Unexpected reactivity of pyridinium salts toward alkynyl Fischer complexes to produce oxo-heterocycles

Article abstract of DOI:10.1002/aoc.4202

The unprecedented reaction of ketone-containing aromatic pyridinium salts 3a-e and alkynyl Fischer complexes 1a-f proceeds via a mild domino process to provide 4,6-disubstituted pyran-2-ones 5a-k and 2,3,5-trisubstituted furans 6a-h (45-97%). According of the results of isotopic labeling experiments, a mechanism involving an initial Michael addition appears to be the key step, obtaining a mesomeric structure responsible for the formation of both products.

Full text of DOI:10.1002/aoc.4202

Received: 14 August 2017
DOI: 10.1002/aoc.4202
Revised: 1 November 2017
Accepted: 2 November 2017
F U L L P A P E R
Unexpected reactivity of pyridinium salts toward alkynyl
Fischer complexes to produce oxo‐heterocycles
María Inés Flores‐Conde1 | Fabiola N. de la Cruz2 | Julio López1 | J. Óscar C. Jiménez‐Halla1 |
Eduardo Peña‐Cabrera1 | Marcos Flores‐Álamo3
| Francisco Delgado4 | Miguel A. Vázquez1
1 Departamento de Química, Universidad
The unprecedented reaction of ketone‐containing aromatic pyridinium salts
3a‐e and alkynyl Fischer complexes 1a‐f proceeds via a mild domino process
to provide 4,6‐disubstituted pyran‐2‐ones 5a‐k and 2,3,5‐trisubstituted furans
6a‐h (45‐97%). According of the results of isotopic labeling experiments, a
mechanism involving an initial Michael addition appears to be the key step,
obtaining a mesomeric structure responsible for the formation of both products.
de Guanajuato, Noria Alta S/N, 36050
Guanajuato, Gto, México
2 Facultad de Ciencias Químicas,
Universidad Autónoma de Coahuila, Blvd.
Venustiano Carranza e Ing. J. Cárdenas
Valdez S/N, 25280 Saltillo, Coah, México
3 Facultad de Química, Universidad
Nacional Autónoma de México, Av.
Insurgentes Sur S/N, 04510 CDMX,
México
4 Departamento de Química Orgánica,
Escuela Nacional de Ciencias Biológicas‐
IPN, Prolongación Carpio y Plan de Ayala
S/N, 11340 CDMX, México
KEYWORDS
Alkynyl Fischer carbene, disubstituted 2H‐pyran‐2‐one, pyridine ylide, trisubstituted furan
Correspondence
Miguel A. Vázquez, Departamento de
Química, Universidad de Guanajuato,
Noria Alta S/N, 36050, Guanajuato, Gto.,
México.
Email: mvazquez@ugto.mx
Funding information
Dirección de Apoyo a la Investigación y al
Posgrado, Grant/Award Number: 811/
2016; Consejo Nacional de Ciencia y
Tecnología, Grant/Award Numbers:
218003 and 241803; UG‐CONACYT,
Grant/Award Number: 260373
1 | INTRODUCTION
Michael additions and cyclopropanations as the most
representative,[3] depending on the electrophile used
Since their discovery in 1935, pyridinium ylides have
been studied extensively.[1] These compounds have the
advantage of being easily‐prepared building blocks while
and sometimes related with pKa value of the associated
ions (however, the latter is not always a trustworthy
factor).[4]
also possessing
a
wide range of applications as
On the other hand, particular attention has been paid
to the use of Fischer carbenes to prepare a wide range of
chemical scaffolds. Our research group alone has provided
evidence for the synthesis of ortho‐ and para‐quinones,
phenols, 4‐amino‐1‐azadienes, N‐benzyl pyrroles, NH
pyrroles, among others, when alkoxy alkynyl carbenes
nucleophiles. In particular, pyridines, quinolones,
indolizines and other molecules have been prepared
using the pyridinium ylide platform.[2] In this sense,
these compounds are involved in a range of processes
such as multicomponent reactions, 1,3‐cycloadditions,
Appl Organometal Chem. 2017;e4202.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4202

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FLORES‐CONDE ET AL.
were employed. Thus, it can be said that these platforms
are effective in the synthesis of a variety of heteroatom‐
containing compounds.[5]
cyclocondensations
of
1,3‐
and
1,4‐dicarbonyl
compounds in the Feist‐Bénary and Paal‐Knorr methods,
respectively, to more elegant alternatives using diverse
carbonyl‐containing substrates and metallic catalysts
(Scheme 1) in routes involving copper (A and B),
mercury (C), gold and silver (D), palladium (E), gold
(F), indium (G), ruthenium (H and I), or employing
Fischer carbene complexes.[11]
Of the more than 20 million registered chemical
compounds, about one half contain heterocycles and a
large number of these have some biological activity.[6]
This reason has motivated the development and increas-
ing diversity of synthetic methodologies for preparing
heterocycles. Indolizine and related groups are found
in a wide range of natural products, as exemplified by
the natural products swainsonine and monomorine I.[7]
One interesting methodology used to construct this
chemical skeleton involves the use of pyridinium ylides
and electron‐deficient ynamides.[8] However, beyond its
frequent occurrence in nature, this structure commonly
exhibits a range of biological activities, for instance
against bacteria, viruses and parasites, regulating tumor
genesis, diminishing inflammation, abating pain,
preventing oxidation, and inhibiting enzymes, as well
as further uses in materials science or industrial
processes.[9]
Pyranones, for their part, are valuable building blocks
that have been used extensively in diversity‐oriented
synthesis.[12] In particular, pyran‐2‐ones are associated
with divergent pharmacological activities such as cycloox-
ygenase‐2 inhibition, immunosuppression of organisms,
inhibition of HIV protease, or reduction of inflamed tis-
sues, to mention just a few.[13] Among the reported
methods of preparation, some are remarkable due to their
flexibility in terms of substrates used to achieve the goal. In
Scheme 1, several methods are depicted for obtaining a
wide variety of substitution patterns on the heterocyclic
ring, highlighting route K, which is based on the reactivity
of pyridinium salts, as well as routes L and P where alkynyl
Fischer carbenes were utilized. In particular, under the
conditions employed therein, the organometallic fragment
is preserved after the work up, unlike the route reported
here. Methods J, O, N and M also provide access to this
desired nucleus through simple protocols.[14]
Polysubstituted furans are other important class of
five‐membered heterocycles that can be found in many
natural, pharmaceutical and agrochemical products.[10]
Numerous routes to prepare this structure have been
established, ranging from the traditional and simple
SCHEME 1 Highlighted syntheses of
furan and pyran‐2‐one rings

FLORES‐CONDE ET AL.
3 of 12
Motivated by this background, we undertook investi-
gations into the reactivity and scope of pyridinium ylides
and α,β‐unsaturated Fischer complexes, specifically
targeting the construction of compounds with potential
biological applications. The results of this study are
presented herein.
