BF3-mediated oxidative cross-coupling of pyridines with alkynyllithium reagents and further reductive functionalizations of the pyridine scaffold

Article abstract of DOI:10.1055/s-0033-1341235

A set of functionalized alkynylpyridines can be readily obtained using Et₂O·BF₃ as promoter. Alkynyllithium reagents undergo an addition reaction at position C-2 of pyridines that are rearomatized by oxidative treatment with chloranil. These substituted pyridines can be easily converted into more valuable intermediates. Examples of applications are given as well. Finally, the synthesis of piperidines and lactams via first an oxidative BF₃-mediated addition reaction followed by a NaBH ₄ reduction or acidic workup is also described. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1341235

1374▌
PRACTICAL SYNTHETIC PROCEDURES
practical synthetic procedures
BF3-Mediated Oxidative Cross-Coupling of Pyridines with Alkynyllithium
Reagents and Further Reductive Functionalizations of the Pyridine Scaffold
BF3-Mediated Synthesis of Functionalized Alkynylpyridines
Thierry León, Pauline Quinio, Quan Chen, Paul Knochel*
Ludwigs-Maximilians-Universität München, Department Chemie, Butenandtstraße 5–13, Haus F,
81377 München, Germany
Fax +49(89)218077680; E-mail: Paul.Knochel@cup.uni-muenchen.de
PSP
Received: 31.03.2014; Accepted: 02.04.2014
No272
Abstract: A set of functionalized alkynylpyridines can be readily obtained using Et2O·BF3 as promoter. Alkynyllithium reagents undergo
an addition reaction at position C-2 of pyridines that are rearomatized by oxidative treatment with chloranil. These substituted pyridines
can be easily converted into more valuable intermediates. Examples of applications are given as well. Finally, the synthesis of piperidines
and lactams via first an oxidative BF3-mediated addition reaction followed by a NaBH4 reduction or acidic workup is also described.
Key words: cross-coupling, pyridines, alkynyllithiums, BF3, piperidines, lactams
Cl
N
Cl
Cl
1) BF3•OEt2 (1.1 equiv), 0 °C, 10 min
Li (CH2)4Cl
2)
(2a, 1.5 equiv), –30 °C, 1 h
N
3) chloranil (2 equiv), 25 °C, 2 h
1a
3a 81% (10 mmol scale)
75% (1 mmol scale)
Scheme 1 Typical procedure for the transition-metal-free BF3-mediated oxidative alkynylation of pyridines
Introduction
Subsequent oxidative treatment with chloranil resulted in
rearomatization of the ring. Thus, the activation of pyri-
dines with Et2O·BF3 shows high compatibility with lithi-
um species allowing the preparation of a new set of
functionalized alkynylpyridines in good yields. Herein,
we wish to demonstrate the practicality of this protocol
and its scaleability.
The pyridine scaffold has been demonstrated to be of out-
most interest as building block in many compounds of
pharmaceutical and biological interest.1 The derivatiza-
tion of pyridines still represents a major challenge and
much efforts are made to functionalize them in a straight-
forward manner.2 For example, the addition reaction of al-
kynyl moieties to the pyridine ring increases the Scope and Limitations
possibility of further chemical transformations of this N-
Typically, 4-chloropyridine (1a; 1 equiv) was activated
heteroaromatic ring. The introduction of alkynyl groups
are usually carried out by Sonogashira cross-coupling
protocol.3 These methods are well known for their gener-
ality and robustness, but they show some drawbacks,
namely, toxicity and high price of the metal catalysts as
well as the requirement of sophisticated ligands. A transi-
tion-metal-free protocol would be of paramount interest to
circumvent these drawbacks. Recently, we have reported
the beneficial effect of adding Et2O·BF3 to pyridines: a
strong activation of the pyridine ring is produced allowing
