Synthesis of aromatic rings embedded in polycyclic scaffolds by triyne cycloaddition: Competition between carbonylative and non-carbonylative pathways

Article abstract of DOI:10.3390/molecules24030595

Cycloadditions have emerged as some of the most useful reactions for the formation of polycyclic compounds. The carbonylative cycloaddition of triynes can lead to carbonylative and non-carbonylative competitive pathways, each leading to the formation of an aromatic ring. We report herein the one-pot synthesis of fully- and unsymmetrically-substituted tetracyclic 6,5,7,5-troponic and 6,5,6,5-benzenoid scaffolds using pre-organized triynes showing the competition between these two pathways.

Full text of DOI:10.3390/molecules24030595

molecules
Article
Synthesis of Aromatic Rings Embedded in Polycyclic
Scaffolds by Triyne Cycloaddition:
Competition between Carbonylative and
Non-Carbonylative Pathways
Laura Salacz, Nicolas Girard , Jean Suffert * and Gaëlle Blond *
Laboratoire d’Innovation Thérapeutique, Université de Strasbourg, CNRS, 67000 Strasbourg, France;
laura.salacz@etu.unistra.fr (L.S.); nicolas.girard@unistra.fr (N.G.)
* Correspondence: jean.suffert@unistra.fr (J.S.); gaelle.blond@unistra.fr (G.B.); Tel.: +33-(0)368-854-230 (J.S.);
+33-(0)368-854-165 (G.B.)
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Received: 21 January 2019; Accepted: 4 February 2019; Published: 7 February 2019
Abstract: Cycloadditions have emerged as some of the most useful reactions for the formation of
polycyclic compounds. The carbonylative cycloaddition of triynes can lead to carbonylative and
non-carbonylative competitive pathways, each leading to the formation of an aromatic ring. We report
herein the one-pot synthesis of fully- and unsymmetrically-substituted tetracyclic 6,5,7,5-troponic
and 6,5,6,5-benzenoid scaffolds using pre-organized triynes showing the competition between these
two pathways.
Keywords: cyclotrimerization; carbonylative cycloaddition; tropone; benzenoid; polycycles; rhodium
catalysis; one-pot reaction
1. Introduction
In the past century, the advent of modern organic chemistry has triggered a revolution in the
chemical landscape. The vast increase of means of synthesis and analysis has allowed a tremendous
diversification of possibilities, including the ability to synthesize complex structures inspired by
nature [
intensively developed. However, these reactions are necessarily limited by Woodward-Hoffmann
rules, and are therefore limited to classical ring-sizes [ ]. Metal-catalyzed cycloadditions, on the other
1]. Due to the polycyclic nature of many of these scaffolds, cycloaddition reactions have been
2
hand, allow the synthesis of different ring-sizes. Additionally, they can bring together three or more
components for the synthesis of exotic structures. Indeed, in recent years, considerable advances have
been made in the development of [2+2+2] [
other cycloadditions [9–11].
3], [2+2+2+1] [4,5], [3+3+1] [6], [5+2+1] [7,8], and various
The use of alkynes in cycloaddition reactions allows the formation of unsaturated compounds.
They have been extensively used for the synthesis of complex and original structures. Additionally,
the intramolecular cyclotrimerization of alkynes has been applied to the synthesis of many useful
compounds containing a benzene ring, including helicenes [12]. Nevertheless, examples of the
cycloaddition of fully substituted unsymmetrical triynes are scarce in the literature, even though
highly substituted and non-symmetrical polycycles have attracted much attention. Moreover, until
recently, no example combined the cycloaddition of triynes with carbonylative cycloaddition.
In the course of our work on the synthesis of polycyclic compounds containing 7- and 8-membered
rings [13–
16], we recently interested ourselves in the RhI-catalyzed [2+2+2+1] carbonylative
cycloaddition of pre-organized triynes yielding 2,4,6-cycloheptatrienones (Scheme 1a) [17]. These
compounds, more commonly referred as tropones [18], are non-benzenoid aromatic carbonylated
Molecules 2019, 24, 595; doi:10.3390/molecules24030595
www.mdpi.com/journal/molecules

Molecules 2019, 24, 595
2 of 8
7-membered rings that have attracted increasing attention due to their interesting electronic
properties [19 21], their presence in several natural products [22 23], and their 8 system, which
gives them importance as synthons [24].
