Construction of tetralin skeletons based on rhodium-catalysed site-selective ring opening of benzocyclobutenols

Article abstract of DOI:10.1039/c4cc09327e

Tetralins (tetrahydronaphthalenes) are synthesised from benzocyclobutenols based on the rhodium-catalysed site-selective ring opening followed by intermolecular/intramolecular conjugate addition of the resulting arylrhodium species to electron-deficient alkenes. The produced structures make a remarkable contrast with those available from the same compounds under thermal reaction conditions.

Full text of DOI:10.1039/c4cc09327e

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: N. Ishida, N.
Ishikawa, S. Sawano, Y. Masuda and M. Murakami, Chem. Commun., 2014, DOI: 10.1039/C4CC09327E.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/chemcomm

Page 1 of 4
ChemComm
Chemical Communications
RSCPublishing
View Article Online
DOI: 10.1039/C4CC09327E
COMMUNICATION
Construction of tetralin skeletons based on rhodium-
catalysed site-selective ring opening of
benzocyclobutenols
Cite this: DOI: 10.1039/x0xx00000x
Naoki Ishida, Norikazu Ishikawa, Shota Sawano, Yusuke Masuda and
Masahiro Murakami*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
Tetralins (tetrahydronaphthalenes) are synthesised from bond is formally inserted into the C(sp3)–C(sp3) bond of the
benzocyclobutenols based on the rhodium-catalysed site- cyclobutene ring.
selective
ring
opening
followed
by
intermolecular/intramolecular conjugate addition of the
resulting arylrhodium species to electron-deficient alkenes.
The produced structures make a remarkable contrast with
those available from the same compounds under thermal
reaction conditions.
Tetralin is a key structural motif found in a wide variety of bioactive
molecules including natural products such as heritonine,1 cycloolivil,2
morphine3 and daunorubicin.4 The development of efficient methods
for the construction of tetralin skeleton has been a subject of intense
research. We report herein a new protocol to prepare tetralin
derivatives from benzocyclobutenols based on their site-selective ring
opening under the catalysis of rhodium.5-8 2-Hydroxytetralins are
stereoselectively synthesised by an insertion reaction of vinyl ketones
Scheme 1 Thermal reaction of 1a and 2a.
On the other hand, we have reported a different type of ring
into the C(sp2)–C(sp3) bond of benzocyclobutenols. The rhodium- opening reaction of benzocyclobutenols; a rhodium complex prompts
catalysed rearrangement of 1-alkenylbenzocyclobutenols furnishes 2- ring opening selectively at the C(sp2)–C(sp3) bond to furnish an ortho-
tetralones. The produced structures make a remarkable contrast with acylmethyl-substituted arylrhodium intermediate.5,13,14 The subsequent
those available from the same compounds under thermal reaction intermolecular addition across the C–C triple bond of alkynes generates
conditions.
alkenylrhodium species, which then undergoes intramolecular addition
A [4+2] cycloaddition reaction of o-quinodimethanes with alkenes onto the carbonyl group to construct dihydronaphthalene frameworks.
presents one of the most reliable synthetic pathways to tetralin In a formal sense, a C–C triple bond is inserted into the C(sp2)–C(sp3)
skeletons.9 For example, when benzocyclobutenols are heated, a bond of the cyclobutene ring in an atom-economical way. This finding
thermal ring opening reaction takes place with outward rotation of the led us to explore new synthetic pathways leading to tetralins
hydroxyl group10 to stereoselectively furnish the hydroxy-substituted o- (tetrahydronaphthalenes) from benzocyclobutenol derivatives.
quinodimethanes. A regioselective [4+2] cycloaddition reaction with
We first carried out a thermal reaction of 1a and 2a at 100 °C for 30
electron-deficient alkenes follows in an endo fashion.11 Thus, simple min in the absence of a rhodium catalyst. The thermal ring-opening
heating of a toluene solution of benzocyclobutenol 1a and methyl vinyl reaction of 1a was so slow that 90% of 1a was recovered. Next, 1a was
ketone (2a) at the refluxing temperature (bath temperature: 130 °C) reacted with 2a in the presence of [Rh(OH)(nbd)]2 under otherwise
gave 1-hydroxytetralin 3 in a diastereoselective fashion (Scheme 1). It identical conditions. The C–C double bond of 2a was successfully
has been also known that treatment of benzocyclobutenols with inserted into the C(sp2)–C(sp3) bond of 1a to produce 2-hydroxytetralin
butyllithium generates an oxyanion intermediate, which follows an 4a in 82% yield with a trace amount of the minor diastereomer
analogous pathway even at −78 °C.12 In these cases, the C–C double (diastereomeric ratio, dr = 15:1).
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 1

