Base-Promoted β-C(sp3)-H Functionalization of Enaminones: An Approach to Polysubstituted Pyridines

Article abstract of DOI:10.1021/acs.joc.5b00635

A convenient one-pot base-promoted synthesis of polysubstituted pyridines from 1-arylethylamines and ynones through the direct β-C(sp³)-H functionalization of enaminones under metal-free conditions has been developed. An intermolecular Michael addition reaction and an intramolecular condensation were involved in this procedure, which features high regioselectivity, high efficiency, and environmental friendliness. Various polysubstituted pyridines were provided in up to 92% yield for 34 examples.

Full text of DOI:10.1021/acs.joc.5b00635

Article
pubs.acs.org/joc
Base-Promoted β‑C(sp3)−H Functionalization of Enaminones: An
Approach to Polysubstituted Pyridines
Jinhai Shen, Dingding Cai, Changsheng Kuai, Yunqi Liu, Ming’e Wei, Guolin Cheng, and Xiuling Cui*
Key Laboratory of Xiamen Marine and Gene Drugs, Institutes of Molecular Medicine and School of Biomedical Sciences, Huaqiao
University & Engineering Research Center of Molecular Medicine, Ministry of Education, Xiamen 361021, China
S
* Supporting Information
ABSTRACT: A convenient “one-pot” base-promoted synthesis of polysubstituted pyridines from 1-arylethylamines and ynones
through the direct β-C(sp3)−H functionalization of enaminones under metal-free conditions has been developed. An
intermolecular Michael addition reaction and an intramolecular condensation were involved in this procedure, which features
high regioselectivity, high efficiency, and environmental friendliness. Various polysubstituted pyridines were provided in up to
92% yield for 34 examples.
Scheme 1. Synthesis of N-Heterocycles from Enaminones
INTRODUCTION
■
Pyridine represents one of the most prevalent structural
heterocycles in natural products, pharmaceuticals, and advanced
materials.1 Consequently, extensive research has focused on
building this motif.2 Among which, the condensation of
carbonyl compounds with ammonia is well-documented as
the traditional method.3 Recently, transition-metal-catalyzed
C−H functionalization and cycloaddition reactions4 and metal-
free pyridine synthesis5 have provided complementary path-
ways. Despite these advances, the development of a more
flexible and operationally simple method using readily available
starting materials with broad functional group tolerability is still
highly desirable.
β-Enaminones are gaining increased interest as attracting
building blocks due to the ambident nucleophilicity of
enamines and the ambident eletrophilicity of enones.6 Among
which, N-propargyl β-enaminones have been used as
intermediates for the synthesis of polysubstituted pyrroles
and pyridines in the present of base or transition metal by the
groups of Cacchi,7 Wan,8 and Saito9 (Scheme 1, a). N-Allyl β-
enaminones have been employed in the copper-mediated
aerobic synthesis of 3-azabicyclo[3.1.0]hex-2-enes and 4-
carbonylpyrroles by the Chiba group (Scheme 1, b).10 Recently,
we reported a base-promoted intramolecular condensation of
N-benzyl β-enaminones for the synthesis of substituted pyrroles
through a direct activation of the sp3 C−H bond adjacent to
nitrogen (Scheme 1, c).11 In 2011, the Knochel group reported
a novel substrate-controlled regioselective arylation of sub-
stituted Boc-piperidines,12 in which, when the α-C of the
nitrogen atom was occupied by a methyl group (2-methyl-
piperidine), the arylation unexpectedly occurred at the β-C
position. In our continuing efforts in enaminone chemistry,11,13
we explore the possibility of direct β-C(sp3)−H functionaliza-
tion of N-(α-substituted)-benzyl-β-enaminones. As a result, a
novel protocol to build polysubstituted pyridines from simple
1-arylethylamines and ynones under mild reaction conditions
has been established (Scheme 1, d).
Received: March 20, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00635
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
RESULTS AND DISCUSSION
Scheme 2. Reactions of 1-Phenylethylamine 4a with Various
Ynones 3
■
Initially, (Z)-1,3-diphenyl-3-((1-phenylethyl)amino)prop-2-en-
1-one 1aa was chosen as a model substrate to optimize the
reaction parameters. A series of DMSO-tailored heterogeneous
base systems were tested first. As seen from Table 1, all the
Table 1. Optimization of the Reaction Conditions for the
a
Cyclization of Compound 1aa to 2aa
b
entry
base
solvent
temp (°C)
t (h)
yield (%)
1
2
KOtBu
NaOtBu
LiOtBu
NaOMe
KOH
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
80
80
12
12
18
36
12
36
36
36
12
36
36
36
12
10
8
61
53
3
80
37
4
80
36
5
80
59
6
NaOH
80
56
7
DBU
80
32
8
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
80
38
9
NMP
80
45
10
11
12
13
14
15
toluene
CH3CN
dioxane
DMSO
DMSO
DMSO
DMSO
DMSO
80
NR
trace
NR
73
80
80
90
100
110
100
100
78 (77)
73
c
16
d
4
65
17
36
71
a
Reaction conditions: 1a (0.25 mmol), base (0.5 mmol), 1 mL of
b
solvent under air. Yields were determined by GC, isolated yield in
c
d
parentheses. NR = no reaction. Under O2. 0.25 mmol of base. DMF
= N,N-dimethylformamide. NMP = N-methyl-2-pyrrolidone. DMSO =
dimethyl sulfoxide.