–
,
π
A major challenge with the formation of carbonylated compounds by [2+2+2+1] carbonylative
cycloaddition of triynes is the competing byproduct arising from the non-carbonylative pathway.
During our seminal work, we hypothesized that favoring the carbonylative pathway could be achieved
by using a substrate containing a cyclic core allowing the constriction of the reactant in order to place
the reactive moieties at an ideal distance to undergo fast cyclization. With this strategy, we reported the
synthesis of fully- and unsymmetrically-functionalized fused 6,6,7,5- and 6,6,6,5-tetracycles obtained
through, respectively, the carbonylative and non-carbonylative reaction pathway (Scheme 1a).
Remarkably, during this study, evidence was found that the formation of 6-membered rings from
the tethers of the triynes is challenging in this process. In following work, we explored the possibilities
offered by tethers leading to the formation of 5-membered cycles (Scheme 1b).
These would allow the formation of novel 6,5,7,5,- and 6,5,6,5-fused tetracycles containing an
aromatic tropone or benzenoid moiety. In addition to the generated structural diversity, the envisioned
products would comprise an oxygenated quaternary carbon center at a ring junction, allowing
post-functionalization as well as the modification of the spatial conformation.
Y
Y
(a) Previous work
X
X
R1
+
R3
R1
n = 1
X, Y = O, NTs, C(CO2Et)2
R1 = H
R2, R3 = alkyl, aryl
R3
R2
O
Y
R2
14-68%
R3
n
22-58%
R2
X
R1
O
O
C2H5
O
1
(b) This work
+
R1
R1
C2H5
n = 0, X = CH2, Y = O
R1 = OH, OMe
R2 = H, C5H11
R3 = C2H5
R2
R2
2
3
Scheme 1. [2+2+2+1] cycloaddition of unsymmetrically fully substituted triynes (
our group; (
reaction of pre-organized triynes containing shorter tethers.
a
) Previous work in
b
) this work on the competition of carbonylative and non-carbonylative pathways of the
2. Results
With the previous results in hand, and having observed that the formation of 6-membered rings
is challenging in this process, we chose to investigate the formation of 6,5,7,5-polycyclic tropones and
6,5,6,5-polycylic benzenoids. We therefore synthesized substrates 1a
tether. Commercial cyclohexenone was first iodinated using the described conditions [25]. The resulting
2-iodocyclohexenone then underwent Sonogashira cross-coupling in standard conditions with
1-heptyne and ethynyltrimethylsilane yielding respectively with 87% yield and with 93% yield. The
–d (Scheme 2), containing an alkyl
5
6
7
resulting enynones were then submitted to a Grignard reaction with propargyl bromide in the presence
of a catalytic amount of mercuric chloride to avoid polymerization of the reagent, giving tertiary
alcohols
8 and 9 in high yields. The terminal alkynes were then deprotonated by ethylmagnesium
bromide and reacted with paraformaldehyde to give propargylic alcohols 10 and 11 in 74% and 83%
yield, respectively. These underwent Williamson reaction with commercial 1-bromo-2-pentyne in
biphasic media, leading to the formation of corresponding substrate 1a in 97% yield and 1b through
base-mediated desilylation in 74% yield. The free alcohols were methylated selectively by the action of
methyl iodide to give pre-organized triynes 1c and 1d in good yields.

Molecules 2019, 24, 595
3 of 8
Br
R2
[PdCl2(PPh3)2] cat.
CuI cat.
Mg
HgCl2 cat.
I2, K2CO3
O
R2
O
O
R2
NEt3
I2 cat.
DMAP cat.
