Synthesis of hindered 1-arylnaphthalene derivatives via ring expansion of benzocyclobutenones

Article abstract of DOI:10.1021/ol016956b

Chemical equation presented Various 1-arylnaphthalenes, including highly substituted derivatives, are accessible via a simple two-step process. Treatment of alkenylbenzocyclobutenones with aryllithium provides two-carbon expanded dihydronaphthalenes, whic

Full text of DOI:10.1021/ol016956b

ORGANIC
LETTERS
2002
Vol. 4, No. 2
229-232
Synthesis of Hindered 1-Arylnaphthalene
Derivatives via Ring Expansion of
Benzocyclobutenones
Toshiyuki Hamura, Makoto Miyamoto, Takashi Matsumoto, and Keisuke Suzuki*
Department of Chemistry, Tokyo Institute of Technology, and CREST, Japan Science
and Technology (JST) Corporation, O-okayama, Meguro-ku, Tokyo 152-8551, Japan
ksuzuki@chem.titech.ac.jp
Received October 25, 2001
ABSTRACT
Various 1-arylnaphthalenes, including highly substituted derivatives, are accessible via a simple two-step process. Treatment of
alkenylbenzocyclobutenones with aryllithium provides two-carbon expanded dihydronaphthalenes, which are readily dehydrated by MsCl−
Et3N or PPTS in MeOH.
Biaryl linkages are embedded as a key structural motif in
various compounds ranging from biologically active natural
products such as vancomycin to structually defined ligands
and materials such as BINAP.1 Herein, we report a new
synthetic method of hindered 1-arylnaphthalenes starting
from benzocyclobutene derivatives2 that is comprised of two
processes as shown in eq 1: (1) the reaction of vinylbenzo-
cyclobutenone I with an aryllithium to generate an alkoxide
intermediate II, which undergoes a ring enlargement in situ
to give dihydronaphthalene III3,4 and (2) the dehydration of
III effected by either of the two protocols (vide infra) to
give 1-arylnaphthalene IV.
(1) For recent reviews, see: (a) Bringman, G.; Breuning, M.; Tasler, S.
Synthesis 1999, 525-558. Bringman, G.; Walter, R.; Weirich, R. Angew.
Chem., Int. Ed. Engl. 1990, 29, 977-991. (b) Stanforth, S. P. Tetrahedron
1998, 54, 263-303.
(2) Matsumoto, T.; Hamura, T.; Kuriyama, Y.; Suzuki, K. Tetrahedron
Lett. 1997, 38, 8985-8988. Matsumoto, T.; Hamura, T.; Miyamoto, M.;
Suzuki, K. Tetrahedron Lett. 1998, 39, 4853-4856.
(3) For selected examples, see: (a) Spangler, L. A.; Swenton, J. S. J.
Org. Chem. 1984, 49, 1800-1806. Swenton, J. S.; Anderson, D. K.; Jackson,
D. K.; Narasimhan, L. J. Org. Chem. 1981, 46, 4825-4836. (b) Hickman,
D. N.; Hodgetts, K. J.; Mackman, P. S.; Wallace, T. W.; Wardleworth, J.
M. Tetrahedron 1996, 52, 2235-2260. Hickman, D. N.; Wallace, T. W.;
Wardleworth, J. M. Tetrahedron Lett. 1991, 32, 819-822. (c) Winters, M.
P.; Stranberg, M.; Moore, H. W. J. Org. Chem. 1994, 59, 7572-7574.
(4) For reviews on the charge-accelerated rearrangements, see: Wilson,
S. R. Org. React. (N. Y.) 1993, 43, 93-250. Bronson, J. J.; Danheiser, R.
L. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 5, pp 999-1035.
Two isomeric benzocyclobutenones, 1 and 2, were pre-
pared by the [2 + 2] cycloaddition of benzyne and ketene
silyl acetal as reported before,5 which in turn were converted
to the model substrates 3-6. For example, treatment of 1
(5) Hosoya, T.; Hasegawa, T.; Kuriyama, Y.; Matsumoto, T.; Suzuki,
K. Synlett 1995, 177-179. Hosoya, T.; Hasegawa, T.; Kuriyama, Y.; Suzuki,
K. Tetrahedron Lett. 1995, 36, 3377-3380. Hosoya, T.; Hamura, T.;
Kuriyama, Y.; Matsumoto, T.; Suzuki, K. Synlett 2000, 520-522.
10.1021/ol016956b CCC: $22.00 © 2002 American Chemical Society
Published on Web 12/19/2001

