Copper-Catalyzed [4 + 1] Annulation between α-Hydroxy Ketones and Nitriles: An Approach to Highly Substituted 3(2H)-Furanones

Article abstract of DOI:10.1021/acs.joc.5b00356

A copper-catalyzed [4 + 1] annulation between α-hydroxy ketones and nitriles has been developed. The reaction provides a facile and efficient method for the construction of a wide range of highly substituted 3(2H)-furanones, a class of important compounds

Full text of DOI:10.1021/acs.joc.5b00356

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Article
Copper-Catalyzed [4+1] Annulation Between alpha-Hydroxy Ketones
and Nitriles: An Approach to Highly Substituted 3(2H)-Furanones
Haitao He, Chaorong Qi, Xiaohan Hu, Lu Ouyang, Wenfang Xiong, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b00356 • Publication Date (Web): 16 Apr 2015
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Copper-Catalyzed [4+1] Annulation Between α-Hydroxy Ketones
and Nitriles: An Approach to Highly Substituted 3(2H)-Furanones
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Haitao He, Chaorong Qi, * Xiaohan Hu, Lu Ouyang, Wenfang Xiong, and Huanfeng Jiang*
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School of Chemistry and Chemical Engineering, State Key Lab of Luminescent Materials and Devices, South China University
of Technology, Guangzhou 510640, China
Fax: (+) (+86) 20ꢀ8711ꢀ2906; Eꢀmail: crqi@scut.edu.cn or jianghf@scut.edu.cn
R1
O
CuI/DBU
R4-CN
O
O
R1
R2
R3
R2
R3
=
O
O
R4
R1
CN
O
O
OH
+
O
CuI/DBU
R4-CN
R2
R3
O
R4-CN
=
O
O
CN
Abstract: A copperꢀcatalyzed [4+1] annulation between αꢀhydroxy ketones and
nitriles has been developed. The reaction provides a facile and efficient method for
the construction of a wide range of highly substituted 3(2H)ꢀfuranones, a class of
important compounds known to be associated with several biological activities.
INTRODUCTION
The synthesis of 3(2H)ꢀfuranones has attracted tremendous interest in the past
decades because of the importance of these fiveꢀmembered heterocycles in
biologically active natural products1 and pharmacologically interesting compounds.2
Three representative examples, namely the antimicrobial active 14ꢀnorpseurotin A,
the antitumor active nemoralisin A, and parvifloranine A, which were recently
isolated from Aspergillus sydowi,3 Aphanamixis grandifolia, 4 and Geijera parviflora,
5 respectively, are shown in Figure 1.
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O
O
O
O
O
OH
O
O
O
NH
N
OH
O
O
HO
OMe
H
OH
O
OH
O
O
O
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Parvifloranine A
Nemoralisin A
14-Norpseurotin A
Figure 1. Naturally occurring products containing the 3(2H)ꢀfuranone skeleton.
After the pioneering work by Smith and coꢀworkers who established a general
approach to substituted 3(2H)ꢀfuranones via acidꢀpromoted cyclization/dehydration of
1ꢀhydroxyꢀ2,4ꢀdiketones,6 many elegant strategies for the construction of these
important class of compounds have been developed, mainly through A)
intramolecular cyclization via C5ꢀO1 bond formation6,7 and B) intramolecular
cyclization via C2ꢀO1 bond formation8 (Figure 2). In contrast, the
transitionꢀmetalꢀcatalyzed or metal free intermolecular annulations for the synthesis
of 3(2H)ꢀfuranones have been scarcely explored.9 Thus, from the viewpoints of
starting material availability and step economy, the design of versatile intermolecular
annulations between readily available substrates for constructing 3(2H)ꢀfuranones is
highly desirable.
In 2011, we have reported a carbon dioxide triggered and copperꢀcatalyzed domino
process for the synthesis of fully substituted 3(2H)ꢀfuranones from propargylic
alcohols and nitriles.10 Despite the synthetic value of the transformation,
2,2,4ꢀtrisubstituted 3(2H)ꢀfuranones could not be synthesized by this method.
Moreover, the reaction required a large excess of nitriles as solvent, which also
constitutes a major limitation for the substrate scope and thus restricts its use. These
drawbacks prompted us to reinvestigate the transformation. And more recently, we
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have successfully developed an efficient and green method for the synthesis of
αꢀhydroxy ketones from propargylic alcohols.11 Based on our previous work
mentioned above, we envisioned that a more facile and versatile approach to highly
substituted 3(2H)ꢀfuranones would be achieved via an intermolecular [4+1]
annulation of readily available αꢀhydroxy ketones12 with various nitriles. Herein, we
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wish to report in detail our research results.
O
R3
R4
R2
R1
intramolecular cyclization
via C5-O1 bond formation
previous work
O
O
R3
R2
R1
intramolecular cyclization
via C2-O1 bond formation
O
previous work
R3
R4
R2
R1
O
R4
O
this work
O
R3
R4
R2
R1
intermolecular [4+1] annulation
O
Figure 2. Synthetic Strategies to 3(2H)ꢀfuranones.
RESULTS AND DISCUSSION
We started our study by examining the model reaction of
3ꢀhydroxyꢀ3ꢀmethylꢀ1ꢀ(pyridinꢀ2ꢀyl) butanꢀ2ꢀone (1a) and 4ꢀacetylbenzonitrile (2a),
and the results are summarized in Table 1. To our delight, when the reaction was
carried out in the presence of 20 mol% of CuI and 0.50 equiv. of
o
1,8ꢀdiazabicyclo[5.4.0]ꢀundecꢀ7ꢀene (DBU) in wet methanol at 100 C, the desired
product, 5ꢀ(4ꢀacetylphenyl)ꢀ2,2ꢀdimethylꢀ4ꢀ(pyridinꢀ2ꢀyl)furan ꢀ3(2H)ꢀone (3aa), was
obtained in an excellent yield after 24 h (entry 1). Two control experiments revealed
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Table 1. Optimization of the Reaction Conditionsa
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9
O
N
O
O
Catalyst, Base
Solvent
CN
+
N
O
O
OH
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1a
2a
3aa
Entry
1
Catalyst
CuI
ꢀ
Base
Solvent
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
DMF
Temperature (oC)
Yield (%)b
DBU
DBU
ꢀ
100
100
100
100
100
100
100
100
100
100
100
100
70
93（85）
n.r.c
trace
66
2
3
CuI
4
CuBr
DBU
DBU
DBU
Et3N
5
Cu(OAc)2
CuCF3SO3
CuI
68
6
58
7
51
8
CuI
DABCO
DBU
DBU
DBU
DBU
DBU
DBU
19
9
CuI
31
10
11
12
13
14
CuI
THF
47
CuI
1,4ꢀDioxane
EtOH
45
CuI
69
CuI
MeOH
71
CuI
MeOH
120
66
a Reaction conditions: 1a (0.25 mmol), 2a (0.30 mmol), catalyst (0.05 mmol), base (0.125 mmol),
H2O (0.5 mmol), solvent (1 mL), 24 h. b GC yield with dodecane as internal standard. Number in
parentheses is the yield of isolated product. c n.r. = No reaction.
that both copper salt and organic base are required for the transformation to proceed
(entries 2 and 3). Among a variety of the copper catalysts, CuI was found to be the
most effective for the reaction (entries 4ꢀ6). Moreover, the use of other organic
bases such as triethylamine (NEt3) or 1,4ꢀdiazabicyclo[2.2.2]octane (DABCO)
resulted in a dramatic decrease in the yield (entries 7 and 8). The effect of solvent on
the yield of 3aa was then investigated and it was shown that the solvent has an
important influence to the reaction. Methanol is proven to be the most suitable
media for the transformation while other solvents such as DMF, THF, 1,4ꢀdioxane or
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ethanol gave inferior results (entries 9ꢀ12). Further optimization showed that both
decreasing and increasing the reaction temperature lead to an obvious decrease in the
yield of the product (entries 13 and 14).With the optimized reaction conditions in
hand, the scope of this transformation was examined by using various nitriles and
αꢀhydroxy ketones. Gratifyingly, a wide range of benzonitriles with different
substitution patterns could be used in this reaction, affording the corresponding
products in moderate to excellent yields (Table 2). Noteworthy, the present catalytic
system tolerates different functional groups at position 3 and 4 of the aryl ring of the
benzonitriles, including acetyl, ester, cyano, trifluomethyl, nitro, methylsulfonyl,
halogen functionalities as well as methyl ether (3aaꢀ3ao and 3aq). The data also
shows that the electronic nature of the substituents on the aryl ring of the benzonitriles
affects the yields of the desired products significantly. In general, benzonitriles with
electronꢀwithdrawing or electronꢀneutral substituents gave higher yields (3aaꢀ3ak)
than those containing electronꢀdonating group (3al and 3aq). Moreover, 4ꢀsubstituted
substrates gave better yields than 3ꢀsubstituted ones, while oꢀsubstituted benzonitrile
such as 2ꢀfluorobenzonitrile (3p) only gave trace amount of the desired product (3ap),
and most of the starting material was recovered. We assume that steric hindrance
reduces the reactivity greatly.