I
HO
benzene, 0 °C
1 h
Et2O, 0 °C - rt
30 min
THF/H2O 1/1
rt, 3.5 h
8, R2 = C5H11 : 78%
9, R2 = TMS : quant.
6, R2 = C5H11 : 87%
7, R2 = TMS : 93%
4
5 : 87%
1. EtMgBr
THF, 50 °C, 1 h
2. (CH2O)n
20 h
O
R2
O
R2
1. NaH
DMF, 0 °C, 1h
OH
R2
1-bromopent-2-yne
Bu4N.HSO4 cat.
Et
Et
MeO
HO
HO
2. MeI
0 °C - rt, 15 h
DCM/NaOH 50% 2/1
rt, 3.5 h
10, R2 = C5H11 : 74%
11, R2 =TMS : 83%
1c, R2 = C5H11 : 64%
1d, R2 = H : 75%
1a, R2 = C5H11 : 97%
1b, R2 = H : 74%
Scheme 2. Synthesis of substrates 1a–d.
With these triynes in hand, we investigated the competitive pathways of rhodium-catalyzed
[2+2+2+1] and [2+2+2] cycloadditions of 5-atom-tethered-triynes to study the impact of the tether size
as well as potential alternative carbon monoxide sources in these processes.
2.1. Use of Mo(CO)6 as CO Source for the [2+2+2+1] Carbonylative Cycloaddition
Due to its high toxicity and the necessary setup, and despite its frequent utilization in industry,
the use of carbon monoxide is often deemed unpractical by synthetic chemists. Consequently, many
alternatives have been developed in recent years. Mo(CO)6 is one of the most used metallic CO
sources, particularly as a carbonylative cycloaddition catalyst or in palladium-catalyzed carbonylative
cycloaddition [26–28]. However, to the best of our knowledge, no example combining CO-donation by
molybdenum and rhodium-catalyzed carbonylative cycloaddition have been reported. We therefore
elected to study the possibility of combining the reactivity of rhodium catalysts in cycloaddition
reactions with the CO-donating ability of molybdenum complex Mo(CO)6.
In a first experiment, substrate 1a was used with 10 equivalents of molybdenum hexacarbonyl and
5 mol% of rhodium catalyst (Table 1, entry 1). In this case, tropone 2a and benzenoid 3a were obtained
in a 1/3 ratio, respectively, and the formation of a third compound, 12, by [2+2+2] cyclotrimerization
and dehydration was also observed. Interestingly, the dehydrated troponic analog of 2a was not
detected, indicating that dehydration and carbon monoxide insertion are mutually exclusive in these
conditions. This experiment seems to indicate that no ligand transfer from the molybdenum to the
rhodium takes place and that all the CO ligands of the rhodium catalyst undergo migratory insertion.
This observation could be explained in the presence of a strongly coordinating solvent, however, in this
case, no satisfactory explanation could be found.
A second experiment without molybdenum was done and reached full conversion overnight
(entry 2). However, we observed similar results as those observed in entry 1, confirming our first
hypothesis that all the CO insertion results from the rhodium catalyst.
Then using high loading catalyst (25 mol% of [Rh(CO)2Cl]2) at room temperature, full conversion
was achieved in 10 min and in this case only one carbon monoxide ligand per molecule of catalyst was
inserted in the products (entry 3).
Another experiment using only Mo(CO)6 lead to the sole formation of dehydrated compound 12
,
indicating that the molybdenum complex does not enable CO migratory insertion (entry 4). However,
ligand exchange between CO and alkyne moieties seems to occur, as this step is necessary for the
formation of compound 12. Moreover, comparison of entries 1 and 4 indicates that rhodium has a
higher affinity for the multiple bonds, as the formation of 12 is not a competing process whether

Molecules 2019, 24, 595
4 of 8
Mo(CO)6 is present in the media or not (entries 1, 2 and 4). In order to verify that CO transfer between
molybdenum and rhodium does not occur, we conducted two additional experiments in toluene at
higher temperature under micro-wave irradiation (entries 5 and 6). In both cases, the amount of
tropone 2a obtained was consistent with very low or no participation of the molybdenum complex,
and only the yield of dehydrated compound 12 increased, as can be expected at a higher temperature.