the scope of yonones was explored. The results showed that
both electron-withdrawing and electron-donating substituents
on R1 and R2 were well-tolerated. 1,3-Diarylynones containing
electrodonating groups, such as −Me (2ba−2da, 2pa−2qa),
−OMe (2ea−2ga, 2ra), and −tBu (2ka), provided the
corresponding pyridines in good yields (53−75%). The
reactions of 1,3-diarylynones with electrowithdrawing groups
(−F and −CF3) also took place efficiently (72−79%, Scheme 2,
2ha−2ia, 2la, and 2sa). On the other hand, the steric hindrance
did not influence the transformation obviously. The ortho
substituents on R1 (2da and 2ga) gave similar yields to the
corresponding substrates with para and meta substituents (2da
vs 2ba, 2ca and 2ga vs 2ea, 2fa). Halogen, including F, Cl, and
Br, were all well-tolerated (2ha−2ja and 2sa−2ua, 53−79%
yield), which makes this reaction particularly attractive for
increasing the molecular complexity by plenty of transition-
metal-catalyzed coupling reactions. The fused aryl and
heteroaryl groups, such as naphthyl, thienyl, and furanyl, were
also suitable substrates and provided the corresponding
pyridines (2ma−2oa, 2va) in 54−82% yields. When R1 or R2
was an alkyl group, no desired product was obtained.
base/DMSO systems could promote the formation of 2,4,6-
triphenylpyridine 2aa (entries 1−6). The combination of
KOtBu/DMSO was found to be the most effective (yield of 2aa
being 61%, entry 1). Organic base, such as DBU (1,8-
diazabicyclo[5.4.0]undec-7-ene), also worked, albeit in a low
yield (32%, entry 7). Further screening solvents showed that
this reaction was highly solvent-dependent. Moderate to good
yields were achieved in DMSO, DMF, and NMP (entries 2, 8,
9). Toluene, CH3CN, and dioxane, however, led to no reaction
or low yields (entries 10−12). A 78% yield of the desired
product was achieved when the temperature was raised to 100
°C (entry 14). Further increasing the reaction temperature
accelerated this transformation, but the yield was not improved
(entry 15). O2 atmosphere and decreasing the amount of
KOtBu from 2 equiv to 1 equiv resulted in lower yields (entries
16 and 17). Finally, the optimal condition was identified as 2
equiv of KOtBu in DMSO at 100 °C under an air atmosphere.
Since the enaminones 1 could be readily prepared from
ynones 3 and 1-arylethylamines 4 via Michael addition reaction,
a straightforward “one-pot” strategy was adopted to directly
synthesize the polysubstituted pyridines 2 from ynones 3 and 1-
arylethylamines 4, avoiding isolation of the intermediate
enaminones 1 (Scheme 2). To our delight, 2,4,6-triphenylpyr-
idine 2aa was obtained from this one-pot strategy in a similar
isolated yield as that from enaminone 1aa (76% vs 77%). Next,
The scope of 1-arylethylamines 4 was investigated as well
(Scheme 3). 1-Phenylethylamines with both electron-with-
drawing and electron-donating as well as halogen substitutents,
such as methyl, methoxy, fluoro, chloro, and bromo, afforded
the corresponding 2,4,6-triarylpyridines in appreciable yields
(58−86%, 2ab−2af). 1-(Naphthalen-2-yl)ethylamine and 1-
B
DOI: 10.1021/acs.joc.5b00635
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Scheme 3. Reaction of 1,3-Diphenylprop-2-yn-1-one 3a with
Various 1-Arylethylamines 4
Scheme 5. Controlled Experiments
(thiophen-2-yl)ethylamine proceeded smoothly and produced
the desired pyridines 2ag and 2ah in excellent yields (92% and
90%, respectively). In terms of the R4 group, the aryl group
worked well under the optimized reaction conditions (57%,
Scheme 2, 2ai). The alkyl group (1-phenylpropan-1-amine, for
example) remained inert; only the enaminone intermediate was
obtained.
with 2 equiv of electrophiles (TMSCl and benzaldehyde) under
the standard reaction conditions, the desired product 2aa was
not detected (eq 2). These results indicated that this KOtBu-
mediated reaction might be an anion-initiated reaction to the
target products. When N-propenyl enaminone 6, prepared from
base-promoted alkene isomerization of N-allyl enaminone 5,16
was treated under the standard conditions for 12 h (eq 3), the
desired pyridine product 7 was obtained in 75% yield. This
result indicated that an N-alkenyl enaminone intermediate
might be involed in this reaction.
On the basis of the literatures and aforementioned
observations, a tentative reaction mechanism for the formation
of functionalized pyridines 2 was proposed, as depicted in
Scheme 6. The initial Michael addition reaction of 1-
2,4,6-Triarylpyridines (TAPs, Krohnke pyridines) are useful
̈
intermediates in the synthesis of drugs, herbicides, insecticides,
and desiccants and are also widely used in supramolecular
chemistry.14 However, unsymmetrical 2,4,6-triarylpyridines are
challenging targets for most reported methods.15 To further the
extensive application of our methodology, the synthesis of
unsymmetrical 2,4,6-triarylpyridine has been explored as well
(Scheme 4). As seen in Scheme 4, four unsymmetrical 2,4,6-
Scheme 4. One-Pot Synthesis of Unsymmetrical 2,4,6-
Triarylpyridines
Scheme 6. Proposed Reaction Mechanism
triarylpyridines were obtained in moderated to good isolated
yields (56−83%), suggesting that this protocol could be used
for preparation of unsymmetrical pyridines directly from simple
amines and ynones.
To gain further insight into the possible reaction mechanism,
some controlled experiments were carried out (Scheme 5). The
radical scavengers, TEMPO (2,2,6,6-tetramethylpiperidinooxy)
and 1,1-diphenylethylene, did not inhibited this transformation
(eq 1), which indicated that a radical pathway might not be
involved in this reaction. When enaminone 1aa was treated
arylethylamines 3 and ynones 4 provided the enaminones 1.
Deprotonation of 1 by KOtBu generated the anion
intermediates A.11,17 Subsequently, a base-promoted hydrox-
ylation gave the α-hydroxy enaninones B.18 Intermediate B
then underwent dehydration to give N-alkenyl enaminone C.
Base-promoted 1,5-H shift led to intermediate D, which further
gave the intermediate E by intramolecular electrocyclization.
