Palladium-Catalyzed Regio- and Stereoselective Synthesis of (E)-1,3-Bissilyl-6-arylfulvenes from Aryl Iodides and Silylacetylenes

Article abstract of DOI:10.1021/acs.orglett.9b00144

An efficient synthetic route to (E)-1,3-bissilyl-6-arylfulvenes has been developed. The reaction of aryl iodides with trimethylsilylacetylene in the presence of a catalytic amount of PdBr₂ gives 6-aryl-1,3-bis(trimethylsilyl)fulvenes in good to

Full text of DOI:10.1021/acs.orglett.9b00144

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Palladium-Catalyzed Regio- and Stereoselective Synthesis of (E)‑1,3-
Bissilyl-6-arylfulvenes from Aryl Iodides and Silylacetylenes
Souta Suzuki, Hidenori Kinoshita,* and Katsukiyo Miura*
Department of Applied Chemistry, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakura-ku,
Saitama 338-8570, Japan
S
* Supporting Information
ABSTRACT: An efficient synthetic route to (E)-1,3-bissilyl-6-arylfulvenes has been developed. The reaction of aryl iodides
with trimethylsilylacetylene in the presence of a catalytic amount of PdBr2 gives 6-aryl-1,3-bis(trimethylsilyl)fulvenes in good to
excellent yields with complete regio- and stereoselectivity. The reaction involves trimerization of trimethylsilylacetylene and
cleavage of one silyl group. The silylated fulvenes obtained could be converted into halogenated fulvenes by site-selective
halodesilylation. The halogenated fulvenes underwent the Stille coupling leading to the corresponding arylated fulvenes.
Scheme 1. Syntheses of Fulvenes
ulvene, whose chemical formula is the same as that of
benzene (C6H6), is a cyclic cross-conjugated compound
F
and colored hydrocarbon. Since fulvene and its derivatives
show unique physical and chemical properties,1 they appear as
key structural motifs in a wide variety of systems ranging from
biologically active compounds2 to organometallic com-
pounds.3,4 Substituted fulvenes are also receiving much
attention as organic molecular materials for use in semi-
conductors5 and solar cell applications.6
Conventional fulvene synthesis involves condensation of
aldehydes or ketones with sodium cyclopentadienide (Scheme
1, eq 1).7 Pyrrolidine-promoted8a−c and catalyzed8d syntheses
of fulvenes from cyclopentadiene itself have also been achieved
(eq 2). However, these approaches are not efficient with
respect to the regio-controlled introduction of substituents on
the cyclopentadiene ring carbons. The Pd-catalyzed cyclo-
addition between alkynes and haloalkenes lends access to
fulvenes bearing substituents on the ring carbons (eq 3).9
Syntheses of pentasubstituted fulvenes from symmetrical
internal alkynes have also been reported (eq 4).10 Several
intriguing syntheses of substituted fulvenes by Pd11 or other
transition metal12 catalysts, such as Tanaka’s Rh catalyzed
regioselective synthesis of substituted silylfulvenes from
unsymmetrical internal alkynes (eq 5),13 have been reported
to date. However, most of these reactions exhibit low to
moderate efficiencies and the preparation of haloalkenes or
more complicated compounds is required as substrates. Hence,
developing efficient methods for regio-controlled syntheses of
substituted fulvenes from commercially or readily available
starting materials is desirable. Over the course of our study on
Pd-catalyzed construction of multisubstituted benzenes,14 we
unexpectedly found that the reaction of iodobenzene with an
excess of trimethylsilylacetylene gave (E)-1,3-bis-
(trimethylsilyl)-6-phenylfulvene as a single isomer (eq 6, R =
Ph). Aryl iodides are commercially available compounds and
more accessible substrates than the corresponding β-
haloalkenes (eqs 3 and 4 vs eq 6). Therefore, the direct use
of aryl iodides for the substituted fulvene synthesis is highly
Received: January 13, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b00144
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
advantageous. Herein, we report our results on the novel
palladium-catalyzed cycloaddition to form (E)-6-aryl-1,3-
bissilylfulvenes with complete regio- and stereoselectivity.
