Divergent pathways to isophthalates and naphthalate esters from methyl coumalate

Article abstract of DOI:10.1016/j.tetlet.2018.09.058

Methyl coumalate readily reacts with enamines at ambient temperature to give lactones, which can be further transformed into isophthalates and tetrahydronaphthoates. Both cyclic and acyclic enamines show good reactivity. Dehydrogenation of tetrahydronaphthoate 4a was achieved on a hundred-gram scale.

Full text of DOI:10.1016/j.tetlet.2018.09.058

Accepted Manuscript
Divergent Pathways to Isophthalates and Naphthalate Esters From Methyl Cou-
malate
Huangchao Yu, George A. Kraus
PII:
S0040-4039(18)31160-2
https://doi.org/10.1016/j.tetlet.2018.09.058
TETL 50297
DOI:
Reference:
Tetrahedron Letters
To appear in:
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Revised Date:
Accepted Date:
25 July 2018
21 September 2018
24 September 2018
Please cite this article as: Yu, H., Kraus, G.A., Divergent Pathways to Isophthalates and Naphthalate Esters From
Methyl Coumalate, Tetrahedron Letters (2018), doi: https://doi.org/10.1016/j.tetlet.2018.09.058
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Divergent Pathways to Isophthalates and
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Huangchao Yu , George A. Kraus

1
Tetrahedron Letters
Divergent Pathways to Isophthalates and Naphthalate Esters From Methyl Coumalate
Huangchao Yua , George A. Kraus a, 
a Department of Chemistry, Iowa State University, Ames, IA 50010,U.S.A.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Methyl coumalate readily reacts with enamines at ambient temperature to give lactones, which
can be further transformed into isophthalates and tetrahydronaphthoates. Both cyclic and acyclic
enamines show good reactivity. Dehydrogenation of tetrahydronaphthoate 4a was achieved on a
hundred-gram scale.
Available online
Keywords:
pyrone
enamine
Diels-Alder
naphthale
A number of pyrones have been employed in cycloaddition
reactions.1 The most common cycloaddition reaction of pyrones
is the Diels-Alder reaction. This area has been reviewed by
Posner.2 Van Saun has reported that the reaction between pyrone
and enamines provided benzoates at elevated temperature.3 Kraus
and co-workers have shown that ketals reacted with methyl
coumalate (1) to provide excellent yields of aromatic esters.4 This
reaction, shown in Scheme 1, occurred through a vinyl ether
intermediate and is an example of an inverse electron demand
Diels-Alder reaction. The reaction of methyl coumalate with a
pre-formed vinyl ether is also known5 and generates bicyclic
lactone intermediates which can be converted into natural
products6,7,8 and into isophthalates.9
successful with the enamines of cyclohexanone and ethyl 4-
oxocyclohexane-1-carboxylate.
Scheme 2. Tetrahydronaphthoate synthesis via a tandem
Diels-Alder/elimination.
Scheme 1. Methyl coumalate reacts with ketal.
Interestingly, the reaction of methyl coumalate with the
enamine of cyclopentanone in DCM afforded products in 23%
yield as 3:1 mixture of diastereomers that lacked aromatic ring
protons in the proton NMR. The major diastereomer showed the
M/Z+ at 195, the carbon resonances at 207.1 ppm and 166.8 ppm,
and the three proton resonances at 7.08 ppm (1H, singlet), 7.03
ppm (1H, quartet), and 1.83 ppm (3H, doublet) support the
structure shown in Scheme 3. This reaction presumably occurs
via the Michael addition adduct 5, which fragments to form an
iminium intermediate 6 which is converted into 7. The E
conformation of the major product was confirmed by the NOE
Although the ketal required 200 °C for a successful reaction,
we report herein that the use of the pyrrolidine enamine shown in
Scheme
2
allows the cyclization/elimination to the
tetrahydronaphthoate to proceed at ambient temperature without
isolation of the lactone. We believe that the unfavorable
nonbonded interactions in the tricyclic lactone 3 led to a bicyclic
amino acid that readily extruded carbon dioxide and pyrrolidine
to produce 4a. An alternative pathway that the lactone 3 released
CO2 through a retro Diels-Alder process, and then the elimination
of pyrrolidine to give 4a is also possible. This reaction was
———
 Corresponding author. Tel.: +1-515-294-7794; e-mail: gakraus@iastate.edu