with 2-propenyllithium followed by trapping of the resulting
alkoxide in situ with methyl triflate (Et2O, -78 f 25 °C)
and acid hydrolysis (2 M H2SO4, 25 °C) gave 3 in 84% yield.
A similar sequence of reactions starting from 1 and 2-cis-
butenyllithium afforded 4. In a similar manner, the benzo-
cyclobutenones 5 and 6, the regio isomers of 3 and 4,
respectively (see the position of MeO- group), were obtained
by adding the corresponding alkenyllithium to the isomeric
ketone 2 followed by the methylation-hydrolysis sequence.
product 9 in high yield. When the above-mentioned reaction
was warmed to -25 °C, monitoring by TLC showed that
the initially observed products at -78 °C converged to a
single compound, and the workup gave the alcohol 9 in 81%
yield (see run 2, Scheme 1).6 Interestingly, the product 9
was far more stable than expected and was readily isolated
with silica gel preparative thin-layer chromatography without
dehydration. On the other hand, the dehydration could be
achieved by either of two straightforward protocols as
described below.
This reaction pattern was amenable to various substrate
combinations, and some representative results are sum-
marized in Table 1. Upon treatment of 3 with 1-naphthyl-
lithium, the reaction sequence occurred at -78 °C, thereby
giving the alcohol 10 in 70% yield (run 2).7 Likewise, the
reaction proved to be applicable to substrate 4 with an
additional methyl group on the olefin. Upon treatment of 4
with phenyllithium (-78 °C f room temperature), the
alcohol 11 was obtained as a single isomer (stereochemistry
unassigned) in 85% yield (run 3).7 Similarly, treatment of
the benzocyclobutenone 5, isomeric to 3, with 2-methoxy-
phenyllithium (-78 °C f room temperature) gave the
alcohol 12 in 77% yield (run 4).7
Scheme 1 shows the preliminary experiments on the
benzocyclobutenone 3. Upon treatment of 3 with phenyl-
lithium6 (1.3 equiv) in THF at -78 °C, the starting material
Scheme 1
Furthermore, we became able to synthesize such sterically
congested compounds as 13 and 14 by the reaction of 6 with
the corresponding aryllithiums (runs 5 and 6).8 It is notable
that these compounds were mainly composed of the cis
isomers with respect to the relation of the hydroxy and the
methyl groups as evidenced by the X-ray analysis (see
below).9 The molecular motion in these compounds appeared
to be restricted, not surprisingly, in the vicinity of the bond
between the aryl group and the dihydronaphthalene moiety.
3 was quickly consumed, and immediate quenching with H2O
gave a mixture of three products, 7-9 (run 1). Though the
ring-opened compound 8 was the major product, the domi-
nant species in the reaction seemed to be the lithium alkoxide
7′ judging from the following additional facts. (1) When the
reaction was quenched with TMSCl, the silyl ether 7′′ was
obtained in 78% yield along with small amounts of 8 (8%)
and 9 (10%). (2) D2O-quenching gave the deuterated ketone
8′ (85% D) with the Z geometry, whose structure was
determined by NOE experiment. Thus, the ring-opened
ketone 8 is most probably an artifact produced from 7′ after
the quenching.
These ring-enlarged products 9-14 are intriguing in their
own right, but they could also be dehydrated to give the
corresponding biaryls by either of the following two man-
ners: methanesulfonyl chloride and Et3N at room temperature
(method A) or PPTS (pyridinium p-toluenesulfonate) in
MeOH at 60 °C (method B). For example, the alcohol 9
was subjected to the conditions of method A, where a smooth
After a series of optimization experiments, we were
pleased to find suitable conditions to obtain the ring-enlarged
(6) Generated from the aryl bromide (1.3 equiv) and t-BuLi (2.5 equiv)
in THF at -78 °C. n-BuLi was not effective.
(7) All new compounds were fully characterized by spectroscopic means
and combustion analysis. See Supporting Information.
230
Org. Lett., Vol. 4, No. 2, 2002

