139 mg, 0.691 mmol), which was dissolved in
CH2Cl2 (30 mL), and a solution of TMEDA (3.5 mL) and CuI (162
mg, 0.851 mmol) was added. After 20 min at rt, NH4Clsatd was added,
the solution extracted with Et2O, dried over MgSO4, and filtered, and
solvent removed. Recrystallized from Et2O: white solid; mp 126−127
2-Butyl-3-(3-ethynylbenzilidene)isoindolin-1-one (Z-10).
1
Prepared by procedure C using 8: yellow oil; H NMR (300 MHz,
1
CDCl3) δ 7.84 (td, J = 7.5, 0.9 Hz, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.59
(tdd, J = 7.5, 0.6 Hz, 1H), 7.50 (m, 2H),7.45 (m, 1H), 7.34 (m, 2H),
6.68 (s, 1H), 3.61 (m, 2H), 3.11 (s, 1H), 1.19 (m, 2H), 0.89 (m, 2H),
0.64 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) 168.8, 138.3,
135.6, 135.5, 133.2, 132.0, 131.3, 130.1, 129.3, 128.6, 128.3, 123.4,
122.3, 119.4, 105.1, 83.2, 77.9, 41.4, 30.4, 19.8, 13.6; IR (film, KBr)
3293, 2958, 1707, 1654, 1095 cm−1; HRMS (ASAP) calcd for
C21H20NO [M + H]+ 302.1545, found 302.1538.
N-Butyl-2-((trimethylsilyl)ethynyl)benzamide (11). Prepared
by procedure D using N-butyl-2-iodobenzamide40 and trimethylsily-
lacetylene: yield 1.8 g (97%); orange oil; 1H NMR (400 MHz, CDCl3)
δ 8.11 (m, 1H), 7.67 (br s, 1H), 7.53 (m, 1H), 7.41 (m, 2H), 3.49 (dt,
J = 7.2, 5.6 Hz, 2H), 1.63 (m, 2H), 1.44 (m, 2H), 0.97 (t, J = 7.2 Hz,
3H), 0.29 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 165.9, 135.6,
134.2, 130.4, 130.3, 129.3, 119.3, 103.8, 101.7, 40.1, 31.8, 20.5, 14.0,
0.1; IR (film, KBr) 3393, 2958, 2157, 1652 cm−1; HRMS (ASAP) cald
for C16H24NOSi [M + H]+ 274.1627, found 274.1629.
°C; H NMR (400 MHz, CDCl3) δ 7.90 (dd, J = 8.0, 1.6 Hz, 2H),
7.59 (dd, J = 7.6, 1.6 Hz, 2H), 7.45 (m, 4H), 6.72 (br t, 2H), 3.52 (dt,
J = 7.2, 5.6 Hz, 4H), 1.66 (m, 4H), 1.49 (m, 4H), 0.96 (t, J = 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) 166.3, 138.3, 134.5, 130.5, 130.1,
129.7, 118.1, 81.5, 78.6, 40.1, 31.7, 20.4, 14.0; IR (film, KBr) 3293,
2917, 2384, 1642, 1384, cm−1; HRMS (ESI) calcd for C26H28N2O2Na
[M + Na]+ 423.2043, found 423.2025.
