Synthesis of naphthalene amino esters by the blaise reaction of o -alkynylarenenitriles

Article abstract of DOI:10.1021/jo500137m

The action of a Reformatsky reagent on o-alkynylarenenitriles provides a convenient access to naphthalene amino esters via tandem 6-endo-dig carbannulation of in situ generated Blaise reaction intermediates. The products are formed in moderate to good yields with high chemo- and regioselectivity.

Full text of DOI:10.1021/jo500137m

Note
pubs.acs.org/joc
Synthesis of Naphthalene Amino Esters by the Blaise Reaction of
o‑Alkynylarenenitriles
Karuppusamy Sakthivel and Kannupal Srinivasan*
School of Chemistry, Bharathidasan University, Tiruchirapalli 620 024, Tamil Nadu, India
S
* Supporting Information
ABSTRACT: The action of a Reformatsky reagent on o-alkynylarenenitriles provides a convenient access to naphthalene amino
esters via tandem 6-endo-dig carbannulation of in situ generated Blaise reaction intermediates. The products are formed in
moderate to good yields with high chemo- and regioselectivity.
he Blaise reaction, which involves the addition of a
Reformatsky reagent to nitrile, is an important carbon−
lation of β-enaminoesters with alkynes.17 The development of
new methods for the access of functionalized naphthalenes is
actively pursued owing to the widespread applications of
substituted naphthalenes in academia and industry and the
occurrence of the naphthalene core in many natural products,
pharmaceuticals, and functional materials.18 In this context, the
present method would be an interesting and useful addition to
the existing methods.
T
carbon bond forming reaction.1 A zinc bromide complex of β-
enaminoester is generated as an intermediate in the reaction,
and the intermediate after acidic or basic workup gives β-
ketoester or β-enaminoester (Scheme 1, eq 1). The reaction has
been exploited in the synthesis of numerous heterocycles and
natural products.1,2 In recent years, the Blaise reaction
intermediates have been trapped with suitable partners in a
tandem manner, which has provided access to a variety of
compounds. Thus, the trapping of the intermediates with acetic
anhydride,3 propiolates,4 epoxides,5 1,4-benzoquinones,6 1,3-
enynes,7 nitriles,8 isocyanates,9 and nitroolefins10 have yielded
α-acyl-β-enaminoketoesters (subsequently, pyrazoles), 2-pyr-
idones, α-aminomethylene-γ-butyrolactones, benzofuran-2-
ones, pyridines, pyrimidin-4-ones, pyrimidin-2,4-diones, and
pyrroles, respectively. A palladium-catalyzed intramolecular N-
alkylative/arylative trapping of the intermediate has furnished
indoles,11 and a chemoselective intramolecular alkylation of the
intermediate has afforded various N-fused heterocyclic
compounds via exo-cyclic enamino esters.12 An interesting
addendum to the list is Lee’s tandem alkenylation of the Blaise
reaction intermediates with unactivated alkynes, which has
resulted in various α-vinylated β-enaminoesters (Scheme 1, eq
2).13,14 The work caused us to envisage that an intramolecular
version of the reaction using o-alkynylarenenitriles as substrates
would result in naphthalene amino esters through tandem 6-
endo-dig carbannulation of in situ generated Blaise reaction
intermediates (Scheme 1, eq 3).
To test our hypothesis, we required a variety of o-
alkynylarenenitriles with various substitution patterns. They
were prepared from appropriate o-haloarenenitriles and
terminal acetylenes by a standard Sonogashira coupling
procedure. The requisite o-haloarenenitriles were in turn
prepared from the corresponding o-haloarenecarbaldehydes
by heating with hydroxylamine hydrochloride and DMSO.19
We began the study with the generation of methyl zincbromo-
acetate in situ from methyl bromoacetate and activated zinc and
its addition to o-alkynylbenzonitrile 1a in THF under reflux
conditions. To our delight, the desired naphthalene amino ester
2a was obtained in 65% isolated yield after 2 h. After several
attempts, we found that the yield of 2a could be improved to
81% when solvent was switched to 1,4-dioxane (under reflux)
and 5 equiv of methyl bromoacetate and 7.5 equiv of zinc were
used for the formation of the Reformatsky reagent (Table 1,
entry 1). Under these optimized conditions, we investigated the
scope of the reaction for various o-alkynylarenenitriles using
different Reformatsky reagents (Table 1).20 The reaction of 1a
with ethyl zincbromoacetate afforded the respective naphtha-
lene amino ester 2b in almost similar yield (83%) (entry 2).