C17
O12
C14
O15
O16
O13
C10
C9
C24
C23
C22
C8
C25
C5
2 | RESULTS AND DISCUSSION
C18
N4
C20
C21
C7
C6
With the aim of establishing a new path for the synthesis
of a family of indolizidines, alkynyl carbene 1a (1.2 mol
equiv.) was treated with pyridinium salt 3a (1.0 mol
equiv.) under different chemical conditions. Attempts to
use acetonitrile, toluene and THF as solvents at room
temperature, and TEA or DIPEA as bases, found no
success in the preparation of indolizine 4a, although
complete consumption of the reagents took place.
Conversely, a mixture of 2H‐pyran‐2‐one 5a, furan 6a
and pentacarbonyl pyridine chromium complex 7a was
always obtained, with varying product ratios depending
on the chosen conditions, but with THF being the best
option as solvent (Scheme 2).
O19
C3
C1
C2
FIGURE 1 ORTEP diagram of indolizine 4b
These results were surprising, especially given that we
unambiguously established that 3a undergoes a (3+2)
cycloaddition when reacted with dimethylacetylene
dicarboxylate (K2CO3, THF, rt, 4 h, 65%),[15a] an organic
analogue of Fischer complexes 1, affording indolizine 4b
(Figure 1)[15b] as the major product (Scheme 3). Moreover,
this kind of cycloaddition has been reported in the
reaction of alkenyl carbenes with 1,3‐dipoles such as
nitrilimines, where Δ2‐pyrazolines were formed.[16]
It should be stated at this point that there is a clear
difference in the reactivity of pyridinium salts with these
groups of compounds (alkynyl ester vs alkynyl carbene),
despite their structural similarities. For this reason, our
investigations turned toward understanding the potential
of the unexpected products 5 and 6. Normally, unsatu-
rated carbenes undergo 1,2‐, 1,4‐ or 1,6‐additions in the
presence of carbon nucleophiles, depending on their
hardness and steric bulk.[17] For this reason, a complete
SCHEME 3 Dipolar cycloaddition of pyridinium ylide 3a and
DMAD
study was designed to fully unveil the reactivity of these
particular nucleophiles (pyridinium ylides). Thus, during
the optimization stage, several sets of conditions were
evaluated to determine the best result. Reaction of
carbene 1a with salt 3a in THF at reflux, with TEA as
base, afforded pyranone 5a in 30% yield and the oxidized
alkynyl carbene as products; meanwhile, keeping the
reactants constant but changing the base for a stronger
one (LDA) at –78 °C furnished a mixture in which
pyranone 5a was formed in a similar yield (28%) but furan
6a was also obtained in 15%. To determine which factor
(temperature or base) played the decisive role in the final
outcome, an additional experiment was performed with
1a and 3a using TEA at room temperature, leading to an
SCHEME 2 Reaction between alkynyl
Fischer carbene 1a and pyridine salt 3a.
Reaction conditions: (a) TEA, THF, rt,
12 h, 5a (45%), 6a (29%), 7a (26%). (b) TEA,
CH3CN, rt, 12 h, 5a (40%), 6a (24%), 7a
(36%). (c) TEA, PhMe, rt, 12 h, 5a (32%), 6a
(23%), 7a (45%). (d) DIPEA, THF, rt, 12 h,
5a (41%), 6a (24%), 7a (35%). (e) DIPEA,
CH3CN, rt, 12 h, 5a (38%), 6a (21%), 7a
(41%). (f) DIPEA, PhMe, rt, 12 h, 5a (28%),
6a (20%), 7a (52%)

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FLORES‐CONDE ET AL.
improvement of the yield (42% for 5a and 30% for 6a). The
influence of microwave irradiation on the selectivity was
also tested, finding that for short exposures (THF, 70 °C,
30 min, 150 W, closed system) the reaction was incom-
plete, with a 1:3 product ratio (5a:6a), but after 3.5 h the
reaction was complete, with a ratio of 4:1. At this point
the best results were achieved using THF and TEA at
room temperature. However, to cover wider aspects of
the synthesis, two experiments using either AgOAc or
CuOAg as catalyst (20% mol) were carried out, leading
to similar results for both cases: neither 5a nor 6a was
formed as only a small quantity of salt 3a reacted with 1a.
Nevertheless, the latter was found to be completely
consumed. After these assays, the optimization process
suggested that this combinatorial method could be applied
in the synthesis of molecules with a variety of substituents.
The scope of this reaction is summarized in Table 1.
alkenyl groups were present in 1 and only pyran‐2‐ones
were formed (Table 1, entries 13‐15). Addressing the dif-
ferences between the substitution patterns of carbenes 1
with aromatic scaffolds, electron‐releasing groups
increased the efficiency of the reaction compared with
neutral or electro‐withdrawing groups (Table 1, entries
1, 8 and 12). Moreover, a similar electronic effect seems
to operate under the influence of salts 3 where R2 was
substituted with different groups (Table 1, entries 4 and 7),
showing a preference for those salts bearing an electron‐
releasing group.
In addition, electronic activation of R2 seems to play a
non‐determinant role for the final composition of the
mixture (at least at the level of the influence exerted by
R1) since similar results in yield and selectivity were
observed when reacting substrates such as heteroaromatic
carbene 1e (Table 1, entries 13 and 14). Similarly, substi-
tution at the pyridinium ring did not affect the final yield
(Table 1, entries 1 and 3), which was the reason we
decided to work with the simplest structure.
According to the results displayed in Table 1, the
reaction favors the formation of pyran‐2‐ones 5 over
furans 6 in practically all cases. When comparing the var-
iability of the groups on the alkynylcarbene 1, a strong
structural and electronic influence was clearly expressed,
since no furans were formed when heteroaromatic or
Another remarkable difference was observed with the
metallic fragment [(CO)5M] of the alkynyl carbene, as
suggested by a number of studies wherein reactivity is
TABLE 1 Divergent synthesis of pyranone (5) and furan (6) derivativesa
Entry
Carbene
1a
Salt
3a
R1
R2
R3
5 (%)b
6 (%)b
Yield (%)c
1
Ph
Ph
H
5a (45)
6a (29)
74
2
2ad
1a
1a
1a
2ad
1a
1b
2bd
1b
1c
3a
3b
3c
3d
3d
3e
3a
3a
3c
3d
3a
3a
3d
3a
Ph
Ph
H
5a (56)
5a (42)
5b (58)
5c (57)
5c (62)
5d (55)
5e (49)
5e (66)
5f (31)
5g (53)
5h (36)
5i (58)
5j (59)
5k (48)
6a (39)
6a (30)
6b (24)
6c (24)
6c (27)
6d (30)
6e (33)
6e (31)
6f (14)
6g (18)
6h (20)
6i (0)
95
72
82
81
89
85
82
97
45
71
56
58
59
48
3
Ph
Ph
NMe2
H
4
Ph
4‐OMe‐C6H4
4‐Me‐C6H4
4‐Me‐C6H4
4‐Cl‐C6H4
Ph
5
Ph
H
6
Ph
H
7
Ph
H
8
4‐Me‐C6H4
4‐Me‐C6H4
4‐Me‐C6H4
3‐Me‐C6H4
3‐CF3‐C6H4
3‐thienyl
3‐thienyl
c‐1‐C6H9
H
9
Ph
H
10
11
12
13
14
15
4‐OMe‐C6H4
4‐Me‐C6H4
Ph
H
H
1d
1e
1e
1f
H
Ph
H
4‐Me‐C6H4
Ph
H
6j (0)
H
6k (0)
aReaction conditions: 1 or 2 (1.5 equiv.), 3 (1.0 equiv.), TEA (1.0 equiv.), THF, rt, 12 h.