2
Tetrahedron
experiment, where no signal was observed between the terminal
substituted isophthalates were obtained in good yields by
methyl group and the methyl ester.
hydrolysis in basic methanol/water solution in one pot. Enamine
12b, 12d and 12e, with substituents at ortho, meta and para
position on the aromatic ring afforded corresponding products in
good yields. The enamine of isobutyraldehyde did not react with
1.
Scheme 3. Mechanism for formation of 7.
In contrast, the reaction between the morpholine enamine of
3-methylbutanal and methyl coumalate in dichloromethane
generated the stable bicyclic lactone 9 as a mixture of
diastereomers (8:1 ratio) in 98% yield (entry 3). The NOE
experiment indicated that the isopropyl group is in equatorial
position of the major product.
The proton NMR spectrum confirmed the trans-relationship of
the amine and the isopropyl group. The yield of this
cycloaddition was solvent dependent with lower yields in toluene
(87%), methanol (60%) and dioxane (63%), as shown in Table 1.
a Used K2CO3 as the base
Scheme 5. Synthesis isophthalic acids
Table 1. D-A reaction of methyl coumalate and enamine 8
The tetrahydronaphthoate 4a was produced on a hundred-
gram scale, and was readily converted into naphthalene diester 14
in 80% yield over two steps as depicted in Scheme 6. Diester 14
is a monomer for the production of polyethylene naphthalates, a
class of polymers with mechanical properties superior to those of
polyethylene terephthalate (PET).10
Entry
Solvent
Toluene
DCM
Time (mins)
Yield (%)a
1
2
3
4
5
6
7
8
90
90
120
90
90
90
90
90
87
94
98b
75
74
86
60
63
Scheme 6. Dehydrogenation of diester 4a
In conclusion, the reaction of methyl coumalate with enamines
provides convenient routes to substituted isophthalic acids or
naphthoates depending on the structure of the enamine.
DCM
THF
Diethyl ether
DMF
References and notes
Methanol
1,4-dioxane
1.
2.
Ohkata, K.; Akiba, K-Y. Advances in Heterocyclic Chemistry,
1996, 65, 283-374.
(a) Posner, G. H.; Edited By: Trost, B. M. Stereocontrolled
Organic Synthesis, 1994, 177-191; (b) Afarinkia, K.; Vinader, V.;
Nelson, T. D.; Posner, G. H. Tetrahedron, 1992, 48, 9111-9171.
Gingrich, H. L.; Roush, D. M.; Van Saun, W. A. J. Org. Chem.
1983, 48, 4869-4873.
a Yields were calculated based on 1H NMR
b Isolated yield
3.
Lactone 9 could readily be converted into the isophthalates 10
and 11 in 89% combined yield using potassium carbonate in
methanol at ambient temperature (Scheme 4).
4.
5.
Kraus, G. A.; Lee, J. J. Tetrahedron, 2013, 54, 2366-2368.
Markó, I. E.; Evans, G. R. Tetrahedron Lett., 1993, 34, 7309-
7312.
Shimo, T.; Muraoka, F.; Somekawa, K. Nippon Kagaku Kaishi,
1989, 1765-1771.
Slack, R. D.; Siegler, M. A.; Posner, G. H. Tetrahedron Lett.,
2013, 54, 6267-6270.
Okura, K.; Tamura, R.; Shigehara, K.; Masai, E.; Nakamura, M.;
Otsuka, Y.; Katayama, Y.; Nakao, Y. Chem. Lett., 2014, 43, 1349-
1351.
6.
7.
8.
9.
Kraus, G. A.; Wang, S. RSC Advances, 2017, 7, 56760-56763.
10. (a) Hine, P. J.; Astruc, A.; Ward, I. M. J. Appl. Polym. Sci., 2004,
93, 796-802. (b) Lillwitz, L. D. Appl. Catal., A., 2001, 221, 337-
358.
Scheme 4. Synthesis of isophthalate
Extension of this transformation to other aldehyde enamines
afforded the products depicted below in Scheme 5. Phenyl

3
Highlights
1. First report of the reaction between methyl
coumalate and enamines
2. Direct synthesis of isophthalic acids and
naphthalic diesters in good yields
3. Diels-Alder reaction proceeded at ambient
temperature
4. Two-step, chromatography-free process