In other words, our experiments showed that, in these conditions, Mo(CO)6 is not efficient as
a CO source in rhodium-catalyzed [2+2+2+1] carbonylative cycloaddition of triynes. Additionally,
an equilibrium of approximately 1/3 in favor of the non-carbonylative pathway is observed in the
presence of the rhodium catalyst, catalytic loading notwithstanding. Moreover, we observed the
emergence of a new competitive [2+2+2]/elimination pathway. However, a higher content in metal
complex in the media and a higher temperature favor the dehydration process, indicating a Lewis-acid
mediated reaction.
Table 1. Use of Mo(CO)6 as CO source for the [2+2+2+1] carbonylative cycloaddition and competing
pathways of triyne 1a.
O
O
O
O
[RhCl(CO)2]2 (mol%)
Mo(CO)6 (eq)
C2H5
O
C5H11
C2H5
HO
+
+
C2H5
C5H11
C2H5
C5H11
HO
HO
DCE, T (°C)
time (h)
C5H11
2a
3a
12
1a
[Rh]
(mol%)
Mo(CO)6 Temperature
Conv.
(%)
Entry
Time (h)
2a a
3a a
12 a
◦
(eq)
( C)
1 b
2
5
5
25
-
5
10
-
-
10
10
10
rt
rt
rt
rt
50
100
18
18
0.17
18
0.75
0.5
100
100
100
90
100
89
24 (19)
25
(27)
0
25
71 (41)
75
(43)
0
62
5 (5)
0
(30)
90
13
3
4 b
5 c
6 c
5
23
54
17
b
a 1H NMR ratio, isolated yield in brackets; reaction conducted in DCE; c reaction conducted in toluene under
MW irradiation.
2.2. Use of Carbon Monoxide Gas as CO Source for the [2+2+2+1] Carbonylative Cycloaddition
In order to avoid the formation of a third compound by dehydration and increase molecular
diversity, methoxy-protected substrates 1c and 1d were used to study the rhodium-catalyzed formation
of 6,5,7,5- and 6,5,6,5-fused tetracycles.
A first experiment using 5 mol% of rhodium catalyst was conducted on substrates 1c and 1d
(Table 2, entries 1 and 2). Identically to substrate 1a, a 1/3 ratio of carbonylated compounds 2c,d and
[2+2+2] cycloaddition compounds 3c
a low amount of demethoxylation products 12
,
d
is observed. Despite the protection of the alcohol functionality,
13 is observed. Because Mo(CO)6 is not efficient as
–
a CO source, the use of carbon monoxide was considered. Under 2 atm of CO, the proportion of
carbonylative pathway increases, as does the demethoxylation (entries 3 and 4). It is probable that
a higher pressure of CO reduces the electron density on the rhodium due to retrodonation of the
rhodium to the CO ligand, increasing the Lewis-acid character and thus enabling the elimination.
This supposition is supported by entry 5, where 10 atm of CO lead to the formation of 12 as the
major product. This entry also supports previous studies indicating that a higher pressure hinders
the rhodium-catalyzed carbonylative cycloaddition processes [29]. In order to enrich the media in
carbon monoxide without hampering the carbonylative pathways, we bubbled the media with carbon
monoxide for 15 min before applying pressure in a closed vessel (entry 6). Interestingly, full conversion
was not achieved overnight and an additional 8 h were necessary to reach completion (entry 7). In these
conditions, the products 2c
, 3c and 12 are obtained in equimolar ratio. When the carbon monoxide is
bubbled in a solution containing only the catalyst prior to the addition of the substrate, the carbon

Molecules 2019, 24, 595
5 of 8
monoxide insertion increases, and the demethoxylative pathway becomes the minority (entry 8). The
conversion, however, is lowered, which seems to indicate a saturation of the catalyst by the CO. The
same tendency can be observed when the CO is bubbled in the media containing only the substrate
prior to the addition of the catalyst (entry 9).