the efficient and regioselective addition of alkyl- and aryl-
magnesium or zinc reagents in the absence of a transition
metal.4 Interestingly, we found that the addition of al-
kynyllithium derivatives to BF3-activated pyridines al-
lowed a novel regioselective alkynylation process.5
with Et2O·BF3 (1.1 equiv, 0 °C, 15 min), followed by the
addition of 6-chlorohex-1-ynyllithium (2a; 1.5 equiv, –30
°C, 1 h). Subsequent rearomatization by treatment with
chloranil (2 equiv, 25 °C, 2 h) afforded the 2,4-disubstitut-
ed pyridine (3a) in 75% isolated yield on a 1 mmol scale
(Scheme 1). This addition reaction was also performed on
a larger scale as well. Thus, the upscaling of 3a to a 10
mmol scale was performed leading to a slightly improved
yield of 81% (Scheme 1). With these conditions in hand,
the alkynylation of a range of pyridines was examined on
a 1 mmol and 10 mmol scale (Table 1). Thus, 4-chloropyr-
idine (1a) was alkynylated with phenylethynyllithium
(2b) and with oct-1-ynyllithium (2c) to afford the expect-
ed pyridines 3b and 3c in 65 and 75% yield, respectively,
on a 1 mmol scale. Upscaling to 10 mmol of latter reac-
tions gave excellent yields in the range of 55–81% (Table
1, entries 1 and 2). Isonicotinonitrile (1b) reacted with
(cyclohex-1-en-1-ylethynyl)lithium (2d) and with 6-chlo-
rohex-1-ynyllithium (2a) affording the corresponding di-
SYNTHESIS 2014, 46, 1374–1379
Advanced online publication: 24.04.2014
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1341235; Art ID: ss-2014-t0215-psp
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
BF3-Mediated Synthesis of Functionalized Alkynylpyridines
1375
substituted pyridines 3d and 3e in 77–86% yield on a 10 factorily alkynylated with oct-1-ynyllithium (2c) to give
mmol scale. Similar results were obtained on a 1 mmol the 2,6-disubstituted pyridine 3f in moderate yields of 52–
scale (entries 3 and 4). Picolinonitrile (1c) was also satis- 55% (entry 5).
Table 1 Direct Alkynylation of Pyridine Derivatives 1 Using Various Alkynyllithiums 2 Leading to Products 3
Entry
Substrate 1
RLi 2
Product 3
Scale (mmol)
Yield (%)a
Cl
Cl
Li
10
1
81
75
N
1
N
2b
1a
3b
Cl
Li
10
1
55
65
H13C6
2
3
1a
N
C6H13
2c
3c
CN
CN
Li
10
1
77
76
N
N
2d
1b
3d
CN
Li
10
1
86
89
4
5
1b
Cl(H2C)4
N
(CH2)4Cl
2a
3e
10
1
52
55
N
CN
2c
N
CN
H13C6
1c
3f
Br
Li
Br
N
N
6
1
52
63
6
MeO
OMe
1d
1d
2e
3g
Br
10
1
73
76
N
7
2b
3h
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1374–1379

1376
T. León et al.
PRACTICAL SYNTHETIC PROCEDURES
Table 1 Direct Alkynylation of Pyridine Derivatives 1 Using Various Alkynyllithiums 2 Leading to Products 3 (continued)
Entry
Substrate 1
RLi 2
Product 3
Scale (mmol)
Yield (%)a
Br
Li
10
1
61
65
8
1d
N
2f
3i
Br
Br
N
10
1
75
82
9
2b
N
1e
3j
3k
3l
t-Bu
t-Bu
10
1
60
66
10b
11b
12b
2a
N
N
(CH2)4Cl
1f
Li
F
N
F
8
1
60
68
N
1g
2g
N
10
1
54
50
2b
N
1h
3m
a Yield of isolated analytically pure compounds.
b Reaction time: 2 h.
Interestingly, the described protocol showed a compatibil- products 3k and 3l in 60–68% yield (entries 10 and 11).
ity with the use of bromopyridines such as 4-bromopyri- Finally, the reaction of pyridine 1h with phenylethynyl-
dine (1d) or 3-bromopyridine (1e). Thus, when 1c was lithium (2b) allowed the formation of 2-(phenylethyn-
submitted to the standard reaction conditions with aryle- yl)pyridine (3m) in 50–54% yield (entry 12). It should be
thynyllithium species 2b and 2e, the corresponding 2,4- noted that alkylpyridines and unsubstituted pyridines re-
disubstituted pyridines 3g,h were obtained in 52–76% quired longer reaction time (2 h) to achieve almost full
yield (entries 6 and 7). When cyclopropylethynyllithium conversion, showing that they are probably less activated
reagent 2f was used, 4-bromo-2-(cyclopropylethynyl)pyr- as substrates.