When tert-butyl zincbromoacetate was employed in the
reaction, 1a did not undergo any change even after 12 h
(entry 3), probably due to the lower nucleophilicity of the
Earlier methods reported for the synthesis of naphthalene
amino esters include addition of α-lithio derivatives of 2-
alkylbenzonitriles to α,β-unsaturated carboxylic acids or esters
via tandem Michael addition/enolate coupling,15 copper(I)
cyanide-mediated cascade cyclization of 4-(2-bromoaryl)-2-
butenoates,16 and hypervalent iodine(III)-mediated benzannu-
Received: January 20, 2014
Published: March 7, 2014
© 2014 American Chemical Society
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Note
Scheme 1. Inter- and Intramolecular Tandem Alkenylation of Blaise Reaction Intermediates
reagent caused by the bulky tert-butyl group. Next, we tested
the suitability of o-alkynylarenenitriles 1b−g having different
aromatic rings (R1) attached to the yne unit. The presence of
phenyl rings with electron-donating and halogen substituents
was tolerated (entries 4−7) as well as the bulky naphthyl ring
(entry 8) and the heteroaromatic thienyl ring, albeit in low
yield in the latter case (entry 9). However, the reaction failed
for a terminal acetylene 1h, in which R1 = H (entry 10), likely
due to abstraction of the acidic terminal acetylenic hydrogen by
the Reformatsky reagent.21 We then examined o-alkynylbenzo-
nitriles 1i−r bearing one or two methoxy groups on the main
aryl ring (entries 11−20). The yields were comparatively low
and the reaction time was longer (6 h) when an alicyclic ring or
aliphatic chain was linked to the yne unit (entries 12−14). The
reaction did not take place when a p-nitrophenyl group was
attached to the yne unit (entry 20). Except for these pitfalls, all
other o-alkynylbenzonitriles furnished the corresponding
naphthalene amino esters in moderate to good yields (entries
11 and 15−19). Finally, we tested the tetrahydrobenzo-
thiophene-based o-alkynylarenenitrile 1s, which also afforded
the corresponding amino ester 2r in 45% yield (entry 21). All
the products were thoroughly characterized by various
spectroscopic techniques, and for one of the products, 2i, the
structure was further confirmed by X-ray analysis.22
In all the successful reactions mentioned above, we obtained
only naphthalene amino esters 2 as single or only isolable
products. Obviously, the initially formed Blaise reaction
intermediate has acted as a carbon nucleophile and attacked
the triple bond in a tandem manner via 6-endo-dig cyclization
mode producing the carbannulated product 2. The high chemo-
and regioselectivities of the reactions are noteworthy. We did
not observe any products 3−5 arising from 5-exo-dig
carbannulation or 6-endo-dig/5-exo-dig hydroamination (when
the Blaise reaction intermediate acts as a N-nucleophile)
(Scheme 2). It may be noted that Lee’s alkenylation of Blaise
reaction intermediates with alkynes (Scheme 1, eq 2) was
applicable mainly to terminal alkynes and only one internal
alkyne (methyl phenyl acetylene) has been successfully
employed in the reaction.13 In contrast, our intramolecular
strategy is applicable only to internal diaryl or alkylaryl alkynes.
In summary, we have developed a convenient protocol for
the synthesis of naphthalene amino esters from o-alkynylarene-
nitriles and Reformatsky reagents. The reaction proceeds in a
highly chemo- and regioselective manner via tandem 6-endo-dig
carbannulation of in situ formed Blaise reaction intermediates.
EXPERIMENTAL SECTION
■
General Remarks. Melting points were determined using an
apparatus by the open capillary tube method and are uncorrected. The
1H and 13C NMR spectra were recorded on a 400 MHz NMR
spectrometer. HRMS (ESI) were recorded on Q-TOF mass
spectrometers. Low resolution mass spectra (ESI) were recorded on
LC-MS spectrometers. Elemental analyses were performed on a CHN
analyzer. X-ray crystallographic data were collected on a CCD
diffractometer using graphite-monochromated Mo Kα radiation. Thin
layer chromatography (TLC) was performed on precoated alumina
sheets and detected under UV light. Silica gel (100−200 mesh) was
used for column chromatography.
