Facile carbolithiation of bent alkyne without catalyst. Tandem route to dibenzo[b, f]pentalenes from dibenzocyclooctadiyne

Article abstract of DOI:10.1246/cl.2008.1296

Nucleophilic addition of RLi to a triple bond of dibenzocy-cloocta[a, e]diyne provides dibenzo[b, f]pentalene motif through trans-annulation of the resulting vinyllithium. Dibenzopentalene anion thus formed reacts with various electrophiles such as aldehydes, alkyl halides, acid halide, and Me ₃SiCl to give the corresponding products. Copyright

Full text of DOI:10.1246/cl.2008.1296

1296
Chemistry Letters Vol.37, No.12 (2008)
Facile Carbolithiation of Bent Alkyne without Catalyst.
Tandem Route to Dibenzo[b,f]pentalenes from Dibenzocyclooctadiyne
Govindarajulu Babu, Akihiro Orita,ꢀ and Junzo Oteraꢀ
Department of Applied Chemistry, Okayama University of Science, Ridai-cho, Okayama 700-0005
(Received September 24, 2008; CL-080919; E-mail: orita@high.ous.ac.jp, otera@high.ous.ac.jp)
Nucleophilic addition of RLi to a triple bond of dibenzocy-
R1
1) R1Li
2) R2R3CO
3) H+
cloocta[a,e]diyne provides dibenzo[b,f]pentalene motif through
trans-annulation of the resulting vinyllithium. Dibenzopentalene
anion thus formed reacts with various electrophiles such as alde-
hydes, alkyl halides, acid halide, and Me3SiCl to give the corre-
sponding products.
THF
R2
R3 OH
1
2
R1Li
R2R3CO
H+
R1
R1
-
On account of its great promise for providing highly substi-
tuted alkenes,1 carbometalation of alkynes with organometallic
nucleophiles is still a challenge to synthetic chemists, because
the acetylenic bond is rather inert towards nucleophilic attack
unless alkynes bear heteroatom functions.2 The superbase gener-
ated from t-BuOK and BuLi was employed for overcoming the
low reactivity of diphenylacetylene, but double ortho metalation
of the aromatic rings inevitably occurred leaving the triple bond
untouched.3 Although carbometalation with alkyllithium re-
agents in the presence of TMEDA has found limited utility,4 re-
cent progress of catalytic protocols has met with remarkable suc-
cess even for unfunctionalized alkynes.5 On the other hand, bent
acetylenes undergo uncatalyzed reverse-demand Diels–Alder re-
actions induced by strain release.6 We postulated therefore that
strained alkynes must undergo nucleophilic attack even without
catalyst. In this study, we investigated nucleophilic addition of
alkyllithium reagents to highly strained 5,6,11,12-tetradehydro-
dibenzo[a,e]cyclooctene (1).7 Moreover, it has been found that
the initial nucleophilic addition triggers spontaneous trans-annu-
lar cyclization, and in situ trapping of the resulting intermediate
with an electrophile affords diversely substituted dibenzo[b,f]-
pentalenes, a unique class of molecules which have been receiv-
ing much attention due to their anti-aromaticity.8
4
3
-
R1= Bu, R2= H, R3= Ph (75%, 2a),
p-Cl-C6H4 (73%, 2b),
p-NO2C6H4 (76%, 2c),
2-naphthyl (62%, 2d), C7H15 (64%, 2e)
R1= Bu, R2, R3= -(CH2)5- (64%, 2f)
R1= Et, R2= H, R3= Ph (69%, 2g)
R1= Me, R2= H, R3= Ph (72%, 2h)
Scheme 1. Three component reaction through nucleophilic ad-
dition of R1Li to a triple bond of 1 followed by trans-annulation.
R1
R1= Bu, R2= COPh (78%, 5a)
R1= Bu, R2= Me (61%, 5b)
R1= Bu, R2= Me3Si (57%, 5c)
R1= Me, R2= Me (63%, 5d)
5
R2
Scheme 2. Structures of 5.
(FVP),12 dehydration13 and transition-metal-catalyzed14 or
anionic trans-annulation.15
As expected, nucleophilic addition of alkyllithiums took
place smoothly (Scheme 1). Presumably, a thermodynamic ad-
vantage gained by release of the strain upon sp-to-sp2 hybridiza-
tion change contributes to the facile addition. The resulting
vinylic anions 3 spontaneously underwent trans-annular addition
onto another triple bond. The newly formed vinylic anions 4
could be in situ trapped by various electrophiles. As an electro-