Table 2. Use of carbon monoxide as CO source for the [2+2+2+1] carbonylative cycloaddition and
competing pathways of triyne 1c,d.
O
O
O
[RhCl(CO)2]2 (5 mol%)
CO (atm)
O
R2
C2H5
C2H5
+
+
MeO
C2H5
C2H5
MeO
MeO
O
DCE, rt
time (h)
R2
R2
R2
1c R2 = C5H11
1d R2 = H
2c R2 = C5H11
2d R2 = H
3c R2 = C5H11
3d R2 = H
12 R2 = C5H11
13 R2 = H
Entry
R2
PCO (atm)
Time (h) Conversion (%)
2 a
3 a
12, 13 a
1
2
3
4
5
1c
1d
1c
1d
1c
1c
1c
1c
1c
-
-
2
2
10
2
2
2
2
18
18
18
18
18
18
26
26
26
100
100
100
100
100
73
100
90
91
2c, 22
2d, 25
2c, 33
2d, 29 (29)
2c, 25
2c, 26
2c, 34 (17)
2c, 33
2c, 36
3c, 73
3d, 75
3c, 46
3d, 43 (43)
3c, 31
3c, 25
3c, 32 (24)
3c, 33
3c, 32
12, 0
13, <5
12, 21
13, 17
12, 44
12, 22
12, 33 (20)
12, 23
6 b
7 b
8 c
9 d
12, 23
b
c
a 1H NMR ratio, isolated yield in brackets; media bubbled with CO for 15 min; solution of catalyst bubbled
with CO for 15 min, then substrate was added; d solution of substrate bubble with CO for 15 min, then catalyst
was added.
With substrates 1c,d we were able to synthesize five new tetracyclic compounds containing
aromatic rings, as well as to observe the emergence of a new competitive [2+2+2]/elimination pathway.
The latter is directly dependent on the employed CO-pressure, possibly due to a stronger Lewis-acidity
of the rhodium catalyst. Moreover, the proportion of this process, in comparison to that of the simple
[2+2+2] cycloaddition, increases when the media is saturated in carbon monoxide by bubbling.
2.3. Mechanistic Proposals
Scheme 3 summarizes the proposed mechanism for carbonylative cycloaddition, cyclotrimerization
and cyclotrimerization/elimination processes based on previous studies [17
dimeric pre-catalyst first undergoes ligand exchange with CO to form catalytic species [RhCl(CO)3] or if
the coordination bond with the bridging chloride is preserved. L’ in can therefore be another CO ligand
or the second half of the dimeric catalyst. The two alkyne moieties of substrate , ideally placed by the
cyclic core, then coordinate to the metallic center, displacing the CO ligands and forming intermediate
This 18-electron complex can undergo a [2+2+M] cyclometallation, yielding either a 16-electron complex
or an 18-electron complex C0, which is stabilized by the chelation of the third alkyne moiety. Migratory
insertion of CO can take place in the Rh-Csp2 bond of intermediate
to access intermediate , where the
electron-deficient complex is stabilized by the chelation of the third alkyne. This triple bond undergoes
migratory insertion, forming 8-membered rhodacycle , which, after reductive elimination, releases
troponic compound and catalytic species
. Complex C0, being already chelated by the third alkyne
moiety, can undergo direct migratory insertion of the multiple bond, yielding 7-membered rhodacycle E0
,30]. It is unsure if the
A
1
B.
C
C
D
E
2
A
.
DFT calculations on the [2+2+2+1] carbonylative cycloaddition of enediynes have shown that late stage
CO insertion is highly disfavored, thus E0 undergoes direct reductive elimination to release benzenoid
compound 3 in the media [31,32].
