Highly regioselective ring-opening coupling of diarylmethylenecyclopropa[b] naphthalenes with Grignard reagents

Article abstract of DOI:10.1039/c3cc00171g

Highly regioselective ring-opening coupling reactions of diarylmethylenecyclopropa[b]naphthalenes with Grignard reagents have been developed, which provide differently substituted β-vinylic naphthalenes in moderate to excellent yields.

Full text of DOI:10.1039/c3cc00171g

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Highly regioselective ring-opening coupling of
diarylmethylenecyclopropa[b]naphthalenes with
Grignard reagents†
Cite this: Chem. Commun., 2013,
49, 4788
Received 8th January 2013,
Accepted 29th March 2013
ab
Jian Cao,a Xian Huangz and Luling Wu*a
DOI: 10.1039/c3cc00171g
www.rsc.org/chemcomm
Highly regioselective ring-opening coupling reactions of diaryl-
methylenecyclopropa[b]naphthalenes with Grignard reagents have
been developed, which provide differently substituted b-vinylic
naphthalenes in moderate to excellent yields.
The addition of organomagnesium compounds across carbon–carbon
unsaturated bonds (carbomagnesation) is one of the principal and
important methods employed for the generation of Grignard reagents
with concomitant C–C bond formation, providing a straightforward
entry into Grignard reagents having a unique carbon skeleton.1,2
Recently, highly regioselective carbomagnesation of carbon–carbon
unsaturated systems including alkenes, 1,3-butadienes, alkynes, enynes
and allenes by employing transition metal complexes as catalysts has
also been achieved, providing a variety of advanced organomagnesium
reagents which are ready to be converted to useful compounds by
reaction with various electrophiles (Scheme 1, eqn (1)–(3)).3 In these
studies, what should be particularly noted is that Terao and Kambe
reported interesting nickel-catalyzed regioselective carbomagnesation of
Scheme 1 Previous studies on highly regioselective carbomagnesation of
carbon–carbon unsaturated systems and our observation.
methylenecyclopropanes, wherein the selective cleavage of the proximal physical, theoretical, and synthetic viewpoints.6,7 In this regard,
or the distal carbon–carbon bond of the MCPs has been achieved with we have reported a manganese(III) acetate-mediated cyclization
different Grignard reagents (Scheme 1, eqn (4)).4
of diarylmethylenecyclopropa[b]naphthalenes with nucleophiles for
During our recent systematic study on methylenecyclopro- the synthesis of 1,2-benzanthracenes and a highly regioselective
pane (MCP) chemistry,5 we became interested in the chemistry Pd(0)-catalyzed [3+2] cycloaddition reaction of diarylmethylene-
of the analogous diarylmethylenecyclopropa[b]naphthalenes, cyclopropa[b]naphthalenes with alkenes, alkynes or arynes to
which are a class of highly reactive but thermally stable and produce 1(3)-alkylidene-2,3-dihydro-1H-cyclopenta[b]naphthalene,
readily accessible unsaturated hydrocarbons. Because of their 1-alkylidene-1H-cyclo-penta[b]naphthalene and 11-diarylmethylene-
unusual structure, which contains a triafulvene, a [3]radialene, 11H-benzo[b]fluorine derivatives.8 In the continuous exploration of
and a cycloproparene, they have attracted much attention from the synthetic utility of these interesting compounds, we are inter-
ested in the reaction of diarylmethylenecyclopropa[b]naphthalenes
with Grignard reagents in the presence of palladium catalysts.
Herein, we wish to report such a reaction involving a naphthyl-
magnesium species through the selective cleavage of the carbon–
carbon bond of the three-membered ring controlled by palladium
a Department of Chemistry, Zhejiang University, Hangzhou 310028, P. R. China.
E-mail: wululing@zju.edu.cn
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China
† Electronic supplementary information (ESI) available: Experimental details and (pre)catalysts (Scheme 1, eqn (5)).
