Convenient synthesis of α,β-unsaturated γ-butyrolactones and γ-butyrolactams via decarboxylative iodination of paraconic acids and β-carboxyl-γ-butyrolactams using 1,3-diiodo-5,5-dimethylhydantoin

Article abstract of DOI:10.1039/c5ob01574j

A convenient synthetic approach to α,β-unsaturated γ-butyrolactones and α,β-unsaturated γ-butyrolactams is developed. The reaction proceeds via decarboxylative iodination of paraconic acids and β-carboxyl-γ-butyrolactams, employing 1,3-diiodo-5,5-dimethylhydantoin (DIH) under irradiation, followed by dehydroiodination of β-iodo-γ-butyrolactones and γ-butyrolactams providing good yields of α,β-unsaturated γ-butyrolactones and γ-butyrolactams, which are synthetically useful building blocks in organic synthesis.

Full text of DOI:10.1039/c5ob01574j

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Convenient synthesis of α,β-unsaturated
γ-butyrolactones and γ-butyrolactams via
decarboxylative iodination of paraconic acids and
β-carboxyl-γ-butyrolactams using 1,3-diiodo-5,5-
dimethylhydantoin†
Cite this: DOI: 10.1039/c5ob01574j
Supasorn Phae-nok, Chutima Kuhakarn, Manat Pohmakotr, Vichai Reutrakul and
Darunee Soorukram*
A convenient synthetic approach to α,β-unsaturated γ-butyrolactones and α,β-unsaturated γ-butyrolac-
tams is developed. The reaction proceeds via decarboxylative iodination of paraconic acids and β-car-
boxyl-γ-butyrolactams, employing 1,3-diiodo-5,5-dimethylhydantoin (DIH) under irradiation, followed by
dehydroiodination of β-iodo-γ-butyrolactones and γ-butyrolactams providing good yields of α,β-unsatu-
rated γ-butyrolactones and γ-butyrolactams, which are synthetically useful building blocks in organic
synthesis.
Received 29th July 2015,
Accepted 15th September 2015
DOI: 10.1039/c5ob01574j
www.rsc.org/obc
Introduction
Five-membered ring heterocycles are an important class of
compounds. In particular, α,β-unsaturated γ-butyrolactones (or
butenolides) and α,β-unsaturated γ-butyrolactams are among
advanced synthetic intermediates that find major applications
in medicinal chemistry and organic synthesis. They have been
used in a range of reactions, such as vinylogous additions to
electrophiles,1 conjugate additions,2 and pericyclic reactions.3
The ubiquity of α,β-unsaturated γ-butyrolactones and α,β-un-
saturated γ-butyrolactams has been highlighted in naturally
occurring compounds, for example, rollicosin,4c (−)-incrusto-
porine,4i spirofragilide, labdadienolide A, and (+)-erysotr-
amidine that possess important biological properties
including antibiotic, antitumor, anti-inflammatory, and anti-
HIV activities (Fig. 1).4 Not surprisingly, the development of
efficient synthetic routes for the preparation of α,β-unsaturated
γ-butyrolactones and γ-butyrolactams has been an area of
long-standing importance to synthetic chemists.5
Fig. 1 Natural compounds containing α,β-unsaturated γ-butyrolactone
and γ-butyrolactam units.
Among several synthetic routes, the oxidative decarboxyla-
tion of aliphatic carboxylic acids is an important and useful
conversion to access alkenes. The existing methods usually
require Pb(OAc)4/Cu(OAc)2 for mediating oxidative elimination
of the corresponding radical intermediates.6 Recently, catalytic
decarbonylative or decarboxylative elimination of carboxylic
acids to yield alkenes has also received much attention.7 In
modern organic synthesis, metal-free reactions which avoid
the use of heavy metals have been of particular interest. As a
consequence, the conversion of carboxylic acids to alkenes via
a simple consecutive decarboxylative halogenation (halodecarb-
oxylation)8 followed by dehydrohalogenation leading to the
synthesis of α,β-unsaturated γ-butyrolactones and γ-butyrolac-
tams was investigated. On the basis of our recent report on
Department of Chemistry and Center of Excellence for Innovation in Chemistry
(PERCH-CIC), Faculty of Science, Mahidol University, Rama VI Road, Bangkok
10400, Thailand. E-mail: darunee.soo@mahidol.ac.th; Fax: +662 354 7151;
Tel: +662 201 5148
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c5ob01574j
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Table 1 Optimization of the reaction conditions for the decarboxylative
iodination followed by Et3N-promoted dehydroiodination of 1a a
Scheme 1 Proposed synthetic scheme for the synthesis of α,β-unsatu-
rated γ-butyrolactones and γ-butyrolactams from paraconic acids and
β-carboxyl-γ-butyrolactams.
decarboxylative fluorination,9 it was envisaged that paraconic
acids and β-carboxyl-γ-butyrolactams 1 would undergo de-
carboxylative iodination to give β-iodo-γ-butyrolactones
2
which, after dehydroiodination, would provide α,β-unsaturated
γ-butyrolactones and γ-butyrolactams 3 (Scheme 1). Inspired
by the work reported by Gandelman and co-workers on decar-
boxylative iodination, employing commercially available 1,3-
diiodo-5,5-dimethylhydantoin (DIH)10 as an initiator and
iodine source,11 we describe herein a convenient synthetic
approach to α,β-unsaturated γ-butyrolactones and γ-butyro-
lactams via decarboxylative iodination of paraconic acids
and β-carboxyl-γ-butyrolactams using DIH under irradiative
conditions followed by base-promoted dehydroiodination
(Scheme 1). Notably, DIH has been extensively explored by
Togo and others.12 However, to the best of our knowledge, the
use of DIH for decarboxylative iodination followed by base
mediated dehydroiodination has never been reported.
Entry
DIH (equiv.)
Solvent
Time (h)
% Yield of 3a b
1 c
2
3
4
5
1
1
1
0.5
1
1
1
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
CH2Cl2
EtOAc
MeCN
8
8
0.5
1
0.5
0.5
0.5
67
95
92
66
27
15
56
6
7
a Unless stated otherwise, the reaction was carried out using 1a
(0.5 mmol) in a refluxing solvent (2 mL) under irradiation with a 100
W
tungsten lamp. b Yield of analytically pure 3a after column
chromatography (SiO2). c The reaction was carried out at reflux without
irradiation.
treatment of the crude product with Et3N cleanly provided 3a
in 92% isolated yield (Table 1, entry 3). The yield was drasti-
cally lower when DIH was employed in a lesser amount (0.5
equiv.) (Table 1, entry 4). Finally, other simple organic solvents
including CH2Cl2, EtOAc and MeCN were screened and
ClCH2CH2Cl was proved to be the optimal solvent (Table 1,
entry 3 vs. entries 5–7). At this stage, the optimal reaction con-
ditions for decarboxylative iodination followed by base-pro-
Results and discussion
Our study commenced with the optimization of reaction con-
ditions using paraconic acid 1a13 as the model substrate.
