Rhodium(III)-catalyzed oxidative olefination of picolinamides: Convenient synthesis of 3-alkenylpicolinamides

Article abstract of DOI:10.1002/adsc.201300895

A rhodium(III)-catalyzed selective olefination of picolinamide derivatives has been developed. The reaction shows high regioselectivity, low catalyst loading (0.5 mol%), high yield and good functional group tolerance, providing a convenient strategy for the synthesis of 3-alkenylpicolinamides.

Full text of DOI:10.1002/adsc.201300895

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DOI: 10.1002/adsc.201300895
Rhodium(III)-Catalyzed Oxidative Olefination of Picolinamides:
G
Convenient Synthesis of 3-Alkenylpicolinamides
Jun Zhou,a Bo Li,a Zhen-Chao Qian,a and Bing-Feng Shia,b,*
a
Department of Chemistry, Zhejiang University, Hangzhou 310027, Peopleꢀs Republic of China
Fax : (+86)-571-8795-1895, phone: (+86)-571-8795-1352; e-mail: bfshi@zju.edu.cn
State Key Laboratory of Bioorganic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese
b
Academy of Sciences, Shanghai 200032, Peopleꢀs Republic of China
Received: October 6, 2013; Revised: December 26, 2013; Published online: March 11, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300895.
Abstract: A rhodiumACTHNUTRGNE(NUG III)-catalyzed selective olefina- group tolerance, providing a convenient strategy for
tion of picolinamide derivatives has been developed. the synthesis of 3-alkenylpicolinamides.
The reaction shows high regioselectivity, low catalyst
À
loading (0.5 mol%), high yield and good functional Keywords: C H activation; oxidative olefination;
pyridines; rhodium
Introduction
groups under very similar conditions (Figure 1A).[8,9]
These works demonstrated the superior capability of
Pyridines are among the most prevalent scaffolds in RhACTHNUTRGNEUNG
(III) catalysts owing to their high efficiency.[9]
biologically active compounds such as pharmaceuti- However, despite the partial success of Rh
cals and agrochemicals, and also serve as building lyzed C H functionalization of arenes and electron-
(III)-cata-
À
blocks for natural product and pharmaceutical synthe- rich heterocycles, reports on Rh
G
sis.[1] Several processes for the synthesis of these privi- tive olefination of pyridines remain rare, partly due to
leged motifs have been established due to the contin- the poor electron density of the pyridyl ring and the
ued importance of the pyridine core in both biological strong coordination of the nitrogen atom (Fig-
and chemical fieds.[2] Among them, the transition ure 1B).[10–12] Li has reported the Rh
À
metal-catalyzed direct C H functionalization of pyri-
dines is a particularly attractive route to these struc-
tures.[3] Great successes have been made to the transi-
tion metal-catalyzed direct arylation and alkylation of
pyridines.[4] However, in sharp contrast to those ex-
tensive studies, the oxidative olefination of pyridines
has so far received much less attention. Early efforts
mainly relied on the use of palladium or nickel cata-
lysts, and many of these methods suffer from low re-
action efficiency, limited substrate scope, require
a large excess of pyridines, employ symmetrical al-
kynes with little functionality or prefunctionalized al-
kenyl iodides as the coupling partners.[5]
À
Recently, the transition metal-catalyzed C H bond
olefination has emerged as an efficient and viable syn-
thetic alternative method to the traditional cross-cou-
pling strategy for the atom- and step-economical in-
stallation of the alkenyl functionality.[6,7] Recently,
Satoh and Miura, Glorius, Li, and Bergman and
Ellman et al have demonstrated that Cp*Rh
complexes were competent catalysts for the oxidative
olefination of arenes bearing different directing Figure 1. RhACHTNUGTRNE(NUG III)-catalyzed oxidative olefination reactions.
ACHTUNGERTN(NUNG III)Ln
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RhodiumACHTUNTRGNEU(GN III)-Catalyzed Oxidative Olefination of Picolinamides
Table 2. Scope of the olefins.[a]
olefination and oxidative annulation of isonicotin-
amides.[11a,b] Very recently, we have reported the Rh-
ACHTUNGTRENNUNG(III)-catalyzed oxidative olefination of 2-aminopyri-
ACHTUNGTRENNUNG
dine derivatives and the application of this protocol
to the expeditious synthesis of naphthyridinones.[11c]
To further explore the potential of Rh
functionalization of pyridines, herein, we report an
extensive study of the Rh(III)-catalyzed olefination of
ACHTUNGTREN(NGNU III)-catalyzed
AHCTUNGTRENNUNG
picolinamide derivatives with lower catalyst loadings
(0.5 mol%),[12] and broader substrate scope on a gram
scale (Figure 1C).
Results and Discussion
We initially employed our reported conditions for the
oxidative Heck reaction of N,N-diethylpicolinamide
(1a) with ethyl acrylate, to our delight, the olefinated
product 2a was obtained in quantitative yield
(Table 1, entry 1).[11c,13] Encouraged by this promising
result, we further applied this reaction protocol to pi-
colinamides bearing different directing groups
(Table 1). Notably, a series of N,N-dialkyl-substituted
picolinamides reacted with ethyl acrylate under the
standard conditions to afford the olefinated products
in good yields (entries 1–6, 72%–81%). However, the
reaction failed to give any desired product when the
N-substituent is phenyl or with Weinreb amide (en-
tries 7–9, 1g–1i).
[a]
We next explored the coupling of 1a with a series
of activated olefins (Table 2, entries 1–5). Acrylates
readily coupled with 1a in comparably good yields
(entries 2–4, 4b–d). Styrene and diethyl vinylphospho-
Yields are given for isolated products after chromatogra-
phy.