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Interestingly, the dicyano aromatic compounds pꢀbenzenedinitrile (2c) and
mꢀbenzenedinitrile (2n) could selectively undergo single or double annulations with
1a, dependant on the amount of 1a present. Thus, two structurally attractive products
3ac' and 3an', both of which contain two 3(2H)ꢀfuranone motifs, could be obtained in
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Table 2. Substrate scope of nitrilesa,b
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O
O
N
CuI, DBU
+
R CN
N
MeOH, 24h
R
O
OH
O
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2a-u
1a
3aa-3an'
O
O
N
N
N
R'
O
O
O
R'
F
3am, R' = COMe, 56%
3an, R' = CN, 61%
3ao, R' = F, 55%
3aa, R' = COMe, 85%
3ab, R' = CO2Me, 78%
3ac, R' = CN, 77%
3ad, R' = CF3, 52%
3ae, R' = NO2, 80%
3af, R' = SO2Me, 87%
3ag, R' = F, 65%
3ah, R' = Cl, 73%
3ai, R' = Br, 57%
3aj, R' = I, 54%
3ap, trace
N
O
O
O
N
O
O
O
O
N
O
3ak, R' = H, 53%
3al, R' = OMe, 30%
3ac', 73%e
3aq, 40%
O
O
N
O
O
N
O
N
O
NH
3an', 79%e
3as, 23%
O
N
O
O
N
N
O
O
O
N
3at, 73%c
3au, 67%d
3ar, 58%
a
Reaction conditions: αꢀhydroxy ketone 1a (0.25 mmol), nitrile (0.30 mmol), CuI (0.05 mmol),
o
b
c
DBU (0.125 mmol), H2O (0.5 mmol), MeOH (1 mL), 100 C, 24 h. Isolated yields. The
o
d
o
e
reaction was carried out at 120 C. The reaction was carried out at 140 C. 0.55 mmol nitrile
was added.
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high yields when treating 2c and 2n with 2.2 equiv of 1a under standard reaction
conditions, respectively. Heteroaromatic nitriles such as nicotinonitrile (2r) and
2ꢀcyanopyrrole (2s) could also participate in the reaction to generate the desired
products, albeit in lower yields. We also examined the reactivity of aliphatic nitriles in
this catalytic system. Satisfactorily, both acetonitrile (2t) and pentanenitrile (2u)
entered the reaction smoothly, furnishing the desired products 3as and 3at in good
yields, although higher temperatures are required in these cases.
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Subsequently, the scope of αꢀhydroxy ketones was examined (Table 3). The
transformation proceeds very efficiently with a wide range of 2ꢀpyridyl substituted
αꢀhydroxy ketones, affording the corresponding products in moderate to high yields
(3baꢀ3ia). It was found that sterically less bulky αꢀhydroxy ketones were favourable
to the reaction. When the substrates contain bulky alkyl groups (1f) or phenyl group
(1g) on the alkyl chain adjacent to the hydroxyl group, lower yields was observed.
However, cyclohexylꢀ and cyclopentylꢀsubstituted substrates worked well to furnish
the spirocyclic products in high yields (3ha and 3ia). Pleasingly, 3ꢀpyridyl, 4ꢀpyridyl
and 2ꢀquinolinyl substituted αꢀhydroxy ketones underwent the reaction to generate the
corresponding products 3ja, 3ka and 3la in 35%, 62% and 76% yields, respectively.
When aromatic αꢀhydroxy ketones containing different substituents at the paraꢀ,
metaꢀ, and ortho positions of the aromatic ring were examined for the reaction, we
found that the reactivity of this type of compounds is quite sensitive to both electronic
and steric factors. Hence, the substrates bearing electronꢀwithdrawing substituents at
the paraꢀ or metaꢀposition of the phenyl ring, such as 1mꢀ1o, were compatible with
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Table 3. Substrate scope of αꢀhydroxy ketones a,b
R1
O
5
O
6
7
8
9
R2
R3
O
CuI, DBU
MeOH
R2
R3
R1
CN
+
O
O
OH
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3ba-3pa
2a
1b-p
O
O
O
N
N
N
O
O
O
O
O
O
3ca, 86%
3da, 84%
3ba, 79%
O
O
N
O
N
N
O
O
O
O
O
O
Ph
5
3ea, 83%
3fa, 58%
3ga, 70%
N
O
O
N
O
N
O
O
O
O
O
O
3ja, 35%c
H3COOC
3ha, 90%
3ia, 75%
N
O
O
N
O
O
O
O
O
O
O
3ma, 68%c
3la, 76%c
3ka, 62%
O2N
NO2
O2N
O
O
O
O
O
O
O
O
O
3oa, 75%d
3pa, traced
3na, 80%d
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a
Reaction conditions: αꢀhydroxy ketone (0.25 mmol), 2a (0.30 mmol), CuI (0.05 mmol), DBU
5
6
7
8
(0.125 mmol), H2O (0.5 mmol), MeOH (1 mL), 100 oC, 24 h. b Isolated yields. c The reaction was
carried out at 120 oC. d The reaction was carried out at 140 oC.
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the reaction, and were efficiently transformed into the corresponding products in good
to high yields (3maꢀ3oa). When the orthoꢀposition substituted substrate,
2ꢀmethylꢀ4ꢀ(2ꢀnitrophenyl)butꢀ3ꢀynꢀ2ꢀol (1p) was employed, only trace amount of
product was observed. Furthermore, the reaction with the substrates bearing
electronꢀneutral or electronꢀdonating groups on the aromatic ring failed to yield even
a trace of the desired products, and increasing the temperature just led to the
decomposition of the substrates.
Surprisingly, when we treated 1a under the optimized reaction conditions with ethyl
(ethoxymethylene)cyanoacetate (2v), which is a versatile building block in organic
synthesis,13 none of the desired products was observed. However,
a
2,2,4ꢀtrisubstituted 3(2H)ꢀfuranone derivative,
2,2ꢀdimethylꢀ4ꢀ(pyridinꢀ2ꢀyl)furanꢀ3(2H)ꢀone (3av), was isolated in 85% yield. It is
very interesting because in this transformation, nitrile 2v just provides a carbon atom
for the assembly of 3av. Since the reaction provides a facile access to
2,2,4ꢀtrisubstituted 3(2H)ꢀfuranones, which are often difficult to synthesize by the
methods already reported,6ꢀ10 we decided to further investigate this reaction by using
various αꢀhydroxy ketones (Table 4). It was found that the results are quite similar to
those presented in Table 3. Thus, 2ꢀpyridiyl substituted αꢀhydroxy ketones could be
efficiently converted into the corresponding products (3av and 3cv-3hv) in moderate
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to high yields. But for phenyl substituted substrates, only those containing
5
6
7
electronꢀwithdrawing groups could be tolerated. For example, αꢀhydroxy ketone 1n
8
9
o
could take part in the reaction at a higher temperature (120 C), giving rise to the
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desired product 3nv in 41% yield.
Table 4. Synthesis of various 2,2,4ꢀtrisubstituted 3(2H)ꢀfuranonesa,b
R1
O
O
R2
R3
OH
O
CuI, DBU
R1
R2
R3
3av, 3cv-3hv, 3nv
+
O
O
MeOH, 24h
CN
2v
O
1a, 1c-1h, 1n
O
N
O
O
O
N
N
N
O
O
O
O
3dv, 72%
5
3av, 85%
3cv, 77%
3ev, 79%
O2N
O
O
N
N
O
N
O
O
O
Ph
O
O
3nv, 41%c
3gv, 83%
3fv, 55%
3hv, 76%
a Reaction conditions: 1 (0.25 mmol), 2v (0.30 mmol), CuI (0.05 mmol), DBU (0.125 mmol), H2O
o
c
(0.5 mmol), MeOH (1 mL), 100 C, 24 h. b Isolated yields. The reaction was carried out at 120
oC.
Furthermore, we applied our method to the synthesis of 4ꢀ(3ꢀacetylphenyl)ꢀ2,2ꢀ
dimethylꢀ5ꢀ(4ꢀ(methylsulfonyl)phenyl)furanꢀ3(2H)ꢀone (3qf), a potent selective
COXꢀ2 inhibitor, which was previously prepared by Shin and coꢀwokers through a
multistep procedure.2d,2e Satisfyingly, just by mixing the commercially available
nitrile 2f and 1q in wet methanol in the presence of CuI and DBU at 120 oC, the
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desired product 3qf could be obtained in 45% yield after 24 hours (Scheme 1). This
example highlights the advantages of our protocol in the construction of highly
functionalized 3(2H)ꢀfuranones in terms of step economy and simple operation.
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Scheme 1. Synthesis of 3qf
O
CuI(20 mol%)
DBU(0.5 equiv)
O
O
O
S
O
N
+
O
H2O (0.5 mmol)
MeOH (1 mL)
120oC, 24h
O
O
OH
1q, 0.25 mmol
S
O
2f, 0.5 mmol
3qf, 45% yield
For a deeper understanding of the reaction mechanism, several experiments were
conducted. First, the reaction of acetic acid (4) with 1a under standard conditions
was investigated. However, the desired product 3at was not observed (Eq. 1).