We commenced optimization of the reaction using
iodobenzene (1a) and trimethylsilylacetylene (2a) (Table 1).
the long reaction period. Next, the reaction time was
scrutinized (entries 19−21). A prolonged reaction time
dramatically improved the yield of 3aa, and the reaction
carried out for 72 h gave fulvene 3aa in 85% isolated yield
(entry 20). A slightly improved yield was observed when the
reaction was conducted for 6 days (entry 21). Neither higher
nor lower reaction temperatures accelerated the formation of
3aa. A large-scale reaction with 10 mmol of 1a also proceeded
smoothly to give 3aa in 83% isolated yield (8.3 mmol, 2.5 g).
With the optimized reaction conditions in hand, we tested
the substrate scope (Table 2). The reaction of 1-iodonaph-
a
Table 1. Optimization of Reaction Conditions
a
Table 2. Synthesis of Arylfulvenes 3
b
entry
cat.
solvent
time (h)
yield of 3aa (%)
c
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OH)2
PdCl2
PdBr2
PdI2
PdCl2 + NaI
PdBr2 + NaI
PdI2 + NaI
PdBr2 + NaI
PdBr2 + NaI
PdBr2 + KI
PdBr2 + LiI
PdBr2 + TBAI
PdBr2 + NaI
PdBr2 + NaI
PdBr2 + NaI
i-Pr2NEt
THF
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
48
72
17
22
22
27
35
39
trace
21
48
25
32
64(68)
30
41
30
31
28
36
DMSO
CH3CN
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
d
isolated yield
entry
3
Ar
72 h (%)
6 d (%)
1
2
3
4
5
6
7
8
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
1-naphthyl
p-tolyl
p-Ph-C6H4
o-Et-C6H4
p-(Me2N)-C6H4
p-(MeO)-C6H4
m-(MeO)-C6H4
o-(MeO)-C6H4
p-(MeO2C)-C6H4
m-(MeO2C)-C6H4
o-(MeO2C)-C6H4
p-F-C6H4
75
67
41
29
77
96
63
37
94
57
37
52
75
35
65
43
11
54
20
47
72
90
83
41
66
75
83
74
92
41
83
−
69
39
−
81
51
80
73
77
64
42
32
84
24
42
74
97
−
9
10
11
12
13
14
15
16
17
18
19
20
21
e
e
e
f
g
e
9
3ja
3ka
3la
e
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
e
e
(70)
(85)
(87)
3ma
3na
3oa
3pa
3qa
3ra
3sa
3ta
3ua
3va
3wa
3xa
3ya
3ab
3ac
e
p-Cl-C6H4
o-Cl-C6H4
p-Br-C6H4
o-Br-C6H4
e
h
6 d
a
The reaction was carried out with 1a (0.50 mmol), 2a (2.5 mmol),
catalyst (5 mol %), and i-Pr2NEt (0.75 mmol) in solvent (0.5 mL) at
b
30 °C. NMR yield (Bn2O was used as an internal standard). Isolated
o-(F3C)-C6H4
p-(Me(O)C)-C6H4
o-(O2N)-C6H4
2-Br-4-Me-C6H3
9-anthracenyl
9-phenanthryl
2-furyl
1-tosyl-3-indolyl
Ph
Ph
c
yield is shown in parentheses. i-Pr2NEt (0.5 mL) was used.
d
e
Pd(OAc)2 (10 mol %) was used. The iodide (0.050 mmol) was
f
g
h
used. NaI (0.025 mmol) was used. NaI (0.10 mmol) was used.
6
days, 144 h.
The Pd(OAc)2-catalyzed reaction of 1a with 2a (5 equiv) in i-
Pr2NEt at 30 °C gave 3aa in 17% yield (entry 1). The use of
THF as a solvent with 1.5 equiv of i-Pr2NEt slightly improved
the yield of 3aa (entry 2). Phosphines (PPh3, P(o-tol)3, P(2-
furyl)3, PCy3, and dppe), cyclooctadiene, or norbornadiene as
an additive were not effective for this transformation (not
shown). Screening of solvents (entries 2−5) revealed that
DMF was the best solvent for this reaction (entry 5). An
increased amount of Pd(OAc)2 did not improve the yield of
3aa (entry 6). Therefore, other Pd(II) sources were tested
(entries 7−10). Only PdBr2 was more effective than Pd(OAc)2
(entry 9). For further improvement of the catalytic system,
several metal salts were tested as additives (entries 11−17).