Compound
3 can then undergo a rhodium-mediated elimination, which is favored when the
CO pressure, and consequently the catalyst’s Lewis-acidic properties, are increased. This late-stage

Molecules 2019, 24, 595
6 of 8
elimination pathway is favored by the complete conjugation of byproduct 12. With the aromatic
properties of tropones residing in their mesomeric forms, this conjugation is only possible in resonance
extremes, and therefore the elimination does not occur. Conceptually, it is possible to imagine
that this elimination process takes place prior to the cycloaddition reaction. However, in that case,
the dehydrated analog of
pathways go through intermediate
2
should be observed. Indeed, both carbonylative and non-carbonylative
, and if the formation of the benzene ring from there is possible
B
when the substrate possesses an additional unsaturation, the carbonylative reaction should equally
take place.
C2H5
O
O
C2H5
O
CO
Rh Cl
L'
C2H5
O
L'
Rh Cl
R1O
CO
R1O
R1O
O
O
R2
R2
R2
E
2
D
C2H5
O
O
CO
C2H5
O
R1O
C2H5
Cl
L'
CO
R1O
Rh
Cl
L'
R2
Rh
O
R2
R1O
CO
R2
Cl
Rh
3
E'
C2H5
L'
CO
R2
R1O
CO
Rh
Cl
C
L'
OC
R1OH
A
C'
CO
O
O
CO
C2H5
O
R2
L'
Cl
Rh
C2H5
C2H5
R1O
R1O
R2
R2
B
1
12
Scheme 3. Proposed mechanisms for the formation of compounds 2, 3, and 12.
This mechanism allows the rationalization of the observed reaction rates depending on the
length of the tethers. The formation of
and C0 are possible overnight at room temperature with
C
tethers leading to the formation of 5-membered rings, yet the reaction is sluggish when this tether is
homologated [17].
3. Materials and Methods
Procedures for the synthesis of the substrates and the products and full characterization of final
products can be found in the Supplementary Information.
4. Conclusions
To conclude, we have successfully investigated the rhodium-catalyzed cycloaddition reactions of
pre-organized triynes for the synthesis of various and original tetracyclic scaffolds. These compounds,
containing an aromatic motif that can be either a tropone or a benzene ring and are fully unsymmetrical,
have been synthesized with very high combined yields of 80–100%. We have been able to synthesize
three examples of 6,5,7,5-structures and four examples of 6,5,6,5-structures.
Additionally, we have explored the use of Mo(CO)6 as an alternative CO donor. Unfortunately,
these experiments have shown that Mo(CO)6 is not a suitable CO source in these processes, due to a
lack of ligand exchange. On other hand, a new competitive dehydration/cycloisomerization pathway
has been observed and rationalized in terms of Lewis-acidity of the rhodium catalyst. Moreover,

Molecules 2019, 24, 595
7 of 8
the molybdenum species shows a definite selectivity for this pathway, whereas, when combined with
a rhodium catalyst, dehydration becomes minority, due to competition between the metals.
Supplementary Materials: Supplementary Materials are available online.
Author Contributions: Conceptualization, J.S.; methodology, G.B. and L.S.; investigation, L.S.; writing—original
draft preparation, L.S.; writing—review and editing, G.B. and N.G.; supervision, G.B. and J.S.
Funding: The authors gratefully acknowledge the support of Université de Strasbourg et MENRT (L.S.)
for fellowship.
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
2.
3.
4.
5.
Nicolaou, K.C.; Edmonds, D.J.; Bulger, P.G. Cascade Reactions in Total Synthesis. Angew. Chem. Int. Ed. 2006
45, 7134–7186. [CrossRef]
Inglesby, P.A.; Evans, P.A. Higher Order Cycloadditions. In Comprehensive Organic Synthesis II; Elsevier Ltd.:
Amsterdam, The Netherlands, 2014; Volume 5, pp. 656–704. ISBN 9780080977423.
,
Domínguez, G.; Pérez-Castells, J. Recent advances in [2+2+2] cycloaddition reactions. Chem. Soc. Rev. 2011
40, 3430–3444. [CrossRef] [PubMed]
,
Bennacer, B.; Fujiwara, M.; Ojima, I. Novel [2+2+2+1] cycloaddition of enediynes catalyzed by rhodium
complexes. Org. Lett. 2004, 6, 3589–3591. [CrossRef] [PubMed]
Chien, C.W.; Teng, Y.H.G.; Honda, T.; Ojima, I. Synthesis of Colchicinoids and Allocolchicinoids through
Rh(I)-Catalyzed [2+2+2+1] and [2+2+2] Cycloadditions of o-Phenylenetriynes with and without CO.