3,3′-(Ethane-1,2-diylidene)bis(2-butylisoindolin-1-one) (E,Z-
17), (Z,Z-17), (E,E-17). Prepared by procedure C using 16. Crude
ratio of 1.3:2.0:1.2 for ZZ/EZ/EE but after silica plug ratio changed to
1.0:2.9:1.7: orange solid; mp 118−119 °C; 1H NMR (300 MHz,
CDCl3) E,Z-17: δ 8.08 (d, J = 7.8 Hz, 1 H), 7.80 (dt, J = 7.8, 0.6 Hz,
1H), 7.11 (d, J = 12.6 Hz, 1H), 6.66 (d, J = 12.6 Hz, 1H) 4.14 (m,
2H), 3.89 (m, 2H); E,E-17: δ 6.84 (s, 1H), 4.21 (m, 2H); Z,Z-17: δ
6.92 (s, 1H), 3.98 (m, 2H); overlapping signals: 8.0 (m, 3H), 7.94 (m,
3H), 7.66 (m, 8H), 1.86 (m, 12H), 1.56 (m, 12H), 1.07 (m, 18H); 13C
NMR (75 MHz, CDCl3) 168.0, 167.9, 166.3, 166.2, 138.0, 137.9,
137.3, 137.0, 135.4, 135.3, 134.8, 134.7, 132.2, 132.1, 132.0, 130.3,
130.2, 129.4, 129.4, 129.2, 129.1, 127.8, 127.8, 124.1, 124.1, 123.8,
123.8, 123.2, 119.3, 118.9, 105.9, 104.5, 101.4, 100.0, 42.0, 41.9, 39.6,
39.5, 32.1, 31.8, 31.0, 30.8, 20.6, 20.5, 20.5, 20.5, 14.1, 14.1, 14.0, 14.0
(2 signals missing); IR (film, KBr) 2917, 2383, 1692, 1384, cm−1;
HRMS (ESI) calcd for C26H28N2O2Na [M + Na]+ 423.2043, found
423.2032.
N-Butyl-2((trimethylsilyl)buta-1,3-diynyl)benzamide (12).
Prepared first by procedure B using 11 to give N-butyl-2-
ethynylbenzamide followed by procedure E: yellow solid; mp 79−81
1
°C; H NMR (400 MHz, CDCl3) δ 7.94 (dd, J = 7.6, 1.6 Hz, 1H),
7.55 (dd, J = 7.6, 1.6 Hz, 1H), 7.42 (m, 2H), 6.85 (br s, 1H), 3.50 (dt,
J = 7.2, 5.6 Hz, 2H), 1.64 (m, 2H), 1.48 (m, 2H), 0.99 (t, J = 7.2 Hz,
3H), 0.24 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 166.1, 138.1,
134.6, 130.5, 130.0, 129.9, 118.0, 93.7, 87.0, 80.0, 74.3, 40.1, 31.6, 20.4,
14.1, −0.3; IR (film, KBr) 3284, 2959, 2204, 2102, 1643, 1251 cm−1;
HRMS (ESI) calcd for C18H23NOSiNa [M + Na]+ 320.1441, found
320.1438.
N,N′-Dibutyl-2,2′-[2,5-thiophenebis(2,1-ethynediyl)]-
bisbenzamide (18). Prepared by procedure B using 11 to form N-
butyl-2-ethynylbenzamide followed by procedure D using 1,4-
1
dibromothiophene: orange solid; mp 126−127 °C; H NMR (400
MHz, CDCl3) δ 7.97 (m, 2H), 7.60 (m, 2H), 7.46 (m, 4H), 7.21 (s,
2H), 6.91 (br t, 2H), 3.52 (q, J = 6.4H, 4H) 1.63 (m, 4H), 1.44 (m,
4H), 0.92 (t, J = 7.6 Hz, 6H); 13C NMR (100 MHz, CDCl3) 166.6,
136.7, 133.4, 132.7, 130.5, 129.9, 129.6, 124.5, 118.9, 92.8, 87.5, 40.1,
31.8, 20.4, 13.9; IR (film, KBr) 2957, 1642, 1534 cm−1; HRMS (ESI)
calcd for C30H30N2O2SNa [M + Na]+ 505.1920, found 505.1898.
N-Butyl-3-(prop-2-ynylidene)isoindolin-1-one (Z-13, E-13).