A standard screening of solvents, reaction times and the stoi-
chiometry of reagents was performed (Table 1). Under thermal
conditions, 1a was reacted with DIH (1 equiv.) in refluxing
ClCH2CH2Cl for 8 h to give β-iodo-γ-butyrolactone 2a together
with a trace amount of α,β-unsaturated γ-butyrolactone 3a as
observed by TLC and 1H NMR analyses of the crude mixture
(68% conversion based on the recovery of 1a). Without purifi-
cation, the crude mixture was treated with Et3N (2 equiv.) in
CH2Cl2 for 3 h leading to 3a in 67% yield after chromato-
graphic purification (Table 1, entry 1). We were pleased to
observe an improved conversion of 1a to a mixture of 2a and
3a (2a : 3a, 1 : 2, 96% conversion based on the recovery of 1a)
when the reaction was carried out in refluxing ClCH2CH2Cl
under irradiation of a tungsten lamp (100 W) (Table 1, entry
2). Compound 3a was obtained in 95% yield after treatment of
the crude mixture with Et3N. The Et3N-mediated HI elimin-
ation was proved necessary since a prolonged reaction time
(from 8 h to 13 h) led to the incomplete conversion of 1a to 3a;
a mixture of 2a and 3a was obtained (2a : 3a, 1 : 8, 96% conver-
sion based on the recovery of 1a). Gratifyingly, it was found
that decarboxylative-iodination of 1a with DIH (1 equiv.) in
refluxing ClCH2CH2Cl under photolysis reached completion
after 30 min and gave 2a in quantitative yield. Subsequent
moted dehydroiodination of paraconic acids
established (Table 1, entry 3).14
1
were
With the optimized reaction conditions in hand, we next
examined the substrate scope and the results are summarized
in Table 2. In general, the reactions of paraconic acids 1a–1m,
containing mono- and dialkyl groups at the γ-position,
smoothly underwent DIH-mediated decarboxylative iodination
to yield the corresponding β-iodo-γ-butyrolactones 2a–2m. Fol-
lowing Et3N promoted HI elimination of the primarily formed
β-iodo-γ-butyrolactones 2a–2m yielded their corresponding
α,β-unsaturated γ-butyrolactones 3a–3m in good yields
(81–92% yields) (Table 2, entries 1–13). Among these, the
trifluoromethylated butenolide analogue15 3k could also be
synthesized (82% yield) (Table 2, entry 11).
For paraconic acid 1n, bearing a phenyl substituent at the
γ-position, treatment of its β-iodo-γ-butyrolactone 2n with Et3N
according to the standard procedure led to a complex mixture
of unidentified products and no trace of 3n could be detected.
These observed results may result from the polymerization of
product 3n under basic conditions. Fortunately, it was found
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Table 2 Synthesis of α,β-unsaturated γ-butyrolactones and γ-butyrolactams via DIH-mediated decarboxylative iodination followed by dehydroiodi-
nation of paraconic acids and β-carboxyl-γ-butyrolactams
Entry
1
Substrate 1
Product 3; yielda
Entry
13
Substrate 1
Product 3; yielda
2
3
14
15
4
5
16
17
6
7
18
19
8
9
20
21
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Table 2 (Contd.)
Entry
10
Substrate 1
Product 3; yielda
Entry
22
Substrate 1
Product 3; yielda
11
12
23
24
a Isolated yield. b Compounds 3 were obtained after purification of 2 by column chromatography (SiO2, see the Experimental section). The ratio
of products was determined by 1H NMR analysis. c A mixture of diastereomers (dr = 8 : 1; 3,4-cis-4,5-trans/3,4-trans-4,5-trans). d A single isomer
(3,4-cis-4,5-trans).
that compound 2n readily underwent dehydroiodination leading to α,β-unsaturated γ-butyrolactams in moderate to
during column chromatography (SiO2, see the Experimental good yields. Thus, phenyl- and benzyl protected β-carboxyl
section) to afford an inseparable mixture of the expected amides 1r and 1s yielded α,β-unsaturated γ-butyrolactams 3r
α,β-unsaturated γ-butyrolactone 3n together with its deconju- and 3s in 46% and 75% yields, respectively (Table 2, entries 18
gated isomer 3n′ in 62% combined yield (3n : 3n′ = 2 : 1, 1H and 19). Similarly, β-carboxyl amide 1t, bearing a phenyl sub-
NMR analysis) (Table 2, entry 14). Similarly, the reaction of stituent at the γ-position gave a mixture of α,β-unsaturated
paraconic acids 1o and 1p, containing 4-MePh- and 4-ClPh- γ-butyrolactam 3t and its deconjugated isomer 3t′ (76% yield,
1
groups at the γ-positions, also provided the expected buteno- 3t : 3t′ = 3 : 2, H NMR analysis) (Table 2, entry 20). The reac-
lides 3o and 3p together with their deconjugated butenolides tion of 1u and 1v, having an electron donating group, gave the
3o′ and 3p′ in 61% (3o : 3o′; 10 : 1) and 74% (3p : 3p′; 1 : 4) desired α,β-unsaturated γ-butyrolactams 3u (74% yield) and 3v
yields, respectively (Table 2, entries 15 and 16). The formation (62% yield), respectively, each as the sole product (Table 2,
of the deconjugated butenolides 3n′, 3o′, and 3p′ was presum- entries 21 and 22). α-Methylated β-carboxyl-γ-butyrolactams 1w
ably through the corresponding dienols generated from the and 1x also gave the corresponding α,β-unsaturated γ-butyro-
enolization of α,β-unsaturated γ-butyrolactones 3n, 3o, and 3p, lactams 3w and 3x in 33% and 45% yields, respectively
respectively. Notably, deconjugated butenolides have been (Table 2, entries 23 and 24).
widely used in several enantioselective vinylogous additions to
A radical-type mechanism for decarboxylative iodination11a
various Michael acceptors.1 In contrast to 1p, α-methylated of 1 was proposed as shown in Scheme 2. Acyl hypoiodite A
paraconic acid 1q underwent the reaction to give only the was formed from the reaction of 1 with DIH. The homolytic
desired α,β-unsaturated γ-butyrolactone 3q as the sole product cleavage of the O–I bond of the intermediate A followed by dec-
in 45% yield (Table 2, entry 17).
arboxylation of the resulting carboxyl radical B gave the carbon
As an extension of the present protocol, DIH-promoted dec- radical C which was subsequently trapped by an iodine to give
arboxylative iodination followed by Et3N-promoted dehydro- β-iodo-γ-butyrolactones or lactams 2. Finally, dehydroiodina-
iodination can also be applied to the β-carboxyl-γ-butyrolactams tion of 2 provided the desired products 3.