General Procedures for the Synthesis of Naphthalene
Amino Esters 2a−r. To a stirred suspension of zinc dust (3.75
mmol) in anhydrous 1,4-dioxane (5 mL) was added methanesulfonic
acid (5 mol %) and heated to reflux. After 10 min, o-alkynylarenenitrile
1 (0.5 mmol) was added followed by slow addition (15 min) of alkyl
bromoacetate (2.5 mmol) in 1,4-dioxane (1 mL). After 2 h (6 h for
1j−l), the reaction mixture was cooled to room temperature,
quenched with saturated NH4Cl, and extracted with ethyl acetate.
The organic layer was washed with brine, dried over anhydrous
Na2SO4, and evaporated under reduced pressure. The crude product
was purified by column chromatography on silica gel using hexane/
ethyl acetate (9.5/0.5) as eluent to obtain pure naphthalene amino
ester 2.
Methyl 1-Amino-3-phenyl-2-naphthoate (2a). Brown viscous
1
liquid. Yield: 112 mg (81%). H NMR (400 MHz, CDCl3): δ 7.87
(d, J = 8.4 Hz, 1H), 7.75 (d, J = 7.6 Hz, 1H), 7.56−7.52 (m, 1H),
7.49−7.45 (m, 1H), 7.39−7.36 (m, 4H), 7.33−7.30 (m, 1H), 7.13 (s,
1H), 6.02 (brs, 2H), 3.41 (s, 3H); 13C NMR (100 MHz,CDCl3): δ
170.5, 146.3, 143.7, 139.9, 134.9, 128.7, 128.4, 127.91, 127.85, 126.5,
125.5, 122.4, 121.4, 119.1, 107.7, 51.2 ppm; HRMS (ESI): [M + H]+
Calcd for C18H16NO2, 278.1181; found, 278.1165.
Ethyl 1-Amino-3-phenyl-2-naphthoate (2b).15 Brown viscous
1
liquid. Yield: 121 mg (83%). H NMR (400 MHz, CDCl3): δ 7.88
(d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.55 (t, J = 7.4 Hz, 1H),
7.47 (t, J = 7.6 Hz, 1H), 7.40−7.32 (m, 5H), 7.14 (s, 1H), 6.10 (brs,
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Note
a
Table 1. Substrate Scope for the Tandem Carbannulation of Blaise Reaction Intermediates
a
Reaction conditions: nitrile (0.5 mmol), alkyl bromoester (2.5 mmol), zinc (3.75 mmol, preactivated with 5 mol % of methanesulfonic acid) in 1,4-
b
c
dioxane (6 mL) at reflux for 2 h. Isolated yield. Reaction time was 6 h.
2H), 3.94 (q, J = 7.2 Hz, 2H), 0.73 (t, J = 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3): δ 170.1, 146.5, 144.1, 140.1, 134.9, 128.7, 128.4, 128.1,
127.9, 126.5, 125.5, 122.5, 121.5, 119.1, 107.7, 60.4, 13.2 ppm; MS
(ESI): m/z 292 (M + H)+.
Scheme 2. Possible Tandem Carbannulation/
Hydroamination of the Blaise Reaction Intermediates
Methyl 1-Amino-3-(4-methylphenyl)-2-naphthoate (2c). Brown
1
solid. Yield: 115 mg (79%). Mp 78−80 °C. H NMR (400 MHz,
CDCl3): δ 7.84 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.53−
7.49 (m, 1H), 7.45−7.41 (m, 1H), 7.26 (d, J = 8.0 Hz, 2H), 7.18 (d, J
= 8.0 Hz, 2H), 7.12 (s, 1H), 5.94 (brs, 2H), 3.44 (s, 3H), 2.39 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 170.7, 146.1, 140.7, 139.8, 136.1,
135.0, 128.69, 128.68, 128.3, 127.8, 125.4, 122.4, 121.4, 119.1, 108.0,
51.3, 21.2 ppm; HRMS (ESI): [M + H]+ Calcd for C19H18NO2,
292.1338; found, 292.1321.
Methyl 1-Amino-3-(2-methylphenyl)-2-naphthoate (2d). Brown
1
viscous liquid. Yield: 109 mg (75%). H NMR (400 MHz, CDCl3): δ
7.89 (d, J = 8.4 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.56−7.52 (m, 1H),
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Note
7.49−7.45 (m, 1H), 7.21−7.13 (m, 4H), 6.97 (s, 1H), 6.29 (brs, 2H),
3.36 (s, 3H), 2.14 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 170.2,
147.1, 143.8, 139.8, 135.2, 135.0, 129.2, 128.52, 128.51, 128.4, 126.5,
125.4, 125.1, 122.4, 121.5, 119.0, 107.5, 51.1, 20.1 ppm; HRMS (ESI):
[M + H]+ Calcd for C19H18NO2, 292.1338; found, 292.1347.