1
Prepared by procedure C using 12: dark brown oil; H NMR (400
MHz, CDCl3) Z-13: δ 7.82 (ddd, J = 7.6, 1.6, 0.8 Hz, 1H), 7.56 (m,
3H), 5.63 (d, J = 2.8 Hz, 1H), 4.19 (m, 2H), 3.35 (d, J = 2.8 Hz, 1H),
1.75 (m, 2H), 1.40 (m, 2H), 0.96 (t, J = 7.6 Hz, 3H); E-13: δ 8.55 (dt,
J = 7.6 Hz, 0.8 Hz, 1H), 7.84 (ddd, J = 7.6, 1.2, 0.8 Hz, 1H), 7.56 (m,
1576
dx.doi.org/10.1021/jo2021345 | J. Org. Chem. 2012, 77, 1572−1578

The Journal of Organic Chemistry
Note
N,N′-Dibutyl-2,2′-[1,4-(2,5-dimethoxy)phenylenebis(2,1-
ethynediyl)]bisbenzamide (19). Prepared first by procedure B
using 11 to form N-butyl-2-ethynylbenzamide, followed by procedure
D using 1,4-diiodo-2,5-dimethoxybenzene:42 orange solid; mp 123−
129 °C; 1H NMR (300 MHz, CDCl3) δ 8.14 (m, 2H), 7.74 (br t, 2H),
7.63 (m, 2H), 7.46 (m, 2H), 7.05 (s, 2H), 3.92 (s, 6H), 3.51 (dt, J =
5.7, 7.2 Hz, 4H), 1.59 (m, 4H), 1.38 (m, 4H), 0.88 (t, J = 7.5 Hz, 6H);
13C NMR (75 MHz, CDCl3) 166.0, 154.2, 135.6, 133.6, 130.5, 130.5,
129.3, 119.4, 115.3, 113.3, 93.8, 91.7, 56.6, 40.1, 31.9, 20.4, 14.0; IR
(film, KBr) 3283, 2957, 2203, 1642 cm−1; HRMS (ESI) calcd for
C34H37N2O4 [M + H]+ 537.2753, found 537.2753.
3,3′-(2,5-Thiophenebis(methanyl-1-ylidene))bis(2-butyli-
soindolin-1-one) (E,Z-20), (E,E-20), (Z,Z-20). Prepared by
procedure C using 18. Crude ratio of 1:15:44 for ZZ/ZE/EE but
after silica plug ratio changed to 1:2:1: orange solid; mp 174−178 °C;
1H NMR (300 MHz, CDCl3) E,Z-20: δ 7.14 (dd, J = 3.6, 0.9 Hz, 1H),
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7.04 (dd, J = 3.6, 0.9 Hz, 1H), 6.67 (s, 1H), 6.37 (s, 1H), 4.00 (t, J =
7.5 Hz, 2H), 3.88 (t, J = 7.5 Hz, 2H); E,E-20: 7.18 (d, J = 0.3 Hz, 2H),
6.42 (s, 2H), 3.89 (t, J = 7.5, 4H); Z,Z-20: 6.99 (d, J = 0.3 Hz, 2H),
6.64 (s, 2H), 3.98 (t, J = 7.5 Hz, 4H); overlapping signals: 7.86 (m),
7.76 (m), 7.61 (tt, J = 7.5, 1.5 Hz), 7.46 (m) for a total of 24H, 1.73
(m, 6H), 1.44 (m, 12H), 1.13 (m, 6H), 1.00 (dt, 7.5, 1.2 Hz, 9H), 0.80
(dt, 7.5, 3 Hz, 9H); 13C NMR (75 MHz, CDCl3) 168.8, 168.8, 166.6,
138.8, 138.8, 138.3, 138.2, 138.2, 138.1, 136.3, 136.2, 134.8, 134.8,
132.1, 131.8, 131.7, 130.5, 130.5, 129.8, 129.8, 129.4, 129.2, 129.0,
128.8, 128.4, 128.3, 128.2, 123.6, 123.5, 123.4, 123.3, 119.5, 101.5,
101.3, 98.1, 98.0, 41.3, 41.3, 39.5, 39.5, 31.0, 30.9, 30.6, 20.5, 20.0,
20.0, 14.0, 13.9, 13.9 (11 signals missing); IR (film, KBr) 2917, 2347,
1702, 1652, 1384 cm−1; HRMS (ASAP) calcd for C30H31N2O2S [M +
H]+ 483.2106, found 483.2107.
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ylidene))bis(2-butylisoindolin-1-one) (E,Z-21), (E,E-21), (Z,Z-
21). Prepared by procedure C using 19. Crude ratio of 1.3:7.0:10
for ZZ/EZ/EE and after silica plug ratio changed to 1:4:3: orange
(16) Kundu, N. G.; Khan, M. W.; Mukhopadhyay, R. Tetrahedron
1999, 55, 12361−12376.