ChemComm
Page 2 of 4
Journal Name
COMMUNICATION
isopropyl group. Phenyl vinyl ketone also successfully engaged in the
insertion reaction. On the other hand, alkenes lacking electron-
View Article Online
withdrawing groups (e.g. ethylene and styrene) failed to be
DOI: 10.1039/C4CC09327E
incorporated. α,β-Unsaturated ketones possessing a substituent at the
α- or β-position gave significantly lower yield, presumably due to steric
reasons. The use of acrolein and acrylate gave a complex mixture
containing the desired 2-hydroxytetralin (<30% yield).
Scheme 2. Rhodium-catalysed reaction of 1 and 2.
Table 1 Rhodium-catalysed reactions of 1 and 2. a
A
probable mechanistic scenario for the diastereoselective
formation of 4a is depicted in Scheme 3. Initially, the hydroxylic
proton of benzocyclobutenol 1a is exchanged with rhodium to furnish
the rhodium benzocyclobutenolate A. The benzene ring π-coordinates
to the rhodium centre,15 and the π-coordination is retained during the
subsequent β-carbon elimination so that the ipso carbon selectively
migrates on rhodium. Thus, the C(sp2)–C(sp3) bond is selectively
cleaved. The resulting arylrhodium species B undergoes conjugate
addition across 2a, which is taking an s-cis conformation to allow a six-
membered transition state. As a consequence, the (Z)-enolate C is
generated. Then, an intramolecular aldol reaction follows again via a
six-membered transition state, for which chair-like conformation is
assumed to afford syn-aldolate D stereoselectively.16,17 Protonation of
D with water, generated in the first step, or with 1a produces 4a and the
next catalytic cycle starts over.
[Rh]
OH
O
[Rh] OH
Ph
Ph
–H2O
1a
A
[Rh]
Me
O
O
a Reaction conditions: Benzocyclobutenol 1 (0.20 mmol), vinyl ketone 2
(0.40 mmol, 2 equiv), [Rh(OH)(nbd)]2 (2.5 mol %), toluene (1 mL), 100 °C,
0.5 h. Isolated yields of the major diastereomer were shown. Dr were
determined by NMR analysis of the crude reaction mixture. b 1 h. c
[Rh(OH)(cod)]2 (2.5 mol %) was employed as the catalyst.
[Rh]
Me
O
2a
O
Ph
Ph
B
C
‡
[Rh]
Me
Next examined was the construction of tetralones from 1-
alkenylbenzocyclobutenol 5a, which was easily prepared by addition of
alkenyllithium to benzocyclobutenone. When 5a was simply heated at
80 °C in C6D6 for 4.5 h, 1-tetralone 6a was obtained in 91% yield, as
previously reported with analogous substrates (Scheme 4).18 4π-Ring
opening of 5a is followed by 6π-electrocyclic ring closure to afford 6a.
O
O
O
Me
O[Rh]
Ph
Ph
H
D
O
In sharp contrast, treatment of 5a with
a catalytic amount of
[Rh(OH)(cod)]2 at 40 °C for 2 h gave 2-tetralone 7a in 83% isolated
yield.19 Mechanistically, it is assumed the site-selective cleavage of the
C(sp2)–C(sp3) bond generates the arylrhodium intermediate F with the
ortho position substituted by an α,β-unsaturated carbonyl group. An
intramolecular conjugate addition reaction follows, and the resulting
oxa-π-allylrhodium G is protonated with water, or with 5a to give 7a.
Thus, the pathway of the intramolecular rearrangement reaction of
5a is also changed by a rhodium complex. In addition, the racemic
mixture of 5a was enantioselectively rearranged when electron-
deficient chiral diphosphine (R)-MeO-F12-BIPHEP20 was employed as
the ligand for rhodium. 2-Tetralone 7a was obtained in 72% yield with
the enantiomeric ratio (er) of 91:9. The reaction conditions were
applied to the synthesis of 7b (er = 84:16) and 7c (er = 99:1).
H2O
– [Rh] OH
Me
OH
Ph
4a
Scheme 3. Proposed mechanism for the formation of 4a.
The scope of the site-selective insertion reaction is shown in Table
1. Although non-substituted benzocyclobutenol (R = H) failed to afford
the 2-hydroxytetralin, substituted benzocyclobutenols reacted with
vinyl ketones to afford 4b-g with dr ranging from 8:1 to >20:1.
Cyclopropyl, methoxy and chloro groups remained intact under the
reaction conditions. The site-selective ring opening was observed even
when the migrating ipso sp2 carbon was obstructed by its ortho-
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 3 of 4