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General procedure
A mixture of paraconic acid or β-carboxyl-γ-butyrolactam 1
(0.5 mmol) and DIH (1 equiv.) in 1,2-dichloroethane (2 mL) was
heated to reflux under irradiation by a tungsten-filament lamp
(100 W) for 30 minutes. The reaction mixture was then cooled
down to room temperature, washed with saturated Na2S2O3
(20 mL), and extracted with CH2Cl2 (3 × 10 mL). The combined
organic layers were washed with saturated NaHCO3 and brine,
dried over anhydrous Na2SO4, and concentrated to give β-iodo-
γ-butyrolactones 2. The obtained crude compounds 2a–2m and
2r–2x were dissolved in dry CH2Cl2 (2 mL) and treated with
Et3N (2 equiv.). The progress of the reaction was monitored by
TLC. After the complete consumption of the starting material,
the reaction mixture was passed through a short column (SiO2,
CH2Cl2) to give the products 3a–3m and 3r–3x, respectively.
Without treatment with Et3N, the crude compounds 2n–2p
were converted into 3n–3p and 3n′–3p′ during purification by
column chromatography (SiO2).
Scheme 2 Proposed mechanism for decarboxylative iodination–
dehydroiodination of paraconic acids and β-carboxyl-γ-butyrolactams.
Conclusions
1-Oxaspiro[4.5]dec-3-en-2-one (3a). Pale yellow oil; Rf = 0.44
1
(CH2Cl2). H NMR (400 MHz, CDCl3): δ = 7.47 (d, J = 5.6 Hz,
In conclusion, we have successfully developed a convenient
synthetic approach to α,β-unsaturated γ-butyrolactones and
γ-butyrolactams from readily available paraconic acids and
β-carboxyl-γ-butyrolactams. Decarboxylative iodination of the
carboxylic acid precursors using commercially available 1,3-
diiodo-5,5-dimethylhydantoin (DIH) under irradiation followed
by dehydroiodination gave good yields of the desired α,β-unsa-
turated γ-butyrolactone and γ-butyrolactam products, which
are synthetically useful building blocks in organic synthesis
and valuable core structures found in biologically active
natural compounds.
1H, CH), 6.01 (d, J = 5.6 Hz, 1H, CH), 1.85–1.32 (m, 10H, 5 ×
CH2). 13C NMR (100 MHz, CDCl3): δ = 172.5 (C), 160.6 (CH),
120.1 (CH), 88.5 (C), 34.6 (2 × CH2), 24.6 (CH2), 22.4 (2 × CH2).
IR (neat): ˜ν = 1744, 1602, 1448, 1209, 1137, 969, 816. MS: m/z
(%) = 153 (4) [M + H]+, 152 (6) [M]+, 149 (100), 135 (12), 121
(16), 95 (38), 81 (32), 57 (30). HRMS (ESI-TOF): calcd for
C9H12O2Na [M + Na]+ 175.0735; found 175.0733.
1-Oxaspiro[4.4]non-3-en-2-one (3b). Pale yellow oil; Rf = 0.44
1
(CH2Cl2). H NMR (400 MHz, CDCl3): δ = 7.39 (d, J = 5.6 Hz,
1H, CH), 6.01 (d, J = 5.6 Hz, 1H, CH), 2.08–1.74 (m, 8H, 4 ×
CH2). 13C NMR (100 MHz, CDCl3): δ = 172.5 (C), 159.0 (CH),
120.2 (CH), 96.8 (C), 36.8 (2 × CH2), 24.6 (2 × CH2). IR (neat):
˜ν = 1738, 1600, 1434, 1153, 934, 817. MS: m/z (%) = 139 (8)
[M + H]+, 138 (10) [M]+, 134 (30), 126 (100), 112 (63), 91 (72),
81 (93), 67 (60), 55 (75). HRMS (ESI-TOF): calcd for C8H10O2Na
[M + Na]+ 161.0578; found 161.0580.
Experimental
General information
The 1H NMR spectra were recorded on a Bruker-400 (400 MHz)
1-Oxaspiro[4.6]undec-3-en-2-one (3c). Pale yellow oil; Rf =
or a Bruker-500 (500 MHz) spectrometer in CDCl3 using tetra- 0.44 (CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 7.48 (d, J =
methylsilane as an internal standard. The 13C NMR spectra 5.6 Hz, 1H, CH), 5.95 (d, J = 5.6 Hz, 1H, CH), 1.96–1.49 (m,
were recorded on a Bruker-400 (100 MHz) or a Bruker-500 12H, 6 × CH2). 13C NMR (100 MHz, CDCl3): δ = 172.6 (C), 161.5
(125 MHz) spectrometer in CDCl3 using solvent peaks as an (CH), 119.1 (CH), 92.0 (C), 37.6 (2 × CH2), 28.9 (2 × CH2), 22.7
internal standard. The IR spectra were recorded on an ALPHA (2 × CH2). IR (neat): ˜ν = 1744, 1604, 1460, 1240, 1162, 939, 815.
FTIR spectrometer. The mass spectra were recorded using a MS: m/z (%) = 126 (62), 91 (100), 79 (89), 66 (51), 55 (45).
