Facile synthesis of spiro oxindoles, azaoxindoles, and dihydroisoquinolone

Article abstract of DOI:10.1080/00397911.2010.492079

Formation of 1-aryl-4-oxo-cyclohexa(e)nonecarboxylates from the Diels-Alder cycloaddition of 2-trimethylsilyloxy-1,3-butadiene and Danishefsky diene with aryl- and pyridylacrylates and further conversion thereof to spirocycles is described. This provides

Full text of DOI:10.1080/00397911.2010.492079

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Facile Synthesis of Spiro Oxindoles,
Azaoxindoles, and Dihydroisoquinolone
Sharada S. Labadie a & Christa Parmer a
a Department of Medicinal Chemistry, Roche Palo Alto LLC, Palo
Alto, California, USA
Published online: 29 Apr 2011.
To cite this article: Sharada S. Labadie & Christa Parmer (2011): Facile Synthesis of Spiro Oxindoles,
Azaoxindoles, and Dihydroisoquinolone, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 41:12, 1742-1751
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Synthetic Communications1, 41: 1742–1751, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.492079
FACILE SYNTHESIS OF SPIRO OXINDOLES,
AZAOXINDOLES, AND DIHYDROISOQUINOLONE
Sharada S. Labadie and Christa Parmer
Department of Medicinal Chemistry, Roche Palo Alto LLC, Palo Alto,
California, USA
GRAPHICAL ABSTRACT
Abstract Formation of 1-aryl-4-oxo-cyclohexa(e)nonecarboxylates from the Diels–Alder
cycloaddition of 2-trimethylsilyloxy-1,3-butadiene and Danishefsky diene with aryl- and
pyridylacrylates and further conversion thereof to spirocycles is described. This provides
an efficient method for spiro oxindoles, azaoxindoles, and dihydroisoquinolones.
Keywords Azaoxindoles; Diels–Alder reaction; dihydroisoquinolone; spirocycles
A concise synthesis of the spirocyclic compounds 1 and 2 was required in one of our
medicinal chemistry projects. A literature search revealed only a limited number of
methods for the synthesis of spirocyclohexanones 1 starting from oxindoles[1] or
indolones[2] or by radical cyclization of appropriately substituted benzamides.[3]
These synthesis were multistep in nature, and the yields of the desired products were
poor. In addition, no syntheses of the spiro-1,4-dihydro-2H-isoquinolin-3-one 2 were
found.[4] It was envisioned that appropriately substituted derivatives of the cyclo-
hexyl compounds 3 and 4 might be useful precursors of the spirocyclohexanones 1
Received January 29, 2010.
Current name and affiliation for Christa Parmer: Christa Tatyosian, Bio-Rad Laboratories,
Hercules, California, USA.
Address correspondence to Sharada S. Labadie, Genentech, MS: 18B, 1 DNA Way, So. San
Francisco, CA 94080-4990, USA. E-mail: labadie.sharada@gene.com
1742

SPIRO OXINDOLES, AZAOXINDOLES, AND DIHYDROISOQUINOLONE
1743
Scheme 1. Synthetic strategy for spirocycles.
and 2 and congeners thereof (Scheme 1).[5] Compounds of type 3 and 4 have been
prepared by the arylation of ethyl 4-oxocyclohex-2-encarboxylates with aryllead(IV)
tricarboxylates[6] and by a tandem Michael–Dieckmann condensation, followed by
decarboxylation.[7] Also, the Diels–Alder reaction[8] of 2-trimethylsilyoxy-1,3-
butadienes with various dienophiles is reported to generate various cyclohexyl
derivatives,[9] but surprisingly this process has not been used to synthesize[10]
1-aryl-4-oxo-cyclohex-2-enone and cyclohexanonecarboxylates 3 and 4. Herein, we
describe the application of this cycloaddition reaction to the generation of various
1-aryl-4-oxo-cyclohexen-2-one and cyclohexanonecarboxylates 3 and 4 and the sub-
sequent conversion thereof into derivatives of the spirocyclic systems 1 and 2.
The cycloaddition of methyl 2-(2-nitrophenyl)acrylate[11] 5a and trans-1-meth-
oxy-3-trimethylsilyloxy-1,3-butadiene 6 (toluene=reflux=20 h), followed by the
deprotection of the silyloxy intermediate (p-toluenesulfonic acid; Scheme 2) provided
the cyclohexenone 3a in 50% yield (entry 1, Table 1). This process also proceeded
well with various substituted methyl 2-(2-nitrophenyl)acrylates and with a methyl
nitropyridylacrylate to afford the corresponding cyclohexenones in good to excellent
yields (entries 2–5, Table 1).
With various cyclohexenones in hand, the conversion thereof into the spiro-
cycles was investigated. Catalytic hydrogenation of 3a (10% Pd-C, ethyl acetate),
at atmospheric pressure, proceeded uneventfully to give 1a in 80% yield (Table 1,
entry 1). The 4-trifluromethyl compound 1b was obtained equally efficiently (entry
2). In contrast, the conversion of the 4,5-dimethoxy and 4-nitro compounds 3c
and 3d into the desired spirocyclic oxindoles was not straightforward under these
conditions. Furthermore, catalytic reduction of the pyridyl compound 3e followed
a different and unexpected reaction course. Thus, hydrogenation of the dimethoxy
Scheme 2. Synthesis of cyclohexenones and their conversion to spiro oxindoles.