bIsolated yields.
cCombined yield (5 + 6).
dM = W, reaction time = 48 h.

FLORES‐CONDE ET AL.
5 of 12
strongly influenced by this moiety.[18] For this particular
case, the results indicated a preference for tungsten over
chromium complexes when comparing yields of the
molecular scaffolds (Table 1, entries 1 and 8, M = Cr vs
2 and 9, M = W). Similar observations have been
established by other researchers interested in understand-
ing the M‐C bond, and the accepted explanation is based
on the notion that a number of the chromium‐containing
intermediates are less stable than those derived from
tungsten.[19] Despite the better results associated with
tungsten complexes 2a‐b (Table 1, entries 2, 6 and 9),
the time required for completion was practically four
times that observed for chromium complex 1a‐b; for this
reason the extended study was performed using only the
second group of substrates.
On the other hand, this methodology showed
limitations related to the structure of the pyridinium salt,
perhaps due to steric effects, as evidenced by the lack of
reactivity of the ylide derived from both neutral and
electronically‐activated coumarins 3f and 3g towards
carbene 1a under the previously optimized conditions,
since only the oxidized ester derived from the alkyne could
be recovered and no traces of 5l‐m/6l‐m were detected
(Scheme 4).
The structures of the formed pyran‐2‐ones, furans
and pyridine chromium complexes were elucidated
1
based on their H and 13C NMR spectroscopic data, as
well as characteristic IR spectroscopic signals. In addi-
tion, the structures of products 5g,[20] 6e[21] and 7a[22a]
were unequivocally determined by X‐ray diffraction
crystallography (Figure 2). Although 7a has been previ-
ously characterized and its crystal structure
reported,[22b] an ORTEP diagram of the compound is
presented here in order to support our mechanistic pro-
posal discussed below. Concerning 5g, there is a devia-
tion of the torsion angle between the planes of the
aryl rings and that of the oxygen‐containing ring (12.6°
(m‐tolyl) and 12.3° (p‐tolyl), respectively). Furan 6e
exhibits larger deviations in this metric (31.7° and
18.5°). In accordance with this 5g displays a short con-
tact of 2.49 Å between H‐4 and O‐2 of two molecules
in the packing array, but this kind of interaction is prac-
tically nonexistent in 6e.
FIGURE 2 ORTEP diagram of pyranone 5g, furan 6e and
complex 7a
A plausible mechanism to explain the formation of
the obtained products is depicted in Scheme 5, featur-
ing a domino process. The first step is proposed to be
SCHEME 4 Non‐viable ylides tested

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FLORES‐CONDE ET AL.
SCHEME 5 Proposed mechanism for
the formation of pyran‐2‐ones 5, furans 6
and metal complexes 7
the corresponding Michael addition of the pyridinium
low yield (12%) in this reaction. In the final step, the
metal fragment undergoes attack by pyridine, causing
delocalization of the electron density, directly yielding
pyranone 5 and complex 7 as a byproduct. On the other
hand, species A (which recalls the reactivity of the
ketene complex involved in photochemical reactions of
Fischer carbenes)[29] would lead to furan 6 through a
5‐endo‐dig ring closure,[30] carried out at the sp carbon
atom of the metallic allene by the ketone oxygen atom,
affording species F after the loss of pyridine. This sub-
salt (derived from 3) to the alkynyl carbene
1
(or 2),[23] resulting in the species A, which has the
alternative resonance structure B (metal allenes are
well known to participate in carbene reactions).[24] In
fact, a number of failed experiments using alkyl
carbenes 1 (R1 = c‐propyl, n‐propyl and trimethylsilyl)
and salt 3a (R2 = Ph) afforded the 1,4‐addition product
in yields ranging from 5 to 15%, along with the oxidized
ester derived from the respective carbene. This observa-
tion, and the presence of G (derived from reaction
toward 5j, Table 1, entry 14; Scheme 5), isolated and
spectroscopically confirmed by HRMS (see Section 6 of
the Supporting Information), would support the pro-
posed initial step of the mechanism, which has also
been proposed in previous reports where α,β‐unsatu-
rated Fischer carbenes are used in the synthesis of het-
erocycles.[5c] To obtain 2‐pyranone 5, B is protonated at
the α position to afford C and then undergoes a 6‐exo‐
trig ring closure,[25] through a nucleophilic attack on
the carbenic carbon by the ketone oxygen atom. This
removes the ethoxy group,[26] and the carbene
undergoes a subsequent oxidation process, as reported
previously for loss of metal fragment,[5a] to afford the
pyranylidene complex D.[27] Successively, D undergoes
a 1,2‐migration of the [(CO)5M] fragment[28] to obtain
the zwitterionic compound E with the consequent loss
of pyridine. Addressing this step of the reaction, an
experiment was performed in which 1a was combined
with 3a, using pyridine instead of TEA as base, in order
to prove the influence of external pyridine during this
step. We observed that only 5a was formed in a very
sequently generates furan
6
by demetallation,
explaining the results observed during the experiments.
A labeling experiment was performed to clarify the
mechanistic steps of this process (Scheme 5). Carbene 1a
and salt 3a were reacted under the conditions described
above and then exposed to an equimolar amount of
D2O, producing pyranone d‐5a, as evidenced by NMR
and HRMS experiments.[31] This finding is consistent with
the proposal of a Michael adduct B undergoing deutera-
tion at the α carbon atom, and with the absence of furan
d‐6a in the mixture.
In a final attempt to achieve more selective results for
this methodology, an additional experiment was
performed using carbene complex 2a to probe the effects
of drastic temperatures on the optimized system. When a
mixture of 2a and 3a was refluxed (PhMe, TEA, 110 °C,
4 h), the pyran‐2‐one 5a was formed almost exclusively
(94%). This fact indicates that pyran‐2‐ones show a pref-
erence to be formed under thermodynamic conditions
(a previous experiment revealed that refluxing THF is
not enough to ensure selectivity). With this evidence,
some of the reactions of Table 1 were repeated to

FLORES‐CONDE ET AL.