The addition of 10 mol % of NaI improved the yield of 3aa up
to a 68% isolated yield (entry 12). Other combinations, such as
PdCl2−NaI and PdI2−NaI, had minimal effects on the reaction
(entries 11 and 13). Other metal iodides and TBAI were not
effective, and the yield of 3a did not exceed 68% (entries 12 vs
16−18). Although the role of NaI is not clear in this stage, it is
possible that the NaI stabilizes the Pd species in situ15 during
46
−
−
a
All reactions were carried out with 1 (0.50 mmol), 2 (2.5 mmol),
PdBr2 (0.025 mmol), NaI (0.050 mmol), and i-Pr2NEt (0.75 mmol)
in DMF (0.5 mL) at 30 °C for 72 h or 6 days.
thalene (1b) for 72 h gave the corresponding fulvene 3ba as
dark red crystals in 75% isolated yield. The structure of 3ba
was clearly confirmed by X-ray crystal structure analysis.16
A
prolonged reaction for 6 days improved the yield of 3ba up to
83%. Therefore, a 6-day reaction was also conducted, when the
fulvenes 3 were obtained in low to moderate yields after 72 h
of stirring. A variety of electronically and sterically diverse aryl
iodides 1c to 1u were treated with 2a under the optimized
reaction conditions. The following tendencies were recognized
for the reaction. (1) The electronic nature of the substituents
on the aromatic ring of aryl iodides did not affect the reactivity.
B
DOI: 10.1021/acs.orglett.9b00144
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(2) The steric effect of the substrates was extremely important
for this reaction. The presence of an ortho-substituent in 1
severely decelerated the reaction (entries 4, 8, 11, 16, 17, 19,
and 20). 9-Iodoanthracene (1v), 9-iodophenanthrene (1w),
and 2-iodofuran (1x) were good reaction partners in this
transformation (entries 21−23). The reaction with 3-iodo-1-
tosyl-1H-indole (1y) also gave the corresponding fulvene 3ya
in moderate yield (entry 24). Other silyl groups on the alkyne
terminus were examined by using 2b and 2c. The yields of
fulvenes 3ab and 3ac were lower than that of 3aa (entries 25
and 26). The steric hindrance of the silyl moiety on the sp-
carbon also affected the yield of this transformation.
Scheme 3. Mechanistic Aspects
A plausible mechanism of this transformation is outlined in
Scheme 2. Arylpalladiums 5 generated from Pd(0) and 1 are
Scheme 2. Plausible Mechanism
As a result, 3ba was recovered intact, and no silyl scrambling of
3ba was observed. This fact is in contradiction with the
intermolecular process.
The reactions of 12 and 15 with 2a proceed probably via
cyclopentadienylcarbinylpalladiums A1 (Scheme 4), corre-
Scheme 4. Rational Explanation for Formation of 13/14/16
converted into trienylpalladiums 8 by sequential intermolecular
carbopalladation via vinyl- and dienylpalladiums 6 and 7.
Then, intramolecular carbopalladation, that is syn addition, of
8 forms cyclopentadienylcarbinylpalladiums 9 as a single
diastereomer.9 Reductive elimination of benzyl iodides 10
occurs from benzyl palladium iodide complexes 9 to generate
the active Pd(0) species. Finally, elimination of TMS-I from 10
provides only one double bond isomer, (E)-isomers of 3.
