Cationic rhodium(I)/modified-BINAP catalyzed [2+2+2] cycloaddition of alkynes with nitriles

Article abstract of DOI:10.1002/ejoc.200600347

Cationic rhodium(I)/modified-BINAP complexes catalyze a chemo- and regioselective [2+2+2] cycloaddition of a wide variety of alkynes and nitriles leading to highly functionalized pyridines under mild reaction conditions. The asymmetric variant of this rea

Full text of DOI:10.1002/ejoc.200600347

FULL PAPER
DOI: 10.1002/ejoc.200600347
Cationic Rhodium(I)/Modified-BINAP Catalyzed [2+2+2] Cycloaddition of
Alkynes with Nitriles
Ken Tanaka,*[a] Nanami Suzuki,[a] and Goushi Nishida[a]
Keywords: Alkynes / Catalysis / Cycloaddition / Nitriles / Pyridines / Rhodium
Cationic rhodium(I)/modified-BINAP complexes catalyze a
chemo- and regioselective [2+2+2] cycloaddition of a wide
variety of alkynes and nitriles leading to highly function-
alized pyridines under mild reaction conditions. The asym-
metric variant of this reaction, enantioselective desymmetri-
zation of substituted malononitriles, also proceeded to give
enantio-enriched bicyclic pyridines which possess a tertiary
or quaternary stereocenter.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
We recently reported the cationic rhodium(I)/H8-BINAP
[2,2Ј-bis(diphenylphosphanyl)-5,5Ј,6,6Ј,7,7Ј,8,8Ј-octahydro-
1,1Ј-binaphthyl] catalyzed chemo-, regio-, and enantioselec-
tive cross cyclotrimerization of two different alkynes.[15]
This catalyst was successfully applied to the [2+2+2] cyclo-
addition of alkynes with isocyanates, isothiocyanates, and
carbon disulfide leading to substituted heterocycles.[16] In
this paper, we describe a cationic rhodium(I)/modified-BI-
NAP catalyzed [2+2+2] cycloaddition of a wide variety of
alkynes and nitriles under mild reaction conditions.
Introduction
Transition-metal-catalyzed or -mediated [2+2+2] cyclo-
additions of alkynes with nitriles leading to substituted pyr-
idines have been developed using a number of transition-
metal complexes.[1] Since the pioneering works by Yama-
zaki and Wakatsuki,[2] Vollhardt,[3] and Bönnemann,[4] co-
balt catalysts have been most widely used for this transfor-
mation, and numerous examples, including the synthesis of
natural products[5] and oligopyridines,[6] have been re-
ported.[7]
Ruthenium catalysts are highly efficient for activated ni-
triles (e.g., electron-deficient nitriles, dicyanides, and α-halo
nitriles) and tethered 1,6-diynes under mild reaction condi-
tions.[8] Nickel,[9] titanium,[10] and tantalum[11] complexes
are also effective for this transformation, although stoichio-
metric amounts of metals are required. Recently, (N-hetero-
cyclic carbene)nickel complexes have been found to catalyze
the [2+2+2] cycloaddition of internal alkynes with inacti-
vated nitriles at room temperature.[12] Although rhodium
catalysts can catalyze pyridine annulation at elevated tem-
perature, the efficiency is low due to the formation of a
large amount of arene by-products other than the desired
pyridines.[13] Recently, the novel enantioselective [2+2+2]
cycloaddition of alkynes with nitriles leading to axially chi-
ral pyridines was reported by using chiral (cyclopen-
tadienyl)cobalt complexes.[14] In view of the application to
such enantioselective [2+2+2] cycloaddition, the develop-
ment of Rh-based catalysts is an attractive target.
Results and Discussion
We first examined various rhodium catalysts to promote
[2+2+2] cycloaddition of the malonate-derived internal 1,6-
diyne 1a with the nitrile 2a, activated by the electron-de-
ficient ethoxycarbonyl group. Among the rhodium catalysts
examined, [Rh(cod)2]BF4/BINAP showed the highest cata-
lytic activity. The use of neutral RhI complexes or conven-
tional phosphane ligands (e.g., dppe, dppb, dppf, Ph3P)
showed no catalytic activity.