Thermo Finnigan Polaris Q mass spectrometer. The high HRMS (ESI-TOF): calcd for C10H14O2Na [M + Na]+ 189.0891;
resolution mass spectra were recorded on a HR-TOF-MS Micro- found 189.0892.
mass model VQ-TOF2 mass spectrometer. Melting points were
1-Oxaspiro[4.7]dodec-3-en-2-one (3d). Pale yellow oil; Rf =
recorded using a M-565 Büchi melting point apparatus and are 0.40 (CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 7.53 (d, J =
uncorrected. Column chromatography was performed using 5.6 Hz, 1H, CH), 5.99 (d, J = 5.6 Hz, 1H, CH), 2.04–1.43 (m,
Merck silica gel 60 (0.063–0.200 mm) (Art 7734). 1,2-Dichloro- 14H, 7 × CH2). 13C NMR (100 MHz, CDCl3): δ = 172.5 (C), 161.1
ethane (ClCH2CH2Cl) and dichloromethane (CH2Cl2) were (CH), 120.0 (CH), 92.1 (CH), 33.4 (2 × CH2), 27.9 (2 × CH2), 24.4
distilled over calcium hydride and stored over activated mole- (CH2), 22.4 (2 × CH2). IR (neat): ˜ν = 1745, 1600, 1465, 1161,
cular sieves (4 Å). Other common solvents [acetone, CH2Cl2, 1023, 818. MS: m/z (%) = 180 (11) [M]+, 133 (36), 109 (52), 95
hexanes, and ethyl acetate (EtOAc)] were distilled before use. (78), 91 (84), 81 (89), 79 (100), 67 (55), 55 (65). HRMS
Compounds 1 were synthesized according to the literature (ESI-TOF): calcd for C11H16O2Na [M + Na]+ 203.1048; found
procedures.13
203.1049.
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5,5-Dimethylfuran-2(5H)-one (3e). Pale yellow oil; Rf = 0.33 (2 × CH), 128.3 (CH), 124.7 (2 × CH), 119.3 (CH), 88.9 (C), 26.3
1
(CH2Cl2). H NMR (400 MHz, CDCl3): δ = 7.41 (d, J = 5.6 Hz, (CH3). IR (neat): ˜ν = 3087, 1747, 1447, 765, 697. MS: m/z (%) =
1H, CH), 5.99 (d, J = 5.6 Hz, 1H, CH), 1.49 (s, 6H, 2 × CH3). 13
C
175 (4) [M + H]+, 174 (9) [M]+, 159 (39), 131 (100), 103 (78), 77
NMR (100 MHz, CDCl3): δ = 172.4 (C), 161.2 (CH), 119.9 (CH), (51). HRMS (ESI-TOF): calcd for C11H10O2Na [M + Na]+
86.6 (C), 25.3 (2 × CH3). IR (neat): ˜ν = 1732, 1461, 1258, 1117, 197.0578; found 197.0578.
1016, 795. MS: m/z (%) = 113 (40) [M + H]+, 112 (11) [M]+,
77 (87), 51 (39). HRMS (ESI-TOF): calcd for C6H8O2Na mp 70–72 °C (CH2Cl2); Rf = 0.61 (CH2Cl2). H NMR (400 MHz,
[M + Na]+ 135.0422; found 135.0423.
CDCl3): δ = 7.82 (d, J = 5.7 Hz, 1H, CH), 7.61–7.52 (m, 2H,
5-Phenyl-5-(trifluoromethyl)furan-2(5H)-one (3k). White solid;
1
5,5-Diethylfuran-2(5H)-one (3f). Pale yellow oil; Rf = 0.44 ArH), 7.51–7.40 (m, 3H, ArH), 6.39 (d, J = 5.7 Hz, 1H, CH).
1
(CH2Cl2). H NMR (400 MHz, CDCl3): δ = 7.29 (d, J = 5.7 Hz, 13C NMR (100 MHz, CDCl3): δ = 169.7 (C), 150.8 (CH), 130.9
1H, CH), 6.08 (d, J = 5.7 Hz, 1H, CH), 1.88 (dq, J2 = 7.3 Hz, J1 = (C), 130.2 (CH), 130.0 (3 × CH), 126.6 (CH), 124.2 (CH), 122.4
14.6 Hz, 2H, CH2), 1.77 (dq, J2 = 7.3 Hz, J1 = 14.6 Hz, 2H, CH2), (q, J = 280.3 Hz, CF3), 87.4 (q, J = 32.2 Hz, C). 19F NMR
0.86 (t, J = 7.3 Hz, 6H, 2 × CH3). 13C NMR (100 MHz, CDCl3): (376 MHz, CDCl3): δ = −76.9 (s, 3 F). IR (neat): ˜ν = 3117, 1797,
δ = 172.9 (C), 158.9 (CH), 121.6 (CH), 92.0 (C), 29.5 (2 × CH2), 1775, 1292, 1171, 761, 694. MS: m/z (%) = 228 (1) [M]+, 159
7.7 (2 × CH3). IR (neat): ˜ν = 1750, 1603, 1460, 1224, 1133, 950, (100), 131 (48), 103 (43), 77 (26). HRMS (ESI-TOF): calcd for
820. MS: m/z (%) = 140 (19) [M]+, 133 (47), 126 (89), 95 (75), 81 C11H7F3O2Na [M + Na]+ 251.0296; found 251.0296.
(100), 67 (88), 55 (81). HRMS (ESI-TOF): calcd for C8H12O2Na
[M + Na]+ 163.0735; found 163.0734.
5-Butylfuran-2(5H)-one (3l). Pale yellow oil; Rf = 0.44
(CH2Cl2). H NMR (400 MHz, CDCl3): δ = 7.47 (dd, J2 = 1.3 Hz,
J2 = 5.7 Hz, 1H, CH), 6.11 (dd, J3 = 1.9 Hz, J2 = 5.7 Hz, 1H, CH),
1
5-Ethyl-5-methylfuran-2(5H)-one (3g). Pale yellow oil; Rf
=
0.40 (CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 7.36 (d, J = 5.08–5.01 (m, 1H, CH), 1.84–1.81 (m, 2H, CH2), 1.50–1.30 (m,
5.6 Hz, 1H, CH), 6.03 (d, J = 5.6 Hz, 1H, CH), 1.86 (dq, J2
=
4H, 2 × CH2), 0.92 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (100 MHz,
7.3 Hz, J1 = 14.6 Hz, 1H, CHH), 1.76 (dq, J2 = 7.3 Hz, J1 = 14.6 CDCl3): δ = 173.2 (C), 156.3 (CH), 121.5 (CH), 83.4 (C), 32.8
Hz, 1H, CHH), 1.47 (s, 3H, CH3), 0.88 (t, J = 7.3 Hz, 3H, CH3). (CH2), 27.0 (CH2), 22.4 (CH2), 13.8 (CH3). IR (neat): ˜ν = 1747,
13C NMR (100 MHz, CDCl3): δ = 172.6 (C), 160.2 (CH), 120.7 1601, 1466, 1162, 1024, 818. MS: m/z (%) = 140 (17) [M]+, 133
(CH), 89.3 (C), 31.2 (CH2), 23.5 (CH3), 8.0 (CH3). IR (neat): ˜ν = (40), 95 (90), 81 (100), 67 (89), 55 (98). HRMS (ESI-TOF): calcd
1745, 1603, 1459, 1235, 1130, 950, 819. MS: m/z (%) = 127 (21) for C8H12O2Na [M + Na]+ 163.0735; found 163.0729.