1744
S. S. LABADIE AND C. PARMER
Table 1. Formation of spiro oxindole via cyclohexenones as in Scheme 2
Entry
Cyclohexenone
Yielda (%)
Spiro oxindole
Yielda (%)
1
50
80
2
82
80
3
80
50b
c
—
4
92
d
—
5
71
aAll are isolated yields and are not optimized.
bHydrogenation in the presence of Pd-C and subsequent treatment with Zn=AcOH was required for the
formation of 1c.
cAn inseparable mixture of the desired product and a side product with 16 mass units higher was
obtained.
dNone of the desired spirocycle was formed.

SPIRO OXINDOLES, AZAOXINDOLES, AND DIHYDROISOQUINOLONE
1745
compound, 3c did not go to completion, and a compound believed to be the nitroso
cyclohexanone was formed. This supposition was supported by its mass spectral
molecular weight and by conversion into the desired spirocycle 1c upon further
reduction with zinc in acetic acid solution. Catalytic reduction of 3d did appear to
give the desired spirocyclic compound 1d, but it was admixed with an inseparable
impurity having very similar thin-layer chromatography (TLC) polarity and a mass
spectral molecular weight 16 mass units higher than that expected for 1d. In the case
of pyridyl compound 3e, none of the expected spirocyclic compound was formed.
Instead, the tricyclic compound 7, an azahexahydrocarbazole, was formed exclus-
ively.[12] This compound obviously was formed by Michael addition of the anilino
moiety to the enone system, indicating that reduction of the enone double bond must
be considerably slower than that of the nitro group. This result contrasted sharply
with those obtained for compounds 3a–c where reduction of the enone double bond
must have occurred prior to that of the nitro group, resulting in the formation of the
spirocyclic oxindoles 1a–c (Scheme 3). These results suggested that reduction of
nitropyridylcyclohexanones corresponding to 4a would indeed produce the desired
spirocyclic systems, and this prompted us to devise a synthesis of such compounds.
The Diels–Alder reaction of the methyl nitropyridylacrylate 5e with 2-trimethylsilyloxy-
1,3-butadiene 8 (Scheme 4) produced the required cyclohexanone 4a, palladium-
catalyzed hydrogenation of which did indeed give the expected spirocycle 1e (entry 1,
Table 2). Several other pyridyl-containing cyclohexanones were also prepared and
converted into the desired spirocyclic azaoxindoles (Table 2).
Finally, the Diels–Alder cycloaddition of ethyl 2-(2-cyanophenyl)acrylate 9
and trans-1-methoxy-3-trimethylsilyloxy-1,3-butadiene
6 provided ethyl 1-(2-
cyanophenyl)-4-oxo-cyclohex-2-enecarboxylate 10 in 67% yield. Ethyl 2(2-cyano-
pheyl)acrylate was prepared by the Suzuki coupling between the 2-cyanobenzene-
boronic acid and ethyl 2-bromoacrylate in 30% yield. The required conversion of
the cyano moiety into the intermediate aminomethyl compound turned out to be
nontrivial. Nevertheless, this transformation did occur since catalytic hydrogenation
of 10 over Pd=C followed by hydrogenation over neutral Raney nickel (commercial
Scheme 3. Mechanism of spirocycle and hexahydrocarbazole formation.