Thus, we explored the scope of this process with respect
to 1,6-diynes using 3% [Rh(cod)2]BF4/BINAP as catalyst
(Table 1). The reaction of the malonate-derived 1,6-diyne
1a, dimethoxypropane-derived 1,6-diyne 1b, and tosyl-
amide-derived 1,6-diyne 1c with 2a afforded the corre-
sponding pyridines in excellent yield (Entries 1–3). The di-
propargyl ether derivative 1d, which has no tertiary center
on the tether chain, also reacted with 2a to afford the ex-
pected pyridine in excellent yield (Entry 4). The use of ter-
minal 1,6-diyne 1e lowered the yield of the desired pyridine
due to the competitive diyne cyclotrimerization (Entry 5).
Next, the scope of nitriles was investigated by using 3%
[Rh(cod)2]BF4/BINAP as catalyst. The reactions of the
electron-deficient nitriles 2a–c with 1a afforded the corre-
sponding pyridines in almost quantitative yield (Entries 1,
[a] Department of Applied Chemistry, Graduate School of Engi-
neering, Tokyo University of Agriculture and Technology,
Koganei, Tokyo 184-8588, Japan
Fax: +81-42-388-7037
E-mail: tanaka-k@cc.tuat.ac.jp
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2006, 3917–3922
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3917

K. Tanaka, N. Suzuki, G. Nishida
FULL PAPER
Table 1. Rhodium-catalyzed [2+2+2] cycloaddition of 1,6-diynes
with nitriles.
Scheme 1. Rhodium-catalyzed [2+2+2] cycloaddition of 1,7- and
1,8-diynes with ethyl cyanoformate.
[a] Yield of isolated products. [b] Ligand: Segphos [(4,4Ј-bi-1,3-
benzodioxiol)-5,5Ј-diylbis(diphenylphosphane)]. [c] Catalyst: 10%.
[d] Catalyst: 20%. [e] Ligand: H8-BINAP.
Scheme 2. Rhodium-catalyzed chemoselective [2+2+2] cycload-
dition of 1,6-diynes with malononitrile.
6, and 7). In the cases of inactivated nitriles 2d and 2e, the
reactions proceeded in good yield using terminal diyne 1e
and excess nitriles (2d: 5.0 equiv., Entry 8; 2e: solvent, En-
try 9). The reactions of heteroatom-substituted nitriles 2f–h
were also investigated. Although high catalyst loading (10–
20%) and elevated temperature (80 °C) were required, the
sulfur-containing nitriles 2f and 2g could participate in this
cycloaddition to give the corresponding pyridines (En-
tries 10 and 11).[17] Cyanamide 2h was a reactive substrate
to give the corresponding aminopyridine at 40 °C (En-
try 12).[18]
Scheme 3. Rhodium-catalyzed chemoselective [2+2+2] cycload-
dition of a 1,6-diyne with acrylonitrile.
The formation of not only a five-membered ring but also
six- and seven-membered rings was possible using the 1,7-
diyne 1f and 1,8-diyne 1g, respectively (Scheme 1).
The regioselectivity of the present pyridine synthesis was
then investigated using the unsymmetrical 1,6-diyne 1h
The present RhI-catalyzed reaction exhibited an interest- which has a methyl and a phenyl group at each terminal
ing chemoselectivity. The reaction of the 1,6-diynes 1a and position. The reaction of 1h with ethyl cyanoformate (2a)
1e with malononitrile (2i) in the presence of 3–5% [Rh- in the presence of 5% [Rh(cod)2]BF4/Segphos at room tem-
(cod)2]BF4/H8-BINAP selectively afforded the correspond- perature afforded the corresponding pyridines 6ha and 7ha
ing monopyridines 3ai and 3ei, respectively, without the for- in good yield, preferably 6ha over 7ha. Similarly, the reac-
mation of bipyridines 4 (Scheme 2).[19]
Another interesting chemoselectivity is shown in dominant isomer (Scheme 4).
tion of 1h with malononitrile (2i) afforded 6hi as the pre-
Scheme 3. Grigg et al. reported that a 1,6-diyne selectively
We also investigated the pyridine synthesis by cycload-
reacted with the double bond of acrylonitrile (2j) in the dition of an untethered monoalkyne with 2a. The reaction
presence of 2% RhCl(PPh3)3 at 82 °C for 6 h which af- of 1-dodecyne (8, 2.0 equiv.) with 2a (2.0 equiv.) in the pres-
forded a nitrile in 59% yield.[20] On the other hand, the 1,6- ence of [Rh(cod)2]BF4/BINAP (0.05 equiv.) at 60 °C af-
diyne 1e selectively reacted with the cyano group of 2j in the forded the corresponding pyridines 9 and 10 in high yields;
presence of 3% [Rh(cod)2]BF4/BINAP at room temperature 9 was obtained as the major isomer (Scheme 5).
which afforded the vinylpyridine 3ej in good yield without
Finally, the asymmetric variant of this reaction, the
enantioselective desymmetrization of substituted malononi-
the formation of nitrile 5.[21]
3918
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3917–3922

Catalyzed [2+2+2] Cycloaddition of Alkynes with Nitriles
FULL PAPER
lysts for chemo- and regioselective [2+2+2] cycloaddition
of a wide variety of alkynes and nitriles leading to highly
functionalized pyridines under mild reaction conditions.