J. Org. Chem. 2018, 83, 11623–11644. [CrossRef] [PubMed]
6.
7.
8.
Kim, S.Y.; Lee, S.I.; Choi, S.Y.; Chung, Y.K. Rhodium-Catalyzed Carbonylative [3+3+1] Cycloaddition of
Biscyclopropanes with a Vinyl Substituent To Form Seven-Membered Rings. Angew. Chem. Int. Ed. 2008, 47,
4914–4917. [CrossRef] [PubMed]
Wender, P.A.; Gamber, G.G.; Hubbard, R.D.; Zhang, L. Three-Component Cycloadditions: The First Transition
Metal-Catalyzed [5+2+1] Cycloaddition Reactions. J. Am. Chem. Soc. 2002, 124, 2876–2877. [CrossRef]
[PubMed]
Wang, Y.; Wang, J.; Su, J.; Huang, F.; Jiao, L.; Liang, Y.; Yang, D.; Zhang, S.; Wender, P.A.;
Yu, Z. A Computationally Designed Rh (I) -Catalyzed Two-Component [5+2+1] Cycloaddition of
Ene-vinylcyclopropanes and CO for the Synthesis of Cyclooctenones. J. Am. Chem. Soc. 2007, 129,
10060–10061. [CrossRef]
9.
Brummond, K.M.; Kent, J.L. Recent advances in the Pauson-Khand reaction and related [2+2+1]
cycloadditions. Tetrahedron 2000, 56, 3263–3283. [CrossRef]
10. Salacz, L.; Girard, N.; Suffert, J.; Blond, G. Carbonylative cycloaddition for the synthesis of medium-sized
carbo- and heterocycles. Monatshefte Chem. 2018, 149, 671–686. [CrossRef]
11. Park, J.H.; Chang, K.-M.; Chung, Y.K. Catalytic Pauson–Khand-type reactions and related carbonylative
cycloaddition reactions. Coord. Chem. Rev. 2009, 253, 2461–2480. [CrossRef]
12. Shibata, Y.; Tanaka, K. Rhodium-catalyzed [2+2+2] cycloaddition of alkynes for the synthesis of substituted
benzenes: Catalysts, reaction scope, and synthetic applications. Synthesis 2012, 44, 323–350. [CrossRef]
13. Blouin, S.; Gandon, V.; Blond, G.; Suffert, J. Synthesis of Cyclooctatetraenes through a Palladium-Catalyzed
Cascade Reaction. Angew. Chem. Int. Ed. 2016, 55, 7208–7211. [CrossRef] [PubMed]
14. Joussot, J.; Schoenfelder, A.; Suffert, J.; Blond, G. Synthesis of original polycycles containing five-, six- and
seven-membered rings through cyclocarbopalladations/C–H activation cascade reactions. C. R. Chim. 2017
20, 665–681. [CrossRef]
,
15. Petrignet, J.; Boudhar, A.; Blond, G.; Suffert, J. Step-economical synthesis of taxol-like tricycles through a
palladium-catalyzed domino reaction. Angew. Chem. Int. Ed. 2011, 50, 3285–3289. [CrossRef] [PubMed]
16. Charpenay, M.; Boudhar, A.; Blond, G.; Suffert, J. An expeditious and atom-economical synthesis of a new
generation of substituted [4.6.4.6]fenestradienes. Angew. Chem. Int. Ed. 2012, 51, 4379–4382. [CrossRef]
[PubMed]
17. Salacz, L.; Girard, N.; Blond, G.; Suffert, J. Synthesis of Polyheterocyclic Tropones by [2 + 2 + 2 + 1]
Carbonylative Cycloaddition of Triynes. Org. Lett. 2018, 20, 3915–3918. [CrossRef] [PubMed]

Molecules 2019, 24, 595
8 of 8
18. Pauson, P.L. Tropones and tropolones. Chem. Rev. 1955, 55, 9–136. [CrossRef]