Furthermore, acetamide (5) could not react with 1a under the same conditions as
well (Eq. 2). These results reveal that neither carboxylic acid nor amide is the
intermediate of the reaction, although it is wellꢀknown that nitriles could undergo
hydration to generate the corresponding amides or carboxylic acids.14 However,
treatment of 2ꢀmethylꢀ3ꢀoxoꢀ4ꢀ(pyridinꢀ2ꢀyl)butanꢀ2ꢀyl acetate (6) with 0.5 equiv of
o
DBU in methanol at 100 C for 8 hours led to 3at (86% , Eq. 3), indicating that
compound 6 might be the intermediate for the formation of 3at.15
As for the the reaction of ethyl (ethoxymethylene)cyanoacetate (2v), we suppose
that under our reaction conditions hydrogen cyanide might be formed through the
cleavage of the C(sp2)ꢀCN bond of 2v; 16 and then the in situ generated HCN reacts
with αꢀhydroxy ketones to furnish the corresponding products. In order to prove our
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O
N
O
standard conditions
standard conditions
(1)
CH3COOH
+
N
O
OH
OH
1a
1a
4
3at (0%)
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O
O
O
N
(2)
(3)
CH3CONH2
+
N
N
O
5
3at (0%)
DBU (0.5 equiv.)
O
N
O
MeOH (1 mL)
100 oC, 8 h
O
O
3at (86%)
6, 0.25 mmol
hypothesis of the formation of HCN during the reaction, we used indicator paper to
detect the putative HCN under different reaction conditions. As can be seen from
Table 5, when the combination of 2v, CuI, DBU, H2O and MeOH was heated at 100
oC for 3 h, the indicator paper turned roseꢀred, indicating that HCN was generated in
situ (entry 1). Moreover, in the absence of CuI or DBU, the mixture did not produce
any detectable HCN (entries 2ꢀ4). These results indicated that the cooperation of CuI
and DBU played a key role in the in situ formation of HCN.
Table 5. Detection of HCN by indicator paperaa
Entry
2v
√
CuI
√
DBU
H2O
√
MeOH
Roseꢀred
1
2
3
4
+
ꢀ
√
√
√
√
√
√
√
√
ꢀ
√
√
√
ꢀ
√
√
a Reaction conditions: 2v (0.30 mmol), CuI (0.05 mmol), DBU (0.125 mmol), H2O (0.5 mmol),
o
MeOH (1 mL). The mixture was heated under 100 C for 3 h. “ꢀ” means negative result; “+”
means positive result.
On the basis of the aboveꢀdescribed observations and previous reports,14
a
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plausible mechanism is illustrated in Scheme 2, which is consistent with the one we
previously proposed.10 Initially, an oxy anion species A is formed from αꢀhydroxy
ketones 1 in the presence of DBU, which subsequently undergoes a nucleophilic
attack to the carbonꢀnitrogen triple bond of the nitrile 2 under the assist of copper
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catalyst,
generating ester intermediate C via B. Then, the baseꢀpromoted
intramolecular Claisen condensation takes place to give intermediate D, which
undergoes dehydration to afford the final product 3. As for the mechanism of the
reaction of ethyl (ethoxymethylene)cyanoacetate (2v), hydrogen cyanide is formed in
situ from 2v in the presence of CuI and DBU, and then reacts with αꢀhydroxy
ketones by following the steps described above to furnish the corresponding products.
However, the mechanism of the formation of HCN from 2v in detail is unclear yet.
Scheme 2. Proposed reaction mechanism
O
O
O
R2
R3
R2
R3
OH
R2
R3
R1
DBU
R1
A
R1
R4
O
DBUH
[Cu]
O
1
DBU
NH
R4 C N [Cu]
B
2
O
R1
R1
R4
R2
R3
O
R2
R3
O
R2
R1
H2O
NH3
DBU
R4
R4
O
R3
H2O
O
O
HO
C
D
O
3
O
CuI, DBU
HCN
O
O
H2O/MeOH
CN
CONCLUSION
In summary, we have successfully developed a facile and versatile protocol for the
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straightforward construction of a wide range of highly substituted 3(2H)ꢀfuranones
via a copperꢀcatalyzed [4+1] annulation between αꢀhydroxy ketones and nitriles.
Especially, the reaction of ethyl (ethoxymethylene)cyanoacetate provides an easy
entry to 2,2,4ꢀtrisubstituted 3(2H)ꢀfuranones, which are difficult to obtain by the
methods already reported. The mechanism of the transformation was also discussed.
The important features of the present methodology include the use of readily available
substrates and cheap catalysts, wide substrate scope, high functional group tolerance,
and an easy workꢀup procedure. Further investigation of the pharmacological
properties of the compounds synthesized herein and the application of ethyl
(ethoxymethylene)cyanoacetate as a HCN equivalent for the synthesis of nitriles are
ongoing in our laboratory.
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EXPERIMENTAL SECTION
General methods. 1H and 13C NMR spectra were recorded by using a 400 MHz NMR
spectrometer. The chemical shifts are referenced to signals at 7.26 and 77.0 ppm, respectively, and
CDCl3 is used as a solvent with TMS as the internal standard. Mass spectra were recorded on a
gas chromatographꢀmass spectrometer. The data of HRMS was carried out on a highꢀresolution
mass spectrometer (LCMSꢀITꢀTOF). IR spectra were obtained either as potassium bromide pellets
or as liquid films between two potassium bromide pellets with an infrared spectrometer. Melting
points were determined with a digital melting point measuring instrument. Compounds 1a-n were
synthesized according to the literature procedures.8 Other substrates were commercially purchased
and used without further purification.
General procedure for the preparation of 3(2H)-furanones (3): To a 15 mL dried Schlenk tube,
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the mixture of αꢀketols (0.25 mmol), nitriles (0.30 mmol), CuI (0.05 mmol), DBU (0.125 mmol),
H2O (0.5 mmol), and methanol (1 mL) was added successively. The Schlenk tube was then sealed
and heated at the selected temperature under magnetic stirring for 24 h. After the reaction was
completed, the mixture was concentrated in vacuum and the crude residue was separated by
column chromatography on silica gel with petroleum ether/ethyl acetate (2:1 to 10:1) to give the
desired products 3.
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5-(4-Acetylphenyl)-2,2-dimethyl-4-(pyridin-2-yl)furan-3(2H)-one (3aa). Brown oil (65.3 mg,
85%). 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 4.4 Hz, 1 H), 7.93 (d, J = 8.5 Hz, 2 H), 7.80 –
7.74 (m, 3H), 7.59 (d, J = 7.9 Hz, 1 H), 7.26 – 7.23 (m, 1 H), 2.62 (s, 3 H), 1.60 (s, 6 H). 13C
NMR (100 MHz, CDCl3) δ 204.6, 197.3, 179.2, 149.6, 149.5, 139.3, 136.6, 134.0, 129.1, 127.9,
124.8, 122.7, 114.5, 88.0, 26.7, 23.3. IR (KBr): 2979, 2930, 1690, 1600, 1386, 1265, 1173, 1061,
905, 744, 607 cmꢀ1. HRMSꢀESI (m/z): calcd for C19H17NNaO3 [M + Na]+: 330.1101; found
330.1104.
Methyl 4-(5,5-dimethyl-4-oxo-3-(pyridin-2-yl)-4,5-dihydrofuran-2-yl)benzoate (3ab). Brown
oil (62.9 mg, 78%). 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 4.7 Hz, 1 H), 8.02 (d, J = 8.5 Hz, 2
H), 7.79 – 7.72 (m, 3 H), 7.58 (d, J = 7.9 Hz, 1 H), 7.26 – 7.20 (m, 1 H), 3.93 (s, 3 H), 1.59 (s, 6
H). 13C NMR (100 MHz, CDCl3) δ 204.7, 179.3, 166.2, 149.7, 149.5, 136.6, 133.9, 132.9, 129.2,
128.8, 124.8, 122.6, 114.5, 88.0, 52.4, 23.3. IR (KBr): 3057, 2981, 1726, 1696, 1603, 1474, 1386,
1280, 1173, 1109, 1062, 906, 775, 707, 610 cmꢀ1. HRMSꢀESI (m/z): calcd for C19H18NO4 [M +
H]+: 324.1230; found 324.1226.
4-(5,5-Dimethyl-4-oxo-3-(pyridin-2-yl)-4,5-dihydrofuran-2-yl)benzonitrile (3ac). Light yellow
solid (55.8 mg, 77%), mp: 129ꢀ130 °C. 1H NMR (400 MHz, CDCl3) δ 8.53 (s, 1 H), 7.83 (d, J =
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8.4 Hz, 2 H), 7.80 – 7.75 (m, 1 H), 7.70 – 7.59 (m, 3 H), 7.25 (s, 1 H), 1.59 (s, 6 H). 13C NMR
(100 MHz, CDCl3) δ 204.5, 178.0, 149.4, 149.2, 136.7, 134.1, 131.8, 129.4, 124.7, 122.9, 118.0,
115.1, 99.9, 88.1, 23.2. IR (KBr): 2981, 2931, 2230, 1696, 1601, 1474, 1387, 1258, 1170, 1063,
905, 848, 796, 749, 611 cmꢀ1. HRMSꢀESI (m/z): calcd for C18H15N2O2 [M + H]+: 291.1128; found
291.1123.