7 of 12
TABLE 2 Selective synthesis of pyran‐2‐ones (5) from alkynyl carbenes and pyridinium ylidesa
Entry
Carbene
2a
Salt
3a
R1
R2
R3
5 (%)b
1
Ph
Ph
H
5a (94)
5c (89)
5d (86)
5e (95)
5h (79)
5i (77)
5k (73)
2
3
4
5
6
7
2ac
1a
2bc
1d
1e
3d
3e
3a
3a
3a
3a
Ph
4‐Me‐C6H4
H
H
H
H
H
H
Ph
4‐Me‐C6H4
4‐Me‐C6H4
3‐CF3‐C6H4
3‐thienyl
c‐1‐C6H9
Ph
Ph
Ph
Ph
1f
aReaction conditions: 1 or 2 (1.5 equiv), 3 (1.0 equiv), TEA (1.0 equiv), PhMe, 110 °C, 4 h.
bIsolated yields.
cM = W, reaction time = 6 h.
corroborate the reproducibility of the selectivity, and the
results are depicted in Table 2.
4 | EXPERIMENTAL SECTION
Regardless of the existence of methodologies for the
regioselective preparation of saturated structures similar
to 5,[32] in the method reported herein only one stage is
required for completion, while the atom‐economy and
substituent tolerance are comparable with other routes.
Furthermore, although the selectivity is diminished in
its milder version, the reaction shows the advantage of
generating products and byproducts with considerable
potential in fields such as drug discovery.
4.1 | General procedure for the synthesis
of Alkynyl Fischer carbenes (1a‐f and 2a‐c)
The carbenes were prepared according to literature
methods described in references 5a‐c.
4.2 | General procedure for the synthesis
of pyridinium salts (3a‐g)
To an oven‐dried 25 ml round‐bottomed flask was added
3.7 mmol of the corresponding α‐bromoketone, and this
was dissolved in 5 ml of anhydrous CH3CN. Slowly,
3.7 mmol of the selected pyridine was added dropwise
and the mixture was stirred until a yellow solid precipi-
tated. The product was then filtered and washed with
acetone to remove colored impurities. Finally, a white
solid was afforded in yields higher than 90% and stored
at low temperature.
3 | CONCLUSION
In summary, an unexpected reaction between chromium
and tungsten alkynyl Fischer carbene complexes 1a‐f
and 2a‐c and the pyridinium salts 3a‐e is reported,
leading to highly functionalized pyran‐2‐ones 5a‐k and
furans 6a‐h in moderate to good yields (45‐97%), as well
as excellent total conversion. In addition, the synthesis
could be modulated to enhance selectivity toward
compounds 5 (73‐95%) by means of thermodynamic
control, and the reaction proved to be effective for a wide
variety of substituents, mainly aromatic groups. The sub-
strates follow a probable reaction pathway consisting of
4.3 | General procedure for the synthesis
of pyran‐2‐ones (5a‐k) and trisubstituted
furans (6a‐k)
A) Combinatorial method: To a 50 ml oven‐dried round‐
bottomed flask was added 0.85 mmol (1 equiv) of the cor-
responding pyridinium salt 3 and the container was deox-
ygenated by flushing with nitrogen for 5 min. Next, 10 ml
of anhydrous THF was added to dissolve the solid,
0.85 mmol of TEA was slowly added, and the mixture
was stirred for 40 min. To another dried flask was placed
0.86 mmol (1.2 equiv) of carbene 1, and the flask was
a
1,4‐addition/ring‐closure/1,2‐migration/demetallation
cascade process for pyran‐2‐ones 5, and another involving
1,4‐addition/ring‐closure/demetallation steps, concluding
in the formation of furans 6. This method represents a
marked contrast from the conventional reactivity of
pyridinium salts, leading to oxo compounds instead of
the expected aza structures.

8 of 12
FLORES‐CONDE ET AL.
deoxygenated as previously described. The contents of the
first flask were then added to the second flask via cannula
and the final mixture was stirred for 12 h. The reaction
was monitored by TLC until completion, at which point
the crude product was purified by column chromatography
using hexanes as eluent. After complex 7 (yellow fraction)
was separated, the polarity of the eluent was increased
(Hex/AcOEt) and the corresponding pyran‐2‐one 5 and
furan 6 were isolated and individually recovered after evap-
oration of the fractions under reduced pressure. B) Selective
method: The quantities of the reagents were kept the same
as in the combinatorial method, but THF is substituted by
anhydrous PhMe and the mixture heated to reflux instead
of room temperature for 4‐6 h. After purification, pyran‐2‐
ones 5 were recovered as the sole products.
H‐14), 6.97 (s, 1H, H‐5), 6.48 (s, 0.65 Hz, H‐3, ≈ 35% D).13C
NMR (125 MHz, CDCl3) δ (ppm): 162.6 (C‐2), 160.3 (C‐6),
155.5 (C‐4), 135.9 (C‐11), 131.5 (C‐7), 130.9 (C‐10), 130.6
(C‐14), 129.2 (C‐8), 128.9 (C‐9), 126.7 (C‐12), 125.7 (C‐13),
109.2 (C‐3), 101.3 (C‐5). HRMS (ESI+): m/z calcd for
C17H13DO2+ [M+H]+, 250.0988; found 250.0975.
4.3.4 | 6‐(4‐Methoxyphenyl)‐4‐phenyl‐2H‐
pyran‐2‐one (5b)
Yield method A: 58% (yellow solid, mp = 133‐134 °C). IR
1
νmax (cm‐1):1181 (C‐O), 1719 (C=O). H NMR (500 MHz,
CDCl3) δ (ppm): 7.84 (d, J = 10.0 Hz, 2H, H‐12), 7.64‐
7.62 (dd, J1 = 5.0 Hz, J2 = 10.0 Hz, 2H, H‐8), 7.50‐7.49
(m, 3H, H‐9, H‐10), 6.97 (d, J = 10.0 Hz, 2H, H‐13), 6.84
(s, 1H, H‐5), 6.39 (s, 1H, H‐3), 3.86 (s, 3H, OCH3). 13C
NMR (125 MHz, CDCl3) δ (ppm): 162.7 (C‐6), 161.8
(C=O), 160.4 (C‐4), 155.8 (C‐7), 136.2 (C‐11), 130.5 (C‐
10), 129.1 (C‐9), 127.3 (C‐12), 126.6 (C‐8), 124.0 (C‐14),
114.3 (C‐13), 107.9 (C‐3), 99.8 (C‐5), 55.3 (OCH3). HRMS
(ESI+): m/z calcd for C18H15O3+[M+H]+, 279.1016;
found, 279.0982.