C
DOI: 10.1021/acs.joc.5b00635
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
4-(4-Methoxyphenyl)-2,6-diphenylpyridine (2ea).15c Pale yellow
solid (111.2 mg, 66%), mp: 99−101 °C. 1H NMR (400 MHz, CDCl3)
δ 8.24−8.15 (m, 4H), 7.84 (s, 2H), 7.69 (d, J = 8.8 Hz, 2H), 7.53−
7.46 (m, 4H), 7.44 (d, J = 7.2 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 3.86
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.5, 157.4, 149.6, 139.7,
131.3, 128.9, 128.6, 128.3, 127.1, 116.6, 114.5, 55.4.
Finally, the desired product 2 was formed spontaneously by
dehydration of E.
CONCLUSION
■
In conclusion, an efficient approach to polysubstituted
pyridines in moderate to excellent yields from readily available
1-arylethylamines and ynones has been developed. The novel
direct N-β-C(sp3)−H functionalization of enaminones was
applied in this reaction. This protocol only required 2 equiv of
KOtBu as an additive, used air as an oxidant, and generated 2
equiv of H2O as sole byproduct, which made this process
environmentally friendly. This highly practical and modular
synthesis represents an alternative method to synthesize
pyridine with a broad substrate scope, high atom efficiency,
and important synthetic potential of the products.
4-(3-Methoxyphenyl)-2,6-diphenylpyridine (2fa). Yellow oil
1
(126.4 mg, 75%). H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 7.2
Hz, 4H), 7.87 (s, 2H), 7.58−7.39 (m, 7H), 7.32 (d, J = 7.6 Hz, 1H),
7.24 (d, J = 10.0 Hz, 1H), 7.00 (dd, J = 8.1, 2.2 Hz, 1H), 3.89 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 160.2, 157.5, 150.1, 140.6, 139.6,
130.2, 129.0, 128.7, 127.1, 119.6, 117.1, 114.5, 113.0, 55.4; HRMS
(ESI) m/z calcd for C24H20NO (MH+) 338.1545, found 338.1541.
4-(2-Methoxyphenyl)-2,6-diphenylpyridine (2ga). Pale yellow
solid (107.8 mg, 64%), mp: 120−121 °C. 1H NMR (400 MHz,
CDCl3) δ 8.17 (d, J = 7.5 Hz, 4H), 7.85 (s, 2H), 7.49 (t, J = 7.5 Hz,
4H), 7.41 (dt, J = 12.5, 6.2 Hz, 4H), 7.11−7.01 (m, 2H), 3.84 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 156.7, 156.6, 147.9, 139.8, 130.5,
130.0, 128.8, 128.6, 128.4, 127.1, 121.0, 119.7, 111.4, 55.6; HRMS
(ESI) m/z calcd for C24H20NO (MH+) 338.1545, found 338.1543.
4-(4-Fluorophenyl)-2,6-diphenylpyridine (2ha).15c Pale yellow
solid (86.1 mg, 53%), mp: 127−129 °C. 1H NMR (400 MHz,
CDCl3) δ 8.19 (d, J = 7.5 Hz, 4H), 7.82 (s, 2H), 7.71 (dd, J = 8.5, 5.4
Hz, 2H), 7.51 (t, J = 7.5 Hz, 4H), 7.44 (t, J = 7.1 Hz, 2H), 7.22 (dd, J
= 15.0, 6.5 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 163.4 (d, J =
249.1 Hz), 157.6, 149.2, 139.5, 135.2 (d, J = 3.2 Hz), 129.2, 129.0 (d, J
= 8.3 Hz), 128.8, 127.2, 116.9, 116.1 (d, J = 21.7 Hz).
EXPERIMENTAL SECTION
Unless otherwise stated, all commerical materials and solvents were
used directly without further purification. Melting points were
determined in open glass capillaries and were uncorrected. H NMR
■
1
spectra were recorded on 400 MHz spectrometers, and 13C NMR
spectra were recorded on a 100 MHz spectrometer. Chemical shifts
(in ppm) were referenced to tetramethylsilane (δ = 0 ppm) in CDCl3
as an internal standard at room temperature. 13C NMR spectra were
obtained by using the same NMR spectrometers and were calibrated
with CDCl3 (δ = 77.00 ppm). High-resolution mass spectra (HRMS)
were equipped with an ESI source and a TOF detector. Column
chromatography was performed on silica gel (70−230 mesh ASTM)
using the reported eluents. Thin-layer chromatography (TLC) was
carried out on 4 × 15 cm plates with a layer thickness of 0.2 mm (silica
gel 60 F254). The α,β-ynones 3 were prepared according to the
literatures.19
4-(3-Fluorophenyl)-2,6-diphenylpyridine (2ia). Pale yellow solid
1
(128.4 mg, 79%), mp: 138−139 °C. H NMR (400 MHz, CDCl3) δ
8.22 (d, J = 7.4 Hz, 4H), 7.87 (s, 2H), 7.50 (dt, J = 27.3, 7.3 Hz, 9H),
7.19 (t, J = 7.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 163.27 (d, J
= 246.9 Hz), 157.7, 148.9, 141.3 (d, J = 7.6 Hz), 139.7, 130.7 (d, J =
8.3 Hz), 129.2, 128.7, 127.1, 122.9 (d, J = 2.8 Hz), 116.9, 115.8 (d, J =
21.1 Hz), 114.2 (d, J = 22.3 Hz); HRMS (ESI) m/z calcd for
C23H17FN (MH+) 326.1345, found 326.1345.
4-(4-Chlorophenyl)-2,6-diphenylpyridine (2ja).15c White crystal-
General Procedure for Synthesis of Polysubstituted
Pyridines 2. 1-Arylethylamines 4 (0.5 mmol), α,β-ynones 3 (0.5
mmol), and 2 mL of DMSO were added to a 5 mL Schlenk tube
equipped with magnetic stirring. The mixture was stirred at ambient
temperature. After completion of Michael addition (monitored by
TLC), 2 equiv of KOtBu was added, and the mixture was heated to
100 °C, and stirred under air atmosphere. After completing reaction,
the mixture was diluted with ethyl acetate (10 mL) and washed with
brine (3 × 10 mL). The organic phase was dried over anhydrous
Na2SO4 and filtered. The solvents were evaporated, and the residue
was purified by silica gel column chromatography with EA/petroleum
ether (1:10) as the eluent to afford the products 2.