The asymmetric variant of this reaction, enantioselective
desymmetrization of substituted malononitriles, was also
demonstrated to give enantio-enriched bicyclic pyridines
which possess a tertiary or quaternary stereocenter.
Experimental Section
Scheme 4. Rhodium-catalyzed regioselective [2+2+2] cycloaddition
of an unsymmetrical 1,6-diyne with nitriles.
General Methods: 1H NMR spectra were recorded with a JEOL
AL 300 (300 MHz) spectrometr. 13C NMR spectra were obtained
with complete proton decoupling with a JEOL AL 300 (75 MHz)
spectrometer. HRMS data were obtained with a JEOL JMS-700
spectrometer. Infrared spectra were obtained with a JASCO A-302
spectrometer. (R)-Xyl-Solphos was obtained from Solvias AG un-
der their University Ligand Kit program. Segphos and H8-BINAP
were obtained from Takasago International Corporation. Anhy-
drous CH2Cl2 (No. 27,099-7), (CH2Cl)2 (No. 28,450-5), and
CH3CN (No. 27,100-4) were obtained from Aldrich and used as
received. All reagents were obtained from commercial sources and
used as received, unless otherwise indicated. All reactions were car-
ried out under argon or nitrogen in oven-dried glassware, unless
otherwise indicated.
Scheme 5. Rhodium-catalyzed regioselective [2+2+2] cycloaddition
of 1-dodecyne with ethyl cyanformate.
triles, is shown in Scheme 6.[22] The 1,6-diyne 1a smoothly
reacted with monosubstituted malononitrile (2k, 1.1 equiv.)
in the presence of 5% [Rh(cod)2]BF4/(R)-xyl-Solphos[23] at
room temperature to give the enantio-enriched bicyclic pyr-
idine (+)-3ak, which has a tertiary stereocenter, in 91%
yield with 64% ee. Furthermore, the reaction of 1a with
sterically demanding disubstituted malononitrile (2l,
2.0 equiv.) proceeded in the presence of 5% [Rh(cod)2]BF4/
(R)-BINAP at room temperature to give the enantio-en-
Starting Materials: The diynes 1a,[24] 1b,[25] 1c,[26] 1d,[27] and 1e[28]
and the nitriles 2k[29] and 2l[29] were prepared according to litera-
ture procedures.
(3-But-2-ynyloxyprop-1-ynyl)benzene (1h): To a stirred suspension
of sodium hydride (50% in mineral oil, 0.49 g, 10.3 mmol) in THF
(25 mL) was added a THF (25 mL) solution of (3-bromoprop-1-
ynyl)benzene[30] (1.00 g, 5.1 mmol) at room temperature, and the
resulting mixture was stirred at room temperature for 10 min. 2-
Butyn-1-ol (0.40 g, 5.6 mmol) was added, and the resulting mixture
riched bicyclic pyridine (+)-3al, which possesses a quater- was stirred at room temperature for 4 h. The reaction mixture was
extracted with diethyl ether. The organic layer was washed with
brine, dried with Na2SO4, and concentrated. The crude product
was purified by silica gel column chromatography (hexane/ethyl
acetate, 20:1) and afforded 1h (0.51 g, 2.8 mmol, 36% yield) as a
nary stereocenter, in 75% yield with 33% ee.
yellow oil. IR (neat): ν = 2850, 1440, 1340, 1650, 760, 685 cm–1.
˜
1H NMR (CDCl3, 300 MHz): δ = 7.40–7.49 (m, 2 H), 7.28–7.35
(m, 3 H), 4.46 (s, 2 H), 4.28 (q, J = 2.4 Hz, 2 H), 1.88 (t, J =
2.4 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 131.7, 128.4,
128.2, 122.5, 86.5, 84.5, 83.1, 74.4, 57.2, 57.1, 3.6 ppm. HRMS
(EI): calcd. for C13H12O [M]+ 184.0888; found 184.0859.