Table 1
a Major isomer was cis with respect to the hydroxy and the methyl groups, as determined by X-ray analysis. The ratio of the stereoisomers is shown in
parenthesis. b Yields from the dihydronaphthalene. c Method A: MsCl, Et3N. d Method B: PPTS in MeOH at 60 °C.
elimination occurred to give 1-arylnaphthalene 15 in quan-
titative yield (run 1, Table 1). Similarly, the alcohols 10 and
11 were converted to the arylnaphthalenes 16 and 17.
However, method A proved to be ineffective for the
dehydration of the alcohols 12-14 due to the high steric
hindrance around the hydroxy group. However, method B
nicely provided the arylnaphthalenes in excellent yields (runs
4-6).9 Runs 5 and 6 illustrate that the reaction sequence is
applicable to the synthesis of such sterically congested tri-
and tetrasubstituted biaryls as 19 and 20, which are difficult
to obtain via conventional methods.10
In summary, vinylbenzocyclobutenone undergoes two-
carbon expansion of the cyclobutenes and provides a facile
(8) Representative experimental procedures: Synthesis of alcohol 13.
To a solution of 4-bromo-m-xylene (34 mg, 0.18 mmol) in THF (1.0 mL)
was slowly added t-BuLi (1.64 M in pentane, 0.22 mL, 0.36 mmol) at -78
°C, and the reaction mixture was further stirred for 40 min; to the stirred
solution was added benzocyclobutene 5 (32.7 mg, 0.141 mmol) in THF
(1.2 mL). After the mixture was warmed to 25 °C in 1 h and stirred for an
additional 1 h, the reaction was quenched with water. The products were
extracted with Et2O (×3), dried (Na2SO4), and concentrated in vacuo. The
residue was purified with PTLC (hexane/EtOAc ) 8/2) to give alcohol 13
(43.5 mg, 91%, d.s. 16:1). Recrystallization from hexane/Et2O gave colorless
prisms: mp 144.5-147.0 °C.
(9) The minor isomers of the alcohols 13 and 14, in which the hydroxyl
and the methyl moieties are trans, were converted to the corresponding
arylnaphthalenes by treatment with PPTS in MeOH at 40 °C. Representative
experimental procedures: Synthesis of arylnaphthalene 19. A solution of
alcohol 13 (34.5 mg, 0.102 mmol) and PPTS (13 mg, 0.053 mmol) in MeOH
(1.5 mL) was stirred at 60 °C for 10 min. After the mixture was cooled
and saturated aqueous NaHCO3 was added, the products were extracted
with EtOAc (×3), dried (Na2SO4), and concentrated in vacuo. The residue
was purified with PTLC (hexane/CH2Cl2/Et2O ) 8/1/1) to give 19 (30.2
mg, 92%). Colorless prisms: mp 70.8-72.0 °C (hexane).
Org. Lett., Vol. 4, No. 2, 2002
231

synthesis of arylnaphthalene derivatives. Further studies are
currently underway in our laboratories.
Supporting Information Available: General pro-
cedures and spectral data for compounds 7-20. This ma-
terial is available free of charge via the Internet at
http://pubs.acs.org.
(10) If the metal-catalyzed cross-coupling reaction is taken as an example,
the presence of even a single ortho substituent on each aromatic moiety
substantially retards the reaction. For cross-coupling of aryl halides or
triflates with hindered arylmetals, see: Saa´, J. M.; Martorell, G. J. Org.
Chem. 1993, 58, 1963-1966 and references therein.
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