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2,2-Dimethyl-4-(pyridin-2-yl)-5-(4-(trifluoromethyl)phenyl)furan-3(2H)-one (3ad). Light
yellow solid (43.2 mg, 52%), mp: 105ꢀ106 °C. 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 4.5 Hz,
1 H), 7.83 (d, J = 8.4 Hz, 2 H), 7.77 (td, J = 7.8, 1.6 Hz, 1 H), 7.63 – 7.60 (m, 3 H), 7.24 (dd, J =
6.8, 5.5 Hz, 1 H), 1.59 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.6, 178.8, 149.5, 136.7, 133.4
(d, J = 32.5 Hz), 133.3 (d, J = 1.2 Hz), 129.2, 125.1 (q, J = 3.8 Hz), 124.7, 123.6 (d, J = 271 Hz),
122.7, 114.4, 88.0, 23.3. IR (KBr): 2982, 2934, 1699, 1608, 1476, 1388, 1324, 1172, 1131, 1066,
906, 850, 796, 763, 612 cmꢀ1. HRMSꢀESI (m/z): calcd for C18H15F3NO2 [M + H]+: 334.1049;
found 334.1051.
2,2-Dimethyl-5-(4-nitrophenyl)-4-(pyridin-2-yl)furan-3(2H)-one (3ae). Brown solid (62.1 mg,
80%), mp: 117ꢀ119 °C. 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 3.5 Hz, 1 H), 8.22 (d, J = 8.7
Hz, 2 H), 7.91 (d, J = 8.7 Hz, 2 H), 7.79 (t, J = 7.7 Hz, 1 H), 7.66 (d, J = 7.8 Hz, 1 H), 7.27 – 7.25
(m, 1 H), 1.60 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.5, 177.8, 149.4(9), 149.4(5), 149.1,
136.7, 135.89, 130.0, 124.6, 123.2, 123.0, 115.2, 88.3, 23.3. IR (KBr): 2981, 2932, 2216, 1699,
1591, 1523, 1350, 1268, 1172, 1063, 905, 855, 795, 698, 609 cmꢀ1. HRMSꢀESI (m/z): calcd for
C17H15N2O4 [M + H]+: 311.1026; found 311.1027.
2,2-Dimethyl-5-(4-(methylsulfonyl)phenyl)-4-(pyridin-2-yl)furan-3(2H)-one (3af).17 Yellow
solid (74.5 mg, 87%), mp: 138–139 °C. 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 4.2 Hz, 1 H),
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7.98 – 7.90 (m, 4 H), 7.82 – 7.74 (m, 1 H), 7.65 (d, J = 7.8 Hz, 1 H), 7.28 – 7.21 (m, 1 H), 3.07 (d,
J = 1.1 Hz, 3 H), 1.60 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.5, 178.1, 149.4, 149.2, 143.0,
136.7, 135.0, 129.7, 127.1, 124.6, 122.9, 114.9, 88.1, 44.3, 23.2. IR (KBr): 2981, 2929, 1697,
1620, 1385, 1319, 1151, 1063, 961, 770, 554 cmꢀ1. MS (EI) m/z: 343, 342(100), 314, 263, 194,
178, 151, 121, 89, 76.
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5-(4-Fluorophenyl)-2,2-dimethyl-4-(pyridin-2-yl)furan-3(2H)-one (3ag). Light yellow solid
(45.9 mg, 65%), mp: 94–95 °C. 1H NMR (400 MHz, CDCl3) δ 8.58 – 8.57 (m, 1 H), 7.79 – 7.71
(m, 3 H), 7.58 (d, J = 7.9 Hz, 1 H), 7.26 – 7.21 (m, 1 H), 7.08 – 7.02 (m, 2 H), 1.58 (s, 6 H). 13C
NMR (100 MHz, CDCl3) δ 204.5, 179.4, 165.0 (d, J = 254 Hz), 150.0, 149.4, 136.8, 131.3 (d, J =
9.0 Hz), 126.0 (d, J = 3.2 Hz), 125.0, 122.5, 115.5 (d, J = 22.0 Hz), 113.0, 87.8, 23.3. IR (KBr):
2981, 2930, 1695, 1608, 1509, 1474, 1412, 1386, 1260, 1234, 1155, 1063, 906, 845, 747, 609 cmꢀ1.
HRMSꢀESI (m/z): calcd for C17H15FNO2 [M + H]+: 284.1081; found 284.1084.
5-(4-Chlorophenyl)-2,2-dimethyl-4-(pyridin-2-yl)furan-3(2H)-one (3ah). Light yellow solid
(54.4 mg, 73%), mp: 137–138 °C. 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 4.5 Hz, 1 H), 7.76
(td, J = 7.7, 1.5 Hz, 1 H), 7.66 (d, J = 8.7 Hz, 2 H), 7.57 (d, J = 7.8 Hz, 1 H), 7.34 (d, J = 8.7 Hz, 2
H), 7.23 (dd, J = 6.9, 5.5 Hz, 1 H), 1.58 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.5, 179.3,
149.9, 149.5, 138.4, 136.7, 130.2, 128.5, 128.3, 124.9, 122.6, 113.5, 87.8, 23.3. IR (KBr): 2980,
2931, 1696, 1614, 1472, 1384, 1234, 1175, 1092, 1063, 906, 838, 794, 744, 609 cmꢀ1. HRMSꢀESI
(m/z): calcd for C17H15ClNO2 [M + H]+: 300.0786; found 300.0787.
5-(4-Bromophenyl)-2,2-dimethyl-4-(pyridin-2-yl)furan-3(2H)-one (3ai). Light yellow solid
(48.9 mg, 57%), mp: 130–131 °C. 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 4.3 Hz, 1 H), 7.75 (t,
J = 7.7 Hz, 1 H), 7.59 – 7.56 (m, 3 H), 7.50 (d, J = 8.4 Hz, 2 H), 7.26 – 7.18 (m, 1 H), 1.57 (s, 6
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H). 13C NMR (100 MHz, CDCl3) δ 204.6, 179.3, 149.9, 149.5, 136.6, 131.5, 130.3, 128.7, 126.9,
124.8, 122.6, 113.6, 87.8, 23.3. IR (KBr): 2979, 2930, 1695, 1613, 1491, 1382, 1256, 1174, 1064,
1011, 905, 793, 609 cmꢀ1. HRMSꢀESI (m/z): calcd for C17H15BrNO2 [M + H]+: 344.0281; found
344.0278.
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5-(4-Iodophenyl)-2,2-dimethyl-4-(pyridin-2-yl)furan-3(2H)-one (3aj). Light yellow solid (52.8
mg, 54%), mp: 125–126 °C. 1H NMR (400 MHz, CDCl3) δ 8.56 (d, J = 4.2 Hz, 1 H), 7.74 (m, 3
H), 7.56 (d, J = 7.9 Hz, 1 H), 7.42 (d, J = 8.3 Hz, 2 H), 7.26 – 7.20 (m, 1 H), 1.57 (s, 6 H). 13C
NMR (100 MHz, CDCl3) δ 204.6, 179.5, 149.9, 149.5, 137.5, 136.6, 130.2, 129.3, 124.8, 122.6,
113.7, 99.4, 87.8, 23.3. IR (KBr): 2977, 2928, 1694, 1610, 1470, 1400, 1282, 1173, 1062, 1007,
905, 764, 609 cmꢀ1. HRMSꢀESI (m/z): calcd for C17H15INO2 [M + H]+: 392.0142; found 392.0145.
2,2-Dimethyl-5-phenyl-4-(pyridin-2-yl)furan-3(2H)-one (3ak). 10 Yellow oil (35.0 mg, 53%).
1H NMR (400 MHz, CDCl3) δ 8.59 (d, J = 3.6 Hz, 1 H), 7.74 (t, J = 7.4 Hz, 1 H), 7.68 (d, J = 7.4
Hz, 2 H), 7.53 (d, J = 7.8 Hz, 1 H), 7.48 (t, J = 7.4 Hz, 1 H), 7.36 (t, J = 7.6 Hz, 2 H), 7.24 – 7.19
(m, 1 H), 1.58 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.7, 180.5, 150.3, 149.6, 136.5, 132.1,
129.8, 128.8, 128.2, 124.9, 122.4, 113.4, 87.7, 23.3. MS (EI) m/z: 265 [M+], 264(100), 222, 179,
151, 105, 77, 43.
5-(4-Methoxyphenyl)-2,2-dimethyl-4-(pyridin-2-yl)furan-3(2H)-one (3al). Brown oil (22.2 mg,
30%). 1H NMR (400 MHz, CDCl3) δ 8.60 (d, J = 4.1 Hz, 1 H), 7.74 (t, J = 7.6 Hz, 1 H), 7.68 (d, J
= 8.7 Hz, 2 H), 7.53 (d, J = 7.8 Hz, 1 H), 7.24 – 7.19 (m, 1 H), 6.85 (d, J = 8.7 Hz, 2 H), 3.83 (s, 3
H), 1.57 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.4, 180.1, 162.8, 150.7, 149.5, 136.5, 125.1,
122.2, 122.1, 113.7, 112.1, 87.4, 55.4, 23.4. IR (KBr): 2978, 2930, 1691, 1606, 1512, 1473, 1387,
1261, 1182, 1063, 906, 840, 763, 591 cmꢀ1. HRMSꢀESI (m/z): calcd for C18H18NO3 [M + H]+:
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5-(3-Acetylphenyl)-2,2-dimethyl-4-(pyridin-2-yl)furan-3(2H)-one (3am). Brown oil (42.9 mg,
56%). 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 4.3 Hz, 1 H), 8.36 (s, 1 H), 8.08 (d, J = 7.8 Hz, 1
H), 7.91 (d, J = 7.8 Hz, 1 H), 7.79 (t, J = 7.7 Hz, 1 H), 7.63 (d, J = 7.8 Hz, 1 H), 7.48 (t, J = 7.8
Hz, 1 H), 7.25 – 7.24 (m, 1 H), 2.51 (s, 3 H), 1.61 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.6,
197.0, 179.5, 149.8, 149.3, 137.0, 136.8, 133.1, 131.4, 130.4, 129.1, 128.6, 124.9, 122.7, 113.8,
88.0, 26.5, 23.3. IR (KBr): 2980, 2931, 1691, 1614, 1471, 1427, 1384, 1252, 1172, 1063, 907, 794,
592 cmꢀ1. HRMSꢀESI (m/z): calcd for C19H17NNaO3 [M + Na]+: 330.1101; found 330.1095.