Representive Procedure for [2+2+2] Cycloaddition of Alkynes with
Nitriles (Table 1, Entry 1): Under Ar, BINAP (7.5 mg, 0.012 mmol)
and [Rh(cod)2]BF4 (4.9 mg, 0.012 mmol) were dissolved in CH2Cl2
(2.0 mL), and the mixture was stirred at room temperature for
5 min. H2 was introduced to the resulting solution in a Schlenk
tube. After stirring at room temperature for 0.5 h, the resulting
solution was concentrated to dryness and the residue dissolved in
CH2Cl2 (2.0 mL). To this solution was added dropwise over 1 min
a solution of dimethyl 2,2-dibut-2-ynylmalonate (1a, 94.5 mg,
0.400 mmol) and ethyl cyanoformate (2a, 43.6 mg, 0.440 mmol) in
CH2Cl2 (1.0 mL) at room temperature. Undissolved substrate was
dissolved by addition of CH2Cl2 (1.0 mL). The mixture was stirred
at room temperature for 3 h. The resulting solution was concen-
trated and purified by silica gel column chromatography (Et2O),
which furnished pyridine 3aa (134.1 mg, 0.400 mmol, Ͼ99% yield)
Scheme 6. Rhodium-catalyzed enantioselective [2+2+2] cycload-
dition of a 1,6-diyne with substituted malononitriles.
Conclusions
In conclusion, we have determined that cationic rhodi-
um(I)/modified-BINAP complexes are versatile new cata- as a pale yellow solid.
Eur. J. Org. Chem. 2006, 3917–3922
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3919

K. Tanaka, N. Suzuki, G. Nishida
FULL PAPER
Pyridine 3aa: M.p. 72.0–74.0 °C. IR (neat): ν = 3350, 2900, 1720,
60.1, 53.2, 40.4, 38.0 ppm. HRMS (EI): calcd. for C18H17NO4
˜
1420, 1200, 1040, 860, 720 cm–1. 1H NMR (CDCl3, 300 MHz): δ = [M]+ 311.1158; found 311.1144.
4.43 (q, J = 7.2 Hz, 2 H), 3.78 (s, 6 H), 3.60 (s, 4 H), 2.49 (s, 3 H),
Pyridine 3ee: Yield 63% (63 mg). Pale yellow solid; m.p. 99.0–
2.39 (s, 3 H), 1.41 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 171.5, 166.9, 150.9, 150.0, 146.8, 136.3, 127.7, 61.5,
59.1, 53.2, 39.9, 39.2, 21.8, 15.4, 14.2 ppm. HRMS (EI): calcd. for
C17H21NO6 [M]+ 335.1369; found 335.1342.
100.0 °C. IR (neat): ν = 1720, 1270, 1150, 870 cm–1. 1H NMR
˜
(CDCl3, 300 MHz): δ = 8.33 (s, 1 H), 7.03 (s, 1 H), 3.76 (s, 6 H),
3.58 (s, 2 H), 3.55 (s, 2 H), 2.51 (s, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 171.5, 156.7, 149.9, 144.6, 133.0, 119.0, 60.1, 53.1,
40.1, 37.9, 24.2 ppm. HRMS (EI): calcd. for C13H15NO4 [M]+
249.1001; found 249.0972.
Pyridine 3ba: Yield 91% (112 mg). Pale yellow oil. IR (neat): ν =
˜
2850, 1710, 1580, 1430, 1380, 1320, 1190, 1110, 1050 cm–1. 1H
NMR (CDCl3, 400 MHz): δ = 4.43 (q, J = 7.2 Hz, 2 H), 3.36 (s, 6
H), 3.36 (s, 2 H), 3.34 (s, 2 H), 2.83 (s, 4 H), 2.45 (s, 3 H), 2.36 (s,
3 H), 1.41 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz):
δ = 167.2, 152.3, 151.4, 146.0, 138.6, 128.2, 75.9, 61.4, 59.2, 47.3,
38.1, 37.5, 21.8, 15.4, 14.3 ppm. HRMS (EI): calcd. for C17H25NO4
[M]+ 307.1784; found 307.1799.
Pyridine 3ef:[31] Yield 60% (93 mg). Pale yellow solid; m.p. 152.0–
1
154.0 °C. H NMR (CDCl3, 300 MHz): δ = 8.48 (s, 1 H), 8.04 (s,
1 H), 7.92 (d, J = 8.4, 2 H), 7.32 (d, J = 8.4, 2 H), 3.77 (s, 6 H),
3.68 (s, 2 H), 3.64 (s, 2 H), 2.41 (s, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 170.8, 157.6, 151.9, 146.0, 144.7, 140.0, 136.0, 129.7,
128.8, 118.2, 59.9, 53.3, 40.2, 38.1, 21.6 ppm.