1
solid; mp 181−186 °C; H NMR (300 MHz, CDCl3) E,Z-21: δ 7.11
(17) Vasilevsky, S. F.; Mikhailovskaya, T. F.; Mamatyuk, V. I.;
Salnikov, G. E.; Bogdanchikov, G. A.; Manoharan, M.; Alabugin, I. V. J.
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(s, 1H), 6.89 (s, 1H), 6.72 (s, 1 H), 6.51 (s, 1H), 3.82 (s, 3H), 3.78 (s,
3H); E,E-21: 7.17 (s, 2H), 6.55 (s, 2H), 3.77 (s, 6H); Z,Z-21: 6.84 (s,
2H), 6.68 (s, 2H), 3.84 (s, 3H). Overlapping signals: 7.60 (24H), 3.92
(m, 12H), 1.78 (m, 6H), 1.48 (m, 6H), 1.27 (m, 8H), 1.00 (m, 16H),
0.73 (t, J = 7.5 Hz, 6H); 13C NMR (75 MHz, CDCl3) 169.1, 169.0,
166.6, 166.6, 151.7, 151.4, 151.4, 151.2, 151.1, 140.0, 138.5, 136.3,
135.6, 135.2, 132.3, 132.2, 132.1, 132.1, 132.0, 131.3, 131.2, 130.7,
129.4, 129.1, 128.7, 128.6, 128.5, 128.3, 124.6, 124.6, 124.4, 124.3,
123.4, 123.4, 123.2, 123.1, 119.8, 119.7, 114.6, 114.3, 114.0, 113.8,
106.6, 106.5, 102.9, 102.8, 56.4, 56.3, 56.2, 56.1, 41.3, 41.3, 40.0, 39.5,
30.7, 30.4, 30.3, 29.8, 20.5, 20.4, 20.0, 19.9, 14.0, 13.9, 13.9, 13.8 (2
signals missing); IR (film, KBr) 2959, 1699, 1471 cm−1; HRMS (ESI)
calcd for C34H37N2O4 [M + H]+ 537.2753, found 537.2756.
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ASSOCIATED CONTENT
■
S
* Supporting Information
(25) Only products resulting from 5-exo ring closure were observed,
as confirmed by NMR and IR. See ref 15.
General experimental methods, 1H and 13C NMR spectra for all
new compounds, and NOESY spectra for cyclized products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(26) Isolated yield after removal of baseline material. Other isomers
could not be identified due to the small amounts isolated from the
reaction.
(27) Isoindolinones 6c, 9, 13, and 15 were found to be light sensitive,
and isomer ratios changed when exposed to UV and visible light. For
this reason, cyclization reactions were performed in the dark,
producing the stated isomer ratio without exposure to light. The
difference in isomer ratios after exposure to UV light helped to identify
signals in the 1H and 13C NMR of these compounds. See the
Supporting Information for spectra.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: seisler@unb.ca.
(28) The vinyl region of all cyclization products that possessed
mixtures of E and Z isomers were diagnostic, with well-resolved
signals.
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ACKNOWLEDGMENTS
■
We thank the Natural Sciences and Engineering Research
Council (NSERC) of Canada, New Brunswick Innovation
Foundation (NBIF), Canadian Foundation for Innovation
(CFI), Harrison McCain Fund, and the University of New
Brunswick for financial support.
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dx.doi.org/10.1021/jo2021345 | J. Org. Chem. 2012, 77, 1572−1578

The Journal of Organic Chemistry
Note
(31) Surprisingly, a small portion of the product mixture consisted of
the E,E isomer when the reaction was performed in the light.
(32) Isomer mixtures formed in Scheme 4, as well as in Scheme 5,
were inseparable.
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(36) This phenomenon helped to identify signals in the 1H NMR of
isomer mixtures of these compounds. See the Supporting Information
for spectra.
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repeating units for use in optoelectronic devices. US Patent 7,754,847,
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