1H, 13C NMR spectra of new compounds. CCDC 903813 and 903814. For ESI and
In a preliminary experiment, we observed that treatment of
crystallographic data in CIF or other electronic format see DOI: 10.1039/
c3cc00171g
1-(diphenylmethylene)-1H-cyclopropa[b]naphthalene (1a) with p-tolyl-
magnesium bromide (2a, 1 M in THF, 1.5 equiv.) in the presence of
Pd(PPh3)4 (5 mol%) in THF at 25 1C for 5 minutes followed by an
aqueous workup gave 2-(2,2-diphenyl-1-(p-tolyl)vinyl)naphthalene (3a)
‡ Prof. Huang passed away on March 6, 2010. He had been fully in charge of this
project. At this moment, Prof. Luling Wu is helping him to finish all the projects
with the help of Prof. Shengming Ma.
c
4788 Chem. Commun., 2013, 49, 4788--4790
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Table 1 Optimization of reaction conditions for the Pd-catalyzed ring-opening
coupling of 1a with 2aa
Table
3
Pd-catalyzed ring-opening coupling of diarylmethylenecyclo-
a
propa[b]naphthalenes 1 with 2a quenching with I2
Entry
Ar
Yield of 3b/%
3/4c
Entry Catalyst (5 mol%) Solvent
Time (min) Yieldb/% (3a : 4a)
1
2
3
4
5
6
7
4-MeOC6H4 (1b)
4-MeC6H4 (1c)
3-MeC6H4 (1d)
3,5-(MeO)2C6H3 (1e)
4-ClC6H4 (1f)
4-FC6H4 (1g)
4-NO2C6H4 (1h)
78 (3f)
86 (3g)
86 (3h)
86/1
98/1
95/1
95/1
96/1
94/1
1c
2
3
4
5
No
THF
THF
THF
PhMe
Dioxane
5
5
5
5
5
No reaction
87 (95 : 5)
91 (98 : 2)
93 (99 : 1)
92 (97 : 3)
Pd(PPh3)4
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
87 (3i)
85 (3j)d
86 (3k)d
Complicated
a
The reaction was conducted with 0.2 mmol of 1a, 0.01 mmol of the
catalyst, 2 mL of solvent, 1.5 equiv. of p-tolylmagnesium bromide (1.0 M
a
The reaction was conducted with 0.2 mmol of 1, 0.01 mmol of the
catalyst, 2 mL of solvent, 1.5 equiv. of p-tolylmagnesium bromide (1.0 M
b
solution in THF) and 0.1 mL of H2O. Yields and radios of 3a and 4a
determined using 1H NMR using dibromomethane as the internal
b
c
solution in THF) and 1.5 equiv. of I2. Isolated yield. NMR yields of 3
c
standard. No reaction occurred in 24 hours.
and 4 determined using 1H NMR using dibromomethane as the
d
internal standard. The reaction time was 5 min.
and 2-(2,2-diphenylvinyl)-3-(p-tolyl)naphthalene (4a) in 87% with a
ratio of 95 : 5 (entry 2, Table 1). When we used Pd(PPh3)2Cl2, 3a was
obtained in 91% yield with a better regioselectivity (98 : 2) (entry 3,
Table 1). Among the solvents examined, toluene was found to be
better than THF, producing 3a in 93% with an excellent regio-
selectivity (99 : 1) within 5 minutes (entry 4, Table 1).
We then examined various electrophilic reagents to quench
the resulting mixture under the optimized reaction conditions.
When D2O was used, 3a0 was obtained in 83% (98% D) yield.
When I2, NBS, allyl bromide and acetyl chloride were employed,
all the reactions proceeded efficiently to give the corresponding
products 3b–3e in moderate to high yields with an excellent
regioselectivity (entries 3–6, Table 2). The regioselectivity of the
resulting compounds was confirmed using X-ray single crystal
diffraction analysis of 3b and 4b9 (Fig. S1, ESI†).
Considering the wide range of applications of aryl iodides, I2
was used as an electrophile to quench the reaction when we next
examined the scope of this reaction with various substrates. In
addition to 1a, diarylmethylenecyclopropa[b]naphthalenes 1b–1g,
which bear substituted phenyl rings as the Ar group in 1, all
smoothly generated the corresponding products in high yields
with good regioselectivities (entries 1–6, Table 3). However, the
Scheme 2 Reaction of 1i, 1j and 1k with 2a.
reaction of 1h bearing nitro substituted phenyl rings only gave
an unidentified mixture (entry 7, Table 3).
The reaction of 1i with 2a gave the desired compounds 3l and 3l0
as a 1 : 1 mixture of inseparable isomers in 88% overall yield
(Scheme 2, eqn (1)). However, the reaction became complicated
when 1h was employed (Scheme 2, eqn (2)). In order to replace the
simple naphthalene with other aryl groups, substrate 1k with two
methoxy groups on the naphthalene ring was employed to react with
2a, the reaction proceeded smoothly to give 3m in 90% yield.
We further examined the reaction of 1a using a variety of Grignard
reagents. It showed that all aryl magnesium bromides efficiently
underwent carbomagnesation to produce the corresponding products
in good yields with high regioselectivity (Table 4).