nate can also couple with 1a in high yields (entry 1 ed smoothly under the standard conditions, and was
and entry 5, 4a and 4e, 74% and 84%, respectively). found to be tolerant of both electron-donating groups
Subsequently, the reactivity of different substituted such as methyl (4f, 4l, 4u), methoxy (4g and 4t) and
N,N-diethylpicolinamides with ethyl acrylate was in- PMP (4q) and electron-withdrawing groups such as
vestigated (Table 3). Generally, the reaction proceed- carboxylate (4k and 4p). It is worth noting that halo-
gen-containing substrates, such as fluoride, chloride,
and bromide, also reacted efficiently, affording the
corresponding olefinated products in high yields (4h–
Table 1. Olefination of N,N-disubstituted picolinamides.[a]
Entry
Substrate
Product
Yield [%][b]
4j, 4m–4o and 4r–4s, up to 100% yields). Moreover,
this transformation also tolerates substrates with sub-
stitutions at the 4-positions (4r–4u). This was in sharp
contrast to the olefination of 2-aminopyridine deriva-
tives, which was very sensitive to steric hindrance.[11c]
However, 4-phenylpicolinamide did not afford the
corresponding products. The quinoline substrate 3w
and 2,6-dicarboxamide 3x can also be converted into
the corresponding olefinated/diolefinated products 4w
and 4x in quantitative yields, respectively. Further-
more, the scope of the substrates can be expanded to
other nitrogen heterocycles, such as isonicotinamide
and pyrimidine, affording the olefinated products 4y
and 4z in moderate yield (20% and 70%, respective-
ly). It is worth noting that the reaction of pyrazine
3aa with ethyl acrylate only gave the alkylated prod-
1
2
3
4
5
6
7
8
9
1a: R1 =R2 =Et
2a
2b
2c
2d
2e
2f
2g
2h
2i
100
72[c]
77
1b: R1 =R2 =i-Pr
1c: R1 =R2 =Cy
1d: R1 =R2 =Bn
81
78
1e: R1, R2 =(CH2)5
1f: R1 =Me, R2 =n-Bu
1g: R1 =R2 =Ph
78[c]
NR
NR
NR
1h: R1 =Me, R2 =Ph
1i: R1 =Me, R2 =OMe
[a]
Conditions A: 1 (0.2 mmol), ethyl acrylate (0.6 mmol),
[Cp*RhCl2]2 (2.5 mol%), AgSbF6 (10 mol%) and
CuACHTUNGTRENNUNG(OAc)2 (2.0 equiv.) in 2 mL of DCE for 24 h.
Yields are given for isolated products after chromatogra-
phy.
Run for 48 h.
[b]
[c]
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Jun Zhou et al.
Table 3. Olefination of N,N-diethylpicolinamides.[a]
[a]
Conditions A: Standard reaction conditions as described in Table 1.
Isolated yields in parentheses were conducted under Conditions B: 1.0-mmol scale with 0.5 mol% [Cp*RhCl2]2.
1.5 equiv. ethyl acrylate, 12 h.
48 h.
[Cp*RhCl2]2 (5 mmol%), 48 h and 39% starting material was recovered.
Ethyl acrylate (6 equiv.), [Cp*RhCl2]2 (5 mol%), AgSbF6 (20 mol%) and CuACTHUNTRGNE(UNG OAc)2 (4 equiv.) in 4 mL of DCE for 24 h.
Starting material 3y was recovered in 80% yield.
[b]
[c]
[d]
[e]
[f]
[g]
uct 4aa in 63% yield via the protonation of the result- tion sequence (Scheme 1), which is also in line with
ing rhodium intermediate instead of b-H elimination. the outcomes of Miura and Li et al.[8a,11a]
More importantly, most of the reactions proceeded
To highlight the utility of the current protocol,
smoothly on a 1-mmol scale with low catalyst loading a series of synthetic transformations has been carried
(0.5 mol%) and the yields maintained good to excel- out starting from the olefination product 4o. As
lent (under Conditions B, 4f, 4h, 4i, 4k, 4m–4t, 4w and shown in Scheme 2, the Suzuki coupling reaction took
4x).[12,14]
place when 4o was reacted with phenylboronic acid in
When secondary picolinamides were coupled to the presence of Pd(PPh3)4 and provided the coupling
AHCTUNGTRENNUNG
ethyl acrylate, the olefination–cyclization products 6a product 4oa in 97% yield. The Heck reaction with 4o
and 6b were obtained in good yields. The E configura- gave the diolefinated products 4ob in 51% yield.
tion of the exocyclic double bond in 6a and 6b was Moreover, ethoxycarbonylation of 4o in the presence
confirmed by NOESY experiments (see the Support- of PdACTHNUTRGNEUNG(PPh3)2Cl2 gave 4oc in 82% yield. Finally, selec-
ing Information). This observed geometry can be ex- tive reduction of the C=C double bond gave 4od in
plained by the cis-amidorhodation/b-hydride elimina- 73% yield.
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RhodiumACHTUNTRGNEU(GN III)-Catalyzed Oxidative Olefination of Picolinamides
tion experiments between 3g and 3h showed that elec-
tron-rich picolinamide 3g was transformed preferen-
tially (Scheme 3B).
À
Finally, to check the reversibility of the C H activa-
tion step, reactions of 1a with/without ethyl acrylate
were carried out in the presence of MeOD as co-sol-
vent, no deuterium incorporation was detected in the
starting material 1a. These deuterium experiments
À
suggest that the C H bond activation step is irreversi-
ble (Scheme 4A). Subsequently, the deuterium kinetic
isotope effect was measured (Scheme 4B). A signifi-
cant intermolecular kinetic isotope effect (KIE) was
À
observed (kH/kD =2.5), indicating that the C H cleav-
Scheme 1. Olefination–cyclization of secondary amides and
the proposed mechanism for the E configuration.
In consideration of the high efficiency of the
RhACHTUNGTRENNUNG(III) catalyst, we conducted some initial mechanis-
tic studies to probe its mode of action. First, intermo-
lecular competition experiments between 1a and 3u
revealed that steric interactions are crucial for this re-
action (Scheme 3A). Then, intermolecular competi- Scheme 3. Intermolecular competition experiments.
Scheme 2. Synthetic transformations of 4o. Reagents and conditions: a) PhB(OH)2, Pd
1008C, 97%; b) n-butyl acrylate, Pd(PPh3)4, DBA, P(t-Bu)3, (i-Pr)2NEt, dioxane,1008C, 51%; c) CO, PdCl
EtOH, 1008C, 82%; d) NiCl2·6H2O/NaBH4, MeOH, 08C, 73%
ACHTUNGTRENNUNG
N
N
CHTUNGTRENNUNG
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Jun Zhou et al.
Scheme 4. Reversibility and KIE study.
linamide 1 (0.2 mmol, 1.0 equiv.), [Cp*RhCl2]2 (0.001 mmol,
2.5 mol%), AgSbF6 (0.02 mmol, 0.1 equiv.), Cu(OAc)2
age is most likely involved in the rate-determining
step.
ACHTUNGTRENNUNG
(0.4 mmol, 2.0 equiv.), acrylate or styrene (0.6 mmol,
3 equiv.) and DCE (2 mL). The solution was stirred at
1208C for 24 h, then cooled to room temperature and con-
centrated aqueous ammonia (2 mL) was added and stirred
for 5 min. The resulting mixture was extracted with DCM.