4.3.1 | Dimethyl 3‐benzoylindolizine‐1,2‐
dicarboxylate (4b)
Yield: 65 % (yellow crystal mp = 165‐166 °C). IR νmax (cm‐1):
1
3105, 3008, 1741, 1699, 1623, 1211. HNMR (500 MHz,
CDCl3) δ (ppm): 9.65 (d, J = 9.0 Hz, 1H, H‐9), 8.39 (d, J =
10.5 Hz, 1H, H‐6), 7.69 (d, J = 8.5 Hz, 2H, H‐12), 7.56
(t, J = 9.0 Hz, 1H, H‐14), 7.50‐7.43 (m, 3H, H‐7, H‐13),
7.12 (t, J = 8.5 Hz, 1H, H‐8), 3.88 (s, 3H, H‐16), 3.31 (s, 3H,
H‐18). 13C NMR (125 MHz, CDCl3) δ (ppm): 52.0 (C‐16),
52.6 (C‐18), 104.3 (C‐3), 116.4 (C‐8), 120.3 (C‐6), 121.2
(C‐11), 128.4 (C‐7), 128.5 (C‐13), 128.9 (C‐9), 129.0 (C‐12),
132.0 (C‐2), 132.2 (C‐14), 138.6 (C‐4), 139.9 (C‐5), 163.7
(C‐15), 165.6 (C‐17), 187.2 (C‐10). HRMS (ESI+): m/z calcd
for C19H15NO5+ [M]+,337.0945; found, 337.0970.
4.3.5 | 4‐Phenyl‐6‐(p‐tolyl)‐2H‐pyran‐2‐one
(5c)
Yield method A: 57%; method B: 89% (yellow solid, mp =
1
114‐115 °C). IR νmax (cm‐1):1081 (C‐O), 1698 (C=O). H
NMR (500 MHz, CDCl3) δ (ppm): 7.79 (d, J = 10.0 Hz,
2H, H‐12), 7.65‐7‐63 (dd, J1 = 5.0 Hz, J2 = 10.0 Hz, 2H,
H‐13), 7.51 (d, J = 5.0 Hz, 3H, H‐ 9, H‐10), 7.28 (d, J =
10.0 Hz, 2H, H‐9), 6.92 (s, 1H, H‐5), 6.44 (s, 1H, H‐3),
2.41 (s, 3H, CH3). 13C NMR (125 MHz, CDCl3) δ (ppm):
162.7 (C=O), 160.6 (C‐6), 155.6 (C‐4), 141.4 (C‐14), 136.1
(C‐11), 130.5 (C‐10), 129.6 (C‐8), 129.1 (C‐9), 128.7 (C‐7),
126.6 (C‐13), 125.6 (C‐12), 108.7 (C‐3), 100.6 (C‐5), 21.4
(CH3). HRMS (ESI+): m/z calcd for C18H15O2+[M+H]+,
263.1067; found, 263.1038.
4.3.2 | 4,6‐diphenyl‐2H‐pyran‐2‐one (5a)
Yield method A: 56%; method B: 94% (white solid, mp =
1
140‐141 °C). IR νmax (cm‐1):1079 (C‐O),1703 (C=O). H
NMR (500 MHz, CDCl3) δ (ppm): 7.90 (d, J = 5.0 Hz,
2H, H‐12), 7.65 (d, J = 5.0 Hz, 2H, H‐8), 7.50 (m, 6H,
H‐9, H‐10, H‐13, H‐14), 6.97 (s, 1H, H‐5), 6.47 (s, 1H,
H‐3). 13C NMR (125 MHz, CDCl3) δ (ppm): 162.6 (C‐
2), 160.3 (C‐6), 155.5 (C‐4), 136.0 (C‐11), 131.4 (C‐7),
130.8 (C‐10), 130.6 (C‐14), 129.2 (C‐8), 128.9 (C‐9),
126.6 (C‐12), 125.7 (C‐13), 109.2 (C‐3), 101.3 (C‐5).
4.3.6 | 6‐(4‐Chlorophenyl)‐4‐phenyl‐2H‐
pyran‐2‐one (5d)
HRMS (ESI+): m/z calcd for C17H13O2 [M+H]+
Yield method A: 55%; method B: 86% (yellow solid, mp =
+
1
249.0910; found, 249.0916.
175‐176 °C). IR νmax (cm‐1): 1090 (C‐O), 1700 (C=O). H
NMR (500 MHz, CDCl3) δ (ppm): 7.82 (d, J = 10.0 Hz, 2H,
H‐13), 7.64‐7.62 (m, 2H, H‐9), 7.52‐7.51 (m, 3H, H‐10, H‐
12), 7.44 (d, J = 10.0 Hz, 2H, H‐8), 6.94 (s, 1H, H‐5), 6.46
(s, 1H, H‐3). 13C NMR (125 MHz, CDCl3) δ (ppm): 162.1
(C‐6), 159.1 (C=O), 155.3 (C‐4), 137.0 (C‐11), 135.8 (C‐7),
130.7 (C‐10), 129.9 (C‐8), 129.2 (C‐12), 126.9 (C‐13), 126.6
(C‐9), 109.4 (C‐3), 101.4 (C‐5). HRMS (ESI+): m/z calcd
for C17H12ClO2+ [M+H]+, 283.0520; found, 283.0492.
4.3.3 | 4,6‐diphenyl‐2H‐pyran‐2‐one‐3‐d (d‐
5a)
Yield method A: 45% (white solid, mp = 140‐141 °C). IR
1
νmax (cm‐1):1079 (C‐O),1703 (C=O). H NMR (500 MHz,
CDCl3) δ (ppm): 7.90 (d, J = 5.0 Hz, 2H, H‐12), 7.65 (d, J
= 5.0 Hz, 2H, H‐8), 7.55‐7.48 (m, 6H, H‐9, H‐10, H‐13,

FLORES‐CONDE ET AL.
9 of 12
NMR (500 MHz, CDCl3) δ (ppm): 7.91‐7.89 (dd, J1
=
5.0 Hz, J2 = 10.0 Hz, 2H, H‐8), 7.79 (m, 1H, H‐9), 7.49 ‐
7.48 (dd, J1 = 5.0 Hz, J2 = 10.0 Hz, 4H, H‐12, H‐13),
7.44‐7.43 (dd, J1 = 5.0 Hz, J2 = 10.0 Hz, 1H, H‐10), 6.95
(s, 1H, H‐5), 6.47 (s, 1H, H‐3). 13C NMR (125 MHz,
CDCl3) δ (ppm): 162.8 (C=O), 160.4 (C‐2), 149.2 (C‐6),
137.6 (C‐12), 131.6 (C‐7), 131.4 (C‐4), 130.9 (C‐15), 128.9
(C‐14), 127.8 (C‐11), 125.8 (C‐8), 125.7 (C‐13), 125.4 (C‐
10), 107.7 (C‐3), 100.8 (C‐5). HRMS (ESI+): m/z calcd for
C15H11O2S+ [M+H]+, 255.0474; found, 255.0483.