19. Mori, A.; Kato, N.; Takeshita, H. Preparation and Thermal Properties of New Liquid Crystals with a
2-Benzoyloxy-2,4,6-cycloheptatrien-1-one Core. J. Mater. Chem. 1991, 1, 799–803. [CrossRef]
20. Takagi, K.; Nishikawa, Y.; Nishioka, N.; Kunisada, H.; Yuki, Y. π-conjugated oligomers containing tropone in
the main chain: Synthesis, characterization, and optical properties. J. Polym. Sci. Part A Polym. Chem. 2002
40, 3927–3937. [CrossRef]
,
21. Sugiyasu, K.; Song, C.; Swager, T.M. Aromaticity in tropone-containing polythiophene. Macromolecules 2006
39, 5598–5600. [CrossRef]
,
22. Bentley, R. A fresh look at natural tropolonoids. Nat. Prod. Rep. 2008, 25, 118–138. [CrossRef] [PubMed]
23. Pietra, F. Revival of Troponoid Chemistry. Acc. Chem. Res. 1979, 12, 132–138. [CrossRef]
24. Nair, V.; Abhilash, K.G. [8+2] Cycloaddition reactions in organic synthesis. Synlett 2008, 301–312. [CrossRef]
25. Krafft, M.E.; Cran, J.W. A convenient protocol for the iodination of unsaturated carbonyl compounds with I2
in an aqueous medium. Synlett 2005, 1263–1266. [CrossRef]
26. Odell, L.R.; Russo, F.; Larhed, M. Molybdenum hexacarbonyl mediated CO gas-free carbonylative reactions.
Synlett 2012, 23, 685–698. [CrossRef]
27. Brummond, K.M.; Chen, D. Mo(CO)6- and [Rh(CO)2Cl]2-Catalyzed Allenic Cyclocarbonylation Reactions of
Alkynones: Efficient Access to Bicyclic Dienediones. Org. Lett. 2008, 10, 1154–1156. [CrossRef]
28. Jeong, N.; Lee, S.J.; Lee, B.Y.; Chung, Y.K. Molybdenium mediated preparation of cyclopentenones.
Tetrahedron Lett. 1993, 34, 4027–4030. [CrossRef]
29. Wang, Y.; Yu, Z. Rhodium-Catalyzed [5+2+1] Cycloaddition of Ene
−
Vinylcyclopropanes and CO: Reaction
Design, Development, Application in Natural Product Synthesis, and Inspiration for Developing New
Reactions for Synthesis of Eight-Membered Carbocycles. Acc. Chem. Res. 2015, 48, 2288–2296. [CrossRef]
30. Teng, Y.H.G. Synthesis of Novel Fused Tropones and Colchicinoids Through Rh(I)-Catalyzed [2+2+2+1]
Cycloaddition of Triynes with Carbon Monoxide. Ph.D. Thesis, Stony Brook University, Stony Brook, NY,
USA, 2011.
31. Montero-campillo, M.M.; Rodrigez-Otero, J.; Cabaleiro-Lago, E. Theoretical Study of the [2+2+2+1]
Cycloaddition Mechanism of Enediynes and Carbon Monoxide Catalyzed by Rhodium. J. Phys. Chem.
2008, 112, 2423–2427. [CrossRef]
32. Wang, H.; Sawyer, J.R.; Evans, P.A.; Baik, M.H. Mechanistic insight into the diastereoselective
rhodium-catalyzed Pauson-Khand reaction: Role of coordination number in stereocontrol. Angew. Chem.
Int. Ed. 2008, 47, 342–345. [CrossRef]
Sample Availability: Samples of the compounds 1a–d, 2a, 2c–d, 3a, 3c–d and 12 are available from the authors.
©
2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).