3-(5,5-Dimethyl-4-oxo-3-(pyridin-2-yl)-4,5-dihydrofuran-2-yl)benzonitrile (3an). Brown solid
(44.0 mg, 61%), mp: 81–82 °C. 1H NMR (400 MHz, CDCl3) δ 8.56 (d, J = 4.5 Hz, 1 H), 8.11 (s, 1
H), 7.99 (d, J = 8.0 Hz, 1 H), 7.83 – 7.76 (m, 2 H), 7.68 (d, J = 7.9 Hz, 1 H), 7.52 (t, J = 7.9 Hz, 1
H), 7.28 – 7.26 (m, 1 H), 1.61 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.5, 177.8, 149.4, 149.1,
136.8, 134.9, 132.9, 132.5, 131.4, 129.0, 124.6, 123.0, 117.9, 114.3, 112.7, 88.1, 23.3. IR (KBr):
2981, 2931, 2232, 1700, 1620, 1472, 1386, 1291, 1159, 1064, 910, 796, 749 cmꢀ1. HRMSꢀEI (m/z):
calcd for C18H15N2O2 [M + H]+: 291.1128; found 291.1124.
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5-(3-Fluorophenyl)-2,2-dimethyl-4-(pyridin-2-yl)furan-3(2H)-one (3ao). Light yellow solid
(38.7 mg, 55%), mp: 76–77 °C. 1H NMR (400 MHz, CDCl3) δ 8.59 (d, J = 2.0 Hz, 1 H), 7.76 (t, J
= 7.7 Hz, 1 H), 7.56 (d, J = 7.7 Hz, 1 H ), 7.47 (t, J = 10.0 Hz, 2 H), 7.35 – 7.30 (m, 7.9 Hz, 1 H),
7.26 – 7.21 (m, 1 H), 7.20 – 7.16 (m, 1 H), 1.58 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.7,
178.8, 162.2 (d, J = 246.6 Hz), 149.8, 149.6, 136.6, 131.8 (d, J = 8.1 Hz), 129.8 (d, J = 8.0 Hz),
124.9, 124.7 (d, J = 3.1 Hz), 122.6, 119.0 (d, J = 21.2 Hz), 115.8 (d, J = 23.8 Hz), 114.0, 87.8,
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23.2. IR (KBr): 2980, 2931, 1697, 1583, 1471, 1386, 1284, 1219, 1159, 1063, 963, 911, 786, 705,
615 cmꢀ1. HRMSꢀESI (m/z): calcd for C17H15FNO2 [M + H]+: 284.1081; found 284.1087.
5-(Benzo[d][1,3]dioxol-5-yl)-2,2-dimethyl-4-(pyridin-2-yl)furan-3(2H)-one (3aq). Yellow oil
(30.7 mg, 40%). 1H NMR (400 MHz, CDCl3) δ 8.61 (d, J = 4.4 Hz, 1 H), 7.76 (t, J = 7.7 Hz, 1 H),
7.54 (d, J = 7.9 Hz, 1 H), 7.32 (dd, J = 8.3, 1.5 Hz, 1 H), 7.23 (dd, J = 6.8, 5.5 Hz, 1 H), 7.16 (d, J
= 1.4 Hz, 1 H), 6.78 (d, J = 8.3 Hz, 1 H), 6.00 (s, 2 H), 1.56 (s, 6 H). 13C NMR (100 MHz, CDCl3)
δ 204.4, 179.7, 151.1, 150.3, 149.4, 147.6, 136.8, 125.2, 124.6, 123.5, 122.4, 112.3, 108.8, 108.2,
101.7, 87.5, 23.3. IR (KBr): 3460, 2979, 2929, 1692, 1597, 1448, 1386, 1240, 1155, 1038, 909,
788, 744, 615 cmꢀ1. HRMS EI (m/z): calcd for C18H16NO4 [M + H]+: 310.1074; found 310.1069.
2,2-Dimethyl-4-(pyridin-2-yl)-5-(pyridin-3-yl)furan-3(2H)-one (3ar). Brown solid (38.5 mg,
58%), mp: 140–141 °C. 1H NMR (400 MHz, CDCl3) δ 8.92 (d, J = 1.5 Hz, 1 H), 8.69 (dd, J = 4.8,
1.4 Hz, 1 H), 8.54 (d, J = 4.7 Hz, 1 H), 8.07 (dt, J = 8.0, 1.9 Hz, 1 H), 7.77 (td, J = 7.8, 1.8 Hz, 1
H), 7.66 (d, J = 7.9 Hz, 1 H), 7.34 (dd, J = 8.0, 4.9 Hz, 1 H), 7.23 (ddd, J = 7.4, 4.9, 1.0 Hz, 1 H),
1.59 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.4, 178.2, 152.3, 149.8, 149.5, 149.4, 136.7,
136.0, 127.0, 124.5, 122.9, 122.8, 114.3, 88.0, 23.3. IR (KBr): 2980, 2929, 1697, 1614, 1469,
1386, 1262, 1175, 1064, 903, 746, 707, 612 cmꢀ1. HRMSꢀESI (m/z): calcd for C16H15N2O2 [M +
H]+: 267.1128; found 267.1126.
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2,2-Dimethyl-4-(pyridin-2-yl)-5-(1H-pyrrol-2-yl)furan-3(2H)-one(3as). Brown solid (14.7 mg,
23%), mp: 91–92 °C. 1H NMR (400 MHz, CDCl3) δ 15.11 (s, 1 H), 8.74 (d, J = 8.2 Hz, 1 H), 8.60
(d, J = 3.4 Hz, 1 H), 7.80 (t, J = 7.8 Hz, 1 H), 7.25 – 7.19 (m, 3 H), 6.45 – 6.44 (m, 1 H), 1.53 (s, 6
H). 13C NMR (100 MHz, CDCl3) δ 204.1, 173.6, 150.9, 146.4, 137.4, 125.0, 124.5, 122.7, 121.1,
116.2, 111.5, 105.5, 86.2, 23.7. IR (KBr): 2980, 2927, 1678, 1576, 1512, 1428, 1275, 1209, 1136,
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1069, 748, 616 cmꢀ1. HRMSꢀESI (m/z): calcd for C15H15N2O2 [M + H]+: 255.1128; found
255.1127.
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2,2,5-Trimethyl-4-(pyridin-2-yl)furan-3(2H)-one (3at). 10 Yellow oil (36.8 mg, 73%). 1H NMR
(400 MHz, CDCl3) δ 8.58 (d, J = 3.1 Hz, 1 H), 8.02 (d, J = 8.0 Hz, 1 H), 7.69 (t, J = 7.7 Hz, 1 H),
7.19 – 7.06 (m, 1 H), 2.71 (s, 3 H), 1.46 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.2, 188.2,
150.7, 148.8, 136.2, 122.4, 121.3, 112.2, 87.8, 23.1, 17.8. MS (EI) m/z: 203 [M+] (100), 188, 160,
117, 90, 78, 63, 43.
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5-Butyl-2,2-dimethyl-4-(pyridin-2-yl)furan-3(2H)-one (3au).10 Yellow oil (41.0 mg, 67%). H
NMR (400 MHz, CDCl3) δ 8.57 (d, J = 4.4 Hz, 1 H), 8.00 (d, J = 8.0 Hz, 1 H), 7.69 (td, J = 7.9,
1.6 Hz, 1 H), 7.12 (dd, J = 6.9, 5.3 Hz, 1 H), 3.21 – 3.14 (t, J = 7.6 Hz, 2 H), 1.75 – 1.67 (m, 2 H),
1.47 – 1.37 (m, 8 H), 0.93 (t, J = 7.3 Hz, 3 H). 13C NMR (101 MHz, CDCl3) δ 204.5, 191.8, 150.7,
148.8, 136.2, 122.5, 121.3, 111.7, 87.6, 30.4, 28.4, 23.1, 22.4, 13.7. IR (KBr): 2960, 2931, 2870,
1693, 1601, 1480, 1395, 1280, 1162, 1110, 1008, 798, 745, 591 cmꢀ1. MS (EI) m/z: 245 [M+], 230,
216(100), 202, 188, 160, 146, 130, 117, 89, 78.
5,5'-(1,4-Phenylene)bis(2,2-dimethyl-4-(pyridin-2-yl)furan-3(2H)-one) (3ac'). Light yellow
solid (82.3 mg, 73%), mp: 183–184 °C. 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 4.1 Hz, 2 H),
7.74 (td, J = 7.8, 1.7 Hz, 2 H), 7.68 (s, 4 H), 7.56 (d, J = 7.9 Hz, 2 H), 7.25 – 7.19 (m, 2 H), 1.57
(s, 12 H). 13C NMR (100 MHz, CDCl3) δ 204.6, 179.2, 149.8, 149.5, 136.6, 133.0, 128.6, 124.8,
122.6, 114.3, 87.9, 23.3. IR(KBr): 2980, 2930, 1695, 1607, 1473, 1383, 1253, 1177, 1063, 905,
792, 741, 610 cmꢀ1. HRMS EI (m/z): calcd for C28H25N2O4 [M + H]+: 453.1809; found 453.1810.