idine (3i) was produced in 61–65% yield (entry 8). 3-Bro-
mopyridine (1e) was treated with phenylethynyllithium
(2b) leading to the corresponding 2,3-disusbtituted pyri-
dine 3j in 82% isolated yield on a 1 mmol scale, although
a slight erosion was seen on a larger scale (entry 9). Re-
markably, electron-rich alkylpyridines, such as 4-tert-bu-
tylpyridine (1f) and 3-picoline (1g), also react well under
the described reaction conditions. Thus, alkylpyridines 1f
In order to show the usefulness of this method, the alkynyl
groups of several alkynylpyridines obtained by our proto-
col were derivatized (Scheme 2). Thus, alkynes 3e and 3i
were submitted to cobalt-mediated intermolecular
Pauson–Khand reaction6 and the resulting adducts 4a,b
were obtained in 60–69% yield.7
Furthermore, the derivatization of BF3-pyridine adducts
obtained by oxidative addition of alkyl- or arylmagnesium
and 1g were independently treated with alkynyllithium re-
agents 2a and 2g, affording the 2,4- and 2,3-disubstituted
reagents was studied briefly.4 Lately, the preparation of
1,2,5,6-tetahydropyridines through a C-2 regioselective
Synthesis 2014, 46, 1374–1379
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
BF3-Mediated Synthesis of Functionalized Alkynylpyridines
1377
addition of organomagnesium reagents to N-benzoylimi-
nopyridinium ylides8 and pyridine N-oxides9 followed by
a NaBH4 in methanol reduction protocol was reported. By
taking advantage of these described protocols, we applied
the NaBH4 reduction to our system. After screening sev-
eral proton sources, NH2OH·HCl and pyridine·HCl were
found to be the best acid promoting a selective reduction.
As a typical example, ethyl nicotinate (1i) was successful-
ly treated with Et2O·BF3 and o-TolMgBr·LiCl. Subse-
quent treatment with NaBH4/pyridine·HCl allowed the
partial reduction to the 1,4,5,6-tetrahydropyridine deriva-
tive 5 in 54% yield (Scheme 3). It should be noted that the
double bond conjugated to the ester was not reduced un-
der these conditions. It was found that these reductive
conditions can also be applied to quinolines. For instance,
when 6-methoxyquinoline (6) was submitted to the latter
reaction conditions, 4-isopropyl-6-methoxy-1,2,3,4-tetra-
hydroquinoline (7) was obtained in 81% yield (Scheme
3). In this particular case, the use of NH2OH·HCl as pro-
ton source gave the best results.
O
CN
H
1) Co2(CO)8 (1.1 equiv)
toluene, 25 °C, 1 h
Cl
2) norbornadiene (3 equiv)
90 °C, 16 h
N
H
CN
N
(CH2)4Cl
3e
4a 69%
O
Br
N
H
1) Co2(CO)8 (1.1 equiv)
toluene, 25 °C, 1 h
2) norbornadiene (3 equiv)
90 °C, 16 h
H
Br
N
3i
4b 60%
Scheme 2 Cobalt-mediated intermolecular Pauson–Khand reactions
of alkynes 3e and 3i
Acidic hydrolysis of BF3-pyridine intermediates bearing a
methoxy group can be also carried out, allowing the effi-
cient synthesis of γ-lactams.10 6-Methoxynicotinate (1j)
was successfully reacted with i-PrMgCl·LiCl in the pres-
ence of Et2O·BF3, subsequent workup with HCl in aque-
ous solution allowed the formation of the methyl 4-
isopropyl-6-oxo-1,4,5,6-tetrahydropyridine-3-carboxyl-
ate (8) in 97% yield (Scheme 4).
1) BF3·OEt2 (1.1 equiv)
CO2Et
THF, 0 °C, 15 min
CO2Et
2) o-TolMgBr·LiCl (1.5 equiv)
–30 °C, 2 h
N
N
1i
BF3
Conclusion
NaBH4 (3.0 equiv)
Py·HCl (3.0 equiv)
In summary, a practical and direct oxidative cross-
coupling of pyridines with alkynyllithium species is de-
scribed. The absence of transition metals makes this syn-
thesis an amenable protocol for larger preparatory scales.
The method also shows a good compatibility with various
functional groups. Additionally, we have also reported re-
ductive or hydrolytic conditions to derivatize the BF3-pyr-
idine intermediates formed by our addition protocol
leading to piperidine or lactam derivatives. We are cur-
rently extending this methodology to other heterocycles in
our laboratories.