The organic layer was dried over Na2SO4, concentrated
under reduced pressure and purified by silica gel chromatog-
raphy.
Conclusions
In conclusion, we have developed an efficient
RhACHTUNGTRENNUNG(III)-catalyzed oxidative olefination of picolina-
mides with carboxamides as directing groups.[15] The
reaction protocol provides an expedient route to the
functionalization of pyridine derivatives with several
advantages, including low catalyst loading (0.5 mol%
in most cases), high yield and good functional group
tolerance. Further studies on the mechanism of this
reaction and its synthetic application are underway.
(For 1-mmol scale reaction with 0.5mol% catalyst): To
a 50-mL Schlenck tube filled with nitrogen, was added pico-
linamide 1 (1 mmol, 1.0 equiv-), [Cp*RhCl2]2 (0.005 mmol,
0.5 mol%), AgSbF6 (0.02 mmol, 0.02 equiv.), CuACHTUNGTRENNUNG(OAc)2
(4 mmol, 2.0 equiv.), acrylate (3 mmol, 3 equiv.) and DCE
(10 mL). The solution was stirred at 1208C for 24 h, then
cooled to room temperature and concentrated aqueous am-
monia (5 mL) was added and stirred for 5 min. The resulting
mixture was extracted with DCM. The organic layer was
dried over Na2SO4, concentrated under reduced pressure
and purified by silica gel chromatography.
Experimental Section
General Methods
Ethyl
(E)-3-[2-(diethylcarbamoyl)pyridin-3-yl]acrylate
(2a): 1H NMR (400 MHz, CDCl3): d=8.58 (d, J=4.4 Hz,
1H), 7.95 (d, J=7.6 Hz, 1H), 7.68 (d, J=16.0 Hz, 1H), 7.34
(dd, J1 =7.8 Hz, J2 =5.0 Hz, 1H), 6.46 (d, J=16.4 Hz, 1H),
4.24 (q, J=7.1 Hz, 2H), 3.62 (q, J=7.2 Hz, 2H), 3.11 (q, J=
7.1 Hz, 2H), 1.28–1.35 (m, 6H), 1.08 (t, J=7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=167.2, 165.8, 154.9, 150.1,
138.5, 134.2, 127.3, 123.8, 122.2, 60.7, 42.8, 39.3, 14.1, 13.8,
12.7; HR-MS (EI-TOF): m/z=276.1474, calcd. for
C15H20N2O3 (M+): 276.1474.
DCE, DCM and DMF were dried with CaH2 and distilled.
Dioxane was dried with Na and distilled. The other materi-
als and solvents were purchased from Aladdin and other
commercial suppliers and used without additional purifica-
tion. NMR spectra were recorded on a Bruker Avance oper-
ating at 400 MHz (for 1H NMR) and 100 MHz (for
13C NMR) using TMS as internal standard. Chemical shifts
are given relative to CDCl3 (7.26 ppm for 1H NMR,
77.0 ppm for 13C NMR) and (CD3)2SO (2.50 ppm for
1H NMR, 40.5 ppm for 13C NMR). Mass spectroscopy data
of the products were collected on an HR-MS-TOF instru-
ment.
Ethyl
(E)-3-[2-(diisopropylcarbamoyl)pyridin-3-yl]acry-
late (2b): 1H NMR (400 MHz, CDCl3): d=8.57 (d, J=
4.4 Hz, 1H), 7.94 (d, J=8.4 Hz, 1H), 7.73 (d, J=16.0 Hz,
1H), 7.31 (dd, J1 =7.8 Hz, J2 =5.0 Hz, 1H), 6.46 (d, J=
16.0 Hz, 1H), 4.24 (q, J=7.2 Hz, 2H), 3.52–3.62 (m, 1H),
3.40–3.50 (m, 1H), 1.63 (d, J=6.8 Hz, 6H), 1.31 (t, J=
7.2 Hz, 3H), 1.12 (d, J=6.8 Hz, 6H); 13C NMR (100 MHz,
CDCl3): d=167.1, 165.8, 156.0, 150.3, 138.7, 134.0, 126.6,
123.4, 121.8, 60.7, 50.9, 46.1, 20.5 (2ꢂC), 20.2 (2ꢂC), 14.1;
General Procedure for RhACTHNUTRGNE(UNG III)-Catalyzed Oxidative
Olefination of Picolinamides
(For 0.2-mmol scale reaction with 2.5mol% catalyst): To
a 20-mL Schlenck tube filled with nitrogen, was added pico-
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RhodiumACHTUNTRGNEU(GN III)-Catalyzed Oxidative Olefination of Picolinamides
HR-MS (EI-TOF): m/z=304.1787, calcd. for C17H24N2O3
(M+): 304.1787.
13C NMR (100 MHz, CDCl3): d=167.2, 166.3, 155.0, 150.1,
138.8, 134.3, 127.3, 123.8, 121.7, 51.8, 42.8, 39.3, 13.9, 12.7;
HR-MS (EI-TOF): m/z=262.1316, calcd. for C14H18N2O3
(M+): 262.1317.
Ethyl (E)-3-[2-(dicyclohexylcarbamoyl)pyridin-3-yl]acry-
late (2c): 1H NMR (400 MHz, CDCl3): d=8.56 (d, J=
4.8 Hz, 1H), 7.94 (d, J=8.0 Hz, 1H), 7.73 (d, J=15.6 Hz,
1H), 7.32 (dd, J1 =8.0 Hz, J2 =4.4 Hz, 1H), 6.46 (d, J=
16.0 Hz, 1H), 4.24 (q, J=7.2 Hz, 2H), 3.11 (t, J=11.8 Hz,
1H), 2.88–2.99 (m, 1H), 2.64–2.79 (m, 2H), 1.83–1.91 (m,
2H), 1.61–1.77 (m, 7H), 1.40–1.54 (m, 3H), 1.22–1.36 (m,
6H), 0.83–1.02 (m, 3H); 13C NMR (100 MHz, CDCl3): d=
167.3, 165.9, 156.3, 150.3, 138.9, 134.0, 126.5, 123.3, 121.7,
60.7, 59.8, 56.2, 30.9, 29.6, 26.5, 25.6, 25.2, 25.0, 14.1; HR-MS
(EI-TOF): m/z=384.2421, calcd. for C23H32N2O3 (M+):
384.2413.