[M + H]+, 126 (100) [M]+, 112 (48), 95 (76), 81 (90), 67 (78),
55 (84). HRMS (ESI-TOF): calcd for C7H10O2Na [M + Na]+ (CH2Cl2). H NMR (400 MHz, CDCl3): δ = 7.40 (dd, J2 = 1.4 Hz,
149.0578; found 149.0579. J2 = 5.7 Hz, 1H, CH), 7.34–7.27 (m, 2H, ArH), 7.25–7.17 (m, 3H,
5-Phenethylfuran-2(5H)-one (3m). Pale yellow oil; Rf = 0.48
1
5-Isopropyl-5-methylfuran-2(5H)-one (3h). Pale yellow oil; ArH), 6.11 (dd, J3 = 2.0 Hz, J2 = 5.7 Hz, 1H, CH), 5.05–4.98 (m,
1
Rf = 0.42 (CH2Cl2). H NMR (400 MHz, CDCl3): δ = 7.34 (d, J = 1H, CH), 2.90–2.72 (m, 2H, CH2), 2.14–2.03 (m, 1H, CHH),
5.7 Hz, 1H, CH), 5.97 (d, J = 5.7 Hz, 1H, CH), 1.91 (hept, J = 6.9 2.00–1.88 (m, 1H, CHH). 13C NMR (100 MHz, CDCl3): δ = 173.0
Hz, 1H, CH), 1.37 (s, 3H, CH3), 0.91 (d, J = 6.9 Hz, 3H, CH3), (C), 156.1 (CH), 140.2 (C), 128.6 (2 × CH), 128.5 (2 × CH), 126.4
0.88 (d, J = 6.9 Hz, 3H, CH3). 13C NMR (100 MHz, CDCl3): δ = (CH), 121.6 (CH), 82.4 (C), 34.9 (CH2), 31.3 (CH2). IR (neat): ˜ν =
172.7 (C), 159.7 (CH), 120.8 (CH), 91.7 (C), 35.5 (CH), 21.3 3085, 3062, 1744, 1601, 1454, 1159, 1102, 815, 752, 699. MS:
(CH3), 17.7 (CH3), 17.2 (CH3). IR (neat): ˜ν = 1744, 1603, 1457, m/z (%) = 189 (9) [M + H]+, 188 (10) [M]+, 178 (14), 105 (24),
1249, 1120, 948, 819. MS: m/z (%) = 141 (28) [M + H]+, 140 97 (38), 91 (100), 77 (34), 65 (24), 55 (16). HRMS (ESI-TOF):
(100) [M]+, 138 (22). HRMS (ESI-TOF): calcd for C8H12O2Na calcd for C12H12O2Na [M + Na]+ 211.0735; found 211.0738.
[M + Na]+ 163.0735; found 163.0732.
5-Ethyl-5-phenylfuran-2(5H)-one (3i). Pale yellow oil; Rf
5-Phenylfuran-2(5H)-one (3n) and 5-phenylfuran-2(3H)-one
(3n′). A 2 : 1 mixture of 3n and 3n′ was obtained as an orange
=
0.53 (CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 7.63 (d, J = semi-solid after column chromatography (SiO2, 20% EtOAc in
5.6 Hz, 1H, CH), 7.42–7.28 (m, 5H, ArH), 6.08 (d, J = 5.6 Hz, hexanes). 3n; Rf = 0.20 (20% EtOAc in hexanes), 3n′; Rf = 0.38
1H, CH), 2.19 (dq, J2 = 7.3 Hz, J1 = 14.6 Hz, 1H, CHH), 2.03 (dq, (20% EtOAc in hexanes); 1H NMR (400 MHz, CDCl3, integrated
J2 = 7.3 Hz, J1 = 14.6 Hz, 1H, CHH), 0.89 (t, J = 7.3 Hz, 3H, equally for both isomers): δ = 7.56–7.50 (m, 2H, ArH of 3n′),
CH3). 13C NMR (100 MHz, CDCl3): δ = 172.4 (C), 159.2 (CH), 7.46 (dd, J2 = 1.6 Hz, J2 = 5.6 Hz, 1H, CH of 3n), 7.37–7.26
138.8 (C), 128.8 (2 × CH), 128.1 (CH), 125.0 (2 × CH), 120.0 (each m, 3H, ArH of 3n and 3H, ArH of 3n′), 7.23–7.16 (m, 2H,
(CH), 91.9 (C), 32.7 (CH2), 8.0 (CH3). IR (neat): ˜ν = 3085, 3066, ArH of 3n), 6.16 (dd, J3 = 2.1 Hz, J2 = 5.6 Hz, 1H, CH of 3n),
1752, 1601, 1448, 1210, 1121, 1024, 816, 760, 698. MS: m/z (%) 5.97–5.92 (m, 1H, CH of 3n), 5.72 (t, J = 2.7 Hz, 1H, CH of 3n′),
= 189 (7) [M + H]+, 188 (12) [M]+, 159 (100), 131 (53), 103 (63), 3.35 (d, J = 2.7 Hz, 2H, CH2 of 3n′). 13C NMR (100 MHz,
77 (58), 67 (14), 55 (9). HRMS (ESI-TOF): calcd for C12H12O2Na CDCl3): δ = 175.9 (C of 3n′), 173.1 (C of 3n), 155.8 (CH of 3n),
[M + Na]+ 211.0735; found 211.0733.
153.9 (C of 3n′), 134.2 (1C of 3n and 1C of 3n′), 129.3 (CH of
5-Methyl-5-phenylfuran-2(5H)-one (3j). Pale yellow oil; Rf = 3n), 129.6 (CH of 3n′), 128.6 (2 × CH of 3n′), 129.0 (2 × CH of
1
0.38 (CH2Cl2). H NMR (400 MHz, CDCl3): δ = 7.57 (d, J = 5.6 3n), 126.5 (2 × CH of 3n), 124.7 (2 × CH of 3n′), 120.9 (CH of
Hz, 1H, CH), 7.35–7.29 (m, 4H, ArH), 7.29–7.22 (m, 1H, ArH), 3n), 97.6 (CH of 3n′), 84.3 (CH of 3n), 34.6 (CH2 of 3n′).