4.3.7 | 6‐Phenyl‐4‐(p‐tolyl)‐2H‐pyran‐2‐one
(5e)
Yield method A: 49%; method B: 95% (light brown solid,
mp = 114‐115 °C). IR νmax (cm‐1): 1081 (C‐O), 1698
1
(C=O). H NMR (500 MHz, CDCl3) δ (ppm): 7.79 (d, J =
10.0 Hz, 2H, H‐12), 7.65‐7.63 (dd, J1 = 5.0 Hz, J2
=
10.0 Hz, 2H, H‐13), 7.51 (d, J = 10.0 Hz, 3H, H‐8, H‐14),
7.28 (d, J = 5.0 Hz, 2H, H‐9) 6.92 (s, 1H, H‐5), 6.44 (s,
1H, H‐3), 2.41 (s, 3H, CH3). 13C NMR (125 MHz, CDCl3)
(δ, ppm): 162.7 (C=O), 160.6 (C‐6), 155.6 (C‐4), 141.4 (C‐
10), 136.1 (C‐11), 130.5 (C‐7), 129.6 (C‐8), 129.1 (C‐9),
126.6 (C‐13), 125.6 (C‐12), 108.7 (C‐3), 100.6 (C‐5), 21.4
(CH3). HRMS (ESI+): m/z calcd for C18H15O2+[M+H]+,
263.1067; found, 263.1046.
4.3.11 | 4‐(Thiophen‐3‐yl)‐6‐(p‐tolyl)‐2H‐
pyran‐2‐one (5j)
Yield method A: 59% (brown solid, mp = 186‐187 °C). IR
ν
max (cm‐1): 1076 (C‐O), 1694 (C=O). 1H NMR (500 MHz,
CDCl3) δ (ppm): 7.78 (d, J = 10.0 Hz, 3H, H‐9, H‐12), 7.48‐
7.46 (dd, J1 = 5.0 Hz, J2 = 10.0 Hz, 1H, H‐10), 7.43 (d, J =
5.0 Hz, 1H, H‐8), 7.28 (d, J = 10.0 Hz, 2H, H‐13), 6.90 (s,
1H, H‐5), 6.43 (s, 1H, H‐3), 2.41 (s, 3H, CH3). 13C NMR
(125 MHz, CDCl3) δ (ppm): 163.0 (C=O), 160.6 (C‐6),
149.3 (C‐4), 141.4 (C‐14), 137.6 (C‐7), 129.6 (C‐12), 128.7
(C‐11), 127.9 (C‐10), 125.7 (C‐13), 125.6 (C‐8), 125.4 (C‐9),
107.2 (C‐3), 100.1 (C‐5), 21.4 (CH3). HRMS (ESI+): m/z
calcd for C16H13O2S+ [M+H]+, 269.0631; found, 269.0614.
4.3.8 | 6‐(4‐Methoxyphenyl)‐4‐(p‐tolyl)‐2H‐
pyran‐2‐one (5f)
Yield method A: 31% (yellow solid, mp = 85‐86 °C). IR
1
νmax (cm‐1):1184 (C‐O), 1706 (C=O). H NMR (500 MHz,
CDCl3) δ (ppm): 6.85 (d, J = 5.0 Hz, 2H, H‐8), 7.55 (d, J
= 10.0 Hz, 2H, H‐9), 7.31 (d, J = 10.0 Hz, 2H, H‐12),
6.98 (d, J = 10.0 Hz, 2H, H‐13), 6.85 (s, 1H, H‐5), 6.40 (s,
1H, H‐3), 3.88 (s, 3H, OCH3), 2.43 (s, 3H, CH3). 13C
NMR (125 MHz, CDCl3) δ (ppm): 163.0 (C‐6), 161.7
(C=O), 160.3 (C‐4), 141.0 (C‐14), 133.3 (C‐7), 129.9 (C‐
12), 127.4 (C‐8), 126.6 (C‐9), 124.1 (C‐10), 114.3 (C‐13),
107.4 (C‐3), 99.8 (C‐5), 55.4 (OCH3), 21.4 (CH3). HRMS
(ESI+): m/z calcd for C19H16O3+[M+H]+, 293.1172;
found, 293.1173.
4.3.12 | 4‐(Cyclohex‐1‐en‐1‐yl)‐6‐phenyl‐
2H‐pyran‐2‐one (5k)
Yield method A: 48%; method B: 73% (dark brown solid,
mp = 95‐96 °C). IR νmax (cm‐1):1074 (C‐O), 1700 (C=O).
1H NMR (500 MHz, CDCl3) δ (ppm): 7.84 (dd, J1
=
5.0 Hz, J2 = 10.0 Hz, 2H, H‐14), 7.45‐7.44 (d, J = 5.0 Hz,
3H, H‐15, H‐16), 6.82 (s, 1H, H‐5), 6.58 (s, 1H, H‐8), 6.16
(s, 1H, H‐3), 2.31 (m, 4H, H‐9, H‐12), 1.81‐1.78 (m, 2H,
H‐11), 1.70‐1.66 (m, 2H, H‐10). 13C NMR (125 MHz,
CDCl3) δ (ppm): 166.4 (C=O), 158.8 (C‐6), 155.3 (C‐4),
133.3 (C‐7), 132.8 (C‐8), 131.9 (C‐13), 130.5 (C‐16), 128.8
(C‐14), 125.6 (C‐15), 106.6 (C‐3), 99.2 (C‐5), 26.2 (C‐9),
25.6 (C‐12), 22.3 (C‐10), 21.5 (C‐11). HRMS (ESI+): m/z
calcd for C17H17O2+[M+H]+, 253.1223; found, 253.1195.
4.3.9 | 4‐(m‐Tolyl)‐6‐(p‐tolyl)‐2H‐pyran‐2‐
one (5g)
Yield method A: 53% (pale yellow crystals, mp = 112‐
113 °C). IR νmax (cm‐1):1081 (C‐O), 1698 (C=O). 1H
NMR (500 MHz, CDCl3) δ (ppm): 7.80 (d, J = 10.0 Hz,
2H, H‐14), 7.44‐7.39 (m, 3H, H‐12, H‐15), 7.33‐7.27 (m,
3H, H‐8, H‐9, H‐10), 6.92 (s, 1H, H‐5), 6.43 (s, 1H, H‐3),
2.45 (s, 3H, CH3), 2.42 (s, 3H, CH3). 13C NMR (125 MHz,
CDCl3) δ (ppm): 162.8 (C‐2), 160.4 (C‐6), 155.9 (C‐4),
141.3 (C‐7), 138.9 (C‐11), 136.1 (C‐16), 131.3 (C‐9), 129.6
(C‐15), 129.0 (C‐10), 128.7 (C‐13), 127.3 (C‐12), 125.6 (C‐
14), 123.8 (C‐8), 108.6 (C‐3), 100.8 (C‐5), 21.4 (both
CH3). HRMS (ESI+): m/z calcd for C19H17O2+[M+H]+,
277.1223; found, 277.1236.