Ethyl (E)-3-[2-(dibenzylcarbamoyl)pyridin-3-yl]acrylate
(2d): 1H NMR (400 MHz, CDCl3): d=8.58 (d, J=4.0 Hz,
1H), 7.90 (d, J=8.0 Hz, 1H), 7.81 (d, J=16.0 Hz, 1H),
7.21–7.40 (m, 9H), 7.17 (d, J=7.6 Hz, 2H), 6.39 (d, J=
16.4 Hz, 1H), 4.71 (s, 2H), 4.28 (q, J=6.8 Hz, 2H), 4.17 (s,
2H), 1.33 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=168.2, 165.7, 154.4, 150.0, 138.5, 136.3, 135.7, 134.3, 128.8,
128.6, 128.1, 127.9, 127.8, 127.6, 124.0, 122.7, 60.8, 50.8, 46.7,
14.3; HR-MS (EI-TOF): m/z=400.1784, calcd. for
C25H24N2O3 (M+): 400.1787.
Butyl
(E)-3-[2-(diethylcarbamoyl)pyridin-3-yl]acrylate
(4c): 1H NMR (400 MHz, CDCl3): d=8.57 (d, J=4.4 Hz,
1H), 7.95 (d, J=8.0 Hz, 1H), 7.66 (d, J=16.0 Hz, 1H), 7.34
(dd, J1 =8.4 Hz, J2 =4.8 Hz, 1H), 6.45 (d, J=16.4 Hz, 1H),
4.17 (t, J=6.6 Hz, 2H), 3.60 (q, J=7.1 Hz, 2H), 3.09 (q, J=
7.1 Hz, 2H), 1.60–1.70 (m, 2H), 1.35–1.45 (m, 2H), 1.30 (t,
J=7.2 Hz, 3H), 1.06 (t, J=7.0 Hz, 3H), 0.93 (t, J=7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3): d=167.2, 165.9, 155.0,
150.1, 138.5, 134.2, 127.3, 123.8, 122.2, 64.6, 42.9, 39.3, 30.6,
19.1, 13.8, 13.6, 12.7; HR-MS (EI-TOF): m/z=304.1786,
calcd. for C17H24N2O3 (M+): 304.1787.
tert-Butyl (E)-3-[2-(diethylcarbamoyl)pyridin-3-yl]acrylate
(4d): 1H NMR (400 MHz, CDCl3): d=8.56 (d, J=4.4 Hz,
1H), 7.93 (d, J=8.0 Hz, 1H), 7.56 (d, J=15.6 Hz, 1H), 7.32
(dd, J1 =8.2 Hz, J2 =5.0 Hz, 1H), 6.38 (d, J=16.4 Hz, 1H),
3.60 (q, J=7.1 Hz, 2H), 3.10 (q, J=7.1 Hz, 2H), 1.49 (s,
9H), 1.31 (t, J=7.2 Hz, 3H), 1.07 (t, J=7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=167.3, 165.1, 155.0, 149.9,
137.4, 134.2, 127.5, 124.2, 123.8, 80.9, 42.9, 39.3, 28.1 (3ꢂC),
13.9, 12.8; HR-MS (EI-TOF): m/z=304.1788, calcd. for
C17H24N2O3 (M+): 304.1787.
Ethyl (E)-3-[2-(piperidine-1-carbonyl)pyridin-3-yl]acrylate
1
(2e): H NMR (400 MHz, CDCl3): d=8.60 (s, 1H), 7.96 (d,
Diethyl (E)-{2- [2-(diethylcarbamoyl)pyridin-3-yl]vinyl}-
1
J=8.4 Hz, 1H), 7.72 (d, J=16.0 Hz, 1H), 7.31–7.39 (m,
1H), 6.46 (d, J=16.0 Hz, 1H), 4.26 (q, J=7.1 Hz, 2H), 3.79
(t, J=5.2 Hz, 2H), 3.13 (t, J=5.2 Hz, 2H), 1.64–1.75 (m,
4H), 1.46–1.54 (m, 2H), 1.32 (t, J=7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=166.1, 165.9, 154.9, 150.3, 138.6,
134.2, 123.8, 122.3, 60.8, 47.8, 42.7, 29.7, 26.3, 25.5, 24.5,
14.2; HR-MS (EI-TOF): m/z=288.1478, calcd. for
C16H20N2O3 (M+): 288.1474.
phosphonate (4e): H NMR (400 MHz, CDCl3): d=8.56 (br,
1H), 7.89 (d, J=8.4 Hz, 1H), 7.25–7.47 (m, 2H), 6.31 (t, J=
16.8 Hz, 1H), 4.02–4.13 (m, 4H), 3.55 (q, J=6.9 Hz, 2H),
3.06 (q, J=6.9 Hz, 2H), 1.22–1.33 (m, 9H), 1.03 (t, J=
7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=154.3, 149.6,
142.1 (2ꢂC), 134.1, 123.9, 119.9, 118.0, 62.0, 61.9, 42.8, 39.3,
16.2, 16.1, 13.8, 12.6; HR-MS (EI-TOF): m/z=340.1556,
calcd. for C16H25N2O4P (M+): 340.1552.
Ethyl (E)-3-{2-[butyl
N
Ethyl (E)-3-[2-(diethylcarbamoyl)-6-methylpyridin-3-yl]-
acrylate (4f): H NMR (400 MHz, CDCl3): d=7.83 (d, J=
late (2f): 1H NMR (400 MHz, CDCl3): d=8.59 (d, J=
4.8 Hz, 1H), 7.95 (dd, J1 =6.8 Hz, J2 =4.8 Hz, 1H), 7.69 (dd,
J1 =16.2 Hz, J2 =2.2 Hz, 1H), 6.45 (dd, J1 =7.6 Hz, J2 =
4.8 Hz, 1H), 4.21–4.30 (m, 2H), 3.60 (t, J=7.6 Hz, 1H), 3.14
(s, 1.5H), 3.07 (t, J=7.4 Hz, 1H), 2.79 (s, 1.5H), 1.63–1.74
(m, 2H), 1.39–1.56 (m, 2H), 1.32 (t, J=7.2 Hz, 3H), 1.06–
1.17 (m, 1H), 0.99 (t, J=7.4 Hz, 1.5H), 0.75 (t, J=7.4 Hz,
1.5H); 13C NMR (100 MHz, CDCl3): d=167.7, 167.4, 165.8,
154.9, 154.8, 150.1, 149.9, 138.7, 138.5, 134.4, 134.3, 127.8,
127.5, 123.9, 122.5, 122.3, 60.8, 50.4, 46.9, 36.0, 32.5, 30.0,
29.6, 28.9, 20.1, 19.6, 14.2, 13.9, 13.5; HR-MS (EI-TOF):
m/z=290.1633, calcd. for C16H22N2O3 (M+): 290.1630.