Methyl 1-Amino-3-(4-methoxyphenyl)-2-naphthoate (2e). Or-
35.9, 34.0, 22.9, 14.2, 14.1 ppm; HRMS (ESI): [M + H]+ Calcd for
C18H24NO3, 302.1756; found, 302.1750.
Ethyl 1-Amino-3-heptyl-7-methoxy-2-naphthoate (2l). Brown
1
liquid. Yield: 74 mg (43%). H NMR (400 MHz, CDCl3): δ 7.59
(d, J = 9.2 Hz, 1H), 7.17 (dd, J = 8.8, 2.4 Hz, 1H), 7.06 (d, J = 2.0 Hz,
1H), 6.98 (s, 1H), 5.67 (brs, 2H), 4.42 (q, J = 7.0 Hz, 2H), 3.92 (s,
3H), 2.89 (t, J = 8.0 Hz, 2H), 1.62−1.56 (m, 3H), 1.42 (t, J = 7.2 Hz,
3H), 1.33−1.26 (m, 7H), 0.88 (t, J = 6.6 Hz, 3H); 13C NMR (100
MHz, CDCl3): δ 170.3, 157.2, 144.8, 137.3, 130.4, 129.5, 122.9, 119.7,
118.5, 109.8, 100.9, 60.8, 55.4, 36.2, 31.90, 31.87, 29.8, 29.3, 22.7, 14.3,
14.1 ppm; HRMS (ESI): [M + H]+ Calcd for C21H30NO3, 344.2226;
found, 344.2218.
1
ange liquid. Yield: 103 mg (67%). H NMR (400 MHz, CDCl3): δ
7.87 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.54 (t, J = 7.4 Hz,
1H), 7.47 (t, J = 7.2 Hz, 1H), 7.31 (d, J = 8.4 Hz, 2H), 7.12 (s, 1H),
6.94 (d, J = 8.8 Hz, 2H), 5.95 (brs, 2H), 3.86 (s, 3H), 3.48 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 170.7, 158.5, 146.0, 139.4, 136.1,
134.9, 128.9, 128.6, 128.3, 125.3, 122.3, 121.4, 118.9, 113.5, 108.1,
55.3, 51.3 ppm; HRMS (ESI): [M + H]+ Calcd for C19H18NO3,
308.1287; found: 308.1278.
Ethyl 1-Amino-6,7-dimethoxy-3-phenyl-2-naphthoate (2m).
Brown solid. Yield: 130 mg (74%). Mp 118−120 °C. 1H NMR
(400 MHz, CDCl3): δ 7.36−7.35 (m, 4H), 7.34−7.28 (m, 1H), 7.10
(s, 1H), 7.05 (s, 1H), 7.03 (s, 1H), 5.83 (brs, 2H), 4.03 (s, 3H), 3.99
(s, 3H), 3.91 (q, J = 7.2 Hz, 2H), 0.70 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): δ 170.3, 151.2, 149.2, 145.2, 144.2, 138.8, 131.0,
128.1, 127.8, 126.3, 118.4, 117.3, 107.6, 107.4, 101.1, 60.3, 56.0, 55.9,
13.1 ppm; MS (ESI): m/z 352 (M + H)+. Anal. Calcd for C21H21NO4:
C, 71.78; H, 6.02; N, 3.99. Found: C, 71.90; H, 6.21; N, 4.10.
Ethyl 1-Amino-6,7-dimethoxy-3-(4-methylphenyl)-2-naphthoate
Methyl 1-Amino-3-(4-chlorophenyl)-2-naphthoate (2f). Pale
1
yellow liquid. Yield: 100 mg (64%). H NMR (400 MHz, CDCl3):
δ 7.89 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.57 (t, J = 7.2 Hz,
1H), 7.50 (t, J = 7.0 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4
Hz, 2H), 7.08 (s, 1H), 6.13 (brs, 2H), 3.46 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 170.2, 146.8, 142.3, 138.7, 134.8, 132.4, 129.2, 128.7,
128.6, 128.0, 125.7, 122.5, 121.4, 119.1, 106.9, 51.2 ppm; MS (ESI):
m/z 312 (M + H)+. Anal. Calcd for C18H14ClNO2: C, 69.35; H, 4.53;
N, 4.49. Found: C, 69.55; H, 4.63; N 4.62.