To check the presence of the vinylpalladium intermediate 6
in the catalytic cycle forming 3, the reaction of (Z)-β-
iodoalkenylsilane 11, a precursor of 6 (Ar = Ph), with 2a was
conducted under the same conditions (Scheme 3a). Predict-
ably, 11 was successfully converted into the corresponding
fulvene 3aa in 85% yield, which clearly indicates the
participation of 6 with the formation of 3 from 1 and 2a. In
contrast, the reaction of 12 with 2a gave fulvenes 13 and 14
bearing the diphenylmethylsilyl moiety on the fulvene rings
(Scheme 3b). In addition, (Z)-β-iodoalkenylsilane 15 under-
went the cyclization with 2a to form only fulvene 16, bearing
the tert-butyldimethylsilyl group coming from 15 at C3, as
orange crystals (Scheme 3c). The structure of 16 was
successfully confirmed by X-ray crystal structure analysis,16
and its C−C double bond geometry was assigned to the (E)-
configuration. The silyl moieties in 12 and 15 were thought to
be removed by the sequential elimination of Pd and the silyl
moiety according to our plausible mechanism. However, the
original silyl groups on the sp2-carbons were found on the ring
carbons in 13, 14, and 16. There is a possibility that the silyl
scrambling observed in Scheme 3b and 3c is caused by the
secondary reaction of the initially formed fulvene 3aa. To
ascertain the possibility, the Pd-catalyzed reaction of 12 with
2a was carried out in the presence of fulvene 3ba (Scheme 3d).
sponding to 9. The silyl scrambling can be rationalized by
metallotropic rearrangement of A1 around the cyclopenta-
dienyl ring. Since cyclopenta-2,4-dienylsilanes are known to
easily undergo [1,2]-metallotropic rearrangement,17 the silyl
group can transfer to any carbon of the cyclopentadienyl ring.
Therefore, A1 should be easily isomerized to A2 through A5
by migration of the silyl groups (Si2) coming from the starting
alkenylsilanes. It is also conceivable that other isomers A6 and
A7/A8 are generated from A2 and A4, respectively, by
migration of the trimethylsilyl group (Si1) attached to the sp3-
carbon of the cyclopentadienyl ring. The fulvene products are
formed from these intermediates A6 and A8 with elimination
of the labile Si1 group on the sp3-carbon. The preferred
formation of the scrambling products 13/16 and 14 is
attributable to fast elimination of the Si1 group from A8 and
A6, respectively, because the sterically less hindered silyl group
is more subject to nucleophile-induced elimination than the
bulky silyl group (Si2). The site-selective scrambling at C3 is
likely due to avoiding 1,3-allylic strain caused by the Si2 group
at C1. Consequently, the silyl scrambling strongly supports the
proposed mechanism involving intramolecular carbopallada-
tion of trienylpalladiums 8, and it clearly denies a possibility
C
DOI: 10.1021/acs.orglett.9b00144
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
that the cyclization of 8 to fulvenes 3 proceeds by a common
transmetalation between the alkenylpalladium and the alkenyl
silane in 8 and reductive elimination sequence, such as the
intramolecular Hiyama-type coupling reaction.
We demonstrated the synthetic utility of 1,3-bissilylfulvenes
3 and 16 by further modification via halodesilylation. The
reaction of 16 with NIS gave 17 in good yield, as dark-red
crystals, via site-selective iododesilylation (Scheme 5). The
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b00144.
■
S
Experimental procedures and characterization data; X-
ray crystallographic data for 3ba (CCDC 1885560), 16
(CCDC 1885568), 17 (CCDC 1885569), and 18
(CCDC 1885570) (PDF)
Scheme 5. Regioselective Halodesilylation and
Derivatization
Accession Codes
CCDC 1885560 and 1885568−1885570 contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/
cif, or by emailing data_request@ccdc.cam.ac.uk, or by
contacting The Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: hkino@mail.saitama-u.ac.jp.
*E-mail: kmiura@apc.saitama-u.ac.jp.
ORCID
Hidenori Kinoshita: 0000-0002-9761-9015
Katsukiyo Miura: 0000-0002-4535-8677
Notes
The authors declare no competing financial interest.
only trimethylsilyl group at position 1 was replaced with
iodide, and the regioisomer could not be detected. The Stille
coupling of 17 gave 18 as dark-red crystals in reasonable yield.