Pyridine 3ca: Yield Ͼ99% (150 mg). Pale yellow solid; m.p. 185–
Pyridine 3eg: Yield 35% (39 mg). Pale yellow oil. IR (neat): ν =
˜
187 °C. IR (neat): ν = 1710, 1330, 1160, 1050, 820, 690, 660 cm–1.
2950, 1730, 1590, 1430, 1260, 1060 cm–1. 1H NMR (CDCl3,
300 MHz): δ = 8.28 (s, 1 H), 7.06 (s, 1 H), 3.76 (s, 6 H), 3.56 (s, 2
H), 3.53 (s, 2 H), 2.54 (s, 3 H) ppm. 13C NMR (CDCl3, 75 MHz):
δ = 171.4, 158.2, 149.9, 144.8, 132.1, 116.9, 60.2, 53.2, 40.0, 37.7,
13.6 ppm. HRMS (EI): calcd. for C13H15NO4S [M–OMe]+
250.0538; found 250.0518.
˜
1H NMR (CDCl3, 300 MHz): δ = 7.79 (d, J = 8.1 Hz, 2 H), 7.35
(d, J = 8.1 Hz, 2 H), 4.62 (s, 4 H), 4.43 (q, J = 7.2 Hz, 2 H), 2.44
(s, 3 H), 2.43 (s, 3 H), 2.34 (s, 3 H), 1.40 (t, J = 7.2 Hz, 3 H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 166.2, 149.9, 147.4, 146.5, 144.1,
133.5, 132.8, 130.0, 127.4, 126.5, 61.8, 53.4, 52.8, 21.7, 21.5, 15.4,
14.2 ppm. HRMS (EI): calcd. for C18H21N3O3S [M]+ 359.3285;
found 359.3295.
Pyridine 3eh:[32] Yield 47% (60 mg). Colorless solid; m.p. 147.0–
1
148.0 °C. H NMR (CDCl3, 400 MHz): δ = 8.02 (s, 1 H), 6.53 (s,
Pyridine 3da: Yield Ͼ99% (100 mg). Pale yellow oil. IR (neat): ν =
˜
1 H), 3.78–3.85 (m, 4 H), 3.75 (s, 6 H), 3.50 (s, 4 H), 3.41–3.48 (m,
4 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 171.6, 159.3, 151.5,
142.9, 126.2, 102.6, 66.7, 65.6, 60.5, 53.0, 48.8, 46.1, 40.4,
37.4 ppm.
1
2850, 1710, 1580, 1430, 1300, 1180, 1050, 900, 730 cm–1. H NMR
(CDCl3, 300 MHz): δ = 5.17 (s, 2 H), 5.16 (s, 2 H), 4.46 (q, J =
7.2 Hz, 2 H), 2.62–2.82 (m, 4 H), 1.43 (t, J = 7.5 Hz, 3 H), 1.27 (t,
J = 7.5 Hz, 3 H), 1.20 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 166.8, 153.8, 149.0, 147.3, 134.7, 130.8, 72.5, 72.4,
61.5, 29.2, 23.4, 14.3, 14.1, 12.7 ppm. HRMS (EI): calcd. for
C15H19NO3 [M]+ 202.0550; found 202.0526.
Pyridine 3fa: Yield 84% (88 mg). Colorless oil. IR (neat): ν = 2820,
˜
1700, 1550, 1400, 1290, 1160, 1040, 760 cm–1. 1H NMR (CDCl3,
300 MHz): δ = 4.43 (q, J = 7.2 Hz, 2 H), 2.60–2.85 (m, 8 H), 1.70–
1.88 (m, 4 H), 1.40 (t, J = 7.2 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3 H),
1.18 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ =
168.1, 158.7, 146.1, 145.1, 133.6, 132.2, 61.2, 28.0, 26.0, 22.2, 22.1,
21.4, 14.3, 14.2, 12.8 ppm. HRMS (EI): calcd. for C16H23NO2
[M]+ 261.1729; found 261.1760.