1
(2n). Pale yellow solid. Yield: 128 mg (70%). Mp 205−207 °C. H
NMR (400 MHz, CDCl3): δ 7.25 (d, J = 8.8 Hz, 2H), 7.19 (s, 1H),
7.17 (s, 1H), 7.09 (s, 1H), 7.03 (d, J = 6.8 Hz, 2H), 5.77 (brs, 2H),
4.03 (s, 3H), 3.99 (3H), 3.93 (q, J = 7.0 Hz, 2H), 2.40 (s, 3H), 0.74 (t,
J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 170.4, 151.1, 149.1,
144.9, 141.1, 138.7, 135.9, 131.0, 128.5, 127.9, 118.3, 117.2, 107.9,
107.3, 101.0, 60.3, 56.0, 55.9, 21.1, 13.2 ppm; MS (ESI): m/z 388 (M
+ Na)+. Anal. Calcd for C22H23NO4: C, 72.31; H, 6.34; N, 3.83.
Found: C, 72.56; H, 6.47; N, 3.96.
Methyl 4′-Amino-4-methoxy-1,2′-binaphthyl-3′-carboxylate
(2g). Orange oil. Yield: 107 mg (60%). 1H NMR (400 MHz,
CDCl3): δ 8.31 (d, J = 8.0 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.74 (d, J
= 7.6 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.59−7.49 (m, 2H), 7.46−
7.36 (m, 2H), 7.29 (d, J = 7.6 Hz, 1H), 7.17 (s, 1H), 6.86 (d, J = 7.6
Hz, 1H), 6.27 (brs, 2H), 4.06 (s, 3H), 3.03 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 170.2, 154.4, 146.8, 138.4, 135.1, 134.4, 133.1, 128.6,
128.4, 126.3, 125.6, 125.5, 125.4, 125.2, 124.8, 122.6, 121.9, 121.5,
120.4, 108.8, 103.2, 55.5, 51.0 ppm; HRMS (ESI): [M + H]+ Calcd for
C23H20NO3, 358.1443; found, 358.1430.
Ethyl 1-Amino-6,7-dimethoxy-3-(2-methoxyphenyl)-2-naph-
thoate (2o). Pale orange liquid. Yield: 118 mg (62%). 1H NMR
(400 MHz, CDCl3): δ 7.32−7.27 (m, 2H), 7.10 (s, 1H), 7.03−6.98
(m, 3H), 6.87 (d, J = 8.0 Hz, 1H), 4.02 (s, 3H), 3.98 (s, 3H), 3.94−
Ethyl 1-Amino-3-(thiophen-2-yl)-2-naphthoate (2h). Brown
1
viscous liquid. Yield: 67 mg (45%). H NMR (400 MHz, CDCl3): δ
1
7.79 (d, J = 8.4 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 7.2 Hz,
1H), 7.41 (t, J = 7.2 Hz, 1H), 7.22 (d, J = 5.2 Hz, 1H), 7.19 (s, 1H),
6.98−6.92 (m, 2H), 5.87 (brs, 2H), 3.97 (q, J = 7.0 Hz, 2H), 0.84 (t, J
= 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 169.9, 145.9, 145.3,
134.6, 131.9, 128.7, 128.4, 126.9, 125.8, 125.1, 124.6, 122.8, 121.4,
119.9, 108.6, 60.7, 13.4 ppm; MS (ESI): m/z 320 (M + Na)+. Anal.
Calcd for C17H15NO2S: C, 68.66; H, 5.08, N, 4.71. Found: C, 68.75;
H, 5.20; N, 4.90.
3.85 (m, 2H), 3.72 (s, 3H), 0.75 (t, J = 7.2 Hz, 3H); H NMR (400
MHz, DMSO-d6): δ 7.64 (s, 1H), 7.38−7.34 (m, 1H), 7.29 (d, J = 1.6
Hz, 1H), 7.27 (s, 1H), 7.07−7.01 (m, 2H), 6.96 (brs, 2H), 6.86 (s,
1H), 3.99 (s, 3H), 3.93 (s, 3H), 3.87−3.85 (m, 2H), 3.69 (s, 3H), 0.72
(t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 169.9, 156.3,
151.0, 149.1, 145.1, 135.2, 133.6, 131.2, 129.8, 127.8, 120.6, 119.1,
117.8, 109.9, 108.0, 107.4, 101.2, 59.9, 56.0, 55.9, 55.4, 13.2 ppm; MS
(ESI): m/z 382 (M + H)+. Anal. Calcd for C22H23NO5: C, 69.28; H,
6.08; N, 3.67. Found: C, 69.46; H, 6.17; N, 3.74.