phile, various aldehydes were employable like benzaldehyde,
p-chloro- and p-nitrobenzaldehyde, 2-naphthaldehyde, and hep-
tanal. When the BuLi-initiated reaction was terminated with
cyclohexenone, 1,2-adduct 2f was obtained exclusively in 64%
yield. As a nucleophile, EtLi and MeLi could be used,9 and
the corresponding adducts, 2g and 2h, were obtained in 69 and
72% yields, respectively.10
When other electrophiles such as PhCOCl, MeI, and
Me3SiCl were used, the three-component reaction also proceed-
ed smoothly to afford the desired products 5, respectively
(Scheme 2). Notably, the present method is simpler and more
convenient than those previously reported for the synthesis of
pentalenes, i.e., nucleophilic addition,11 flash vacuum pyrolysis
Aryl halides were not employable as an electrophile in the
three-component process, but incorporation of aryl groups was
feasible by the Suzuki–Miyaura or Stille coupling of iodopenta-
lene 6, which was easily prepared by treatment of 4 with iodine
(Scheme 3). Because it was rather difficult to remove a dibutyl-
dibenzo[b,f]pentalene by-product from the iodide on account of
their similar polarity, the crude mixture obtained after usual
workup was directly used for the next coupling reactions. The
couplings proceeded smoothly to afford the desired products in
good yields.16
In summary, we have shown that the strained acetylenic
bond can readily undergo facile uncatalyzed carbolithiation.
The tandem process initiated by nucleophilic addition of alkyl-
lithium to 1 gives convenient access to diversely substituted
dibenzo[b,f]pentalenes 2, 5, and 7. Further development of this
protocol and photochemical assessment of these compounds are
now in progress.
This work has been supported financially by Grant-in-Aid
for Scientific Research from the Ministry of Education, Culture,
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.12 (2008)
1297
O. Dautel, H. Duong, R. Helgeson, F. Wudl, Angew. Chem.,
Int. Ed. 2002, 41, 3688. c) E. L. Elliott, A. Orita, D.
Hasegawa, P. Gantzel, J. Otera, J. S. Siegel, Org. Biomol.
1) BuLi
2) I2
3) workup
Bu
THF
Chem. 2005, 3, 581. d) M. Muller, V. S. Iyer, C. Kubel, V.
¨
1997, 36, 1607. e) Y.-M. Man, T. C. W. Mak, H. N. C.
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Hasegawa, T. Nakano, J. Otera, Chem.—Eur. J. 2002, 8,
2000.
¨
Enkelmann, K. Mullen, Angew. Chem., Int. Ed. Engl.
¨
6
I
ArB(OH)2 or ArSnBu3
Pd(PPh3)4
DMF
Ar
yield/%
64,a 53b
64a
Ph 7a
m-NO2C6H4 7b
2-thienyl 7c
2-furyl 7d
Bu
7
63,a 60b
70,a 61b
50b
2-pyridyl 7e
aArB(OH)2 (1.5 equiv).
bArSnBu3 (1.2 equiv).
8
9
P. W. Fowler, E. Steiner, R. W. A. Havenith, L. W.
Jenneskens, Magn. Reson. Chem. 2004, 42, S68.
Other nucleophiles such as PhLi, MeMgBr, Bu2CuLi,
BuCuLi, Bu2CuCNLi, BuZnBr, L-selectride, and super-
Hydride were not effective for the nucleophilic addition,
and 1 was recovered.
7
Ar
Scheme 3. Stepwise synthesis of 7.
Sports, Science and Technology, Japan (MEXT), Okayama Pre-
fecture Industrial Promotion Foundation, Electric Technology
Research Foundation of Chugoku and Tokuyama foundation.
10 Representative procedure for 2a: BuLi (1.45 M in hexane,
0.84 mL, 1.21 mmol) was added to a THF solution (10 mL)
of 1 (0.242 g, 1.21 mmol) at ꢁ78 ꢂC, and the mixture was
stirred for 30 min. Benzaldehyde (0.154 g, 1.45 mmol) in
THF (4 mL) was added at this temperature, and the mixture
was stirred for 1 h. After workup with aqueous NH4Cl/
AcOEt, the crude product was subjected to chromatography
on silica gel (7:93 EtOAc/hexane) to give 0.330 g of 2a
This paper is dedicated to Professor Ryoji Noyori on the
occasion of his 70th birthday.
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1
(75%) as red powder. H NMR (500 MHz, CDCl3): ꢀ 7.56
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6
Published on the web (Advance View) December 5, 2008; doi:10.1246/cl.2008.1296