1746
S. S. LABADIE AND C. PARMER
Scheme 4. Synthesis of cyclohexanones and their conversion to spiro azaoxindoles.
Table 2. Formation of spiro azaoxindoles via cyclohexanones as in Scheme 4
Entry
Cyclohexanone
Yielda (%)
Spiro azaoxindole
Yielda (%)
1
50
72
2
71
60
3
53
83
4
47
63
aAll are isolated yields and are not optimized.

SPIRO OXINDOLES, AZAOXINDOLES, AND DIHYDROISOQUINOLONE
1747
Scheme 5. Synthesis of spiro dihydroisoquinolone.
alkaline catalyst washed to neutrality with water) produced the hydroxyl compound
11 (40%, Scheme 5), resulting from overreduction. Presumably the ketone 2 could be
generated by oxidation of 11.
In summary, we have described a simple syntheses of various spirocyclic
oxindole, azaoxindole, and 1,4-dihydro-2H-isoquinolin-2-one containing systems.
We have also demonstrated the utility of the Diels–Alder reaction for the synthesis
of various 1-aryl-4-oxo-cyclohexylcarboxylates, which are useful precursors of the
aforementioned spirocyclic systems.
EXPERIMENTAL
General Procedure for the Cycloaddition of Methyl
2-(2-Nitroaryl)acrylate with trans-1-Methoxy-3-trimethylsilyloxy-
1,3-butadiene
Methyl 1-(2-nitrophenyl)-4-oxo-cyclohex-2-enecarboxylate 3a. A mix-
ture of methyl 2-(2-nitrophenyl)acrylate (0.56 g, 2.7 mmol) and trans-1-methoxy-3-
trimethylsilyloxy-1,3-butadiene (0.89 g, 5.1 mmol) in toluene (5 mL) was heated at
reflux in a sealed tube for 20 h. Solid p-toluenesulfonic acid monohydrate (0.07 g,
0.36 mmol) was added in one portion to the resulting pale yellow solution, and the
heating was discontinued. The resulting red mixture was stirred for one 1 h and then
diluted with ethyl acetate (50 mL). The resulting solution was washed with water
(20 mL) and brine (20 mL), dried (Na2SO4), and concentrated in vacuo. The residue
was purified by flash chromatography (silica gel, 10–30% EtOAc=hexane) to obtain
3a (0.36 g) as a pale yellow oil: 1H NMR (300 MHz, CDCl3) d ¼ 8.07–7.93 (m, 1 H),
7.70–7.58 (m, 1 H), 7.58–7.42 (m, 2 H), 6.87–6.74 (m, 1 H), 6.33 (d, J ¼ 10.2 Hz, 1 H),
3.71 (s, 3 H), 3.36–3.17 (m, 1 H), 3.06–2.83 (m, 1 H), 2.38 (m, 2 H). Anal. calcd. for
C14H13NO5: C, 61.09; H, 4.76; N, 5.09. Found: C, 60.91; H, 4.80; N, 5.12.
The following were prepared in a similar fashion.
Methyl 1-(2-nitro-4-trifluoromethylphenyl)-4-oxocyclohex-2-enecarboxy-
1
late 3b. H NMR (400 MHz, CDCl3) d ¼ 8.31–8.22 (m, 1 h), 7.94–7.82 (m, 1 H),
7.70–7.57 (m, 1 H), 6.80–6.72 (m, 1 H), 6.38 (d, J ¼ 10.1 Hz, 1 H), 3.72 (s, 3 H),
3.35–3.23 (m, 1 H), 3.08–2.92 (m, 1 H), 2.45–2.29 (m, 2 H). Anal. calcd. for
C15H12F3NO5: C, 52.49; H, 3.52; N, 4.08. Found: C, 52.28; H, 3.49; N, 3.97.
Methyl 1-(4,5-dimethoxy-2-nitrophenyl)-4-oxocyclohexen-2-enecarboxy-
late 3c. Mp 149–150 ꢀC (EtOAc=hexane); 1H NMR (300 MHz, DMSO-d6)