4.3.13 | Ethyl 3,5‐diphenylfuran‐2‐carbox-
ylate (6a)
Yield: 39% (pale yellow solid, mp = 92‐93 °C). IR νmax
(cm‐1): 1189 (C‐O), 1706 (C=O). 1H NMR (500 MHz,
CDCl3) δ (ppm): 7.82 (d, J = 10.0 Hz, 2H, H‐11), 7.62 (d,
J = 10.0 Hz, 2H, H‐7), 7.46‐7.37 (m, 6H, H‐8, H‐9, H‐12,
H‐13), 6.85 (s, 1H, H‐4), 4.33 (q, J = 10.0 Hz, 2H,
OCH2CH3), 1.31 (t, J = 5.0 Hz, 3H, OCH2CH3). 13C
NMR (125 MHz, CDCl3) δ (ppm): 159.2 (C=O), 155.8
(C‐5), 138.1 (C‐2), 136.4 (C‐6), 132.1 (C‐3), 129.3 (C‐8),
4.3.10 | 6‐Phenyl‐4‐(thiophen‐3‐yl)‐2H‐
pyran‐2‐one (5i)
Yield method A: 58%; method B: 77% (brown solid, mp =
1
159‐160 °C). IR νmax (cm‐1): 1077 (C‐O), 1691 (C=O). H

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FLORES‐CONDE ET AL.
129.3 (C‐12), 129.0 (C‐9), 128.8 (C‐13), 128.2 (C‐10), 127.9
(C‐7), 124.9 (C‐11), 109.3 (C‐4), 60.7 (OCH2CH3), 14.1
4.3.17 | Ethyl 5‐phenyl‐3‐(p‐tolyl) furan‐2‐
carboxylate (6e)
(OCH2CH3). HRMS (ESI+): m/z calcd for C19H17O3 [M
+
Yield: 33% (white solid, mp = 108‐109 °C). IR νmax (cm‐1):
+H]+, 292.1172; found, 293.1176.
1
1175 (C‐O), 1702 (C=O). H NMR (500 MHz, CDCl3) δ
(ppm): 7.82 (d, J = 10.0 Hz, 2H, H‐11), 7.53 (d, J =
10.0 Hz, 2H, H‐12), 7.49‐7.36 (m, 3H, H‐7, H‐13), 7.24
(d, J = 10.0 Hz, 2H, H‐8), 6.84 (s, 1H, H‐4), 4.32 (q, J =
10.0 Hz, 2H, OCH2CH3), 2.40 (s, 3H, CH3), 1.33 (t, J =
10.0 Hz, 3H, OCH2CH3). 13C NMR (125 MHz, CDCl3) δ
(ppm): 159.2 (C=O), 155.7 (C‐5), 138.1 (C‐2), 137.9 (C‐6),
136.5 (C‐3), 129.4 (C‐12), 129.2 (C‐13), 129.1 (C‐9), 129.0
(C‐10), 128.8 (C‐7), 128.7 (C‐8), 109.4 (C‐11), 60.7
(OCH2CH3), 21.3 (CH3), 14.2 (OCH2CH3). HRMS (ESI+):
4.3.14 | Ethyl 5‐(4‐methoxyphenyl)‐3‐
phenylfuran‐2‐carboxylate (6b)
Yield: 24% (yellow oil). IR νmax (cm‐1): 1175 (C‐O), 1710
1
(C=O). H NMR (500 MHz, CDCl3) δ (ppm): 7.76 (d, J =
10.0 Hz, 2H, H‐11), 7.61 (d, J = 5.0 Hz, 2H, H‐7), 7.43‐
7.37 (m, 3H, H‐8, H‐9), 6.97 (d, J = 10.0 Hz, 2H, H‐12),
6.72 (s, 1H, H‐4), 4.32 (q, J = 10.0 Hz, 2H, OCH2CH3),
3.86 (s, 3H, OCH3), 1.30 (t, J =10.0 Hz, 3H, OCH2CH3).
13C NMR (125 MHz, CDCl3) δ (ppm): 160.3 (C‐13), 159.3
(C=O), 156.0 (C‐5), 137.6 (C‐2), 136.6 (C‐6), 129.3 (C‐7),
128.1 (C‐9), 127.9 (C‐8), 126.5 (C‐11), 114.3 (C‐12), 108.0
(C‐4), 60.6 (OCH3), 55.3 (OCH2CH3), 14.2 (OCH2CH3).
m/z calcd for C20H19O3 [M+H]+, 307.1329; found,
+
307.1345.
HRMS (ESI+): m/z calcd for C20H19O4 [M+H]+,
+
4.3.18 | Ethyl 5‐(4‐methoxyphenyl)‐3‐(p‐
tolyl) furan‐2‐carboxylate (6f)
323.1278; found, 323.1280.
Yield: 14% (brown solid, mp = 98‐99 °C). IR νmax (cm‐1):
1
1172 (C‐O), 1705 (C=O). H NMR (500 MHz, CDCl3) δ
4.3.15 | Ethyl‐3‐phenyl‐5‐(p‐tolyl) furan‐2‐
(ppm): 7.75 (d, J = 10.0 Hz, 2H, H‐11), 7.52 (d, J =
5.0 Hz, 2H, H‐7), 7.22 (d, J = 5.0 Hz, 2H, H‐8), 6.96 (d, J
= 10.0 Hz, 2H, H‐12), 6.71 (s, 1H, H‐4), 4.33 (q, J =
10.0 Hz, 2H, OCH2CH3), 3.86 (s, 3H, OCH3), 2.40 (s, 3H,
CH3), 1.32 (t, J = 10.0 Hz, 3H, OCH2CH3).13C NMR
(125 MHz, CDCl3) δ (ppm): 160.3 (C‐13), 159.3 (C=O),
155.9 (C‐5), 138.1 (C‐2), 137.4 (C‐3), 136.7 (C‐9), 129.3
(C‐6), 129.2 (C‐7), 128.6 (C‐8), 126.4 (C‐11), 122.4 (C‐10),
114.2 (C‐12), 108.0 (C‐4), 60.5 (OCH2CH3), 55.3 (OCH3),
21.2 (CH3), 14.2 (OCH2CH3). HRMS (ESI+): m/z calcd
carboxylate (6c)
Yield: 24% (pale yellow crystals, mp = 108‐109 °C). IR
νmax (cm‐1): 1179 (C‐O), 1709 (C=O). 1H NMR
(500 MHz, CDCl3) δ (ppm): 7.72 (d, J = 10.0 Hz, 2H, H‐
11), 7.61 (d, J = 10.0 Hz, 2H, H‐12), 7.41 (m, 3H, H‐7,
H‐9), 7.25 (m, 3H, H‐8, H‐9), 6.80 (s, 1H, H‐4), 4.33 (q, J
= 10.0 Hz, 2H, OCH2CH3), 2.40 (s, 3H, CH3), 1.31 (t, J =
10.0 Hz, 3H, OCH2CH3). 13C NMR (125 MHz, CDCl3) δ
(ppm): 159.2 (C=O), 156.1 (C‐5), 139.1 (C‐2), 137.7 (C‐6),
136.5 (C‐13), 132.2 (C‐9), 129.5 (C‐12), 129.3 (C‐8), 128.2
(C‐10), 127.9 (C‐7), 126.6 (C‐9), 124.8 (C‐11), 108.7 (C‐4),
60.6 (OCH2CH3), 21.4 (CH3), 14.2 (OCH2CH3). HRMS
for C21H21O4 [M+H]+, 337.1434; found, 337.1440.