5,5'-(1,3-Phenylene)bis(2,2-dimethyl-4-(pyridin-2-yl)furan-3(2H)-one) (3an'). Brown oil (89.1
mg, 79%). 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 4.4 Hz, 2 H), 8.23 (s, 1 H), 7.81 (dd, J = 7.9,
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1.6 Hz, 2 H), 7.73 (td, J = 7.7, 1.7 Hz, 2 H), 7.54 (d, J = 7.9 Hz, 2 H), 7.34 (t, J = 7.9 Hz, 1 H),
7.23 – 7.18 (m, 2 H), 1.55 (s, 12 H). 13C NMR (100 MHz, CDCl3) δ 204.6, 179.1, 149.8, 149.4,
136.5, 132.2, 130.1, 129.2, 128.0, 124.8, 122.5, 113.8, 87.7, 23.3. IR (KBr): 2979, 2931, 1696,
1618, 1473, 1380, 1259, 1161, 1064, 1092, 907, 745, 691, 611 cmꢀ1. HRMSꢀESI (m/z): calcd for
C28H25N2O4 [M + H]+: 453.1809; found 453.1810.
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5-(4-Acetylphenyl)-2-ethyl-2-methyl-4-(pyridin-2-yl)furan-3(2H)-one (3ba). Brown oil (63.3
mg, 79%). 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 4.4 Hz, 1 H), 7.94 (d, J = 8.3 Hz, 2 H), 7.81
(d, J = 8.3 Hz, 2 H), 7.75 (t, J = 7.7 Hz, 1 H), 7.58 (d, J = 7.8 Hz, 1 H), 7.25 – 7.21 (m, 1 H), 2.62
(s, 3 H), 2.04 – 1.93 (m, 2 H), 1.56 (s, 3 H), 0.98 (t, J = 7.4 Hz, 3 H). 13C NMR (100 MHz, CDCl3)
δ 204.7, 197.3, 179.8, 149.6, 149.5, 139.2, 136.5, 133.9, 129.0, 127.9, 124.7, 122.6, 115.9, 90.7,
30.3, 26.7, 21.6, 7.5. IR (KBr): 2974, 2935, 1689, 1600, 1387, 1266, 1175, 1071, 847, 746, 603
cmꢀ1. HRMSꢀESI (m/z): calcd for C20H20NO3 [M + H]+: 322.1438; found 322.1436.
5-(4-Acetylphenyl)-2,2-diethyl-4-(pyridin-2-yl)furan-3(2H)-one (3ca). Brown oil (71.9 mg,
86%). 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 4.8 Hz, 1 H), 7.95 (d, J = 8.3 Hz, 2H), 7.84 (d, J
= 8.3 Hz, 2H), 7.75 (td, J = 7.7, 1.3 Hz, 1 H), 7.58 (d, J = 7.5 Hz, 1 H), 7.22 (dd, J = 7.4, 5.0 Hz, 1
H), 2.61 (s, 3 H), 1.99 (q, J = 7.4 Hz, 4 H), 0.95 (t, J = 7.4 Hz, 6 H). 13C NMR (100 MHz, CDCl3)
δ 204.6, 197.2, 180.6, 149.5, 149.5, 139.3, 136.5, 133.9, 128.9, 127.9, 124.6, 122.6, 117.4, 93.7,
29.2, 26.7, 7.3. IR (KBr): 2972, 2940, 1689, 1600, 1505, 1407, 1266, 1171, 1072, 994, 942, 848,
747, 601 cmꢀ1. HRMSꢀESI (m/z): calcd for C21H22NO3 [M + H]+: 336.1594; found 336.1595.
5-(4-Acetylphenyl)-2-isobutyl-2-methyl-4-(pyridin-2-yl)furan-3(2H)-one (3da). Brown oil
(73.1 mg, 84%). 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 4.7 Hz, 1 H), 7.94 (d, J = 8.2 Hz, 2 H),
7.83 – 7.73 (m, 3 H), 7.59 (d, J = 7.9 Hz, 1 H), 7.27 – 7.19 (m, 1 H), 2.61 – 2.60 (m, 3 H), 1.96 –
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1.80 (m, 3 H), 1.55 (s, 3 H), 0.98 (dd, J = 8.6, 6.3 Hz, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.9,
197.3, 179.4, 149.7, 149.5, 139.2, 136.6, 134.0, 129.0, 127.9, 124.7, 122.6, 115.4, 90.7, 45.4, 26.7,
24.2, 23.5, 22.3. IR (KBr): 2957, 2871, 1690, 1600, 1473, 1386, 1266, 1172, 1041, 845, 744, 605
cmꢀ1. HRMSꢀESI (m/z): calcd for C22H24NO3 [M + H]+: 350.1751; found 350.1748.
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5-(4-Acetylphenyl)-2-hexyl-2-methyl-4-(pyridin-2-yl)furan-3(2H)-one (3ea). Brown oil (78.1
mg, 83%). 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 4.3 Hz, 1 H), 7.94 (d, J = 8.2 Hz, 2 H), 7.81
(d, J = 8.2 Hz, 2 H), 7.76 (t, J = 7.7 Hz, 1 H), 7.59 (d, J = 7.8 Hz, 1 H), 7.26 – 7.20 (m, 1 H), 2.61
(s, 3 H), 1.98 – 1.89 (m, 2 H), 1.56 (s, 3 H), 1.37 – 1.20 (d, J = 16.8 Hz, 8 H), 0.85 (t, J = 6.3 Hz,
3 H). 13C NMR (100 MHz, CDCl3) δ 204.7, 197.3, 179.7, 149.6, 149.5, 139.3, 136.6, 134.0, 129.0,
127.9, 124.7, 122.6, 115.7, 90.5, 37.2, 31.5, 29.2, 26.7, 23.0, 22.5, 22.0, 13.9. IR(KBr): 2958,
2856, 1690, 1600, 1408, 1265, 1174, 1042, 846, 747, 607 cmꢀ1. HRMSꢀESI (m/z): calcd for
C24H28NO3 [M + H]+: 378.2064; found 378.2060.
5-(4-Acetylphenyl)-2,2-diisobutyl-4-(pyridin-2-yl)furan-3(2H)-one (3fa). Brown oil (56.9 mg,
58%). 1H NMR (400 MHz, CDCl3) δ 8.57 (s, 1 H), 7.94 (d, J = 8.4 Hz, 2 H), 7.84 – 7.75 (m, 3 H),
7.60 (d, J = 7.4 Hz, 1 H), 7.21 – 7.27 (m, 1 H), 2.61 (s, 3 H), 1.97 – 1.91 (m, 2 H), 1.86 – 1.79 (m,
4 H), 0.94 (dd, J = 7.6, 6.4 Hz, 12 H). 13C NMR (100 MHz, CDCl3) δ 204.9, 197.3, 179.9, 165.4,
149.7, 149.5, 139.3, 136.7, 134.0, 129.0, 128.0, 124.8, 122.7, 93.7, 45.5, 26.7, 24.3, 24.0. IR(KBr):
2958, 2871, 1690, 1600, 1472, 1385, 1265, 1168, 1091, 747, 602 cmꢀ1. HRMSꢀESI (m/z): calcd
for C25H30NO3 [M + H]+: 392.2220; found 392.2219.
5-(4-Acetylphenyl)-2-methyl-2-phenyl-4-(pyridin-2-yl)furan-3(2H)-one (3ga). Brown solid
(64.5 mg, 70%), mp: 133–134 °C. 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 4.3 Hz, 1 H), 7.97 (d,
J = 8.4 Hz, 2H), 7.90 (d, J = 8.5 Hz, 2H), 7.75 (t, J = 7.7 Hz, 1 H), 7.65 – 7.61 (m, 2 H), 7.58 (d, J
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= 7.8 Hz, 1 H), 7.41 – 7.37 (m, 2 H), 7.35 – 7.30 (m, 1 H), 7.25 – 7.22 (m, 1 H), 2.63 (s, 3 H),
1.96 (s, 3 H). 13C NMR (100 MHz, CDCl3) δ 202.2, 197.3, 179.6, 149.4, 149.3, 139.5, 138.0,
136.7, 133.7, 129.2, 128.7, 128.3, 128.0, 124.9, 124.6, 122.8, 114.6, 89.5, 26.7, 24.9. IR (KBr):
3059, 2929, 1687, 1600, 1382, 1265, 1157, 1072, 930, 748, 699, 604 cmꢀ1. HRMSꢀESI (m/z):
calcd for C24H20NO3 [M + H]+: 370.1438; found 370.1430.