NaBH4
CO2Et
CO2Et
MeOH, r.t., 1 h
N
N
H
BF3
5 54%
1) BF3·OEt2 (1.1 equiv)
THF, 0 °C, 15 min
MeO
MeO
2) i-PrMgCl·LiCl (1.2 equiv)
–50 °C, 30 min
N
N
H
6
7 81%
3) NaBH4 (3.0 equiv)
NH2OH·HCl (5.0 equiv)
Procedures
MeOH, r.t., 1 h
All reactions were carried out under argon atmosphere in dried
glassware. Commercially available starting materials were pur-
chased from commercial suppliers and used without further purifi-
cation, unless otherwise stated. THF was continuously refluxed and
freshly distilled from sodium benzophenone ketyl under N2. Yields
refer to isolated compounds estimated to be >95% pure as deter-
mined by 1H NMR and capillary GC analyses.
Scheme 3 Oxidative BF3-mediated cross-coupling of ethyl nicotin-
ate (1i) and 6-methoxyquinoline (6) and their subsequent reduction by
NaBH4, affording 5 and 7
1) BF3·OEt2 (1.1 equiv)
THF, 0 °C, 15 min
CO2Me
HCl
CO2Me
r.t., 2 h
2) i-PrMgCl·LiCl (1.2 equiv)
–50 °C, 30 min
MeO
N
O
N
H
1j
8 97%
Scheme 4 Oxidative BF3-mediated cross-coupling of 6-methoxynicotinate (1j) and subsequent acidic workup, affording 8
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1374–1379

1378
T. León et al.
PRACTICAL SYNTHETIC PROCEDURES
BF3-Mediated Direct Alkynylation of Pyridine Derivatives Us-
ing Alkynyllithium Reagents General Procedure
Piperidine Derivatives; Ethyl 4-(o-Tolyl)-1,4,5,6-tetrahydro-
pyridine-3-carboxylate (5); Typical Procedure
A dry and argon-flushed flask, equipped with a magnetic stirring
bar and a rubber septum was charged with a solution of a pyridine
derivative 1 (1 equiv) in anhydrous THF (0.5 M) and cooled to 0 °C.
Et2O·BF3 (1.1 equiv) was added dropwise and stirred for 15 min at
the same temperature. Then, the reaction mixture was cooled to
–30 °C. An alkynyllithium 2 [1.5 equiv; prepared by adding n-BuLi
(1.5 equiv) to a 0.75 M solution of the alkyne in THF at 0 °C and
stirring for 30 min] was cannulated to the reaction flask and the re-
sulting mixture was stirred at the same temperature for 1 h. Then,
chloranil (2 equiv) was added and the mixture was warmed to r.t.
and continuously stirred for 2 h. Finally, the mixture was quenched
with sat. aq NH4Cl/NH3 (4:1) solution and extracted with EtOAc
(2 × 20 mL). The organic phases were combined and filtered
through a layer of silica gel. The filtrate was concentrated in vacuo.
Purification by flash chromatography furnished the desired product
3 (see Supporting Information for further details).
A dry and argon flushed 10 mL flask, equipped with a magnetic stir-
ring bar and a rubber septum was charged with a solution of ethyl
nicotinate (1i; 149 mg, 1.0 mmol) in anhydrous THF (2 mL) and
cooled to 0 °C. Et2O·BF3 (156 mg, 1.1 mmol) was added dropwise
and stirred for 15 min at the same temperature. The reaction mixture
was cooled to –30 °C followed by the dropwise addition of a THF
solution of o-TolMgBr·LiCl (1.29 mL, 1.16 M, 1.5 mmol), the mix-
ture was stirred at the same temperature for 2 h. A solution of
NaBH4 (114 mg, 3.0 mmol in 2 mL MeOH) and a solution of
pyridine·HCl (347 mg, 3.0 mmol in 1 mL MeOH) were added and
the mixture was warmed up to r.t. and continuously stirred for 1 h.
Finally, the mixture was quenched with aq 1 M NaOH (1 mL) and
extracted with EtOAc (3 × 20 mL). The organic phases were com-
bined and filtered through a layer of silica gel. The filtrate was con-
centrated in vacuo. The crude product was purified by flash
chromatography (SiO2, EtOAc–i-hexane, 1:4) furnishing the com-
pound 5 (131 mg, 54%) as a white solid; mp 131.0–133.1 °C.
4-Chloro-2-(6-chlorohex-1-yn-1-yl)pyridine (3a)
IR (Diamond-ATR, neat): 3293, 1644, 1599, 1218, 1064, 742 cm–1.