1
8.0 Hz, 1H), 7.65 (d, J=16.0 Hz, 1H), 7.19 (d, J=8.0 Hz,
1H), 6.41 (d, J=15.6 Hz, 1H), 4.23 (q, J=7.2 Hz, 2H), 3.61
(q, J=7.2 Hz, 2H), 3.09 (q, J=7.2 Hz, 2H), 2.58 (s, 3H),
1.31 (t, J=7.2 Hz, 6H), 1.08 (t, J=6.8 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=167.2, 165.8, 159.7, 154.2, 138.4,
134.1, 123.9, 123.4, 120.7, 60.3, 42.7, 39.1, 24.1, 13.9, 13.6,
12.5; HR-MS (EI-TOF): m/z=290.1632, calcd. for
C16H22N2O3 (M+): 290.1630.
Ethyl
(E)-3-[2-(diethylcarbamoyl)-6-methoxypyridin-3-
yl]acrylate (4g): 1H NMR (400 MHz, CDCl3): d=7.84 (d,
J=8.8 Hz, 1H), 7.62 (d, J=16.0 Hz, 1H), 6.77 (d, J=8.8 Hz,
1H), 6.30 (d, J=16.4 Hz, 1H), 4.22 (q, J=6.8 Hz, 2H), 3.96
(s, 3H), 3.61 (q, J=7.1 Hz, 2H), 3.10 (q, J=6.9 Hz, 2H),
1.26–1.35 (m, 6H), 1.13 (t, J=7.0 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=167.0, 166.2, 164.2, 153.0, 138.4,
136.6, 120.2, 118.8, 111.8, 60.4, 53.9, 42.8, 39.1, 14.1, 13.9,
12.7; HR-MS (EI-TOF): m/z=306.1577, calcd. for
C16H22N2O4 (M+): 306.1580.
(E)-N,N-Diethyl-3-styrylpicolinamide
(400 MHz, CDCl3): d=8.61 (d, J=4.4 Hz, 1H), 8.15 (d, J=
8.0 Hz, 1H), 7.60 (d, J=7.6 Hz, 2H), 7.38–7.52 (m, 4H),
7.24–7.28 (m, 2H), 3.76 (q, J=7.2 Hz, 2H), 3.25 (q, J=
7.2 Hz, 2H), 1.45 (t, J=7.0 Hz, 3H), 1.19 (t, J=7.0 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=168.1, 153.6, 147.8, 136.5,
132.9, 132.5, 130.0, 128.7, 128.4, 126.8, 123.7, 122.6, 42.9,
39.3, 13.9, 13.0; HR-MS (EI-TOF): m/z=280.1580, calcd for
C18H20N2O (M+): 280.1576.
Ethyl (E)-3-[2-(diethylcarbamoyl)-6-fluoropyridin-3-yl]-
1
acrylate (4h): H NMR (400 MHz, CDCl3): d=8.16 (dd, J1 =
Methyl (E)-3-[2-(diethylcarbamoyl)pyridin-3-yl]acrylate
(4b): 1H NMR (400 MHz, CDCl3): d=8.57 (d, J=4.0 Hz,
1H), 7.94 (d, J=8.0 Hz, 1H), 7.68 (d, J=16.0 Hz, 1H), 7.34
(dd, J1 =7.4 Hz, J2 =4.6 Hz, 1H), 6.45 (d, J=16.0 Hz, 1H),
3.77 (s, 3H), 3.60 (q, J=7.1 Hz, 2H), 3.10 (q, J=7.1 Hz,
2H), 1.30 (t, J=7.2 Hz, 3H), 1.06 (t, J=7.2 Hz, 3H);
8.48 Hz, J2 =3.6 Hz, 1H), 7.66 (d, J=15.6 Hz, 1H), 7.05 (dd,
J1 =8.4 Hz, J2 =2.8 Hz, 1H), 6.45 (d, J=16.0 Hz, 1H), 4.25
(q, J=7.1 Hz, 2H), 3.61 (q, J=7.2 Hz, 2H), 3.14 (q, J=
7.1 Hz, 2H), 1.32 (t, J=7.2 Hz, 6H), 1.12 (t, J=7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=165.4, 165.3, 162.7 (JC,F
=
244.3 Hz), 152.9 (JC,F =13.7 Hz), 139.7 (JC,F =8.4 Hz), 136.8,
Adv. Synth. Catal. 2014, 356, 1038 – 1046
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1043

FULL PAPERS
Jun Zhou et al.
125.1 (JC,F =5.5 Hz), 121.6 (JC,F =1.3 Hz), 110.2 (JC,F
=
14.0, 13.8, 12.6; HR-MS (EI-TOF): m/z=310.1088, calcd.
for C15H19ClN2O3 (M+): 310.1084.
37.4 Hz), 60.4, 42.6, 39.1, 13.8, 13.5, 12.3; HR-MS (EI-TOF):
m/z=294.1379, calcd. for C15H19FN2O3 (M+): 294.1380.
Ethyl (E)-3-[6-chloro-2-(diethylcarbamoyl)pyridin-3-yl]-
acrylate (4i): 1H NMR (400 MHz, CDCl3): d=7.90 (d, J=
8.4 Hz, 1H), 7.63 (d, J=16.0 Hz, 1H), 7.37 (d, J=8.4 Hz,
1H), 6.44 (d, J=15.6 Hz, 1H), 4.24 (q, J=7.1 Hz, 2H), 3.59
(q, J=7.2 Hz, 2H), 3.12 (q, J=7.1 Hz, 2H), 1.30 (t, J=
7.0 Hz, 6H), 1.11 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=165.6 (2ꢂC), 154.8, 151.7, 137.2, 136.8, 126.3,
124.7, 122.6, 60.8, 43.0, 39.5, 14.1, 13.8, 12.7; HR-MS (EI-
TOF): m/z=310.1087, calcd. for C15H19ClN2O3 (M+):
310.1084.
Ethyl (E)-3-[6-bromo-2-(diethylcarbamoyl)pyridin-3-yl]-
acrylate (4j): 1H NMR (400 MHz, CDCl3): d=7.79 (d, J=
8.4 Hz, 1H), 7.61 (d, J=16.0 Hz, 1H), 7.52 (d, J=8.8 Hz,
1H), 6.45 (d, J=15.6 Hz, 1H), 4.24 (q, J=7.2 Hz, 2H), 3.59
(q, J=7.1 Hz, 2H), 3.12 (q, J=7.2 Hz, 2H), 1.30 (t, J=
7.0 Hz, 6H), 1.12 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=165.6, 165.5, 155.2, 142.4, 137.3, 136.4, 128.5,
126.7, 122.7, 60.8, 43.1, 39.6, 14.1, 13.8, 12.7; HR-MS (EI-
TOF): m/z=354.0579, calcd. for C15H19BrN2O3 (M+):
354.0579.