The structures of 17 and 18 were unambiguously established
by X-ray crystal structure analyses.16 The site-selective
iododesilylation of 3aa with NIS also provided 19 in excellent
yield. These observations show that the iododesilylation occurs
depending on not the type of silyl group but the position of the
fulvene ring. It is known that fulvenes react with electrophiles
on position 1 or 4,1 and this fact corresponds to our
experimental observations. Prolonged reaction with an
increased amount of NIS gave 1,3-diiodofulvene 20 in 78%
yield with a trace amount of 19. However, 20 was highly
unstable and decomposed in a couple of minutes under an
ambient atmosphere. The Stille coupling of 19 gave 21 in
moderate yield. Regioselective bromodesilylation of 3ba also
proceeded successfully to form 22. Unfortunately, further
modification of 18 and 21 cannot be achieved in this stage
because 3-halogenated fulvenes are very unstable when
generated from 21 by halodesilylation.
In conclusion, we have developed a novel Pd-catalyzed
cycloaddition for the synthesis of (E)-6-aryl-1,3-bissilylfulvenes
with complete regio- and stereoselectivity in moderate to
excellent yields. This transformation represents a straightfor-
ward method to introduce a 1,3-bissilylfulvenyl moiety into
aromatic rings from readily available substrates. The proposed
mechanism involves inter- and intramolecular carbopalladation
followed by desilylative reductive elimination. The bissilylful-
venes obtained could be converted into halofulvenes by
regioselective halodesilylation, which served as platforms for
further modification to π-extended fulvenes. Further synthetic
utility of the fulvene derivatives is under investigation in this
laboratory.
REFERENCES
■
(1) For recent reviews, see: (a) Finke, A. D.; Diederich, F. 6,6-
Dicyanopentafulvenes: Teaching an Old Dog New Tricks. Chem. Rec.
2015, 15, 19−30. (b) Neuenschwander, M. Low-Temperature Olefin
Syntheses in View of Parent Fulvenes and Fulvalenes. Helv. Chim.
Acta 2015, 98, 731−762. (c) Neuenschwander, M. Substituent Effects
on π-Bond Delocalization of Fulvenes and Fulvalenes. Are Fulvenes
Aromatic? Helv. Chim. Acta 2015, 98, 763−784. (d) Preethalayam, P.;
Krishnan, K. S.; Thulasi, S.; Chand, S. S.; Joseph, J.; Nair, V.;
Jaroschik, F.; Radhakrishnan, K. V. Recent Advances in the Chemistry
of Pentafulvenes. Chem. Rev. 2017, 117, 3930−3989.
(2) (a) MacDonald, J. R.; Muscoplat, C. C.; Dexter, D. L.; Mangold,
G. L.; Chen, S.-F.; Kelner, M. J.; McMorris, T. C.; Von Hoff, D. D.
Preclinical Antitumor Activity of 6-Hydroxymethylacylfulvene, a
Semisynthetic Derivative of the Mushroom Toxin Illudin S. Cancer
Res. 1997, 57, 279−283. (b) Wang, Y.; Wiltshire, T.; Senft, J.; Reed,
E.; Wang, W. Irofulven Induces Replication-Dependent CHK2
Activation Related to P53 Status. Biochem. Pharmacol. 2007, 73,
469−480. (c) Strohfeldt, K.; Tacke, M. Bioorganometallic Fulvene-
Derived Titanocene Anti-Cancer Drugs. Chem. Soc. Rev. 2008, 37,
1174−1187.
(3) For recent reviews, see: (a) Erker, G. Syntheses and Reactions of
Fulvene-Derived Substituted Aminoalkyl-Cp and Phosphinoalkyl-Cp-
Group 4 Metal Complexes. Coord. Chem. Rev. 2006, 250, 1056−1070.
(b) Gleiter, R.; Bleiholder, C.; Rominger, F. α-Metallocenylmethy-
lium Ions and Isoelectronic Fulvene Complexes of d6 to d9 Metals.
Structural Considerations. Organometallics 2007, 26, 4850−4859.
(4) For a recent example of organometallic catalyst, see: Bader, M.;
Marquet, N.; Kirillov, E.; Roisnel, T.; Razavi, A.; Lhost, O.;
Carpentier, J.-F. Old and New C1-Symmetric Group 4 Metallocenes
{(R1R2C)-(R2′R3′R6′R7′-Flu)(3-R3-5-R4-C5H2)}ZrCl2: From Highly
Isotactic Polypropylenes to Vinyl End-Capped Isotactic-Enriched
Oligomers. Organometallics 2012, 31, 8375−8387.