1
line solid (121.1 mg, 71%), mp: 130−132 °C. H NMR (400 MHz,
CDCl3) δ 8.24−8.14 (m, 4H), 7.81 (s, 2H), 7.65 (dd, J = 8.8, 2.1 Hz,
2H), 7.55−7.40 (m, 8H); 13C NMR (100 MHz, CDCl3) δ 157.6,
148.9, 139.4, 137.5, 135.2, 129.3, 129.1, 128.7, 128.4, 127.1, 116.8.
4-(4-(tert-Butyl)phenyl)-2,6-diphenylpyridine (2ka). Yellow oil
1
(96.2 mg, 53%). H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.0
Hz, 4H), 7.88 (s, 2H), 7.69 (d, J = 8.2 Hz, 2H), 7.56−7.48 (m, 6H),
7.43 (t, J = 7.2 Hz, 2H), 1.38 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
157.4, 152.3, 150.0, 139.7, 136.1, 129.0, 128.7, 127.1, 126.8, 126.1,
117.0, 34.7, 31.3; HRMS (ESI) m/z calcd for C27H26N (MH+)
364.2065, found 364.2062.
2,4,6-Triphenylpyridine (2aa).15c White crystalline solid (116.7 mg,
2,6-Diphenyl-4-(4-(trifluoromethyl)phenyl)pyridine (2la). White
1
1
76%), mp: 140−141 °C. H NMR (400 MHz, CDCl3) δ 8.24−8.17
crystalline solid (135.0 mg, 72%), mp: 137−139 °C. H NMR (400
(m, 4H), 7.87 (s, 2H), 7.76−7.71 (m, 2H), 7.53−7.40 (m, 9H); 13C
NMR (100 MHz, CDCl3) δ 157.5, 150.2, 139.6, 139.0, 129.1, 129.0,
128.9, 128.7, 127.2, 127.1, 117.1.
MHz, CDCl3) δ 8.20 (d, J = 7.6 Hz, 4H), 7.85 (dd, J = 12.2, 5.9 Hz,
4H), 7.78 (d, J = 8.3 Hz, 2H), 7.49 (dt, J = 26.3, 7.4 Hz, 6H); 13C
NMR (100 MHz, CDCl3) δ 157.8, 148.8, 139.2, 129.3, 128.8, 128.7,
127.6, 127.1, 126.1 (dd, J = 7.0, 3.4 Hz), 117.0; HRMS (ESI) m/z
calcd for C24H17F3N (MH+) 376.1313, found 376.1310.
2,6-Diphenyl-4-(p-tolyl)pyridine (2ba).15c Pale yellow solid (104.3
mg, 65%), mp: 118−120 °C. 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J
= 7.5 Hz, 4H), 7.85 (s, 2H), 7.62 (d, J = 8.0 Hz, 2H), 7.50 (t, J = 7.5
Hz, 4H), 7.43 (d, J = 7.3 Hz, 2H), 7.30 (d, J = 7.9 Hz, 2H), 2.41 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 157.4, 150.0, 139.6, 139.0,
136.0, 129.8, 128.9, 128.6, 127.1, 126.9, 116.8, 21.2.
4-(Naphthalen-1-yl)-2,6-diphenylpyridine (2ma). Pale yellow solid
1
(135.7 mg, 76%), mp: 134−135 °C. H NMR (400 MHz, CDCl3) δ
8.30−8.17 (m, 5H), 8.03−7.93 (m, 4H), 7.93−7.88 (m, 1H), 7.86 (d, J
= 8.5 Hz, 1H), 7.54 (dd, J = 12.5, 5.6 Hz, 6H), 7.46 (t, J = 6.9 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 157.6, 150.1, 139.6, 136.3,
133.5, 133.4, 129.1, 129.0, 128.7, 128.4, 127.8, 127.2, 126.8, 126.7,
126.5, 124.8 117.3; HRMS (ESI) m/z calcd for C27H20N (MH+)
358.1596, found 358.1594.
2,6-Diphenyl-4-(m-tolyl)pyridine (2ca).15b Pale yellow solid (109.1
1
mg, 68%), mp: 100−101 °C. H NMR (400 MHz, CDCl3) δ 8.21
(ddd, J = 3.3, 2.7, 1.8 Hz, 4H), 7.88 (d, J = 2.4 Hz, 2H), 7.56−7.48 (m,
6H), 7.47−7.39 (m, 3H), 7.29 (dd, J = 4.3, 3.8 Hz, 1H), 2.47 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 157.4, 150.3, 139.6, 139.0, 138.8,
129.7, 129.0, 128.7, 127.9, 127.1, 124.3, 117.1, 21.5.
2,6-Diphenyl-4-(thiophen-2-yl)pyridine (2na).15c Pale yellow solid
1
(128.3 mg, 82%), mp: 163−165 °C. H NMR (400 MHz, CDCl3) δ
2,6-Diphenyl-4-(o-tolyl)pyridine (2da).20 Pale yellow solid (99.5
mg, 62%), mp: 118−120 °C. 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J
= 7.3 Hz, 4H), 7.66 (s, 2H), 7.49 (t, J = 7.5 Hz, 4H), 7.42 (t, J = 7.2
Hz, 2H), 7.32 (d, J = 5.3 Hz, 4H), 2.35 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 156.8, 151.3, 139.8, 139.5, 135.1, 130.7, 129.2, 129.0, 128.7,
128.3, 127.1, 126.1, 119.3, 20.4.
8.17 (d, J = 7.3 Hz, 4H), 7.84 (s, 2H), 7.58 (d, J = 3.5 Hz, 1H), 7.45
(ddd, J = 15.2, 11.0, 6.1 Hz, 7H), 7.16−7.10 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 157.6 142.9, 141.9, 139.3, 129.1, 128.7, 128.3, 127.1,
126.9, 125.2, 115.3.