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2-(4-Acetylphenyl)-3-(pyridin-2-yl)-1-oxaspiro[4.5]dec-2-en-4-one (3ha). Brown oil (78.1 mg,
90%). 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 4.3 Hz, 1 H), 7.94 (d, J = 8.6 Hz, 2H), 7.81 (d, J
= 8.6 Hz, 2H), 7.75 (td, J = 7.8, 1.6 Hz, 1 H), 7.58 (d, J = 7.8 Hz, 1 H), 7.22 (dd, J = 6.8, 5.4 Hz, 1
H), 2.61 (s, 3 H), 1.95 – 1.70 (m, 10 H). 13C NMR (100 MHz, CDCl3) δ 204.4, 197.2, 179.0, 149.7,
149.4, 139.1, 136.4, 134.1, 129.0, 127.8, 124.7, 122.5, 115.1, 31.9, 26.6, 24.4, 21.7. IR (KBr):
2938, 2859, 1684, 1600, 1386, 1266, 1224, 1123, 1059, 954, 919, 846, 747, 605 cmꢀ1. HRMSꢀESI
(m/z): calcd for C22H22NO3 [M + H]+: 348.1594; found 348.1590.
2-(4-Acetylphenyl)-3-(pyridin-2-yl)-1-oxaspiro[4.4]non-2-en-4-one(3ia). Brown solid (62.4 mg,
75%), mp: 89–90 °C. 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 4.3 Hz, 1 H), 7.93 (d, J = 8.2 Hz,
2 H), 7.81 – 7.72 (m, 3 H), 7.60 (d, J = 7.8 Hz, 1 H), 7.25 – 7.21 (m, 1 H), 2.61 (s, 3 H), 2.25 –
2.14 (m, 2 H), 2.13 – 1.98 (m, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.0, 197.3, 179.4, 149.8,
149.6, 139.2, 136.6, 134.1, 129.1, 127.9, 124.8, 122.6, 115.9, 98.0, 37.6, 26.7, 25.7. IR (KBr):
2965, 2927, 1688, 1599, 1386, 1264, 1171, 748, 605 cmꢀ1. HRMSꢀESI (m/z): calcd for C21H20NO3
[M + H]+: 334.1438; found 334.1434.
5-(4-Acetylphenyl)-2,2-dimethyl-4-(pyridin-3-yl)furan-3(2H)-one (3ja). Brown oil (26.8 mg,
35%). 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 28.5 Hz, 2H), 7.96 (d, J = 7.9 Hz, 2H), 7.72 (d, J
= 6.8 Hz, 3H), 7.36 (s, 1H), 2.62 (s, 3H), 1.60 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 204.7,
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197.0, 177.7, 174.5, 149.6, 148.3, 139.4, 137.1, 133.5, 128.5, 128.5, 123.7, 111.4, 26.7, 23.3. IR
(KBr): 2926, 2853, 1690, 1614, 1387, 1266, 1167, 1062, 740, 604 cmꢀ1. HRMSꢀESI (m/z): calcd
for C19H18NO3 [M + H]+: 308.1281; found 308.1281.
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5-(4-Acetylphenyl)-2,2-dimethyl-4-(pyridin-4-yl)furan-3(2H)-one (3ka). Brown oil (46.8 mg,
62%). 1H NMR (400 MHz, CDCl3) δ 8.59 (s, 2H), 7.98 (d, J = 8.0 Hz, 2H), 7.73 (d, J = 8.0 Hz,
2H), 7.28 (s, 2H), 2.64 (s, 3H), 1.59 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 203.9, 197.0, 178.6,
149.7, 139.6, 138.2, 133.3, 128.7, 128.4, 123.8, 112.0, 88.4, 26.7, 23.2. IR (KBr): 2981, 2928,
2854, 1692, 1598, 1390, 1266, 1168, 1054, 831, 605 cmꢀ1. HRMSꢀESI (m/z): calcd for C19H18NO3
[M + H]+: 308.1281; found 308.1282.
5-(4-Acetylphenyl)-2,2-dimethyl-4-(quinolin-2-yl)furan-3(2H)-one (3la). Yellow solid (67.5
mg, 76%), mp: 116ꢀ117 oC. 1H NMR (400 MHz, CDCl3) δ 8.25 – 8.19 (m, J = 8.5 Hz, 1H), 7.95 –
7.86 (m, 5H), 7.84 (d, J = 8.1 Hz, 1H), 7.74 (d, J = 8.5 Hz, 1H), 7.67 (t, J = 7.6 Hz, 1H), 7.54 (t, J
= 7.4 Hz, 1H), 2.60 (s, 3H), 1.64 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 204.8, 197.3, 179.8,
150.3, 147.9, 139.3, 136.5, 134.0, 129.6, 129.3, 129.0, 127.8, 127.5, 127.3, 126.7, 122.4, 114.8,
88.1, 26.7, 23.3. IR (KBr): 3061, 2980, 2928, 1690, 1595, 1507, 1386, 1265, 1176, 1058, 834, 754,
605 cmꢀ1. HRMSꢀESI (m/z): calcd for C23H20NO3 [M + H]+: 358.1438; found 358.1446.
Methyl 4-(2-(4-acetylphenyl)-5,5-dimethyl-4-oxo-4,5-dihydrofuran-3-yl)benzoate (3ma).
Yellow solid (61.6 mg, 68%), mp: 99–100 °C. 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.2 Hz,
2 H), 7.93 (d, J = 8.4 Hz, 2 H), 7.71 (d, J = 8.4 Hz, 2 H), 7.39 (d, J = 8.3 Hz, 2 H), 3.93 (s, 3 H),
2.61 (s, 3 H), 1.59 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.6, 197.1, 177.5, 166.8, 139.3,
134.4, 133.7, 129.9, 129.3, 129.3, 128.7, 128.3, 113.9, 87.8, 52.1, 26.7, 23.3. IR (KBr): 2981,
2953, 1723, 1690, 1596, 1386, 1274, 1189, 1111, 1051, 961, 845, 787, 603 cmꢀ1. HRMSꢀESI (m/z):
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calcd for C22H20NaO5 [M + Na]+: 387.1203; found 387.1198.
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5-(4-Acetylphenyl)-2,2-dimethyl-4-(4-nitrophenyl)furan-3(2H)-one (3na). Brown solid (70.2
mg, 80%), mp: 117–119 °C. 1H NMR (400 MHz, CDCl3) δ 8.22 – 8.18 (m, 2 H), 7.98 (d, J = 8.4
Hz, 2 H), 7.72 (d, J = 8.5 Hz, 2 H), 7.51 (d, J = 8.8 Hz, 2 H), 2.63 (s, 3 H), 1.61 (s, 6 H). 13C NMR
(100 MHz, CDCl3) δ 204.0, 196.9, 178.4, 147.0, 139.7, 136.6, 133.3, 130.0, 128.7, 128.5, 123.8,
112.8, 88.4, 26.7, 23.3. IR (KBr): 2981, 2931, 1690, 1601, 1516, 1386, 1344, 1267, 1168, 1051,
852, 734, 603 cmꢀ1. HRMSꢀESI (m/z): calcd for C20H17NNaO5 [M + Na]+: 374.0999; found
374.0992.
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5-(4-Acetylphenyl)-2,2-dimethyl-4-(3-nitrophenyl)furan-3(2H)-one (3oa). Brown oil (65.6 mg,
75%). 1H NMR (400 MHz, CDCl3) δ 8.21 – 8.16 (m, 2 H), 7.96 (d, J = 8.6 Hz, 2H), 7.71 (d, J =
8.6 Hz, 2H), 7.65 (d, J = 7.8 Hz, 1 H), 7.55 (t, J = 7.8 Hz, 1 H), 2.62 (s, 3 H), 1.61 (s, 6 H). 13C
NMR (100 MHz, CDCl3) δ 204.3, 197.0, 177.9, 148.5, 139.6, 135.4, 133.3, 131.5, 129.7, 128.6,
128.5, 124.3, 122.6, 112.7, 88.2, 26.7, 23.3. IR (KBr): 3084, 2982, 2932, 1689, 1598, 1530, 1386,
1348, 1266, 1169, 1055, 843, 729, 607 cmꢀ1. HRMSꢀESI (m/z): calcd for C20H17NNaO5 [M + Na]+:
374.0999; found 374.1000.
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2,2-Dimethyl-4-(pyridin-2-yl)furan-3(2H)-one(3av). Brown oil (40.3 mg, 85%). H NMR (400
MHz, CDCl3) δ 9.02 (s, 1 H), 8.52 (d, J = 4.2 Hz, 1 H), 8.07 (d, J = 7.9 Hz, 1 H), 7.69 (td, J = 7.8,
1.5 Hz, 1 H), 7.19 – 7.13 (m, 1 H), 1.49 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 203.9, 176.1,
149.4, 149.3, 136.6, 122.2, 120.4, 116.7, 90.6, 23.0. IR (KBr): 3460, 2981, 2930, 1697, 1610,
1477, 1381, 1192, 1068, 885, 794, 745, 618, 509 cmꢀ1. HRMSꢀESI (m/z): calcd for C11H12NO2 [M
+ H]+, 190.0863; found 190.0862.
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2,2-Diethyl-4-(pyridin-2-yl)furan-3(2H)-one (3cv). Yellow oil (42.0 mg, 77%). H NMR (400
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MHz, CDCl3) δ 9.13 (s, 1 H), 8.52 (d, J = 4.4 Hz, 1 H), 8.10 (d, J = 7.9 Hz, 1 H), 7.68 (t, J = 7.7
Hz, 1 H), 7.19 – 7.11 (m, 1 H), 1.89 (q, J = 7.5 Hz, 4 H), 0.86 (t, J = 7.4 Hz, 6 H). 13C NMR (100
MHz, CDCl3) δ 203.72, 177.38, 149.2, 136.6, 122.1, 120.3, 119.6, 96.6, 28.8, 7.2. IR (KBr): 3060,
2979, 2934, 1764, 1692, 1610, 1472, 1375, 1243, 1186, 1055, 905, 793, 745, 619 cmꢀ1.