(5) (a) Aqad, E.; Leriche, P.; Mabon, G.; Gorgues, A.;
Khodorkovsky, V. Novel D-π-A Chromophores Based on the Fulvene
Accepting Moiety. Org. Lett. 2001, 3, 2329−2332. (b) Andrew, T. L.;
D
DOI: 10.1021/acs.orglett.9b00144
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Cox, J. R.; Swager, T. M. Synthesis, Reactivity, and Electronic
Properties of 6,6-Dicyanofulvenes. Org. Lett. 2010, 12, 5302−5305.
(6) (a) An, Q.; Zhang, F.; Zhang, J.; Tang, W.; Deng, Z.; Hu, B.
Versatile Ternary Organic Solar Cells: a Critical Review. Energy
Environ. Sci. 2016, 9, 281−322. (b) Dahlstrand, C.; Jahn, B. O.;
Grigoriev, A.; Villaume, S.; Ahuja, R.; Ottosson, H. Polyfulvenes:
Polymers with “Handles” That Enable Extensive Electronic Structure
Tuning. J. Phys. Chem. C 2015, 119, 25726−25737. (c) Godman, N.
P.; Balaich, G. J.; Iacono, S. T. First Preparation of Low Band Gap
Fulvene-Modified Polynorbornene via Ring-Opening Metathesis
Polymerization. Chem. Commun. 2016, 52, 5242−5245.
Synthesis and Catalytic Activity of Tunable Cyclopentadienyl
Rhodium(III) Complexes with Pendant Amides. Angew. Chem., Int.
Ed. 2017, 56, 3590−3593.
(14) Kinoshita, H.; Takahashi, H.; Miura, K. Regioselective
Synthesis of Multisubstituted Benzenes by Palladium-Catalyzed
Intermolecular Reaction of β-Iodo-β-silylstyrenes with Alkynes. Org.
Lett. 2013, 15, 2962−2965.
(15) Parisotto, S.; Palagi, L.; Prandi, C.; Deagostino, A. Cooperative
Iodide Pd(0)-Catalysed Coupling of Alkoxyallenes and N-Tosylhy-
drazones: A Selective Synthesis of Conjugated and Skipped Dienes.
Chem. - Eur. J. 2018, 24, 5484−5488.
(16) See the Supporting Information.
̈
(7) (a) Thiele, J. Ueber Ketonreactionen bei dem Cyclopentadien.
(17) For the silyl-transfer of cyclopentadienyl silane, see: Sergeyev,
N. M.; Avramenko, G. I.; Kisin, A. V.; Korenevsky, V. A.; Ustynyuk, Y.
A. Nuclear Magnetic Resonance Spectroscopy of Metal Cyclo-
pentadienyls V. Metallotropic Rearrangement in Silicon Cyclo-
pentadienyls: 1,2 Shift and Spectral Regularities in σ-Cyclo-
pentadienyls. J. Organomet. Chem. 1971, 32, 55−77.
Ber. Dtsch. Chem. Ges. 1900, 33, 666−673. (b) Thiele, J.; Balhorn, H.
̈
Ueber Abkommlinge des Fulvens, 4. Condensationsproducte des
̈
Cyklopentadiens. Liebigs Ann. Chem. 1906, 348, 1−15. (c) Erden, I.;
Xu, F.-P.; Sadoun, A.; Smith, W.; Sheff, G.; Ossun, M. Scope and
Limitations of Fulvene Syntheses. Preparation of 6-Vinyl-Substituted
and − Functionalized Fulvenes. First Examples of Nucleophilic
Substitution on a 6-(Chloromethyl)fulvene. J. Org. Chem. 1995, 60,
813−820. (d) Chajara, K.; Ottosson, H. An Improved Pathway to 6,6-
Disubstituted Fulvenes. Tetrahedron Lett. 2004, 45, 6741−6744.
(8) (a) Stone, K. J.; Little, R. D. An Exceptionally Simple and
Efficient Method for the Preparation of a Wide Variety of Fulvenes. J.