Table 2 Pd-catalyzed ring-opening coupling of 1a with 2a, quenching with
various electrophilic reagentsa
Entry
E+
E
Yield of 3b/%
3/4c
Although the detailed mechanism of the present ring-
opening coupling reaction has not yet been clarified, we would
like to propose the reaction pathways shown in Scheme 3.
First, the reduction of Pd(PPh3)2Cl2 with two equivalents of
Grignard reagents affords Pd0(PPh3)2. Subsequently, oxidative
addition of Pd0(PPh3)2 with the cyclopropane C–C bond of
1
2
3
4
5
6
H2Od
H
D
I
Br
Allyl
Ac
82 (3a)
93/1
95/1
94/1
90/1
95/1
95/1
D2Oe
83, 98% D (3a0)
87 (3b)
I2
NBS
Allyl bromide
Acetyl chloride
82 (3c)
80 (3d)
87 (3e)
a
The reaction was conducted with 0.2 mmol of 1a, 0.01 mmol of the catalyst, diarylmethylenecyclopropa[b]naphthalene generates metalla-
cyclobutane A.7 This metallacyclobutane A leads to the nucleophilic
2 mL of solvent, 1.5 equiv. of p-tolylmagnesium bromide (1.0 M solution in
THF) and 1.5 equiv. of electrophilic reagent. b Isolated yield. c NMR yields of
attack of Grignard reagents at the less sterically hindered side
to yield dimetallic intermediate B with a high regioselectivity.
3 and 4 determined using NMR using dibromomethane as the internal
standard. d 0.1 mL of H2O was used. e 0.1 mL of D2O was used.
c
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Table
4
Pd-catalyzed ring-opening coupling of 1a with various Grignard
1995, vol. 2, pp. 951–995; B. J. Wakefield, in Organomagnesium Methods
in Organic Synthesis, Academic Press INC, San Diego, 1995, pp. 73–86;
A. H. Hoveyda and M. T. Didiuk, Curr. Org. Chem., 1998, 2, 489.
2 Nickel-catalyzed carbomagnesation: J. G. Duboudin and B. Jousseaume,
J. Organomet. Chem., 1972, 44, C1; B. B. Snider, M. Karras and R. S. E.
Conn, J. Am. Chem. Soc., 1978, 100, 4624; B. B. Snider, R. S. E. Conn and
M. Karras, Tetrahedron Lett., 1979, 20, 1679; copper-catalyzed carbomagne-
sation: J. G. Duboudin, B. Jousseaume and A. Bonakdar, J. Organomet.
Chem., 1979, 168, 227; titanium-catalyzed carbomagnesation: S. Akutagawa
and S. Otsuka, J. Am. Chem. Soc., 1975, 97, 6870; zirconium-catalyzed
carbomagnesation: U. M. Dzhemilev, O. S. Vostrikova and R. M. Sultanov,
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E. Nakamura, J. Am. Chem. Soc., 2000, 122, 978.
a
reagents 2 quenching with I2
Entry
R
Yield of 3b/%
3c/4
1
2
3
4
5
C6H5 (2b)
83 (3n)
85 (3o)
90 (3p)
86 (3q)d
89 (3r)d
94/1
98/2
96/1
97/2
97/1
4-MeOC6H4 (2c)
4-ClC6H4 (2d)
4-FC6H4 (2e)
2-naphthyl (2f)
a
The reaction was conducted with 0.2 mmol of 1a, 0.01 mmol of the
catalyst, 2 mL of solvent, 1.5 equiv. of aryl magnesium bromide (1.0 M
b
c
solution in THF) and 1.5 equiv. of I2. Isolated yield. NMR yields of 3
and 4 determined using 1H NMR using dibromomethane as the
d
internal standard. The reaction time was 5 min.
3 S. Nii, J. Terao and N. Kambe, J. Org. Chem., 2004, 69, 573; J. Terao,
H. Watabe and N. Kambe, J. Am. Chem. Soc., 2005, 127, 3656; H. Todo,
J. Terao, H. Watanabe, H. Kuniyasu and N. Kambe, Chem. Commun.,
2008, 1332; Y. Fujii, J. Terao, Y. Kato and N. Kambe, Chem. Commun.,
2008, 5836; N. Kambe, Y. Moriwaki, Y. Fujii, T. Iwasaki and J. Terao, Org.
Lett., 2011, 13, 4656; Y. Fujii, J. Terao, Y. Kato and N. Kambe, Chem.