Methyl (E)-6-(diethylcarbamoyl)-5-(3-ethoxy-3-oxoprop-
1-en-1-yl)picolinate (4k): 1H NMR (400 MHz, CDCl3): d=
8.10 (d, J=8.0 Hz, 1H), 8.06 (d, J=8.4 Hz, 1H), 7.67 (d, J=
16.0 Hz, 1H), 6.50 (d, J=16.4 Hz, 1H), 4.21 (q, J=7.2 Hz,
2H), 3.95 (s, 3H), 3.56 (q, J=7.2 Hz, 2H), 3.07 (q, J=
7.1 Hz, 2H), 1.24–1.31 (m, 6H), 1.08 (t, J=7.0 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=166.1, 165.3, 164.6, 154.7,
147.5, 137.4, 135.2, 130.6, 125.0, 124.0, 60.8, 52.8, 43.0, 39.5,
14.0, 13.7, 12.6; HR-MS (EI-TOF): m/z=334.1529, calcd.
for C17H22N2O5 (M+): 334.1529.
Ethyl (E)-3-[5-bromo-2-(diethylcarbamoyl)pyridin-3-yl]-
1
acrylate (4o): H NMR (400 MHz, CDCl3): d=8.61 (d, J=
2.0 Hz, 1H), 8.07 (d, J=1.6 Hz, 1H), 7.59 (d, J=15.6 Hz,
1H), 6.45 (d, J=16.4 Hz, 1H), 4.23 (q, J=7.2 Hz, 2H), 3.59
(q, J=7.1 Hz, 2H), 3.09 (q, J=7.1 Hz, 2H), 1.29 (t, J=
7.0 Hz, 6H), 1.07 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=166.4, 165.4, 153.0, 150.7, 137.1, 136.5, 129.1,
123.5, 120.7, 60.8, 42.9, 39.4, 14.1, 13.9, 12.7; HR-MS (EI-
TOF): m/z=354.0576, calcd. for C15H19BrN2O3 (M+):
354.0579.
Methyl (E)-6-(diethylcarbamoyl)-5-(3-ethoxy-3-oxoprop-
1-en-1-yl)nicotinate (4p): Brown solid; mp 83–858C;
1H NMR (400 MHz, CDCl3): d=9.15 (s, 1H), 8.55 (s, 1H),
7.68 (d, J=16.0 Hz, 1H), 6.56 (d, J=15.6 Hz, 1H), 4.25 (q,
J=7.2 Hz, 2H), 3.99 (s, 3H), 3.62 (q, J=7.1 Hz, 2H), 3.08
(q, J=7.1 Hz, 2H), 1.28–1.36 (m, 6H), 1.08 (t, J=7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3): d=166.4, 165.4, 164.6,
157.9, 150.7, 137.3, 135.2, 127.3, 126.0, 123.4, 60.8, 52.6, 42.8,
39.3, 14.0, 13.8, 12.6; HR-MS (EI-TOF): m/z=334.1522,
calcd. for C17H22N2O5 (M+): 334.1529.
Ethyl (E)-3-[2-(diethylcarbamoyl)-5-(4-methoxyphenyl)-
pyridin-3-yl]acrylate (4q): Yellow solid; mp 122–1248C;
1H NMR (400 MHz, CDCl3): d=8.76 (s, 1H), 8.05 (s, 1H),
7.74 (d, J=16.0 Hz, 1H), 7.53 (d, J=8.4 Hz, 2H), 7.03 (d,
J=8.4 Hz, 2H), 6.53 (d, J=16.0 Hz, 1H), 4.25 (q, J=7.1 Hz,
2H), 3.87 (s, 3H), 3.63 (q, J=7.1 Hz, 2H), 3.17 (q, J=
6.9 Hz, 2H), 1.33 (t, J=7.2 Hz, 3H), 1.31 (t, J=6.8 Hz, 3H),
1.11 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=
167.3, 135.8, 160.1, 152.8, 148.1, 138.7, 136.4, 131.7, 128.8,
128.2, 127.2, 122.2, 114.6, 60.7, 55.3, 42.9, 39.3, 14.1, 13.9,
12.7; HR-MS (EI-TOF): m/z=382.1890, calcd. for
C22H26N2O4 (M+): 382.1893.
Ethyl (E)-3-[2-(diethylcarbamoyl)-5-methylpyridin-3-yl]-
Ethyl (E)-3-[4-chloro-2-(diethylcarbamoyl)pyridin-3-yl]-
1
acrylate (4l): H NMR (400 MHz, CDCl3): d=8.37 (s, 1H),
1
acrylate (4r): H NMR (400 MHz, CDCl3): d=8.44 (d, J=
7.72 (s, 1H), 7.63 (d, J=16.0 Hz, 1H), 6.41 (d, J=16.0 Hz,
1H), 4.20 (q, J=7.1 Hz, 2H), 3.57 (q, J=7.1 Hz, 2H), 3.07
(q, J=7.1 Hz, 2H), 2.35 (s, 3H), 1.27 (t, J=6.8 Hz, 6H),
1.03 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=
167.4, 165.9, 152.3, 150.6, 138.7, 134.4, 133.5, 126.8, 121.8,
60.6, 42.8, 39.3, 18.2, 14.1, 13.9, 12.7; HR-MS (EI-TOF): m/
z=290.1629, calcd. for C16H22N2O3 (M+): 290.1630.
Ethyl (E)-3-[2-(diethylcarbamoyl)-5-fluoropyridin-3-yl]-
acrylate (4m): Brown solid; mp 86–888C; 1H NMR
(400 MHz, CDCl3): d=8.44 (d, J=2.0 Hz, 1H), 7.62–7.69
(m, 2H), 6.45 (d, J=16.0 Hz, 1H), 4.25 (q, J=6.9 Hz, 2H),
3.61 (q, J=7.1 Hz, 2H), 3.10 (q, J=7.1 Hz, 2H), 1.31 (t, J=
7.2 Hz, 6H), 1.08 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz,
5.6 Hz, 1H), 7.77 (d, J=16.0 Hz, 1H), 7.39 (d, J=5.2 Hz,
1H), 6.55 (d, J=16.4 Hz, 1H), 4.24 (q, J=7.2 Hz, 2H), 3.56
(q, J=7.1 Hz, 2H), 3.05 (q, J=7.1 Hz, 2H), 1.30 (t, J=
7.2 Hz, 3H), 1.24 (t, J=6.8 Hz, 3H), 1.08 (t, J=7.0 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=166.7, 165.6, 155.3, 149.5,
144.5, 135.6, 126.6, 126.4, 124.8, 60.8, 42.7, 39.0, 14.1, 13.5,
12.2; HR-MS (EI-TOF): m/z=310.1083, calcd. for
C15H19ClN2O3 (M+): 310.1084.