To a solution of 4-chloropyridine (1a; 1.14 g, 10 mmol) in THF (20
mL) was added Et2O·BF3 (1.56 g, 11 mmol) dropwise at 0 °C. The
reaction mixture was stirred for 15 min and reacted with the lithium
reagent 2a [15 mmol; prepared by adding n-BuLi (15 mmol) to a
0.75 M solution of 6-chlorohex-1-yne in THF (1.75 g, 15 mmol) at
–10 °C and stirring for 30 min]. The crude product was purified by
flash chromatography (SiO2, EtOAc–i-hexane, 1:3) furnishing the
compound 3a (1.85 g, 81%) as a light reddish oil.
1H NMR (300 MHz, CDCl3): δ = 7.74 (d, J = 6.4 Hz, 1 H), 7.19–
6.93 (m, 4 H), 4.74 (br s, 1 H), 4.21 (d, J = 5.0 Hz, 1 H), 4.00 (q, J =
7.0 Hz, 2 H), 3.16–2.90 (m, 2 H), 2.44 (s, 3 H), 2.00–1.81 (m, 1 H),
1.68 (d, J = 13.0 Hz, 1 H), 1.12 (t, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 168.30, 144.39, 143.53, 134.92,
130.20, 127.59, 125.68, 125.26, 97.31, 58.82, 36.25, 32.39, 26.57,
19.17, 14.37.
IR (Diamond-ATR, neat): 2953, 2233, 1543, 1454, 1380, 1101, 825
cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.43 (d, J = 5.4 Hz, 1 H), 7.38 (dd,
J = 2.0, 0.5 Hz, 1 H), 7.21 (dd, J = 5.4, 2.0 Hz, 1 H), 3.59 (t, J = 6.4
Hz, 2 H), 2.50 (t, J = 6.9 Hz, 2 H), 2.01–1.90 (m, 2 H), 1.84–1.72
(m, 2 H).
MS (70 eV, EI): m/z (%) = 245 (55), 216 (68), 200 (39), 172 (100),
154 (41).
HRMS: m/z (M+) calcd for C15H19NO2: 245.1416; found: 245.1406.
γ-Lactam Derivatives; Methyl 4-Isopropyl-6-oxo-1,4,5,6-tetra-
hydropyridine-3-carboxylate (8); Typical Procedure
13C NMR (100 MHz, CDCl3): δ = 2.00, 80.51, 44.70, 31.73, 25.53,
18.75.
A dry and argon flushed 10 mL flask, equipped with a magnetic stir-
ring bar and a rubber septum was charged with a solution of methyl
6-methoxynicotinate (1j; 167 mg, 1.0 mmol) in anhydrous THF (2
mL) and cooled to 0 °C. Et2O·BF3 (156 mg, 1.1 mmol) was added
dropwise and stirred for 15 min at the same temperature. The reac-
tion mixture was cooled to –50 °C followed by dropwise addition of
a THF solution of i-PrMgCl·LiCl (0.93 mL, 1.29 M, 1.2 mmol), and
the mixture was stirred at the same temperature for 30 min. Then,
aq 2 M HCl (1 mL) was added and the mixture was warmed up to
r.t., and stirred for another 2 h. Finally, the mixture was extracted
with EtOAc (3 × 20 mL). The organic phases were combined and
filtered through a layer of silica gel. The filtrate was concentrated in
vacuo. The crude product was purified by flash chromatography
(SiO2, EtOAc–i-hexane 1:2), furnishing the compound 8 (192 mg,
97%) as a white solid; mp 159.2–161.7 °C.
MS (EI, 70 eV): m/z (%) = 227 (5), 192 (90), 164 (100), 151 (25).
HRMS (EI): m/z (M+) calcd for C11H11Cl2N: 227.0269; found:
227.0262.
Cobalt-Mediated Intermolecular Pauson–Khand Reaction; 2-
[(3aS,7aR)-2-(4-Chlorobutyl)-1-oxo-3a,4,7,7a-tetrahydro-1H-
4,7-methanoinden-3-yl)isonicotinonitrile (4a); Typical Proce-
dure
A dry and argon flushed flask, equipped with a magnetic stirring bar
and a rubber septum was charged with Co2(CO)8 (0.464 g, 1.36
mmol, 1.1 equiv), alkyne 3e (0.270 g, 1.23 mmol, 1 equiv), and an-
hydrous toluene (4 mL) at r.t. during 1 h. Then, norbornadiene (0.38
mL, 3.69 mmol, 3 equiv) was added via a syringe and the reaction
mixture was heated to 90 °C. The resulting mixture was stirred at
the same temperature for 16 h. Finally, the crude was concentrated
in vacuo and purified by flash chromatography (SiO2, EtOAc–
i-hexane, 2:8) furnishing the compound 4a (0.287 g, 69%) as a
beige solid; mp 119.3–121.8 °C.