Ethyl 1-Amino-7-methoxy-3-phenyl-2-naphthoate (2i). Orange
1
solid. Yield: 125 mg (78%). Mp 135−137 °C. H NMR (400 MHz,
Ethyl 1-Amino-3-(4-chlorophenyl)-6,7-dimethoxy-2-naphthoate
1
(2p). Semibrown solid. Yield: 123 mg (64%). H NMR (400 MHz,
CDCl3): δ 7.68 (d, J = 8.8 Hz, 1H), 7.39−7.35 (m, 4H), 7.33−7.28
(m, 1H), 7.23 (dd, J = 8.8, 2.4 Hz, 1H), 7.13 (d, J = 2.4 Hz, 1H), 7.11
(s, 1H), 5.81 (brs, 2H), 3.96 (s, 3H), 3.91 (q, J = 7.0 Hz, 2H), 0.71 (t,
J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 170.2, 157.7, 145.0,
144.0, 137.7, 130.3, 130.0, 128.1, 127.9, 126.3, 123.5, 120.1, 119.2,
108.9, 101.1, 60.4, 55.5, 13.1 ppm; MS (ESI): m/z 344 (M + Na)+.
Anal. Calcd for C20H19NO3: C, 74.75; H, 5.96; N, 4.36. Found: C,
74.83; H, 6.02; N, 4.50. Single crystals suitable for X-ray studies were
grown from a solution of 2i in hexane/ethyl acetate (9.5:0.5).
Ethyl 1-Amino-3-cyclopropyl-7-methoxy-2-naphthoate (2j).
CDCl3): δ 7.34 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 7 10 (s,
1H), 7.04 (s, 1H), 6.96 (s, 1H), 5.94 (brs, 2H), 4.03 (s, 3H), 3.99 (s,
3H), 3.94 (q, J = 7.2 Hz, 2H), 0.78 (t, J = 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3): δ 169.9, 151.4, 149.3, 145.7, 142.8, 137.6, 132.2, 130.9,
129.4, 127.9, 118.3, 117.4, 107.4, 106.8, 101.1, 60.3, 56.1, 55.9, 13.3
ppm; MS (ESI): m/z 385 (M)+. Anal. Calcd for C21H20ClNO4: C,
65.37; H, 5.22; N, 3.63. Found: C, 65.50; H, 5.34; N, 3.79.
Ethyl 4′-Amino-4,6′,7′-trimethoxy-1,2′-binaphthyl-3′-carboxy-
late (2q). Pale orange solid. Yield: 116 mg (54%). Mp 128−130 °C.
1H NMR (400 MHz, CDCl3): δ 8.29 (d, J = 8.0 Hz, 1H), 7.67 (d, J =
1
Brown liquid. Yield: 54 mg (38%). H NMR (400 MHz, CDCl3): δ
7.59 (d, J = 8.8 Hz, 1H), 7.16 (dd, J = 9.2, 2.2 Hz, 1H), 7.05 (d, J = 2.0
Hz, 1H), 6.96 (s, 1H), 5.58 (brs, 2H), 4.44 (q, J = 7.2 Hz, 2H), 3.92
(s, 3H), 2.39−2.32 (m, 1H), 1.42 (t, J = 7.0 Hz, 3H), 0.88−0.84 (m,
2H), 0.68−0.64 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 170.3,
157.3, 143.9, 137.4, 130.2, 129.7, 123.1, 119.6, 116.7, 111.8, 100.93,
100.90, 60.8, 55.5, 16.3, 14.3, 7.1 ppm; HRMS (ESI): [M + H]+ Calcd
for C17H20NO3, 286.1443; found, 286.1434.
8.4 Hz, 1H), 7.45−7.41 (m, 1H), 7.38−7.36 (m, 1H), 7.27−7.25 (m,
1H), 7.16 (s, 1H), 7.04 (d, J = 7.6 Hz, 2H), 6.84 (d, J = 7.6 Hz, 1H),
6.11 (brs, 2H), 4.06 (s, 3H), 4.05 (s, 3H), 3.98 (s, 3H), 3.67−3.59 (m,
1H), 3.55−3.46 (m, 1H), 0.22 (t, J = 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3): δ 169.9, 154.5, 151.3, 149.2, 145.8, 137.2, 135.0, 133.6,
131.2, 126.2, 126.0, 125.3, 124.8, 121.8, 119.7, 117.5, 108.5, 107.3,
103.2, 101.3, 59.8, 56.1, 55.9, 55.6, 12.7 ppm; MS (ESI): m/z 432 (M
+ H)+. Anal. Calcd for C26H25NO5: C, 72.37; H, 5.84; N, 3.25. Found:
C, 72.50; H, 5.56; N, 3.38.