Ethyl (E)-3-[4-bromo-2-(diethylcarbamoyl)pyridin-3-yl]-
acrylate (4s): Yellow solid; mp 50–528C; 1H NMR
(400 MHz, CDCl3): d=8.44 (d, J=4.2 Hz, 1H), 7.78 (d, J=
16.4 Hz, 1H), 7.39 (d, J=5.2 Hz, 1H), 6.56 (d, J=16.4 Hz,
1H), 4.25 (q, J=7.2 Hz, 2H), 3.57 (q, J=7.1 Hz, 2H), 3.06
(q, J=7.1 Hz, 2H), 1.31 (t, J=7.2 Hz, 3H), 1.24 (t, J=
7.2 Hz, 3H), 1.09 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=166.3, 165.5, 155.3, 149.5, 144.4, 135.5, 126.6,
126.4, 124.8, 60.7, 42.7, 39.0, 14.1, 13.5, 12.1; HR-MS (EI-
TOF): m/z=354.0579, calcd. for C15H19BrN2O3 (M+):
354.0579.
CDCl3): d=166.4, 165.3, 158.8 (JC,F =257.8 Hz), 150.9 (JC,F
=
4.8 Hz), 138.2 (JC,F =23.6 Hz), 137.2, 129.3 (JC,F =3.9 Hz),
123.4, 120.4 (JC,F =18.7 Hz), 60.7, 42.8, 39.4, 14.0, 13.7, 12.5;
HR-MS (EI-TOF): m/z=294.1375, calcd. for C15H19FN2O3
(M+): 294.1380.
Ethyl (E)-3-[5-chloro-2-(diethylcarbamoyl)pyridin-3-yl]-
acrylate (4n): Brown solid; mp 84–868C; 1H NMR
(400 MHz, CDCl3): d=8.52 (d, J=1.6 Hz, 1H), 7.92 (d, J=
2.0 Hz, 1H), 7.62 (d, J=16.0 Hz, 1H), 6.46 (d, J=16.4 Hz,
1H), 4.24 (q, J=7.2 Hz, 2H), 3.60 (q, J=6.9 Hz, 2H), 3.10
(q, J=7.1 Hz, 2H), 1.31 (t, J=7.2 Hz, 6H), 1.08 (t, J=
6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=166.3, 165.3,
152.7, 148.6, 137.1, 133.6, 132.1, 128.7, 123.4, 60.8, 42.9, 39.4,
Ethyl
(E)-3-[2-(diethylcarbamoyl)-4-methoxypyridin-3-
yl]acrylate (4t): Brown solid; mp 97–1008C; 1H NMR
(400 MHz, CDCl3): d =8.43 (d, J=6.0 Hz, 1H), 7.63 (d, J=
16.0 Hz, 1H), 6.85 (d, J=5.2 Hz, 1H), 6.77 (d, J=16.8 Hz,
1H), 4.22 (q, J=7.1 Hz, 2H), 3.97 (s, 3H), 3.59 (q, J=
6.9 Hz, 2H), 3.07 (q, J=7.2 Hz, 2H), 1.29 (t, J=7.2 Hz,
6H), 1.07 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3):
1044
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ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 1038 – 1046

FULL PAPERS
RhodiumACHTUNTRGNEU(GN III)-Catalyzed Oxidative Olefination of Picolinamides
d=167.3, 166.6, 164.6, 156.5, 151.0, 134.9, 124.1, 116.2, 106.4,
60.2, 55.7, 42.6, 38.9, 14.0, 13.5, 12.3; HR-MS (EI-TOF): m/
z=306.1580, calcd. for C16H22N2O4 (M+): 306.1580.
(ESI): m/z=302.1473, calcd. for C14H21N3O3Na (M+Na+):
302.1475.
Ethyl (E)-2-(7-oxo-6-phenyl-6,7-dihydro-5H-pyrroloACHTUNGTRENNUNG[3,4-
b]pyridin-5-ylidene)acetate (6a): 1H NMR (400 MHz,
CDCl3): d=9.44 (dd, J1 =8.2 Hz, J1 =1.4 Hz, 1H), 8.91 (dd,
J1 =4.8 Hz, J1 =2.0 Hz, 1H), 7.61 (dd, J1 =8.0 Hz, J1 =
4.8 Hz, 1H), 7.47–7.59 (m, 3H), 7.30–7.35 (m, 2H), 5.63 (s,
1H), 4.22 (q, J=7.2 Hz, 2H), 1.29 (t, J=6.8 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=165.7, 164.5, 153.2, 148.1,
147.1, 136.2, 133.1, 129.9, 129.3, 128.8, 128.7, 126.7, 102.5,
60.8, 14.2; HR-MS (EI-TOF): m/z=294.1007, calcd. for
C17H14N2O3 (M+): 294.1004.
Ethyl (E)-3-[2-(diethylcarbamoyl)-4-methylpyridin-3-yl]-
1
acrylate (4u): H NMR (400 MHz, CDCl3): d=8.38 (d, J=
4.8 Hz, 1H), 7.71 (d, J=16.4 Hz, 1H), 7.14 (d, J=4.8 Hz,
1H), 6.33 (d, J=16.0 Hz, 1H), 4.21 (q, J=7.2 Hz, 2H), 3.53
(q, J=7.1 Hz, 2H), 3.03 (q, J=7.2 Hz, 2H), 2.39 (s, 3H),
1.27 (t, J=7.0 Hz, 3H), 1.21 (t, J=7.2 Hz, 3H), 1.05 (t, J=
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=168.0, 166.0,
153.9, 148.8, 147.0, 137.8, 127.2, 125.3 (2ꢂC), 60.7, 42.7, 38.9,
20.2, 14.1, 13.6, 12.2; HR-MS (EI-TOF): m/z=290.1631,
calcd. for C16H22N2O3 (M+): 290.1630.