Pyridine 3ea:[31] Yield 69% (85 mg). Pale yellow oil. 1H NMR
(CDCl3, 300 MHz): δ = 8.59 (s, 1 H), 8.01 (s, 1 H), 4.47 (q, J =
7.2 Hz, 2 H), 3.78 (s, 6 H), 3.69 (s, 2 H), 3.67 (s, 2 H), 1.44 (t, J =
7.2 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 171.1, 165.2,
150.7, 147.1, 145.5, 139.9, 121.2, 61.9, 60.1, 53.3, 40.2, 38.4,
14.3 ppm.
Pyridine 3ga: Yield 63% (62 mg). Pale brown oil. IR (neat): ν =
˜
1
2900, 1720, 1560, 1420, 1310, 1190, 1050 cm–1. H NMR (CDCl3,
300 MHz): δ = 4.44 (q, J = 7.2 Hz, 2 H), 2.80–2.90 (m, 4 H), 2.54
(s, 3 H), 2.34 (s, 3 H), 1.72–1.90 (m, 2 H), 1.47–1.65 (m, 4 H), 1.42
(t, J = 7.2 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 168.1,
152.5, 152.1, 147.0, 138.8, 127.0, 61.5, 31.8, 29.4, 29.1, 26.2, 25.8,
23.2, 15.2, 14.2 ppm. HRMS (EI): calcd. for C15H21NO2 [M]+
247.1572; found 247.1585.
Pyridine 3ab: Yield Ͼ99% (147 mg). Pale yellow solid; m.p. 150.0–
151.0 °C. IR (neat): ν = 2900, 1730, 1430, 1260, 1160, 1060, 920,
˜
680 cm–1. 1H NMR (CDCl3, 300 MHz): δ = 7.82–7.92 (m, 2 H),
7.52–7.62 (m, 1 H), 7.34–7.50 (m, 2 H), 3.81 (s, 6 H), 3.65 (s, 2 H),
3.63 (s, 2 H), 2.46 (s, 3 H), 2.23 (s, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 195.7, 171.6, 153.6, 150.3, 149.6, 136.4, 135.0, 133.3,
130.6, 128.3, 125.8, 59.1, 53.3, 39.8, 39.3, 21.7, 14.7 ppm. HRMS
(EI): calcd. for C21H21NO5 [M–CO2Me]+ 308.1287; found
308.1263.
Pyridine 3ai:[32] Yield 84% (102 mg). Pale yellow solid; m.p. 107–
1
109 °C. H NMR (CDCl3, 300 MHz): δ = 3.83 (s, 2 H), 3.78 (s, 6
H), 3.57 (s, 4 H), 2.42 (s, 1 H), 2.27 (s, 1 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 171.6, 151.2, 149.7, 146.5, 134.0, 125.0, 59.4,
53.3, 39.8, 39.0, 24.7, 21.5, 14.7 ppm.
Pyridine 3ac: Yield 98% (120 mg). Colorless solid; m.p. 100.0–
102.0 °C. IR (neat): ν = 2925, 1730, 1690, 1570, 1420, 1250, 1160,
˜
1
1060, 930, 680 cm–1. H NMR (CDCl3, 300 MHz): δ = 3.78 (s, 6
Pyridine 3ei:[33] Yield 73% (80 mg). Pale brown oil. 1H NMR
(CDCl3, 300 MHz): δ = 8.41 (s, 1 H), 7.32 (s, 1 H), 3.90 (s, 2 H),
3.77 (s, 6 H), 3.63 (s, 2 H), 3.62 (s, 2 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 171.2, 151.4, 148.9, 145.5, 135.7, 118.2, 117.1, 60.1,
53.2, 40.2, 37.9, 26.4 ppm.
H), 3.06 (s, 4 H), 2.67 (s, 3 H), 2.46 (s, 3 H), 2.43 (s, 3 H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 202.8, 171.6, 150.8, 150.1, 149.9,
136.6, 127.6, 59.1, 53.2, 39.8, 39.3, 28.5, 21.7, 15.6 ppm. HRMS
(EI): calcd. for C16H19NO5 [M–Ac]+ 262.1079; found 262.1050.