5.99 (d, J = 5.6 Hz, 1H, CH), 1.76 (s, 3H, CH3). 13C NMR IR (neat): ˜ν = 3090, 3034, 1746, 1454, 1154, 1028, 760, 697. MS:
(100 MHz, CDCl3): δ = 172.4 (C), 160.4 (CH), 139.2 (C), 128.8 m/z (%) = 161 (15) [M + H]+, 160 (87) [M]+, 131 (99), 103 (70), 77
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(100). HRMS (ESI-TOF): calcd for C10H8O2Na [M + Na]+
183.0422; found 183.0430.
1-Phenyl-1H-pyrrol-2(5H)-one (3r). Pale yellow solid; mp
81–85 °C (CH2Cl2); Rf = 0.24 (10% EtOAc in hexanes). H NMR
1
5-(p-Tolyl)furan-2(5H)-one (3o) and 5-(p-tolyl)furan-2(3H)- (400 MHz, CDCl3): δ = 7.68–7.61 (m, 2H, ArH), 7.36–7.28 (m,
one (3o′). A 10 : 1 mixture of 3o and 3o′ was obtained as an 2H, ArH), 7.12 (dt, J2 = 1.9 Hz, J2 = 6.0 Hz, 1H, CH), 7.10–7.04
orange solid after column chromatography (SiO2, 20% EtOAc (m, 1H, ArH), 6.22 (dt, J3 = 1.9 Hz, J2 = 6.0 Hz, 1H, CH), 4.39
in hexanes). 3o; Rf = 0.33 (20% EtOAc in hexanes), 3o′; Rf = (dd, J3 = 1.9 Hz, J2 = 1.9 Hz, 2H, CH2). 13C NMR (100 MHz,
1
0.47 (20% EtOAc in hexanes); mp 49–52 °C (CH2Cl2). H NMR CDCl3): δ = 170.2 (C), 142.2 (CH), 139.0 (C), 129.3 (CH), 129.1
(500 MHz, CDCl3, integrated equally for both isomers): δ = (2 × CH), 124.2 (CH), 118.9 (2 × CH), 53.2 (CH2). IR (neat):
7.49 (dd, J2 = 1.6 Hz, J2 = 5.6 Hz, 1H, CH of 3o), 7.20 (each d, ˜ν = 3350, 3079, 3043, 1681, 1596, 753, 689. MS: m/z (%) = 160 (6)
J = 8.1 Hz, 2H, ArH of 3o and 2H, ArH of 3o′), 7.14 (each d, J = [M + H]+, 159 (38) [M]+, 130 (100), 77 (33). HRMS (ESI-TOF):
8.1 Hz, 2H, ArH of 3o and 2H, ArH of 3o′), 6.20 (dd, J3 = 2.1 Hz, calcd for C10H9NONa [M + Na]+ 182.0582; found 182.0582.
J2 = 5.6 Hz, 1H, CH of 3o), 5.97 (br s, 1H, CH of 3o), 5.70 (t, J =
1-Benzyl-1H-pyrrol-2(5H)-one (3s). Pale yellow oil; Rf = 0.22
2.7 Hz, 1H, CH of 3o′), 3.39 (d, J = 2.7 Hz, 2H, CH2 of 3o′), 2.37 (20% EtOAc in hexanes). 1H NMR (400 MHz, CDCl3): δ =
(s, 3H, CH3 of 3o′), 2.36 (s, 3H, CH3 of 3o). 13C NMR (125 MHz, 7.37–7.19 (m, 5H, ArH), 7.06 (dt, J2 = 1.7 Hz, J2 = 6.0 Hz, 1H,
CDCl3): δ = 173.1 (C of 3o), 173.0 (C of 3o′), 155.8 (CH of 3o), CH), 6.23 (dt, J3 = 1.8 Hz, J2 = 6.0 Hz, 1H, CH), 4.64 (s, 2H,
155.7 (C of 3o′), 139.4 (C of 3o), 138.9 (C of 3o′), 131.3 (C of CH2Ph), 3.88 (br s, 2H, CH2). 13C NMR (100 MHz, CDCl3): δ =
3o′), 131.2 (C of 3o), 129.7 (2 × CH of 3o), 129.4 (2 × CH of 3o′), 171.4 (C), 142.8 (CH), 137.2 (C), 128.7 (2 × CH), 127.9 (3 × CH),
126.5 (2 × CH of 3o), 124.7 (2 × CH of 3o′), 121.0 (CH of 3o), 127.5 (CH), 52.2 (CH2), 45.9 (CH2). IR (neat): ˜ν = 3368, 3063,
96.6 (CH of 3o′), 84.4 (CH of 3o), 34.6 (CH2 of 3o′), 21.2 (CH3 3030, 1659, 1450, 717, 699. MS: m/z (%) = 174 (6) [M + H]+, 173
of 3o), 21.1 (CH3 of 3o′). IR (neat): ˜ν = 3080, 3038, 1795, 1748, (50) [M]+, 172 (72), 106 (40), 91 (100), 77 (27), 65 (34). HRMS
1512, 1306, 1158, 819. MS: m/z (%) = 175 (10) [M + H]+, 174 (ESI-TOF): calcd for C11H11NONa [M + Na]+ 196.0738; found
(52) [M]+, 145 (100), 115 (94), 91 (80), 65 (34). HRMS (ESI-TOF): 196.0734.
calcd for C11H10O2Na [M + Na]+ 197.0578; found 197.0572.