4-(Furan-2-yl)-2,6-diphenylpyridine (2oa).20 White crystalline
solid (117.3 mg, 79%), mp: 170−171 °C. 1H NMR (400 MHz,
D
DOI: 10.1021/acs.joc.5b00635
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
CDCl3) δ 8.22−8.17 (m, 4H), 7.93 (s, 2H), 7.59 (dd, J = 1.8, 0.6 Hz,
1H), 7.54−7.48 (m, 4H), 7.47−7.41 (m, 2H), 6.98 (dd, J = 3.5, 0.5
Hz, 1H), 6.57 (dd, J = 3.4, 1.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
δ 157.5, 152.0, 143.6, 139.5, 139.1, 129.1, 128.7, 127.1, 113.0, 112.1,
108.5.
2,3,4,6-Tetraphenylpyridine (2ai).24 Pale yellow solid (109.2 mg,
57%), mp: 178−181 °C. H NMR (400 MHz, CDCl3) δ 8.19 (d, J =
7.4 Hz, 2H), 7.80 (s, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.46−7.38 (m,
3H), 7.26−7.20 (m, 6H), 7.18−7.05 (m, 5H), 6.94 (d, J = 6.3 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 158.0, 155.6, 150.6, 141.0,
139.8, 139.1, 137.9, 132.8, 131.4, 130.2, 129.3, 129,0, 128.7, 127.9,
127.7, 127.5, 127.3, 127.3, 127.0, 126.6, 120.3.
1
2,4-Diphenyl-6-(p-tolyl)pyridine (2pa and 2ab).21 Pale yellow
solid (2pa: 104.3 mg, 65%; 2ab: 109.1 mg, 68%), mp: 119−120 °C.
1H NMR (400 MHz, CDCl3) δ 8.20 (dd, J = 5.3, 3.3 Hz, 2H), 8.11 (d,
J = 8.2 Hz, 2H), 7.86 (s, 2H), 7.75 (dd, J = 5.2, 3.2 Hz, 2H), 7.55−
7.41 (m, 6H), 7.32 (d, J = 8.0 Hz, 2H), 2.43 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 157.5, 157.4, 150.1, 139.7, 139.2, 139.0, 136.8, 129.4,
129.1, 129.0, 128.9, 128.7, 127.2, 127.1, 127.0, 116.8, 116.8, 21.3.
2,4-Diphenyl-6-(m-tolyl)pyridine (2qa). White crystalline solid
4-Phenyl-2-(thiophen-2-yl)-6-(p-tolyl)pyridine (2pg). Yellow oil
(112.8 mg, 69%). 1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 8.2 Hz,
2H), 7.81−7.65 (m, 5H), 7.53−7.42 (m, 3H), 7.39 (dd, J = 5.0, 1.0
Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.12 (dd, J = 5.0, 3.7 Hz, 1H), 2.41
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.3, 152.6, 150.0, 145.6,
139.1, 138.9, 136.2, 129.4, 129.0, 128.9, 127.9, 127.5, 127.1, 126.9,
124.5, 116.4 115.0, 21.3; HRMS (ESI) m/z calcd for C22H18NS
(MH+) 328.1160, found 328.1158.
2-(4-Methoxyphenyl)-4-phenyl-6-(thiophen-2-yl)pyridine (2rg).
Pale yellow solid (142.3 mg, 83%), mp: 103−105 °C. 1H NMR
(400 MHz, CDCl3) δ 8.17−8.10 (m, 2H), 7.78−7.67 (m, 5H), 7.55−
7.44 (m, 3H), 7.41 (dd, J = 5.0, 1.0 Hz, 1H), 7.14 (dd, J = 5.0, 3.7 Hz,
1H), 7.06−7.00 (m, 2H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 160.6, 156.9, 152.6, 150.1, 145.6, 139.0, 131.7, 129.1, 129.0, 128.3,
127.9, 127.5, 127.1, 124.5, 116.0, 114.6, 114.1, 55.4; HRMS (ESI) m/z
calcd for C22H18NOS (MH+) 344.1109, found 344.1107.
2-(4-Methoxyphenyl)-6-(naphthalen-2-yl)-4-phenylpyridine
(2rh). Pale yellow solid (110.3 mg, 57%), mp: 123−125 °C. 1H NMR
(400 MHz, CDCl3) δ 8.66 (d, J = 1.2 Hz, 1H), 8.37 (dd, J = 8.6, 1.8
Hz, 1H), 8.26−8.17 (m, 2H), 7.99 (d, J = 1.4 Hz, 3H), 7.93−7.88 (m,
1H), 7.86 (d, J = 1.3 Hz, 1H), 7.79 (d, J = 6.9 Hz, 2H), 7.60−7.44 (m,
5H), 7.07 (d, J = 8.9 Hz, 2H), 3.90 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 160.6, 157.3, 157.2, 150.2, 139.3, 137.0, 133.7, 133.5, 132.3,
129.1, 128.9, 128.7, 128.5, 128.3, 127.7, 127.2, 126.4, 126.4, 126.2,
124.9, 116.8, 116.5, 114.1, 55.4; HRMS (ESI) m/z calcd for
C28H22NO (MH+) 388.1707, found 388.1705.
1
(112.4 mg, 70%), mp: 106−108 °C. H NMR (400 MHz, CDCl3) δ
8.19 (d, J = 7.3 Hz, 2H), 8.02 (s, 1H), 7.97 (d, J = 7.7 Hz, 1H), 7.86
(s, 2H), 7.76−7.71 (m, 2H), 7.54−7.36 (m, 7H), 7.25 (d, J = 7.7 Hz,
1H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.7, 157.5,
150.1, 139.7, 139.6, 139.1, 138.3, 129.8, 129.1, 129.0, 128.9, 128.7,
128.6, 127.8, 127.7, 127.2, 124.3, 117.2, 117.1, 21.6; HRMS (ESI) m/z
calcd for C24H20N (MH+) 322.1596, found 322.1592.