Journal Name
ChemComm
COMMUNICATION
from MEXT, and the ACT-C program of the JST. This paper is
dedicated to Professor Ming-Chang P. Yeh (National Taiwan Normal
View Article Online
DOI: 10.1039/C4CC09327E
University) on the occasion of his 60th birthday.
Notes and references
Department of Synthetic Chemistry and Biological Chemistry, Kyoto
University,
Katsura,
Kyoto
615-8510,
Japan.
E-mail:
murakami@sbchem.kyoto-u.ac.jp; Fax: (+81)-75-383-2748; Tel: (+81)-
75-383-2747.
†
Electronic Supplementary Information (ESI) available: Detailed
experimental procedures, and spectral data for all compounds, including
scanned images of and NMR spectra. See
1H 13C
DOI: 10.1039/c000000x/.
Scheme 4. Thermal rearrangement of 5a.
1
Isolation: (a) D. H. Miles, A.-M. Ly, V. Chittawong, A. A. de la Cruz,
E. D. Gomez, J. Nat. Prod., 1989, 52, 896. Synthesis: (b) K. Matsuo,
M. Shindo, Org. Lett., 2010, 12, 5346; (c) S. P. Chavan, S. Garai, U.
R. Kalkote, Tetrahedron, 2012, 68, 8509 and referenced cited therein.
Isolation: (a) H. Tsukamoto, S. Hisada, S. Nishibe, Chem. Pharm.
Bull., 1984, 32, 2730. Synthesis: (b) Y. Moritani, T. Ukita, H.
Ohmizu, T. Iwasaki, J. Chem. Soc., Chem. Commun., 1995, 671.
A review: (a) J. Zezula, T. Hudlicky, Synlett, 2005, 388. Recent
examples: (b) B. M. Trost, W. Tang, F. D. Toste, J. Am. Chem. Soc.,
2005, 127, 14785; (c) K. A. Parker, D. Fokas, J. Org. Chem., 2006,
71, 449; (d) H. Tanimoto, R. Saito, N. Chida, Tetrahedron Lett., 2008,
49, 358; (e) M. Varin, E. Barr, B. Iorga, C. Guillou, Chem. Eur. J.,
2008, 14, 6606; (f) G. Stork, A. Yamashita, J. Adams, G. R. Schulte,
R. Chesworth, Y. Miyazaki, J. J. Farmer, J. Am. Chem. Soc., 2009,
131, 11402; (g) P. Magnus, N. Sane, B. P. Fauber, V. Lynch, J. Am.
Chem. Soc., 2009, 131, 16045; (h) H. Leisch, A. T. Omori, K. J. Finn,
J. Gilmet, T. Bissett, D. Ilceski, T. Hudlicky, Tetrahedron, 2009, 65,
9862; (i) H. Koizumi, S. Yokoshima, T. Fukuyama, Chem. Asian. J.,
2010, 5, 2192.
2
3
Scheme 5. Rhodium-catalysed rearrangement of 5a.
4
5
6
(a) F. Cassinelli, P. Orezzi, G. Microbiol., 1963, 11, 167; (b) A. Di
Marco, M. Gaetani, P. Orezzi, B. M. Scarpinato, R. Silvestrini, M.
Soldati, T. Dasdia, L. Valentini, Nature, 1964, 201, 706; (c) A. Di
Marco, M. Gaetani, L. Dorigotti, M. Soldati, O. Bellini, Cancer
Chemother. Rep., 1964, 38, 31.
(a) N. Ishida, S. Sawano, Y. Masuda, M. Murakami, J. Am. Chem.
Soc., 2012, 134, 17502. For theoretical investigations on the reaction
mechanism, see: (b) Y. Li, Z. Lin, J. Org. Chem., 2013, 78, 11357;
(c) L. Ding, N. Ishida, M. Murakami, K. Morokuma, J. Am. Chem.
Soc., 2014, 136, 169.
For
a
rhodium-catalysed site-selective insertion reaction of
Scheme 6. Asymmetric rearrangement of 5.
carbenoids into benzocyclobutenols constructing indene skeletons: Y.
Xia, Z. Liu, Z. Liu, R. Ge, F. Ye, M. Hossain, Y. Zhang, J. Wang, J.
Am. Chem. Soc., 2014, 136, 3013.
In summary, tetralin skeletons are constructed from
benzocyclobutenols based on the rhodium-catalysed site-selective ring
opening reaction. Vinyl ketones are site-selectively inserted into the
C(sp2)–C(sp3) bond of benzocyclobutenols to produce 2-
hydroxytetralins. 1-Alkenylbenzocyclobutenols are restructured into 2-
tetralones. The obtained tetralins markedly contrast with those given
by the conventional thermal reactions.
7
8
For a rhodium-catalysed insertion reaction of alkynes into
cyclobutenols furnishing mupliply-substituted benzenes: T. Matsuda,
N. Miura, Org. Biomol. Chem., 2013, 11, 3424.
For rhodium-catalysed intramolecular insertion reaction of
unsaturated C–C bonds into benzocyclobutenones: (a) T. Xu, G.
Dong, Angew. Chem., Int. Ed., 2012, 51, 7567; (b) T. Xu, H.-M. Ko,
N. Savage, G. Dong, J. Am. Chem. Soc., 2012, 134, 20005; (c) P.-h.
Chen, T. Xu, G. Dong, Angew. Chem., Int. Ed., 2014, 53, 1674.
This work was supported in part by a Grant-in-Aid for Scientific
Research on Innovative Areas “Molecular Activation Directed toward
Straightforward Synthesis”, a Grant-in-Aid for Scientific Research (B)
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 3