Org. Chem. 1984, 49, 1849−1853. (b) Peloquin, A. J.; Stone, R. L.;
Avila, S. E.; Rudico, E. R.; Horn, C. B.; Gardner, K. A.; Ball, D. W.;
Johnson, J. E. B.; Iacono, S. T.; Balaich, G. J. Synthesis of 1,3-
Diphenyl-6-alkyl/aryl-Substituted Fulvene Chromophores: Observa-
tion of π−π Interactions in a 6-Pyrene-Substituted 1,3-Diphenylful-
̈
vene. J. Org. Chem. 2012, 77, 6371−6376. (c) Erden, I.; Gartner, C.
An Exceptionally Simple and Efficient Synthesis of 6-Methyl-6-
vinylfulvene, and its Oxidative Transformations. Tetrahedron Lett.
2009, 50, 2381−2383. (d) Cosķ un, N.; Erden, I. An Efficient
Catalytic Method for Fulvene Synthesis. Tetrahedron 2011, 67, 8607−
8614.
(9) Lee, G. C. M.; Tobias, B.; Holmes, J. M.; Harcourt, D. A.; Garst,
M. E. A New Synthesis of Substituted Fulvenes. J. Am. Chem. Soc.
1990, 112, 9330−9336.
(10) (a) Silverberg, L. J.; Wu, G.; Rheingold, A. L.; Heck, R. F.
Palladium-Catalyzed Reactions of Vinyl Bromides with Disubstituted
Alkynes: a New Synthesis of Fulvenes. J. Organomet. Chem. 1991, 409,
411−420. (b) Kotora, M.; Matsumura, H.; Gao, G.; Takahashi, T.
Palladium-Catalyzed Coupling of Two Alkynes and an Alkenyl
Iodide: Formation of Pentasubstituted Fulvenes. Org. Lett. 2001, 3,
3467−3470.
(11) (a) Radhakrishnan, U.; Gevorgyan, V.; Yamamoto, Y.
Palladium Catalyzed [2 + 2+1] Cyclotrimerization of Alkynes:
Selective Synthesis of Fulvenes. Tetrahedron Lett. 2000, 41, 1971−
1974. (b) Uemura, M.; Takayama, Y.; Sato, F. Site-Selective Pd-
Catalyzed Coupling of 1,4-Diiodo-1,3-alkadienes with Grignard
Reagents and Its Application to the Synthesis of Fulvenes. Org. Lett.
2004, 6, 5001−5004. (c) Shibata, K.; Satoh, T.; Miura, M. Palladium-
Catalyzed Intermolecular Three-Component Coupling of Organic
Halides with Alkynes and Alkenes: Efficient Synthesis of Oligoene
Compounds. Adv. Synth. Catal. 2007, 349, 2317−2325. (d) Brahim,
́
M.; Ammar, H. B.; Dorcet, V.; Soule, J.-F.; Doucet, H. Palladium-
Catalyzed C−H Bond Functionalization of 6,6-Diphenylfulvenes: An
Easier Access to C1-Arylated and C1,C4-Diarylated Fulvenes. Org.
Lett. 2017, 19, 2584−2587.
(12) (a) Johnson, E. S.; Balaich, G. J.; Fanwick, P. E.; Rothwell, I. P.
Trimerization of tert-Butylacetylene to 1,3,6-Tri(tert-butyl)fulvene
Catalyzed by Titanium Aryloxide Compounds. J. Am. Chem. Soc.
1997, 119, 11086−11087. (b) Chen, Y.; Liu, Y. Gold-Catalyzed
Approach to Multisubstituted Fulvenes via Cycloisomerization of
Furan/Ynes. J. Org. Chem. 2011, 76, 5274−5282.
(13) (a) Shibata, Y.; Tanaka, K. Catalytic [2 + 2+1] Cross-
Cyclotrimerization of Silylacetylenes and Two Alkynyl Esters To
Produce Substituted Silylfulvenes. Angew. Chem., Int. Ed. 2011, 50,
10917−10921. (b) Yoshizaki, S.; Shibata, Y.; Tanaka, K. Fulvene
Synthesis by Rhodium(I)-Catalyzed [2 + 2+1] Cycloaddition:
E
DOI: 10.1021/acs.orglett.9b00144
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