2-(4-Methoxyphenyl)-4,6-diphenylpyridine (2ra and 2ac).22
White crystalline solid (2ra: 111.2 mg, 66%; 2ac: 134.8 mg, 80%),
mp: 106−108 °C. 1H NMR (400 MHz, CDCl3) δ 8.23−8.14 (m, 4H),
7.82 (dd, J = 3.3, 1.3 Hz, 2H), 7.76−7.70 (m, 2H), 7.55−7.40 (m,
6H), 7.07−7.00 (m, 2H), 3.87 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 160.6, 157.3, 157.1, 150.1, 139.7, 139.2, 132.2, 129.1, 128.9, 128.9,
128.7, 128.4, 127.2, 127.1, 116.5, 116.3, 114.1, 55.4.
2-(4-Fluorophenyl)-4,6-diphenylpyridine (2sa and 2ad).23 White
crystalline solid (2sa: 128.4 mg, 79%; 2ad: 76.4 mg, 47%), mp: 133−
135 °C. 1H NMR (400 MHz, CDCl3) δ 8.23−8.16 (m, 4H), 7.88 (d, J
= 1.3 Hz, 1H), 7.83 (d, J = 1.3 Hz, 1H), 7.74 (dd, J = 5.2, 3.2 Hz, 2H),
7.56−7.44 (m, 6H), 7.24−7.14 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 163.6 (d, J = 248.4 Hz), 157.6, 156.5, 150.3, 139.5, 139.0,
135.7 (d, J = 3.1 Hz), 129.1, 129.1, 129.0, 128.9 (d, J = 8.3 Hz), 128.7,
127.8, 127.1, 117.1, 116.8, 115.59 (d, J = 21.6 Hz).
4-Phenyl-2-(thiophen-2-yl)-6-(thiophen-3-yl)pyridine (2vg). Pale
1
yellow solid (89.3 mg, 56%), mp: 119−120 °C. H NMR (400 MHz,
2-(4-Chlorophenyl)-4,6-diphenylpyridine (2ta and 2ae).21 Pale
yellow solid (2ta: 121.1 mg, 71%; 2ae: 98.9 mg, 58%), mp: 120−122
CDCl3) δ 8.05 (dd, J = 3.0, 1.2 Hz, 1H), 7.79 (dd, J = 5.0, 1.2 Hz, 1H),
7.72−7.68 (m, 4H), 7.66 (d, J = 1.4 Hz, 1H), 7.55−7.45 (m, 3H),
7.44−7.36 (m, 2H), 7.13 (dd, J = 5.0, 3.7 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 153.5, 152.7, 150.1, 145.3, 142.1, 138.7, 129.1, 129.0,
127.9, 127.7, 127.1, 126.4, 126.2, 124.6, 124.0, 116.6, 115.0; HRMS
(ESI) m/z calcd for C19H14NS2 (MH+) 320.0568, found 320.0564.
5-Methyl-2,4-diphenylpyridine (7).25 Pale yellow solid (91.9 mg,
75%), mp: 78−79 °C. 1H NMR (400 MHz, CDCl3) δ 8.59 (d, J = 0.4
Hz, 1H), 8.01 (dd, J = 8.4, 1.1 Hz, 2H), 7.61 (s, 1H), 7.51−7.35 (m,
8H), 2.31 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 155.3, 151.2,
149.9, 139.4, 139.3, 129.1, 128.6, 128.6, 128.5, 128.4, 127.9, 126.7,
120.9, 16.9.
1
°C. H NMR (400 MHz, CDCl3) δ8.26−8.16 (m, 4H), 7.88 (s, 2H),
7.73 (d, J = 7.2 Hz, 2H), 7.54−7.48 (m, 6H), 7.45 (d, J = 7.5 Hz, 2H);
13C NMR (101 MHz, CDCl3) δ 157.5, 150.2, 139.6, 139.0, 129.1,
129.0, 128.9, 128.8, 128.7, 128.4, 127.2, 127.1, 117.1.
2-(4-Bromophenyl)-4,6-diphenylpyridine (2ua and 2af).23 Pale
yellow solid (2ua: 104.1 mg, 76%; 2af: 165.6 mg, 86%), mp: 130−131
1
°C. H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 8.0 Hz, 4H), 7.88 (s,
2H), 7.77−7.71 (m, 2H), 7.54−7.48 (m, 6H), 7.47−7.43 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ 157.5, 150.2, 139.6, 139.1, 129.1, 129.0,
129.0, 128.7, 127.2, 127.1, 117.1.
2,4-Diphenyl-6-(thiophen-3-yl)pyridine (2va). Pale yellow solid
(84.5 mg, 54%), mp: 110−111 °C. H NMR (400 MHz, CDCl3) δ
1
ASSOCIATED CONTENT
■
8.17 (d, J = 7.4 Hz, 2H), 8.06 (d, J = 3.0 Hz, 1H), 7.86−7.78 (m, 2H),
7.73 (dd, J = 11.4, 3.9 Hz, 3H), 7.54−7.40 (m, 7H); 13C NMR (100
MHz, CDCl3) δ 157.4, 153.6, 150.1, 142.5, 139.5, 139.0, 129.1, 129.0,
128.9, 128.7, 127.1, 127.1, 126.5, 126.1, 123.8, 116.8, 116.8; HRMS
(ESI) m/z calcd for C21H16NS (MH+) 314.1003, found 314.1001.
2,4-Diphenyl-6-(thiophen-2-yl)pyridine (2ag). Pale yellow solid
S
* Supporting Information
1
Copies of H and 13C NMR spectra for all products. The
Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.joc.5b00635.
1
(144.0 mg, 92%), mp: 102−104 °C. H NMR (400 MHz, CDCl3) δ
AUTHOR INFORMATION
■
8.24−8.12 (m, 2H), 7.82−7.68 (m, 5H), 7.56−7.39 (m, 7H), 7.18−
7.09 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 157.3, 152.7, 150.2,
145.4, 139.0, 138.8, 129.1, 129.1, 129.0, 128.7, 127.9, 127.7, 127.1,
127.0, 124.6, 116.8, 115.3; HRMS (ESI) m/z calcd for C21H16NS
(MH+) 314.1003, found 314.1003.
Corresponding Author
*E-mail: cuixl@hqu.edu.cn.