Ethyl 1-Amino-3-butyl-7-methoxy-2-naphthoate (2k). Brown
1
liquid. Yield: 72 mg (48%). H NMR (400 MHz, CDCl3): δ 7.57
(d, J = 8.8 Hz, 1H), 7.16 (dd, J = 8.8, 2.4, Hz, 1H), 7.05 (d, J = 2.4 Hz,
1H), 6.97 (s, 1H), 5.68 (brs, 2H), 4.41 (q, J = 7.0 Hz, 2H), 3.90 (s,
3H), 2.90 (t, J = 7.8 Hz, 2H), 1.63−1.53 (m, 2H), 1.43−1.34 (m, 5H),
0.92 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 170.3, 157.2,
144.8, 137.2, 130.3, 129.5, 123.0, 119.7, 118.5, 109.8, 100.9, 60.8, 55.4,
Methyl 1-Amino-3-phenyl-6,7,8,9-tetrahydrodibenzo[b,d]thio-
phene-2-carboxylate (2r). Pale yellow solid. Yield: 76 mg (45%).
Mp 146−148 °C. 1H NMR (400 MHz, CDCl3): δ 7.38−7.28 (m, 5H),
7.05 (s, 1H), 5.76 (brs, 2H), 3.37 (s, 3H), 3.15 (d, J = 5.6 Hz, 2H),
2.82 (d, J = 4.0 Hz, 2H), 1.93−1.88 (m, 4H); 13C NMR (100 MHz,
3247
dx.doi.org/10.1021/jo500137m | J. Org. Chem. 2014, 79, 3244−3248

The Journal of Organic Chemistry
Note
CDCl3): δ 170.7, 145.4, 143.4, 142.5, 139.1, 135.5, 129.1, 127.92,
127.85, 126.5, 126.3, 113.8, 109.1, 51.1, 27.3, 26.0, 22.9, 22.5 ppm;
HRMS (ESI): [M + H]+ Calcd for C20H20NO2S, 338.1215; found,
338.1207.
(16) Reddy, R. S.; Prasad, P. K.; Ahuja, B. B.; Sudalai, A. J. Org. Chem.
2013, 78, 5045.
(17) Gao, P.; Liu, J.; Wei, Y. Org. Lett. 2013, 15, 2872.
(18) (a) Ward, R. S. Nat. Prod. Rep. 1999, 16, 75. (b) Ragot, J. P.;
Steeneck, C.; Alcaraz, M. -L.; Taylor, R. J. K. J. Chem. Soc., Perkin
Trans. 1 1999, 1073. (c) Ukita, T.; Nakamura, Y.; Kubo, A.;
Yamamoto, Y.; Kotera, J.; Ikeo, T. J. Med. Chem. 1999, 42, 1293.
ASSOCIATED CONTENT
■
S
* Supporting Information
(d) Watson, M. D.; Fechtenkotter, A.; Mullen, K. Chem. Rev. 2001,
̈
̈
1
Copies of H and 13C NMR spectra for all products and X-ray
101, 1267. (e) de Koning, C. B.; Rousseau, A. L.; van Otterlo, W. A. L.
structural information of 2i (CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
Tetrahedron 2003, 59, 7.
(19) Augustine, J. K.; Bombrun, A.; Atta, R. N. Synlett 2011, 2223.
(20) We also tested an o-alkenylarenenitrile A under the reaction
conditions, and it afforded only the β-enaminoester B. Character-
ization data for compound B: Yellow viscous liquid. Yield: 132 mg
(90%). 1H NMR (400 MHz, CDCl3): δ 8.20 (brs, 2H), 7.71 (d, J = 8.0
Hz, 1H), 7.53−7.48 (m, 2H), 7.41−7.25 (m, 7H), 7.06 (d, J = 16.0
Hz, 1H), 4.73 (s, 1H), 4.19 (q, J = 7.2 Hz, 2H), 1.29 (t, J = 7.2 Hz,
3H); 13C NMR (100 MHz,CDCl3): δ 170.2, 160.5, 137.2, 135.1,
130.6, 129.5, 128.9, 128.7, 128.5, 127.9, 127.6, 126.8, 126.1, 125.8,
87.2, 58.2, 14.6 ppm; HRMS (ESI): [M + H]+ Calcd for C19H19NO2,
294.1494; found, 294.1493.