Pyridine 3ed: Yield 87% (108 mg). Colorless solid; m.p. 109.0–
Pyridine 3ej: Yield 59% (62 mg). Pale yellow solid; m.p. 66.5–
110.0 °C. IR (neat): ν = 2950, 1720, 1430, 1260, 1160, 1050, 880,
68.5 °C. IR (neat): ν = 3200, 1720, 1420, 1270, 1160, 1060, 920,
˜
˜
730, 690 cm–1. 1H NMR (CDCl3, 300 MHz): δ = 8.53 (s, 1 H), 890 cm–1. H NMR (CDCl3, 300 MHz): δ = 8.41 (s, 1 H), 7.27 (s,
7.85–7.96 (m, 2 H), 7.58 (s, 1 H), 7.38–7.50 (m, 3 H), 3.78 (s, 6 H), 1 H), 6.79 (dd, J = 10.8, 17.4 Hz, 1 H), 6.12 (d, J = 17.4 Hz, 1 H),
1
3.664 (s, 2 H), 3.655 (s, 2 H) ppm. 13C NMR (CDCl3, 75 MHz): δ
= 171.5, 156.4, 150.4, 145.2, 139.5, 134.6, 128.7, 128.6, 126.9, 116.5,
5.44 (d, J = 10.8 Hz, 1 H), 3.77 (s, 6 H), 3.61 (s, 2 H), 3.59 (s, 2 H)
ppm. 13C NMR (CDCl3, 75 MHz): δ = 171.4, 154.6, 150.0, 145.1,
3920
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3917–3922

Catalyzed [2+2+2] Cycloaddition of Alkynes with Nitriles
FULL PAPER
136.9, 134.9, 117.6, 116.8, 60.2, 53.2, 40.2, 38.1 ppm. HRMS (EI):
calcd. for C14H15NO4 [M]+ 261.1001; found 261.0960.
2.41 (s, 3 H), 2.36 (s, 3 H), 1.74 (s, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 171.73, 171.71, 152.3, 150.5, 149.8, 136.0, 133.1,
130.6, 128.1, 127.1, 125.4, 123.4, 59.2, 53.2, 45.4, 42.8, 40.2, 38.9,
25.7, 21.7, 15.9 ppm. HRMS (EI): calcd. for C24H26N2O4 [M]+
406.1893; found 406.1888. Chiralpak AD-H, hexane/2-PrOH, 95:5,
1.0 mL/min, retention times: 10.0 min (major isomer) and 8.9 min
(minor isomer).
Pyridine 6ha: Yield 74% (84 mg). Pale yellow oil. IR (neat): ν =
˜
2850, 1720, 1580, 1420, 1320, 1190, 1140, 1060, 1030, 900, 730,
700 cm–1. 1H NMR (CDCl3, 300 MHz): δ = 7.33–7.46 (m, 3 H),
7.19–7.30 (m, 2 H), 5.20 (s, 2 H), 5.01 (t, J = 2.1 Hz, 2 H), 4.13 (q,
J = 7.2 Hz, 2 H), 2.56 (s, 3 H), 0.99 (t, J = 7.2 Hz, 3 H) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 166.8, 150.3, 148.8, 148.0, 136.2,
135.2, 128.9, 128.5, 128.0, 127.9, 73.3, 72.6, 61.4, 22.0, 13.5 ppm.
HRMS (EI): calcd. for C17H17NO3 [M]+ 283.1208; found 283.1251.
Supporting Information (see footnote on the first page of this arti-
1
cle): H NMR spectra of product pyridines and diyne 1h.
Pyridine 7ha: Yield 12% (14 mg). Colorless oil. IR (neat): ν = 1700,
˜
Acknowledgments
1420, 1200, 1140, 1040, 920, 780, 730, 690 cm–1. 1H NMR (CDCl3,
300 MHz): δ = 7.70–7.80 (m, 2 H), 7.36–7.55 (m, 3 H), 5.40 (t, J
= 2.1 Hz, 2 H), 5.17 (s, 2 H), 4.47 (q, J = 7.2 Hz, 2 H), 2.46 (s, 3
H), 1.45 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (CDCl3, 75 MHz): δ
= 166.3, 151.1, 149.0, 147.7, 138.3, 134.2, 129.1, 128.7, 127.7, 126.2,
73.9, 72.8, 61.6, 15.7, 14.3 ppm. HRMS (EI): calcd. for C17H17NO3
[M]+ 283.1208; found 283.1137.
This work was supported by Uehara Memorial Foundation. We
thank Solvias AG for the gift of (R)-xyl-Solphos under their Uni-
versity Ligand Kit program and Takasago International Corpora-
tion for the gift of Segphos and H8-BINAP.