1748
S. S. LABADIE AND C. PARMER
d ¼ 7.74–7.64 (m, 1 H), 6.99–6.88 (m, 2 H), 6.32–6.18 (m, 1 H), 3.89 (d, J ¼ 4.1 Hz,
6 H), 3.57 (s, 3 H), 3.01–2.88 (m, 1 H), 2.81–2.60 (m, 1 H), 2.50 (dt, J ¼ 1.7, 3.7 Hz,
2 H). Anal. calcd. for C16H17NO7: C, 57.31; H, 5.11; N, 4.18. Found: C, 57.29; H,
4.93; N, 4.17.
Methyl 1-(2,4-dinitrophenyl)-4-oxo-cyclohex-2-enecarboxylate 3d. 1H
NMR (300 MHz, CDCl3) d ¼ 8.83 (d, J ¼ 2.6 Hz, 1 H), 8.46 (dd, J ¼ 2.6, 8.7 Hz,
1 H), 7.72 (d, J ¼ 8.7 Hz, 1 H), 7.26 (s, 1 H), 6.76 (d, J ¼ 10.2 Hz, 1 H), 6.39 (d,
J ¼ 10.2 Hz, 1 H), 3.72 (s, 3 H), 3.40–3.21 (m, 1 H), 3.10–2.91 (m, 1 H), 2.48–2.32
(m, 2 H), MS (ESI): m=e ¼ 321 (M þ 1).
Methyl 1-(3-nitropyridin-2-yl)-4-oxo-cyclohexen-2-enecarboxylate 3e.
1H NMR (300 MHz, Chloroform-d) d ¼ 8.83 (dd, J ¼ 1.7, 4.7 Hz, 1 H), 8.34 (dd,
J ¼ 1.5, 8.3 Hz, 1 H), 7.52 (dd, J ¼ 4.7, 8.1 Hz, 1 H), 7.05 (d, J ¼ 10.2 Hz, 1 H),
6.22 (d, J ¼ 10.2 Hz, 1 H), 3.73 (s, 3 H), 2.96 (d, J ¼ 9.1 Hz, 2 H), 2.81–2.58 (m,
2 H), MS (ESI): m=z ¼ 277 (M þ 1).
Ethyl 1-(2-cyanophenyl)-4-oxo-cyclohexen-2-enecarboxylate 10. 1H
NMR (300 Hz, CDCl3) d ¼ 7.75 (dd, J ¼ 1.5, 8.3 Hz, 1 H), 7.65–7.56 (m, 1 H),
7.49–7.36 (m, 2 H), 7.07 (d, J ¼ 10.2 Hz, 1 H), 6.33 (d, J ¼ 10.2 Hz, 1 H), 4.32 (q,
J ¼ 7.2 Hz, 2 H), 3.11–2.97 (m, 1 H), 3.04 (s, 1 H), 2.83–2.69 (m, 1 H), 2.53–2.39
(m, 1 H), 2.34–2.20 (m, 1 H); MS (EI): m=z: 269 (Mþ).
General Method for the Cycloaddition with
2-Trimethylsilyloxy-1,3-butadiene 8
Methyl
(3-nitro-pyridin-2-yl)-4-oxo-cyclohexanecarboxylate
4a. A
mixture of methyl 2-(3-nitropyridin-2-yl)acrylate 5e (0.8 g, 3.8 mmol) and 2-
trimethylsilyloxy-1,3-butadiene 8 (1.5 g, 7.0 mmol) in xylenes (5 mL) was maintained
at 130 ꢀC in a sealed tube for 20 h. p-Toluenesulfonic acid monohydrate (0.1 g,
0.5 mmol) was added to the resulting pale yellow, and the heating was discontinued.
The mixture was stirred for 2 h, and the red mixture was diluted with ethyl acetate
(50 mL), washed with water (30 mL) and brine (30 mL), dried (Na2SO4), and concen-
trated in vacuo. The residue was purified by flash chromatography (silica gel,
1
10–40% EtOAc=hexane) to obtain 4a (0.52 g): H NMR (300 MHz, chloroform-d)
d ¼ 8.82 (dd, J ¼ 1.7, 4.7 Hz, 1 H), 8.27 (dd, J ¼ 1.7, 8.1 Hz, 1 H), 7.54–7.40 (m,
1 H), 3.70 (s, 3 H), 2.78–2.44 (m, 8 H); MS (ESI): m=z ¼ 279 (M þ 1).
The following were prepared in a similar fashion:
Methyl 1-(5-methyl-3-nitro-pyridin-2-yl)-4-oxo-cyclohexanecaboxylate 4b.
1
Mp 86–87 ꢀC (EtOAc=hexane); H NMR (300 MHz, CDCl3) d ¼ 8.63 (s, 1 H), 8.06
(d, J ¼ 1.5 Hz, 1 H), 3.69 (s, 3 H), 2.72–2.47 (m, 8 H), 2.47 (s, 3 H). Anal. calcd.
for C14H16N2O5: C, 57.53; H, 5.52; N, 9.58. Found: C, 57.42; H, 5.21; N, 9.56.
Methyl 1-(6-methoxy-3-nitro-pyridin-2-yl)-4-oxo-cyclohexanecaboxylate 4c.
Mp 108–109 ꢀC (EtOAc=hexane); 1H NMR (300 MHz, CDCl3) d ¼ 8.30 (d, J ¼
8.7 Hz, 1 H), 6.80 (d, J ¼ 9.0 Hz, 1 H), 4.03 (s, 3 H), 3.70 (s, 3 H), 2.80–2.43 (m, 8
H). Anal. calcd. for C14H16N2O6: C, 54.54; H, 5.23; N, 9.09. Found: C, 54.44; H,
5.01; N, 9.04.