AUTHOR INFORMATION
Corresponding Author
*E-mail: srinivasank@bdu.ac.in.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank the Council of Scientific and Industrial
Research (CSIR) and Department of Science and Technology
(DST), India for financial support; Sophisticated Analytical
Instrumentation Facility (SAIF), Lucknow for HRMS; DST-
FIST for instrumentation facilities at School of Chemistry,
Bharathidasan University; and Dr. N. Sampath, Sastra
University for X-ray structure determination.
(21) Kim, J. H.; Chun, Y. S.; Lee, S.-G. J. Org. Chem. 2013, 78, 11483.
(22) CCDC 981061 for compound 2i. See the Supporting
Information for details.
REFERENCES
■
(1) For reviews, see: (a) Rathke, M. W.; Weipert, P. In Zinc Enolates:
The Reformatsky and Blaise Reaction in Comprehensive Organic
Reactions; Trost, B. M., Ed.; Pergamon: Oxford, 1991; Vol. 2, pp
277−299. (b) Rao, H. S. P.; Rafi, S.; Padmavathy, K. Tetrahedron
2008, 64, 8037. (c) Denes, F.; Perez-Luna, A.; Chemla, F. Chem. Rev.
2010, 110, 2366.
(2) (a) Hoang, C. T.; Nguyen, V. H.; Alezra, V.; Kouklovsky, C. J.
Org. Chem. 2008, 73, 1162. (b) Hoang, C. T.; Bouillere, F.;
Johannesen, S.; Zulauf, A.; Panel, C.; Pouilhes, A.; Gori, D.; Alezra,
V.; Kouklovsky, C. J. Org. Chem. 2009, 74, 4177. (c) Hertzberg, R.;
Moberg, C. J. Org. Chem. 2013, 78, 9174.
(3) Chun, Y. S.; Lee, K. K.; Ko, Y. O.; Shin, H.; Lee, S.-G. Chem.
Commun. 2008, 5098.
(4) Chun, Y. S.; Ryu, K. Y.; Ko, Y. O.; Hong, J. Y.; Hong, J.; Shin, H.;
Lee, S.-G. J. Org. Chem. 2009, 74, 7556.
(5) Ko, Y. O.; Chun, Y. S.; Kim, Y.; Kim, S. J.; Shin, H.; Lee, S.-G.
Tetrahedron Lett. 2010, 51, 6893.
(6) Chun, Y. S.; Ryu, K. Y.; Kim, J. H.; Shin, H.; Lee, S.-G. Org.
Biomol. Chem. 2011, 1317.
(7) Chun, Y. S.; Lee, J. H.; Kim, J. H.; Ko, Y. O.; Lee, S.-G. Org. Lett.
2011, 13, 6390.
(8) Chun, Y. S.; Kim, J. H.; Choi, S. Y.; Ko, Y. O.; Lee, S.-G. Org. Lett.
2012, 14, 6358.
(9) Chun, Y. S.; Xuan, Z.; Kim, J. H.; Lee, S.-G. Org. Lett. 2013, 15,
3162.
(10) Zhao, M.-N.; Liang, H.; Ren, Z.-H.; Guan, Z.-H. Adv. Synth.
Catal. 2013, 355, 221.
(11) Kim, J. H.; Lee, S.-G. Org. Lett. 2011, 13, 1350.
(12) Kim, J. H.; Shin, H.; Lee, S.-G. J. Org. Chem. 2012, 77, 1560.
(13) Chun, Y. S.; Ko, Y. O.; Shin, H.; Lee, S.-G. Org. Lett. 2009, 11,
3414.
(14) For general reviews on carbozincation of alkynes, see:
(a) Lorthiois, E. Carbozincation of alkenes and alkynes. In The
Chemistry of Organozinc Compounds; Rappoport, Z., Marek, I., Eds.;
Wiley: Chichester, 2006; Part 2, pp 863−978. (b) Lorthiois, E.; Meyer,
C. Carbozincation of Alkenes and Alkynes. Patai’s Chemistry of Functional
Groups; Wiley: New York, 2009.
(15) Kobayashi, K.; Uneda, T.; Takada, K.; Tanaka, H.; Kitamura, T.;
Morikawa, O.; Konishi, H. J. Org. Chem. 1997, 62, 664.
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