ChemComm
Page 4 of 4
Journal Name
COMMUNICATION
9
(a) W. Oppolzer, Synthesis, 1978, 793; (b) J. L. Charlton, M. M.
Alauddin, Tetrahedron, 1987, 43, 2873; (c) J. L. Segura, N. Martín,
Chem. Rev., 1999, 99, 3199; (d) A. Flores-Gaspar, R. Martin,
Synthesis, 2013, 45, 563.
View Article Online
DOI: 10.1039/C4CC09327E
10 A review on torquoselectivity of electrocyclisation reactions: W. R.
Dolbier, Jr., H. Koroniak, K. N. Houk, C. Sheu, Acc. Chem. Res.,
1996, 29, 471.
11 B. J. Arnold, P. G. Sammes, T. W. Wallace, J. Chem. Soc., Perkin
Trans. 1, 1974, 409.
12 (a) W. Choy, H. Yang, J. Org. Chem., 1988, 53, 5796; (b) E. P.
Kündig, G. Bernardinelli, J. Leresche, J. Chem. Soc., Chem.
Commun., 1991, 1713.
13 For palladium-catalysed site-selective ring opening reactions of
benzocyclobutenols: (a) A. Chtchemelinine, D. Rosa, A. Orellana, J.
Org. Chem., 2011, 76, 9157; (b) D. Rosa, A. Chtchemelinine, A.
Orellana, Synthesis, 2012, 44, 1885.
14 For other ring opening reactions of benzocyclobutenols with cleavage
of the C(sp2)–C(sp3) bond, see: (a) R. V. Stevens, G. S. Bisacchi, J.
Org. Chem., 1982, 47, 2396; (b) M. Brands, H. G. Wey, H.
Butenschön, J. Chem. Soc., Chem. Commun., 1991, 1541; (c) A.
Gokhale, P. Schiess, Helv. Chim. Acta, 1998, 81, 251.
15 For π-coordination of the benzene ring to rhodium in a rhodium
benzyl alkolate: P. Zhao, C. D. Incarvito, J. F. Hartwig, J. Am. Chem.
Soc., 2006, 128, 3124.
16 For an aldol reaction of rhodium enolates: G. A. Slough, R. G.
Bergman, C. H. Heathcock, J. Am. Chem. Soc., 1989, 111, 938.
17 For tandem conjugate addition-aldol reactions through rhodium
enolates: (a) S. J. Taylor, M. O. Duffey, J. P. Morken, J. Am. Chem.
Soc., 2000, 122, 4528; (b) K. Yoshida, M. Ogasawara, T. Hayashi, J.
Am. Chem. Soc., 2002, 124, 10984; (c) D. F. Cauble, J. D. Gipson, M.
J. Krische, J. Am. Chem. Soc., 2003, 125, 1110; (d) C.-K. Jung, M. J.
Krische, J. Am. Chem. Soc., 2006, 128, 17051.
18 (a) D. N. Hickman, K. J. Hodgetts, P. S. Mackman, T. W. Wallace, J.
M. Wardleworth, Tetrahedron, 1996, 52, 2235; (b) T. Suzuki, T.
Hamura, K. Suzuki, Angew. Chem., Int. Ed., 2008, 47, 2248.
19 For
a related rhodium-catalysed rearrangement reaction of 1-
alkenylcyclobutanols forming cyclohexanones: (a) T. Seiser, N.
Cramer, Angew. Chem., Int. Ed., 2008, 47, 9294; (b) T. Seiser, N.
Cramer, Chem. Eur. J., 2010, 16, 3383.
20 T. Korenaga, K. Osaki, R. Maenishi, T. Sakai, Org. Lett., 2009, 11,
2325.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012