SPIRO OXINDOLES, AZAOXINDOLES, AND DIHYDROISOQUINOLONE
1749
Methyl 1-(3-nitro-pyridin-4-yl)-4-oxo-cyclohexanecarboxylate 4d. Mp
1
123–125 ꢀC (EtOAc=hexane); H NMR (400 MHz, CDCl3) d ¼ 9.06 (s, 1 H), 8.84
(d, J ¼ 5.6 Hz, 1 H), 7.56 (d, J ¼ 5.6 Hz, 1 H), 3.73 (s, 3 H), 2.88–2.63 (m, 4 H),
2.47–2.21 (m, 4 H). Anal. calcd. for C13H14N2O5: C, 56.11; H, 5.07; N, 10.07. Found:
C, 55.85; H, 4.95; N, 9.96.
General Procedure for the Synthesis of Spirocyclohexanones
Spiro oxindole 1a. A mixture of 3a (0.20 g, 0.7 mmol) and Pd-C (0.05 g) in
ethyl acetate (20 mL) was hydrogenated using a balloon for 20 h. The reaction mix-
ture was filtered through Celite, while washing with ethyl acetate, and the filtrate was
concentrated in vacuo to obtain 1a (0.13 g) as an off-white solid: mp 198–199 ꢀC
1
(EtOAc=hexane) [lit.[2] mp 200–201]; H NMR (300 MHz, CDCl3) d ¼ 8.23 (br. s.,
1 H), 7.30–7.20 (m, 2 H), 7.12–7.03 (m, 1 H), 6.95 (d, J ¼ 7.7 Hz, 1 H), 3.23–3.09
(m, 2 H), 2.58–2.44 (m, 2 H), 2.29–2.11 (m, 4H).
Compound 1b. Mp 232–234 ꢀC (EtOAc=hexane); 1H NMR (300 MHz,
CDCl3) d ¼ 7.67 (br. s., 1 H), 7.39–7.29 (m, 2 H), 7.18–7.15 (m, 1 H), 3.25–3.11
(m, 2 H), 2.54–2.43 (m, 2 H), 2.23 (s, 4 H). Anal. calcd. for C14H12F3NO2: C,
59.37; H, 4.27; N, 4.95. Found: C, 59.10; H, 4.13; N, 4.99.
Compound 1e. Mp 225–226 ꢀC (EtOAc=hexane); 1H NMR (400 MHz,
CDCl3) d ¼ 8.53 (br. s., 1 H), 8.24 (d, J ¼ 3.5 Hz, 1 H), 7.27–7.15 (m, 2 H), 3.06
(ddd, J ¼ 5.6, 9.6, 15.2 Hz, 2 H), 2.76 (dt, J ¼ 5.9, 15.0 Hz, 2 H), 2.34–2.24 (m, 2
H), 2.23–2.14 (m, 2 H); Anal. calcd. for C12H12N2O2: C, 66.65; H, 5.59; N, 12.95.
Found: C, 66.31; H, 5.54; N, 12.81.
1
Compound 1f. Mp 205–207 ꢀC (EtOAc=hexane); H NMR (300 Hz, CDCl3)
d ¼ 8.38 (br. s., 1 H), 8.06 (s, 1 H), 7.07 (s, 1 H), 3.02 (dd, J ¼ 5.8, 9.6 Hz, 2 H),
2.85–2.64 (m, 2 H), 2.39 (s, 3H), 2.32–2.08 (m, 4 H). MS (ESI): m=e ¼ 231 (M þ 1).
Compound 1g. Mp 210–212 ꢀC (EtOAc=hexane); 1H NMR (300 Hz, CDCl3)
d ¼ 8.30 (br. s., 1 H), 7.23 (d, J ¼ 8.7 Hz, 1 H), 6.67 (d, J ¼ 8.7 Hz, 1 H), 3.89 (s, 3 H),
3.18–3.04 (m, 2 H), 2.78–2.64 (m, 2 H), 2.36–2.24 (m, 2 H), 2.13 (m, 2 H). Anal.
calcd. for C13H14N2O3: C, 63.40; H, 5.73; N, 11.38. Found: C, 63.42; H, 5.70; N,
11.43.
Compound 1h. Mp 203–205 ꢀC (EtOAc=hexane); 1H NMR (300 MHz,
CDCl3) d ¼ 8.88 (br. s., 1 H), 8.42 (d, J ¼ 4.9 Hz, 1 H), 8.37 (s, 1 H), 7.23 (d,
J ¼ 4.5 Hz, 1 H), 3.15 (ddd, J ¼ 6.4, 10.0, 15.7 Hz, 2 H), 2.53 (dt, J ¼ 5.4, 15.6 Hz,
2 H), 2.34–2.11 (m, 4 H). Anal. calcd. for C12H12N2O2: C, 66.65; H, 5.59; N,
12.95. Found: C, 66.53; H, 5.52; N, 12.86.
Compound 1c. A mixture of 3c (0.20 g, 0.6 mmol) and Pd-C (0.05 g) in ethyl
acetate (20 mL) was hydrogenated using a balloon for 20 h. The reaction mixture was
filtered through Celite, while washing with ethyl acetate, and the filtrate was concen-
trated in vacuo. The residue was dissolved in dichloromethane (10 mL), and zinc
(0.5 g) and acetic acid (0.5 mL) were added. The mixture was stirred for 20 h at room
temperature. Zinc was removed by filtration through Celite while washing with
dichloromethane. The filtrate was washed with saturated sodium bicarbonate