Ethyl
(E)-2-(6-butyl-7-oxo-6,7-dihydro-5H-pyrroloACHTUNGTRENNUNG[3,4-
b]pyridin-5-ylidene)acetate (6b): 1H NMR (400 MHz,
CDCl3): d=9.34 (dd, J1 =8.2 Hz, J2 =2.6 Hz, 1H), 8.80 (dd,
J1 =4.8 Hz, J2 =2.0 Hz, 1H), 7.51 (dd, J1 =8.0 Hz, J2 =
4.8 Hz, 1H), 5.80 (s, 1H), 4.27 (q, J=7.1 Hz, 2H), 3.84 (t,
J=7.4 Hz, 2H), 1.60–1.70 (m, 2H), 1.35–1.45 (m, 2H), 1.35
(t, J=7.0 Hz, 3H), 0.95 (t, J=7.4 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=165.7, 164.9, 152.6, 148.5, 145.4,
136.0, 128.8, 126.3, 100.3, 60.8, 39.7, 29.8, 20.1, 14.2, 13.7;
HR-MS (EI-TOF): m/z=274.1319, calcd. for C15H18N2O3
(M+): 274.1317.
Ethyl
(4w): Yellow solid; mp 100–1038C; 1H NMR (400 MHz,
CDCl3): d=8.42(s, 1H), 8.10 (d, J=8.0 Hz, 1H), 7.86 (d, J=
(E)-3-[2-(diethylcarbamoyl)quinolin-3-yl]acrylate
ACHTUNGTRENNUNG
8.4 Hz, 1H), 7.82 (d, J=16.0 Hz, 1H), 7.76 (t, J=7.6 Hz,
1H), 7.60 (t, J=7.6 Hz, 1H), 6.58 (d, J=16.4 Hz, 1H), 4.26
(q, J=7.1 Hz, 2H), 3.67 (q, J=7.1 Hz, 2H), 3.14 (q, J=
7.1 Hz, 2H), 1.37 (t, J=7.2 Hz, 3H), 1.33 (t, J=7.4 Hz, 3H),
1.11 (t, J=6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=
167.3, 165.8, 154.6, 147.2, 138.8, 134.6, 130.9, 129.2, 128.0,
127.6, 127.2, 125.0, 121.9, 60.5, 42.8, 39.3, 14.0, 13.7, 12.6;
HR-MS (EI-TOF): m/z=326.1627, calcd. for C19H22N2O3
(M+): 326.1630.
Diethyl 3,3’-[2,6-bis(diethylcarbamoyl)pyridine-3,5-diyl]-
ACHTUNGTRENNUNG(2E,2’E)-diacrylate (4x): Yellow solid; mp 58–608C;
Acknowledgements
1H NMR (400 MHz, CDCl3): d=8.16 (s, 1H), 7.68 (d, J=
16.4 Hz, 2H), 6.51 (d, J=16.0 Hz, 2H), 4.26 (q, J=7.0 Hz,
4H), 3.59 (q, J=6.9 Hz, 4H), 3.13 (q, J=6.9 Hz, 4H), 1.27–
1.35 (m, 12H), 1.08 (t, J=7.2 Hz, 6H); 13C NMR (100 MHz,
CDCl3): d=166.0 (2ꢂC), 165.3 (2ꢂC), 154.3, 140.5, 137.3,
132.5, 128.1, 127.7, 123.1, 60.6 (2ꢂC), 42.8 (2ꢂC), 39.3 (2ꢂ
C), 13.9 (2ꢂC), 13.7 (2ꢂC), 12.5 (2ꢂC); HR-MS (EI-TOF):
m/z=473.2524, calcd. for C25H35N3O6 (M+): 473.2526.
Financial support from the National Science Foundation of
China (21002087, 21272206, J1210042), the Fundamental Re-
search Funds for the Central Universities (2010QNA3033),
Zhejiang Provincial NSFC (Z12B02000), Qianjiang Project
(2013R10033) and the Ministry of Education (SRFDP
20110101110005) is gratefully acknowledged. We also are
thankful for the Scholarship Award for Excellent Doctoral
Student granted by Ministry of Education to J. Z. (2011).
Ethyl
(E)-3-[4-(diethylcarbamoyl)pyridin-3-yl]acrylate
(4y): 1H NMR (400 MHz, CDCl3): d=8.88 (br, 1H), 8.63
(br, 1H), 7.62 (d, J=16.0 Hz, 1H), 7.20 (d, J=4.8 Hz, 1H),
6.52 (d, J=16.4 Hz, 1H), 4.25 (q, J=7.2 Hz, 2H), 3.46–3.80
(m, 2H), 3.07 (q, J=7.2 Hz, 2H),1.31 (t, J=6.8 Hz, 3H),
1.30 (t, J=6.8 Hz, 3H), 1.04 (t, J=7.0 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=167.0, 165.8, 150.6, 148.7, 144.2,
137.7, 126.4, 122.6, 120.5, 60.8, 42.8, 39.1, 14.2, 13.9, 12.6;
HR-MS (ESI): m/z=277.1544, calcd. for C15H21N2O3 (M+
H+): 277.1547.
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(4z): H NMR (400 MHz, CDCl3): d=9.15 (s, 1H), 8.98 (s,
1H), 7.58 (d, J=16.0 Hz, 1H), 6.53 (d, J=16.4 Hz, 1H),
4.24 (q, J=7.1 Hz, 2H), 3.60 (q, J=7.1 Hz, 2H), 3.11 (q, J=
7.1 Hz, 2H), 1.26–1.33 (m, 6H), 1.10 (t, J=7.2 Hz, 3H);
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155.9, 135.3, 125.2, 124.0, 61.0, 42.9, 39.4, 14.1, 13.9, 12.6;
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3-[2-(diethylcarbomoyl)pyrazin-3-yl]propionate
(4aa): 1H NMR (400 MHz, CDCl3): d=8.45 (d, J=2.4 Hz,
1H), 8.33 (d, J=2.4 Hz, 1H), 4.07 (q, J=7.1 Hz, 2H), 3.55
(q, J=7.2 Hz, 2H), 3.13 (q, J=7.1 Hz, 2H), 3.10 (t, J=
7.2 Hz, 2H), 2.81 (t, J=7.2 Hz, 2H), 1.26 (t, J=7.2 Hz, 3H),
1.18 (t, J=7.2 Hz, 3H), 1.09 (t, J=7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=172.7, 166.7, 152.9, 149.7, 143.6,
140.8, 60.3, 42.9, 39.4, 31.3, 28.6, 14.1, 13.9, 12.6; HR-MS
Adv. Synth. Catal. 2014, 356, 1038 – 1046
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1046
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Adv. Synth. Catal. 2014, 356, 1038 – 1046