Author Contributions
The authors declare no competing financial interest.
2-(Naphthalen-2-yl)-4,6-diphenylpyridine (2ah). White crystalline
solid (160.6 mg, 90%), mp: 126−128 °C. 1H NMR (400 MHz,
CDCl3) δ 8.70 (s, 1H), 8.42 (dd, J = 8.6, 1.8 Hz, 1H), 8.29 (dd, J =
5.2, 3.4 Hz, 2H), 8.06 (d, J = 1.3 Hz, 1H), 8.02 (dd, J = 8.9, 5.9 Hz,
2H), 7.93 (dd, J = 8.9, 2.8 Hz, 2H), 7.85−7.77 (m, 2H), 7.62−7.48
(m, 8H); 13C NMR (101 MHz, CDCl3) δ 157.7, 157.4, 150.3, 139.7,
139.1, 137.0, 133.8, 133.6, 129.2, 129.1, 129.1, 128.8, 128.4, 127.8,
127.3, 127.3, 126.5, 126.5, 126.3, 125.0, 117.4, 117.2; HRMS (ESI) m/
z calcd for C27H20N (MH+) 358.1596, found 358.1595.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Program for Minjiang Scholar
(10BS216), Xiamen Southern Oceanographic Center
(13GYY003NF16), and NSF of China (21202048).
E
DOI: 10.1021/acs.joc.5b00635
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(d) Constable, E. C.; Housecroft, C. E.; Neuburger, M.; Phillips, D.;
Raithby, P. R.; Schofield, E.; Sparr, E.; Tocher, D. A.; Zehnder, M.;
Zimmermann, Y. J. Chem. Soc., Dalton Trans. 2000, 2219−2228.
(15) (a) Heravi, M. M.; Bakhtiari, K.; Daroogheha, Z.; Bamoharram,
F. F. Catal. Commun. 2007, 8, 1991−1994. (b) Ren, Z. H.; Zhang, Z.
Y.; Yang, B. Q.; Wang, Y. Y.; Guan, Z. H. Org. Lett. 2011, 13, 5394−
5397. (c) Li, J.; He, P.; Yu, C. Tetrahedron 2012, 68, 4138−4144.
(d) Huang, H.; Ji, X.; Wu, W.; Huang, L.; Jiang, H. J. Org. Chem. 2013,
78, 3774−3782. (e) Mahernia, S.; Adib, M.; Mahdavi, M.; Nosrati, M.
Tetrahedron Lett. 2014, 55, 3844−3846.
(16) Escoubet, S.; Gastaldi, S.; Bertrand, M. Eur. J. Org. Chem. 2005,
3855−3873. Enaminone 6 was an inseparable mixture of syn/anti
isomers (1:4), while the stereochemistry of each isomer was not
assigned.
(17) (a) Campos, K. B. Chem. Soc. Rev. 2007, 36, 1069−1084.
(b) Wang, W.; Dong, X.; Nie, S.; Chen, Y.; Zhang, X.; Yan, M. Org.
Lett. 2013, 15, 6018−6021.
(18) (a) Song, B.; Wang, S.; Sun, C.; Deng, H.; Xu, B. Tetrahedron
Lett. 2007, 48, 8982−8986. (b) Liang, Y. F.; Jiao, N. Angew. Chem., Int.
Ed. 2014, 126, 558−562.
REFERENCES
■
(1) (a) Roth, H. J.; Kleemann, A. Drug Synthesis in Pharmaceutical
Chemistry; John Wiley and Sons: New York, 1988; Vol. 1. (b) Joule, J.
A.; Mills, K. Heterocyclic Chemistry, 4th ed.; Blackwell Science:
Cambridge, 2000; pp 63−120. (c) Olbe, L.; Carlsson, E.; Lindberg,
P. Nat. Rev. Drug Discovery 2003, 2, 132−139. (d) Michael, J. P. Nat.
Prod. Rep. 2005, 22, 627−646.
(2) (a) Henry, G. D. Tetrahedron 2004, 60, 6043−6061. (b) Varela, J.
A.; Saa, C. Chem. Rev. 2003, 103, 3787−3802. (c) Zeni, G.; Larock, R.
C. Chem. Rev. 2006, 106, 4644−4648. (d) Groenendaal, B.; Ruijter, E.;
Orru, R. V. A. Chem. Commun. 2008, 44, 5474−5489. (e) Heller, B.;
Hapke, M. Chem. Soc. Rev. 2007, 36, 1085−1092. (f) Hill, M. D.
Chem.Eur. J. 2010, 16, 12052−12062. (g) Kral, K.; Hapke, M.
Angew. Chem., Int. Ed. 2011, 50, 2434−2435.
(3) (a) Sausins, A.; Duburs, G. Heterocycles 1988, 27, 269−289.
(b) Simon, C.; Constantieux, T.; Rodriguez, J. Eur. J. Org. Chem. 2004,
4957−4980. (c) Frederic, L. M.; Allais, C.; Constantieux, T.;
Rodriguez, J. Chem. Commun. 2008, 44, 4207−4209.
(4) For recent examples, see: (a) Colby, D. A.; Bergman, R. G.;
Ellman, J. A. J. Am. Chem. Soc. 2008, 130, 3645−3651. (b) Liu, S.;
Liebeskind, L. S. J. Am. Chem. Soc. 2008, 130, 6918−6919. (c) Chiba,
S.; Xu, Y.-J.; Wang, Y.-F. J. Am. Chem. Soc. 2009, 131, 12886−12887.
(d) Wang, Y.-F.; Chiba, S. J. Am. Chem. Soc. 2009, 131, 12570−12572.
(e) Ding, S.; Shi, Z.; Jiao, N. Org. Lett. 2010, 12, 1450−1543. (f) Sakai,
T.; Danheiser, R. L. J. Am. Chem. Soc. 2010, 132, 13203−13205.
(g) Nakamura, I.; Zhang, D.; Terada, M. J. Am. Chem. Soc. 2010, 132,
7884−7886. (h) Wang, C.; Li, X.; Wu, F.; Wan, B. Angew. Chem., Int.