Commun., 2009, 1115; Y. Fujii, J. Terao, H. Kuniyasu and N. Kambe,
J. Organomet. Chem., 2007, 692, 375; Z. Lu, G. Chai and S. Ma, J. Am.
Chem. Soc., 2007, 129, 14546; G. Chai, Z. Lu, C. Fu and S. Ma, Adv. Synth.
Catal., 2009, 351, 1946; Z. Lu and S. Ma, Adv. Synth. Catal., 2007,
349, 1225.
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122, 148.
5 Y. Yang and X. Huang, J. Org. Chem., 2008, 73, 4702; W. Chen, C. Su
and X. Huang, Synlett, 2006, 1446; X. Huang, H. Zhou and W. Chen,
J. Org. Chem., 2004, 69, 839; H. Zhou, X. Huang and W. Chen, J. Org.
Chem., 2004, 69, 5471; W. Chen, X. Huang, H. Zhou and L. Ren,
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89, 1161; W. E. Billups, W. A. Rodin and M. M. Haley, Tetrahedron,
1988, 44, 1305; B. Halton, C. J. Randall, G. J. Gainsford and P. J. Stang,
J. Am. Chem. Soc., 1986, 108, 5949; B. Halton, S. J. Buckland, Q. Lu,
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Scheme 3 Proposed mechanism.
Finally, the products 3 were formed via the reductive elimina-
tion and quenching with electrophilic reagents.
In conclusion, we have developed highly regioselective ring-
opening coupling reactions of diarylmethylenecyclopropa[b]-
naphthalenes with Grignard reagents to produce differently
substituted b-vinylic naphthalenes in moderate to excellent
yields under mild conditions. Further studies on the scope,
mechanism, and synthetic applications of this transformation
are being carried out in our laboratory.
We are grateful to the National Natural Science Foundation of
China (Project No. 20872127, 20732005 and J0830431), National
Basic Research Program of China (2009CB825300), CAS Academician
Foundation of Zhejiang Province, and the Fundamental Research
Funds for the Central Universities for financial support.
7 For the fomation of A-type cyclic intermediates, see: P. J. Stang,
L. Song, Q. Lu and B. Halton, Organometallics, 1990, 9, 2149.
8 W. Chen, J. Cao and X. Huang, Org. Lett., 2008, 10, 5537; Y. Lin, L. Wu
and X. Huang, Eur. J. Org. Chem., 2011, 2993; J. Cao, M. Miao,
W. Chen, L. Wu and X. Huang, J. Org. Chem., 2011, 76, 9329.
9 Crystal data for 3b: C31H23I; MW = 522.39; crystal system: triclinic;
%
space group: P1; final R indices [I > 2s(I)] R1 = 0.0359, wR2 = 0.0751,
R indices (all data) R1 = 0.0525, wR2 = 0.0821; a = 7.2201(4) Å,
b = 10.1334(6) Å, c = 17.8528(9) Å; a = 97.658(4)1, b = 96.136(4)1,
g = 106.567(5)1, V = 1226.28(12) Å3, T = 293(2) K, Z = 2; F(000) 524;
reflections collected/unique: 9655/4483 [Rint = 0.0279]; number of
observations [I > 2s(I)]: 3541; parameters: 290. CCDC 903814. Crystal
data for 4b: C31H23I; MW = 522.39; crystal system: triclinic; space
Notes and references
1 P. Knochel, in Comprehensive Organic Synthesis, ed. B. M. Trost and
F. Ian, Pergamon, NewYork, 1991, vol. 4, pp. 865–911; S. V. Ley and
C. Kouklovsky, in Comprehensive Organic Functional Group Transforma-
tions, ed. A. R. Katritzky, O. Meth-Cohn and C. W. Rees, Pergamon,
New York, 1995, vol. 2, pp. 549–603; E. Negishi and D. Choueiry,
in Comprehensive Organic Functional Group Transformations, ed.
A. R. Katritzky, O. Meth-Cohn and C. W. Rees, Pergamon, New York,
%
group: P1; final R indices [I > 2s(I)] R1 = 0.0318, wR2 = 0.0641,
R indices (all data) R1 = 0.0439, wR2 = 0.0707; a = 10.1953(6) Å,
b = 10.2701(7) Å, c = 13.6377(7) Å; a = 68.376(6)1, b = 75.947(5)1,
g = 66.850(6)1, V = 1212.54(13) Å3, T = 293(2) K, Z = 2; F(000) 524;
reflections collected/unique: 8715/4441 [Rint = 0.0284]; number of
observations [I > 2s(I)]: 3691; parameters: 290. CCDC 903813.
c
4790 Chem. Commun., 2013, 49, 4788--4790
This journal is The Royal Society of Chemistry 2013