+
(ESI+): m/z calcd for C20H19O3 [M+H]+, 307.1329;
+
4.3.19 | Ethyl 5‐phenyl‐3‐(3‐
(trifluoromethyl) phenyl) furan‐2‐carboxyl-
ate (6h)
found, 307.1345.
4.3.16 | Ethyl 5‐(4‐chlorophenyl)‐3‐
phenylfuran‐2‐carboxylate (6d)
Yield: 20% (brown solid, mp = 99‐100 °C). IR νmax (cm‐
1
1):1180 (C‐O), 1708 (C=O). H NMR (500 MHz, CDCl3)
Yield: 30% (light brown solid, mp = 91‐92 °C). IR νmax (cm‐
1): 1170 (C‐O), 1700 (C=O). 1H NMR (500 MHz, CDCl3) δ
(ppm): 7.76 (d, J = 5.0 Hz, 2H, H‐11), 7.60 (d, J = 5.0 Hz,
2H, H‐12), 7.54 (d, J = 5.0 Hz, 1H, H‐9), 7.44‐7.36 (m, 4H,
H‐7, H‐8), 6.84 (s, 1H, H‐4), 4.33 (q, J = 10.0 Hz, 2H,
OCH2CH3), 1.31 (t, J = 10.0 Hz, 3H, OCH2CH3). 13C
NMR (125 MHz, CDCl3) δ (ppm): 159.3 (C=O), 156.7 (C‐
5), 138.8 (C‐2), 135.1 (C‐3), 133.4 (C‐13), 133.1 (C‐6),
129.6 (C‐10), 129.4 (C‐8), 129.3 (C‐7), 128.8 (C‐12), 126.6
(C‐9), 125.3 (C‐11), 109.4 (C‐4), 61.4, (OCH2CH3) 14.4
(OCH2CH3). HRMS (ESI+): m/z calcd for C17H11ClO2
([M+H]+‐OEt), 282.0448; found, 282.2744.
δ (ppm): 7.88 (s, 1H, H‐7), 7.84‐7.80 (m, 3H, H‐9, H‐15),
7.65 (d, J = 5.0 Hz, 1H, H‐11), 7.57‐7.53 (dd, J1 = 5.0 Hz,
J2 = 10.0 Hz, 2H, H‐14), 7.46 (t, J = 10.0 Hz, 2H, H‐10),
7.40 (d, J = 10.0 Hz, H‐10), 4.33 (q, J = 10.0 Hz, 2H,
OCH2CH3), 1.30 (t, J = 10.0 Hz, 3H, OCH2CH3). 13C
NMR (125 MHz, CDCl3) δ (ppm): 158.9 (C=O), 156.3 (C‐
5), 138.5 (C‐2), 134.7 (C‐6), 133.0 (C‐3), 132.6 (C‐8),
129.2 (C‐11), 128.9 (C‐14), 128.4 (C‐7), 126.3 (CF3), 124.9
(C‐13), 109.0 (C‐4), 60.9 (OCH2CH3), 14.0 (OCH2CH3).
19F NMR (500 MHz, CDCl3) δ (ppm):‐62.6 (CF3). HRMS
(ESI+): m/z calcd for C20H16F3O3+[M+H]+, 361.1035;
found 361.1004.

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[7] a) D. S. Grum, D. Cook, D. Baucom, I. W. Mott, D. R. Gardner,
R. Creamer, J. G. Allen, J. Nat. Prod. 2013, 76, 1984. b) J. W.
Daly, T. F. Spande, H. M. Garraffo, J. Nat. Prod. 2005, 68, 1556.
4.3.20 | Pentacarbonylpyridinyl-
chromium(0) (7a)
Yield: 52% (yellow crystals, mp = 94‐95 °C). IR νmax (cm‐1):
439, 647, 655, 756, 1445, 1921, 2066, 2922, 3074, 3109. H
[8] J. Brioche, C. Meyer, J. Cossy, Org. Lett. 2015, 17, 2800.
1
[9] a) M. A. M. Behnam, C. Nitsche, V. Boldescu, C. D. Klein,
J. Med. Chem. 2016, 59, 5622. b) P. Chen, A. Chaikuad, P.
Bamborough, M. Bantscheff, C. Bountra, C. Chung, O. Fedorov,
P. Grandi, D. Jung, R. Lesniak, M. Lindon, S. Müller, M.
Philpott, R. Prinjha, C. Rogers, C. Selenski, C. Tallant, T.
Werner, T. M. Willson, S. Knapp, D. H. Drewry, J. Med. Chem.
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NMR (500 MHz, CDCl3) δ (ppm):8.52 (bs, 2H, H‐2), 7.64
(bs, 1H, H‐4), 7.17 (bs, 2H, H‐3).13C NMR (125 MHz,
CDCl3) δ (ppm): 220.7 (COtrans), 214.4 (COcis), 155.4 (C‐
2), 137.2 (C‐4), 124.9 (C‐3). HRMS (ESI+): m/z calcd for
Cr(CO)4 [M+ ‐ C5H4NBr ‐ CO], 163.9202; found 163.9783.
ACKNOWLEDGMENTS
The authors are grateful for financial support from the
Consejo Nacional de Ciencia y Tecnología (CONACYT
CB, research grants 218003 MIFC; 241803, JL and MAV)
and Dirección de Apoyo a la Investigación y al Posgrado
(DAIP, research grant 811/2016, MAV), and thank the
National Laboratory UG‐CONACYT (research project
260373) for analytical characterization.
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ORCID
Marcos Flores‐Álamo
http://orcid.org/0000-0002-2996-
7616
Miguel A. Vázquez http://orcid.org/0000-0002-2240-4669
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