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Pyridine 6hi: Yield 73% (73 mg). Pale yellow oil. IR (neat): ν =
˜
2850, 1580, 1420, 1060, 900, 730, 710 cm–1. 1H NMR (CDCl3,
300 MHz): δ = 7.40–7.53 (m, 3 H), 7.20–7.28 (m, 2 H), 5.17 (s, 2
H), 4.90 (t, J = 2.4 Hz, 2 H), 3.72 (s, 2 H), 2.51 (s, 3 H) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 150.8, 149.0, 146.4, 135.5, 133.3,
129.3, 128.7, 128.6, 128.3, 73.2, 72.6, 24.5, 22.0 ppm. HRMS (EI):
calcd. for C16H14N2O [M]+ 250.1106; found 250.1098.
Pyridine 9: Yield 71% (123 mg). Pale yellow oil. IR (neat): ν =
˜
2850, 1710, 1600, 1210 cm–1. 1H NMR (CDCl3, 300 MHz): δ =
7.75 (s, 1 H), 7.13 (s, 1 H), 4.46 (q, J = 7.2 Hz, 2 H), 2.85 (t, J =
7.8 Hz, 2 H), 2.63 (t, J = 7.8 Hz, 2 H), 1.55–1.85 (m, 4 H), 1.43 (t,
J = 7.2 Hz, 3 H), 1.17–1.39 (m, 28 H), 0.88 (t, J = 6.6 Hz, 6 H)
ppm. 13C NMR (CDCl3, 75 MHz): δ = 165.9, 163.0, 152.9, 147.8,
125.9, 122.8, 61.7, 38.4, 35.2, 31.88, 31.86, 30.3, 30.1, 29.58, 29.55,
29.48, 29.45, 29.34, 29.30, 29.27, 29.16, 22.7, 14.3, 14.1 ppm.
HRMS (ESI): calcd. for C28H49NO2 [M + Na]+ 454.3661; found
454.3660.
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Pyridine 10: Yield 23% (40 mg). Colorless oil. IR (neat): ν = 2850,
˜
1720, 1590, 1450, 1280, 1200, 1080 cm–1. 1H NMR (CDCl3,
300 MHz): δ = 7.48 (d, J = 8.1 Hz, 1 H), 7.17 (d, J = 8.1 Hz, 1 H),
4.44 (q, J = 7.2 Hz, 2 H), 2.70–2.85 (m, 4 H), 1.50–1.78 (m, 4 H),
1.42 (t, J = 7.2 Hz, 3 H), 1.15–1.38 (m, 28 H), 0.88 (t, 6 H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 167.2, 159.9, 148.2, 138.7, 134.9,
124.4, 61.6, 38.0, 32.3, 31.9, 31.3, 29.9, 29.58, 29.55, 29.52, 29.5,
29.4, 29.3, 22.7, 14.2, 14.1 ppm. HRMS (ESI): calcd. for
C28H49NO2 [M+Na]+ 454.3661; found 454.3666.
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Pyridine (+)-3ak: Yield 91% (143 mg). Colorless oil. [α]2D5 = +29.3
(CHCl , c = 2.335, 64% ee). IR (neat): ν = 2900, 1720, 1580, 1430,
˜
3
1260, 1160, 1060, 730, 700 cm–1. 1H NMR (CDCl3, 300 MHz): δ =
7.32–7.14 (m, 5 H), 4.21 (dd, J = 8.4, 6.9 Hz, 1 H), 3.78 (s, 3 H),
3.77 (s, 3 H), 3.74 (s, 2 H), 3.51 (s, 2 H), 3.36 (dd, J = 13.5, 8.4 Hz,
1 H) 3.22 (dd, J = 13.5, 6.9 Hz, 1 H), 2.47 (s, 3 H), 2.05 (s, 3 H)
ppm. 13C NMR (CDCl3, 75 MHz): δ = 171.7, 171.5, 151.4, 150.1,
149.4, 137.2, 133.5, 129.1, 128.6, 127.2, 124.3, 120.0, 59.3, 53.24,
53.22, 39.9, 39.1, 39.0, 38.2, 21.7, 14.3 ppm. HRMS (EI): calcd. for
C23H24N2O4 [M–CO2Me]+ 333.1603; found 333.1589. Chiralpak
AD-H, hexane/2-PrOH, 95:5, 1.0 mL/min, retention times:
25.8 min (major isomer) and 27.9 min (minor isomer).
Pyridine (+)-3al: Yield 75% (122 mg). Colorless oil. [α]2D5 = +2.4
(CHCl , c = 9.520, 33% ee). IR (neat): ν = 2900, 1730, 1580, 1430,
˜
3
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Eur. J. Org. Chem. 2006, 3917–3922
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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3921

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Received: April 23, 2006
Published Online: June 21, 2006
3922
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3917–3922