Ed. 2011, 50, 7162−7166. (i) Ohashi, M.; Takeda, I.; Ikawa, M.;
Ogoshi, S. J. Am. Chem. Soc. 2011, 133, 18018−18021. (j) Kim, D. S.;
Park, J. W.; Jun, C. H. Chem. Commun. 2012, 48, 11334−11336.
(k) Gati, W.; Rammah, M. M.; Rammah, M. B.; Couty, F.; Evano, G. J.
Am. Chem. Soc. 2012, 134, 9078−9081. (l) Yamamoto, S.; Okamoto,
K.; Murakoso, M.; Kuninobu, Y.; Takai, K. Org. Lett. 2012, 14, 3182−
3185. (m) Loy, N. S. Y.; Singh, A.; Xu, X.; Park, C.-M. Angew. Chem.,
Int. Ed. 2013, 52, 2212−2216. (n) Wei, Y.; Yoshikai, N. J. Am. Chem.
Soc. 2013, 135, 3756−3759.
(19) (a) Palimkar, S. S.; Kumar, P. H.; Jogdand, N. R.; Daniel, T.;
Lahoti, R. J.; Srinivasan, K. V. Tetrahedron lett. 2006, 47, 5527−5530.
(b) Cox, R. J.; Ritson, D. J.; Dane, T. A.; Berge, J.; Charmant, J. P. H.;
Kantacha, A. Chem. Commun. 2005, 1037−1039.
(20) Adib, M.; Tahermansouri, H.; Koloogani, S. A.; Mohammadi, B.;
Bijanzadeh, H. R. Tetrahedron lett. 2006, 47, 5957−5960.
(21) Mishra, N. K. Ind. J. Agric. Chem. 1988, 21, 91.
(22) Borthakur, M.; Dutta, M.; Gogoi, S.; Boruah, R. C. Synlett 2008,
3125−3128.
(23) Abu-Orabi, S. T. J. Chem. Eng. Data 1987, 32, 130−131.
(24) Kobayashi, T.; Kawate, H.; Kakiuchi, H.; Kato, H. Bull. Chem.
Soc. Jpn. 1990, 63, 1937−1942.
(25) Kleine, T.; Frohlich, R.; Wibbeling, B.; Wurthwein, E. U. J. Org.
̈
̈
Chem. 2011, 76, 4591−4599.
(5) For recent examples, see: (a) Bezense
̌ ̌
k, J.; Prek, B.; Groselj, U.;
Kasunic, M.; Svete, J.; Stanovnik, B. Tetrahedron 2012, 68, 4719−4731.
̌
(b) Wang, Q.; Wan, C.; Gu, Y.; Zhang, J.; Gao, L.; Wang, Z. Green
Chem. 2011, 13, 578−581. (c) Yan, R.; Zhou, X.; Li, M.; Li, X.; Kang,
X.; Liu, X.; Hou, X.; Huang, G. RSC Adv. 2014, 4, 50369−50372.
(d) Jiang, Y.; Park, C. M.; Loh, T. P. Org. Lett. 2014, 16, 3432−3435.
(e) Stark, D. G.; O’Riordan, T. J.; Smith, A. D. Org. Lett. 2014, 16,
̌ ̌ ̌ ̌
6496−6499. (f) Prek, B.; Groselj, U.; Kasunic, M.; Zupancic, S.; Svete,
J.; Stanovnik, B. Aust. J. Chem. 2015, 68, 184−195. (g) Raji Reddy, C.;
Panda, S. A.; Reddy, M. D. Org. Lett. 2015, 17, 896−899.
(6) For recent reviews, see: (a) Elassar, A.-Z. A.; El-Khair, A. A.
Tetrahedron 2003, 59, 8463−8480. (b) Stanovnik, B.; Svete, J. Chem.
Rev. 2004, 104, 2433−2480. (c) Govindh, B.; Diwakar, B. S.; Murthy,
Y. L. Org. Commun. 2012, 5, 105−119.
(7) Cacchi, S.; Fabrizi, G.; Filisti, E. Org. Lett. 2008, 10, 2629−2632.
(8) Xin, X.; Wang, D.; Li, X.; Wan, B. Tetrahedron 2013, 69, 10245−
10248.
(9) Saito, A.; Konishi, T.; Hanzawa, Y. Org. Lett. 2009, 12, 372−374.
(10) (a) Toh, K. K.; Wang, Y. F.; Ng, E. P. J.; Chiba, S. J. Am. Chem.
Soc. 2011, 133, 13942−13945. (b) Toh, K. K.; Biswas, A.; Wang, Y. F.;
Tan, Y. Y.; Chiba, S. J. Am. Chem. Soc. 2014, 136, 6011−6020.
(11) Shen, J.; Cheng, G.; Cui, X. Chem. Commun. 2013, 49, 10641−
10643.
(12) Seel, S.; Thaler, T.; Takatsu, K.; Zhang, C.; Zipse, H.; Straub, B.
F.; Mayer, P.; Knochel, P. J. Am. Chem. Soc. 2011, 133, 4774−4777.
(13) (a) Cheng, G.; Zeng, X.; Shen, J.; Wang, X.; Cui, X. Angew.
Chem., Int. Ed. 2013, 52, 13265−13268. (b) Wang, X.; Cheng, G.; Cui,
X. Chem. Commun. 2014, 50, 652−654.
(14) (a) Krohnke, F. Synthesis 1976, 1−24. (b) Olenyuk, B.;
̈
Whiteford, J. A.; Frechtenkotter, A.; Stang, P. J. Nature 1999, 398,
̈
796−799. (c) Peter, S.; Gerhard, H.; Elisabeth, H.; Ralf, K.; Hartmann,
K.; Albercht, H.; Norbert, G.; Helmut, W.; Karl-Otto, W.; Uif, M. U.S.
Patent 573,3850, 1998; Chem. Abstr. 1996, 125, 167792w.
F
DOI: 10.1021/acs.joc.5b00635
J. Org. Chem. XXXX, XXX, XXX−XXX