1-Benzyl-5-phenyl-1H-pyrrol-2(5H)-one (3t) and 1-benzyl-
5-(4-Chlorophenyl)furan-2(5H)-one (3p) and 5-(4-chlorophe- 5-phenyl-1H-pyrrol-2(3H)-one (3t′). A 3 : 2 mixture of 3t and 3t′
nyl)furan-2(3H)-one (3p′). A 1 : 4 mixture of 3p and 3p′ was was obtained as a pale brown viscous oil. 3t; Rf = 0.36 (30%
obtained as an orange semi-solid after column chromato- acetone in hexanes), 3t′; Rf = 0.42 (30% acetone in hexanes);
graphy (SiO2, 20% EtOAc in hexanes). 3p; Rf = 0.16 (20% EtOAc 1H NMR (400 MHz, CDCl3, integrated equally for both
in hexanes), 3p′; Rf = 0.33 (20% EtOAc in hexanes); 1H NMR isomers): δ = 7.42–7.24 (each, m, 5H, ArH of 3t and 5H, ArH of
(400 MHz, CDCl3, integrated equally for both isomers): δ = 3t′), 7.23–7.14 (each, m, 1H, ArH of 3t and 3H, ArH of 3t′),
7.47 (d, J = 8.6 Hz, 2H, ArH of 3p′), 7.44 (dd, J2 = 1.6 Hz, J2 = 7.14–7.09 (m, 2H, ArH of 3t), 7.09–7.04 (m, 2H, ArH of 3t),
5.6 Hz, 1H, CH of 3p), 7.31 (each d, J = 8.6 Hz, 2H, ArH of 3p 6.99–6.94 (m, 2H, ArH of 3t′), 7.01 (dd, J2 = 1.6 Hz, J2 = 5.8 Hz,
and 2H, ArH of 3p′), 7.14 (d, J = 8.4 Hz, 2H, ArH of 3p), 6.18 1H, CH of 3t), 6.28 (dd, J3 = 1.6 Hz, J2 = 5.8 Hz, 1H, CH of 3t),
(dd, J3 = 2.1 Hz, J2 = 5.6 Hz, 1H, CH of 3p), 5.92 (br s, 1H, CH 5.27 (t, J = 2.6 Hz, 1H, CH of 3t′), 5.19 (d, J = 15.0 Hz, 1H,
of 3p), 5.72 (t, J = 2.7 Hz, 1H, CH of 3p′), 3.36 (d, J = 2.7 Hz, CHHPh of 3t), 4.88 (br s, 1H, CH of 3t), 4.68 (s, 2H, CH2Ph of
2H, CH2 of 3p′). 13C NMR (100 MHz, CDCl3): δ = 175.5 (C of 3t′), 3.60 (d, J = 15.0 Hz, 1H, CHHPh of 3t), 3.27 (d, J = 2.6 Hz,
3p′), 172.7 (C of 3p), 155.3 (CH of 3p), 153.0 (C of 3p′), 135.5 2H, CH2 of 3t′). 13C NMR (100 MHz, CDCl3): δ = 178.4 (C of
(C of 3p′), 135.3 (C of 3p), 132.8 (C of 3p), 129.3 (2 × CH of 3p), 3t′), 171.3 (C of 3t), 148.1 (CH of 3t), 146.2 (C of 3t′), 137.5
129.0 (2 × CH of 3p′), 127.8 (2 × CH of 3p), 126.8 (C of 3p′), (C of 3t′), 137.3 (C of 3t), 134.4 (C of 3t), 131.7 (C of 3t′), 129.2
126.0 (2 × CH of 3p′), 121.3 (CH of 3p), 98.2 (CH of 3p′), 83.5 (2 × CH of 3t), 128.9 (CH of 3t′), 128.8 (2 × CH of 3t′), 128.7
(CH of 3p), 34.6 (CH2 of 3p′). IR (neat): ˜ν = 3031, 1746, 1682, (2 × CH of 3t), 128.4 (4 × CH of 3t′), 128.3 (CH of 3t), 128.2 (2 ×
1514, 1157, 812. MS: m/z (%) = 195 (13) [M + H]+, 194 (86) [M]+, CH of 3t), 127.5 (2 × CH of 3t and 2 × CH of 3t′), 127.2 (CH of
159 (100), 139 (77), 103 (53), 74 (58). HRMS (ESI-TOF): calcd 3t), 127.1 (CH of 3t′), 126.2 (CH of 3t), 102.4 (CH of 3t′), 65.8
for C10H7ClO2Na [M + Na]+ 217.0032; found 217.0028.
(CH of 3t), 44.3 (CH2 of 3t′), 43.4 (CH2 of 3t), 37.3 (CH2 of 3t′).
5-(4-Chlorophenyl)-3-methylfuran-2(5H)-one (3q). A white IR (neat): ˜ν = 3306, 3061, 3029, 1677, 1453, 843, 768, 698. MS:
solid was obtained after column chromatography (SiO2, 50% m/z (%) = 250 (4) [M + H]+, 249 (22) [M]+, 144 (100), 115 (43), 91
CH2Cl2 in hexanes). Rf = 0.29 (20% EtOAc in hexanes); mp (18), 77 (8). HRMS (ESI-TOF): calcd for C17H15NONa [M + Na]+
1
83–86 °C (CH2Cl2). H NMR (400 MHz, CDCl3): δ = 7.29 (d, J = 272.1051; found 272.1053.
8.5 Hz, 2H, ArH), 7.14 (d, J = 8.4 Hz, 2H, ArH), 7.03 (dd, J3 =
1-Benzyl-5-(p-tolyl)-1H-pyrrol-2(5H)-one (3u). Pale brown
1.7 Hz, J2 = 1.7 Hz, 1H, CH), 5.77 (dd, J4 = 1.7 Hz, J2 = 1.7 Hz, viscous oil; Rf = 0.26 (30% EtOAc in hexanes). 1H NMR
1H, CH), 1.93 (dd, J4 = 1.7 Hz, J3 = 1.7 Hz, 3H, CH3). 13C NMR (400 MHz, CDCl3): δ = 7.26–7.15 (m, 3H, ArH), 7.10 (d, J = 7.8
(400 MHz, CDCl3): δ = 174.0 (C), 147.8 (CH), 135.0 (C), 133.6 Hz, 2H, ArH), 7.05 (d, J = 6.6 Hz, 2H, ArH), 6.91 (dd, J2 = 1.5
(C), 129.9 (C), 129.2 (2 × CH), 127.8 (2 × CH), 81.3 (CH), 10.6 Hz, J2 = 5.9 Hz, 1H, CH), 6.88 (d, J = 8.0 Hz, 2H, ArH), 6.19 (dd,
(CH3). IR (neat): ˜ν = 3064, 1743, 1492, 1042, 823. MS: m/z (%) = J3 = 1.7 Hz, J2 = 5.9 Hz, 1H, CH), 5.10 (d, J = 14.9 Hz, 1H,
210 (11) [M + H]+, 179 (100), 150 (46), 122 (33), 96 (40), 82 (76), CHHPh), 4.77 (br s, 1H, CH), 3.51 (d, J = 14.9 Hz, 1H, CHHPh)
55 (56). HRMS (ESI-TOF): calcd for C11H9ClO2Na [M + Na]+ 2.29 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3): δ = 171.3 (C),
231.0189; found 231.0182.