HRMSꢀESI (m/z): calcd for C13H16NO2 [M + H]+: 218.1176; found 218.1177.
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2-Isobutyl-2-methyl-4-(pyridin-2-yl)furan-3(2H)-one (3dv). Yellow oil (41.8 mg, 72%). H
NMR (400 MHz, CDCl3) δ 9.04 (s, 1 H), 8.52 (d, J = 4.4 Hz, 1 H), 8.09 (d, J = 7.9 Hz, 1 H), 7.68
(t, J = 7.7 Hz, 1 H), 7.19 – 7.10 (m, 1 H), 1.85 – 1.68 (m, 3 H), 1.45 (s, 3 H), 0.94 (d, J = 6.2 Hz, 3
H), 0.90 (d, J = 6.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3) δ 204.0, 176.4, 149.4, 149.3, 136.6,
122.2, 120.4, 117.7, 93.4, 45.1, 24.2, 24.0, 23.5, 22.3. IR (KBr): 3060, 2959, 2929, 1764, 1695,
1610, 1474, 1371, 1243, 1186, 1053, 791, 620 cmꢀ1. HRMSꢀESI (m/z): calcd for C14H18NO2 [M +
H]+: 232.1332; found 232.1336.
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2-Hexyl-2-methyl-4-(pyridin-2-yl)furan-3(2H)-one (3ev). Yellow oil (51.5 mg, 79%). H NMR
(400 MHz, CDCl3) δ 9.06 (s, 1 H), 8.52 (d, J = 4.2 Hz, 1 H), 8.09 (d, J = 7.9 Hz, 1 H), 7.69 (t, J =
7.7 Hz, 1 H), 7.19 – 7.11 (m, 1 H), 1.89 – 1.76 (m, 2 H), 1.45 (s, 3 H), 1.30 – 1.17 (m, 8 H), 0.85
(t, J = 6.3 Hz, 3 H). 13C NMR (100 MHz, CDCl3) δ 203.9, 176.6, 149.3, 149.2, 136.7, 122.2,
120.4, 117.8, 93.3, 36.7, 31.5, 29.2, 22.8, 22.5, 21.9, 14.0. IR (KBr): 3503, 2930, 2860, 1764,
1695, 1610, 1474, 1374, 1243, 1180, 1053, 793, 620 cmꢀ1. HRMSꢀESI (m/z): calcd for
C16H21NNaO2 [M + Na]+: 282.1464; found 282.1467.
2,2-Diisobutyl-4-(pyridin-2-yl)furan-3(2H)-one (3fv). Yellow oil (37.0 mg, 55%). 1H NMR (400
MHz, CDCl3) δ 9.09 (s, 1 H), 8.52 (d, J = 4.4 Hz, 1 H), 8.11 (d, J = 7.9 Hz, 1 H), 7.69 (t, J = 7.7
Hz, 1 H), 7.20 – 7.12 (m, 1 H), 1.86 – 1.80 (m, 2 H), 1.73 – 1.69 (m, 4 H), 0.91 (d, J = 5.9 Hz, 6
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H), 0.86 (d, J = 5.9 Hz, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.0, 176.9, 149.4, 149.3, 136.7,
122.2, 120.4, 119.4, 96.5, 45.3, 24.3, 23.9, 23.7. IR (KBr): 3060, 2957, 2873, 1694, 1611, 1472,
1361, 1244, 1183, 1095, 890, 790, 747, 620 cmꢀ1. HRMSꢀESI (m/z): calcd for C17H23NNaO2 [M +
Na]+, 296.1621; found 296.1624.
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2-Methyl-2-phenyl-4-(pyridin-2-yl)furan-3(2H)-one (3gv). Brown oil (52.5 mg, 83%). 1H NMR
(400 MHz, CDCl3) δ 9.22 (s, 1 H), 8.52 (d, J = 4.4 Hz, 1 H), 8.05 (d, J = 7.9 Hz, 1 H), 7.66 (t, J =
7.7 Hz, 1 H), 7.54 (d, J = 7.9 Hz, 2 H), 7.39 – 7.30 (m, 3 H), 7.18 – 7.11 (m, 1 H), 1.86 (s, 3 H).
13C NMR (100 MHz, CDCl3) δ 201.5, 176.5, 149.3, 149.1, 137.3, 136.6, 128.6, 128.3, 124.5,
122.3, 120.5, 117.0, 92.0, 24.5. IR (KBr): 3060, 2984, 2928, 2855, 1704, 1612, 1476, 1356, 1243,
1180, 1051, 793, 747, 698, 618 cmꢀ1. HRMSꢀESI (m/z): calcd for C16H13NNaO2 [M + Na]+:
274.0838; found 274.0842.
3-(Pyridin-2-yl)-1-oxaspiro[4.5]dec-2-en-4-one (3hv). Light yellow solid (43.9 mg, 76%), mp:
100–101 °C. 1H NMR (400 MHz, CDCl3) δ 9.04 (s, 1 H), 8.51 (d, J = 4.5 Hz, 1 H), 8.08 (d, J =
8.0 Hz, 1 H), 7.67 (t, J = 7.7 Hz, 1 H), 7.21 – 7.08 (m, 1 H), 1.83 – 1.74 (m, 5 H), 1.72 – 1.65 (m,
4 H), 1.44 – 1.35 (m, 1 H). 13C NMR (100 MHz, CDCl3) δ 203.7, 176.2, 149.5, 149.2, 136.6,
122.1, 120.5, 117.3, 92.6, 31.8, 24.4, 21.6. IR (KBr): 3060, 2991, 2935, 2858, 1764, 1691, 1610,
1475, 1376, 1243, 1055, 919, 790 cmꢀ1. HRMSꢀESI (m/z): calcd for C14H15NNaO2 [M + Na]+,
252.0995; found 252.0997.
2,2-Dimethyl-4-(4-nitrophenyl)furan-3(2H)-one (3nv). Yellow solid (23.5 mg, 41%), mp:
176–178 °C. 1H NMR (400 MHz, CDCl3) δ 8.64 (s, 1 H), 8.23 (d, J = 8.1 Hz, 2 H), 7.90 (d, J =
8.2 Hz, 2 H), 1.50 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 203.7, 173.5, 146.6, 136.0, 125.6,
124.0, 114.8, 90.2, 23.0. IR (KBr): 3358, 2991, 2922, 2851, 1763, 1680, 1601, 1510, 1379, 1243,
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1055, 850, 744, 745, 623, 504 cmꢀ1. HRMSꢀESI (m/z): calcd for C12H11NNaO4 [M + Na]+:
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(3qf).2e
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Brown solid (43.2 mg, 45%), mp: 190ꢀ191 °C. 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.2 Hz,
3 H), 7.90 (s, 1 H), 7.82 (d, J = 8.4 Hz, 2 H), 7.52 – 7.46 (m, 2 H), 3.08 (s, 3 H), 2.58 (s, 3 H),
1.60 (s, 6 H). 13C NMR (100 MHz, CDCl3) δ 204.9, 197.7, 175.8, 143.1, 137.7, 134.7, 133.9,
129.7, 129.2, 129.2, 128.0, 127.5, 114.6, 87.9, 44.2, 26.6, 23.2. MS (EI) m/z: 384[M+], 283, 199,
183 (100), 137, 121, 103, 76, 65.
Procedure for the preparation of 2-methyl-3-oxo-4-(pyridin-2-yl)butan-2-yl acetate (6): To a
stirred solution of 3ꢀhydroxyꢀ3ꢀmethylꢀ1ꢀ(pyridinꢀ2ꢀyl)butanꢀ2ꢀone (1a) (1 mmol), pyridine (1.4
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mmol), and 4ꢀ(N,Nꢀdimethylamino)pyridine (DMAP) (0.1 mmol) in dry CH2Cl2 (5 mL) at 0 C
was slowly added acetic anhydride (1.5 mmol). The mixture was warmed to room temperature.
After being stirred over night, the reaction was quenched with 2M aqueous HCl, and the product
was extracted with CH2Cl2. The combined organic extracts were washed with saturated aqueous
NaHCO3 and brine. Then the organic phase was dried over MgSO4, concentrated by rotary
evaporation and separated by column chromatography on silica gel using petroleum ether/ethyl
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acetate (2:1) as eluent to give the desired product 6 (143.7 mg, 65% yield) as a yellow oil. H
NMR (400 MHz, CDCl3) δ 8.51 (d, J = 4.3 Hz, 1 H), 7.66 (td, J = 7.7, 1.8 Hz, 1 H), 7.33 (d, J =
7.8 Hz, 1 H), 7.18 (ddd, J = 7.4, 5.0, 0.9 Hz, 1 H), 4.02 (s, 2 H), 2.11 (s, 3 H), 1.54 (s, 6 H). 13
C
NMR (100 MHz, CDCl3) δ 205.3, 170.6, 154.7, 148.8, 136.5, 124.7, 121.9, 83.8, 45.0, 23.4, 21.1.
IR (KBr): 2991, 2935, 2360, 1732, 1592, 1372, 1257, 1148, 914, 746 cmꢀ1. HRMSꢀESI (m/z):
calcd for C12H15NNaO3 [M + Na]+: 244.0944; found 244.0941.
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