IR (Diamond-ATR, neat): 2955, 2852, 1616, 1364, 1204, 1172, 804
cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.34 (br s, 1 H), 7.36 (d, J = 5.5
Hz, 1 H), 3.74 (s, 3 H), 2.86–2.72 (m, 1 H), 2.65–2.51 (m, 2 H),
1.96–1.76 (m, 1 H), 0.93 (d, J = 6.9 Hz, 3 H), 0.85 (d, J = 6.9 Hz, 3
H).
IR (Diamond-ATR, neat): 2941, 1688, 1584, 1353, 667 cm–1.
13C NMR (75 MHz, CDCl3): δ = 172.30, 167.02, 135.07, 111.16,
51.49, 36.74, 31.89, 31.12, 19.93, 17.82.
1H NMR (400 MHz, CDCl3): δ = 8.94 (br s, 1 H), 7.76 (br s, 1 H),
7.53 (br s, 1 H), 6.35 (br s, 1 H), 6.29 (br s, 1 H), 3.54 (m, 2 H), 3.27
(br s, 1 H), 3.02 (br s, 1 H), 2.65 (br s, 1 H), 2.59 (m, 2 H), 2.49 (br
s, 1 H), 1.86–1.76 (m, 2 H), 1.71–1.56 (m, 2 H), 1.43 (m, 1 H), 1.25
(m, 1 H).
MS (70 eV, EI): m/z (%) = 198 (12), 155 (100), 123 (40).
HRMS: m/z (M+) calcd for C10H15NO3: 197.1052; found: 197.1056.
13C NMR (100 MHz, CDCl3): δ = 209.16, 162.70, 155.67, 150.88,
149.11, 138.21, 137.66, 124.59, 124.20, 121.14, 116.24, 52.33,
48.92, 44.57, 43.97, 43.29, 41.77, 32.47, 25.33, 23.43.
Acknowledgment
We thank the European Research Council (ERC) under the Euro-
pean Community’s Seventh Framework Programme (FP7/2007-
2014) ERC Grant Agreement No. 227763 for financial support. We
MS (EI, 70 eV): m/z (%) = 341 (75), 273 (31), 209 (35), 66 (100).
HRMS (EI): m/z (M+) calcd for C20H19ClN2O: 338.1186); found:
338.1188.
Synthesis 2014, 46, 1374–1379
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
BF3-Mediated Synthesis of Functionalized Alkynylpyridines
1379
also thank BASF SE (Ludwigshafen); W. C. Heraeus (Hanau), and
Chemetall GmbH (Frankfurt) for the generous gift of chemicals.
B. E.; Whitwood, A. C.; Duhme-Klair, A. K.; Lynam, J. M.;
Fairlamb, I. J. S. J. Org. Chem. 2011, 76, 5320.
(4) Chen, Q.; Mollat du Jourdin, X.; Knochel, P. J. Am. Chem.
Soc. 2013, 135, 4958.
(5) Chen, Q.; León, T.; Knochel, P. Angew. Chem. Int. Ed. 2014,
53, in press; DOI: 10.1002/anie.201400750.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
(6) (a) For a recent review of Pauson–Khand reaction, see: The
Pauson–Khand Reaction: Scope, Variations and
Applications; Ríos Torres, R., Ed.; Wiley-VCH: Weinheim,
2012. For examples of application, see: (b) Vázquez-
Romero, A.; Cárdenas, L.; Blasi, E.; Verdaguer, X.; Riera,
A. Org. Lett. 2009, 11, 3104. (c) Kizirian, J.-C.; Aiguabella,
N.; Pesquer, A.; Fustero, S.; Bello, P.; Verdaguer, X.; Riera,
A. Org. Lett. 2010, 12, 5620.
(7) Only one regioisomer was detected by GC analysis. For a
study of regioselectivities in cobalt-mediated intermolecular
Pauson–Khand reaction, see ref. 3b.
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Synthesis 2014, 46, 1374–1379