1750
S. S. LABADIE AND C. PARMER
(20 mL) and brine, dried over sodium sulfate, and concentrated. The residue was tri-
turated with hexane=ethyl acetate to obtain 1c (0.08 g); mp 190–192 ꢀC (EtOAc=
1
hexane); H NMR (300 MHz, CDCl3) d ¼ 8.14 (br. s., 1 H), 6.79 (s, 1 H), 6.58 (s, 1
H), 3.90 (s, 3 H), 3.86 (s, 3 H), 3.27–3.14 (m, 2 H), 2.53–2.41 (m, 2 H), 2.25–2.10
(m, 4 H). Anal. calcd. for C15H17NO4: C, 65.44; H, 6.22; N, 5.09. Found: C,
65.44; H, 6.24; N, 5.14.
1,4-Dihydro-2H-isoquinolin-3-one 11
A mixture of 10 (0.10 g, 0.37 mmol) and Pd-C (0.02 g) in ethyl acetate (10 mL)
was hydrogenated using a balloon for 20 h. The reaction mixture was filtered
through Celite, while washing with ethyl acetate, and the filtrate was concentrated
in vacuo. The residue was dissolved in ethyl acetate (10 mL) and added to a flask
containing Raney Ni (which was washed three times with 5 mL water), and the mix-
ture was stirred for 20 h at room temperature. The catalyst was removed by filtration
through Celite while washing with dichloromethane. The filtrate was concentrated in
vacuo. The residue was purified by flash (silica gel, 5–10% MeOH=DCM) to obtain
11 (0.034 g): mp 192–194 ꢀC (EtOAc=hexane); 1H NMR (300 MHz, CDCl3)
d ¼ 7.45–7.39 (m, 1 H), 7.34–7.20 (m, 2 H), 7.18–7.12 (m, 1 H), 6.04 (br. s., 1 H),
4.50 (d, J ¼ 3.4 Hz, 1 H), 3.77–3.62 (m, 1 H), 2.29–2.16 (m, 2 H), 2.14–1.92 (m, 4
H), 1.76 (m, 2 H). MS (APCI): m=z ¼ 232 (M þ 1).
ACKNOWLEDGMENTS
The authors acknowledge Dr. Francisco Talamas and Dr. Josh Taygerly for
their valuable input and the analytical department for providing the spectroscopic
and physical data.
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