148.2 (CH), 138.7 (C), 137.4 (C), 131.2 (C), 129.8 (2 × CH), 128.6
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(2 × CH), 128.2 (2 × CH), 127.4 (3 × CH), 126.1 (CH), 65.6 (CH), Fund (4-2555) is also gratefully acknowledged for a scholarship
43.3 (CH2), 21.2 (CH3). IR (neat): ˜ν = 3306, 3029, 1665, 1437, to S.P.
816, 756, 700. MS: m/z (%) = 264 (4) [M + H]+, 263 (12) [M]+,
158 (100), 129 (33), 115 (26), 91 (18), 77 (5). HRMS (ESI-TOF):
calcd for C18H17NONa [M + Na]+ 286.1208; found 286.1215.
Notes and references
1-Benzyl-5-(4-methoxyphenyl)-1H-pyrrol-2(5H)-one (3v). Pale
1
brown viscous oil; Rf = 0.32 (40% EtOAc in hexanes). H NMR
(400 MHz, CDCl3): δ = 7.35–7.19 (m, 1H of CH and 2H of ArH),
7.15–7.08 (m, 2H, ArH), 7.03–6.95 (m, 3H, ArH), 6.92–6.86 (m,
2H, ArH), 6.26 (dd, J3 = 1.7 Hz, J2 = 5.8 Hz, 1H, CH), 5.16 (d, J =
15.0 Hz, 1H, CHHPh), 4.84 (br s, 1H, CH), 3.82 (s, 3H, OCH3),
3.58 (d, J = 15.0 Hz, 1H, CHHPh). 13C NMR (100 MHz, CDCl3):
δ = 171.2 (C), 159.9 (C), 148.3 (CH), 137.4 (C), 128.8 (2 × CH),
128.6 (2 × CH), 128.2 (2 × CH), 127.4 (CH), 126.1 (CH), 125.9
(C), 114.5 (2 × CH), 65.3 (CH), 53.3 (CH3), 43.3 (CH2). IR (neat):
˜ν = 3306, 3104, 3064, 3023, 1670, 1510, 1238, 1023, 830, 765,
699. MS: m/z (%) = 280 (16) [M + H]+, 279 (87) [M]+, 188 (67),
174 (100), 131 (26), 91 (47). HRMS (ESI-TOF): calcd for
C18H17NO2Na [M + Na]+ 302.1157; found 302.1161.
3-Methyl-1-phenyl-1H-pyrrol-2(5H)-one (3w). White solid;
mp 81–83 °C (EtOAc/hexanes); Rf = 0.33 (30% EtOAc in
hexanes). 1H NMR (400 MHz, CDCl3): δ = 7.78–7.71 (m, 2H,
ArH), 7.44–7.33 (m, 2H, ArH), 7.16–7.08 (m, 1H, ArH),
6.82–6.76 (m, 1H, CH), 4.33–4.27 (m, 2H, CH2), 1.99–1.93 (m,
3H, CH3). 13C NMR (100 MHz, CDCl3): δ = 170.8 (C), 139.5 (C),
136.8 (C), 134.7 (CH), 129.0 (2 × CH), 123.9 (CH), 118.4 (2 ×
CH), 50.8 (CH2), 11.3 (CH3). IR (neat): ˜ν = 3062, 3041, 1671,
1595, 1496, 1380, 758, 690. MS: m/z (%) = 174 (14) [M + H]+,
173 (28) [M]+, 144 (65), 121 (29), 91 (40), 79 (54). HRMS
(ESI-TOF): calcd for C11H11NONa [M + Na]+ 196.0738; found
196.0730.
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G. Rassu, P. Burreddu, F. Zanardi and G. Casiraghi, J. Org.
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G. Rassu, V. Zambrano, L. Pinna and G. Casiraghi, J. Org.
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L. Deng, J. Am. Chem. Soc., 2010, 132, 9558; (d) H. Huang,
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Chem. Commun., 2011, 47, 1027; (f) V. Kumar and
S. Mukherjee, Chem. Commun., 2013, 49, 11203;
(g) Y.-L. Guo, L.-N. Jia, L. Peng, L.-W. Qi, J. Zhou, F. Tian,
X.-Y. Xu and L.-X. Wang, RSC Adv., 2013, 3, 16973;
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2015, 80, 1985; (i) S. Nakamura, R. Yamaji and M. Hayashi,
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N. S. Stock, A. J. P. White and D. J. Williams, J. Org. Chem.,
1999, 64, 6005; (b) A. Gheorghe, M. Schulte and O. Reiser,
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J.-M. Delcroix, A. Deyine, D. Griffart-Brunet, A. Chiaroni
1-Benzyl-5-(4-methoxyphenyl)-3-methyl-1H-pyrrol-2(5H)-one
(3x). Light brown viscous oil; Rf = 0.36 (30% EtOAc in
hexanes). 1H NMR (400 MHz, CDCl3): δ = 7.33–7.21 (m, 3H,
ArH), 7.15–7.08 (m, 2H, ArH), 6.99–6.93 (m, 2H, ArH),
6.91–6.84 (m, 2H, ArH), 6.63–6.58 (m, 1H, CH), 5.15 (d, J = 14.9
Hz, 1H, CHHPh), 4.72–4.66 (m, 1H, CH), 3.82 (s, 3H, CH3),
3.60 (d, J = 14.9 Hz, 1H, CHHPh) 2.02–1.98 (m, 3H, CH3). 13C
NMR (100 MHz, CDCl3): δ = 171.9 (C), 159.7 (C), 141.2 (CH),
137.6 (C), 133.9 (C), 128.7 (2 × CH), 128.6 (2 × CH), 128.2 (2 ×
CH), 127.3 (CH), 127.0 (C), 114.4 (2 × CH), 63.1 (CH), 55.3
(CH3), 43.7 (CH2), 11.2 (CH3). IR (neat): ˜ν = 3064, 3031, 1678,
1608, 1510, 1242, 1030, 831, 705. MS: m/z (%) = 294 (33)
[M + H]+, 293 (100) [M]+, 202 (77), 188 (61), 145 (24), 91 (37).
HRMS (ESI-TOF): calcd for C19H19NO2Na [M + Na]+ 316.1313;
found 316.1337.
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Acknowledgements
The authors acknowledge financial support from the Thailand
Research Fund (RSA5880013), the Office of the Higher Edu-
cation Commission and Mahidol University under the
National Research Universities Initiative, and the Center of
Excellence for Innovation in Chemistry (PERCH-CIC). Nakhon
Ratchasima Rajabhat University’s Academic Development
Org. Biomol. Chem.
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