Rhodium-catalyzed regioselective carboacylation of olefins: A C-C bond activation approach for accessing fused-ring systems

Article abstract of DOI:10.1002/anie.201202771

Cut and sew: A rhodium-catalyzed regioselective carboacylation reaction of benzocyclobutenones was developed (see scheme). Directed by the pendant olefins, the C1-C2 bond is selectively cleaved rather than the C1-C8 bond. Subsequent alkene insertion leads to complex fused-ring systems. This reaction provides facile access to natural-product-like polycyclic structures in a chemoselective and atom-economic fashion. Copyright

Full text of DOI:10.1002/anie.201202771

Angewandte
Chemie
DOI: 10.1002/anie.201202771
À
C C Activation
À
Rhodium-Catalyzed Regioselective Carboacylation of Olefins: A C C
Bond Activation Approach for Accessing Fused-Ring Systems**
Tao Xu and Guangbin Dong*
Dedicated to Professor Robert H. Grubbs on the occasion of his 70th birthday
Efficiency in the synthesis of a complex molecular target is
greatly dictated by the strategy used for building the key
skeletal structure. In particular, fused rings are extremely
common structural motifs in natural products and drug
molecules, and thus access to these motifs through selective
and atom-economic methods is of significant importance.[1]
Despite the existence of various elegant stepwise cycloaddi-
tion methods for building fused-ring systems,[2] we were
particularly intrigued by a catalytic “cut-and-sew” reaction,
Four-membered ring compounds,[5] in particular, cyclo-
butanones and cyclobutenones,[6] are privileged substrates for
reactions involving the activation and subsequent functional-
ization of C C bonds.[7,8] Not only are they readily accessible
À
from simple starting materials, such as ketones, olefins, and
alkynes,[5] their activation, which is driven by strain relief,
often does not require temporary[9] or permanent directing
groups.[10] Regioselective cleavage of the C1 C8 s bond in
À
benzocyclobutenones with insertion of alkenes and alkynes
has been achieved using either thermal methods or transition
metals (Scheme 2a).[6a] For example, cyclobutenones are
often considered as vinyl-ketene equivalents: the research
group of Danheiser has developed an efficient strategy for the
bringing together of cyclobutenones and electron-rich alkynes
to give polysubstituted phenols through thermal retro-4p cyc-
lization;[11] Schiess et al. reported addition reactions with
benzocyclobutenones that proceeded via vinyl-ketene inter-
mediates.[12] The transition metal mediated insertion of
alkynes into cyclobutenones and cyclobutendiones was first
which involves the oxidative addition of a transition metal to
[3]
À
a C C bond (Scheme 1). In this type of reaction, a key
intermediate, for example, metallocycle B, is formed when
Scheme 1. Cut-and-sew approach involving oxidative addition.
À
À
a relatively inert C C bond is replaced by two reactive M C
bonds, thus representing an unusual strategy for accessing
complex structures that are difficult to access using conven-
tional methods. For example, for substrates such as ketone A,
À
regioselective cleavage of a C C bond followed by intra-
molecular migratory insertion of an unsaturated moiety, such
as an olefin, and reductive elimination would lead to fused-
bicyclic structure C.[4]
[*] Dr. T. Xu, Prof. Dr. G. Dong
Department of Chemistry and Biochemistry
University of Texas at Austin
100 east 24thstreet, Austin, TX 78712 (USA)
E-mail: gbdong@cm.utexas.edu
Homepage: http://gbdong.cm.utexas.edu/
[**] We thank UT Austin and CPRIT for a start-up fund. We also thank
faculty members from the organic division at UT for their generous
support. We acknowledge Dr. V. Lynch for X-ray crystallography. We
thank A. Spangenberg and S. Sorey for their advice on NMR
spectroscopy. We thank Johnson Matthew for a gift of rhodium
salts. We thank Chiral Technologies for their generous donation of
chiral HPLC columns. We appreciate the helpful discussions with
Prof. M. J. Krische, Prof. H. -W. Liu, Prof. S. F. Martin, and Prof. E. V.
Anslyn.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201202771.
À
Scheme 2. C C bond cleavage in cyclobutenones and cyclobutanones.
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
Table 1: Reaction optimization.
reported by the research group of Liebeskind and represents
a practical method for accessing various phenols and qui-
nones.[13,14] Later, the research groups of Kondo and Mitsudo
successfully extended the scope of the reaction to electron-
deficient olefins, norbornene, and ethylene by using rhodium
and ruthenium catalysts.[15] Recently, the insertion of alky-
nylboronates into cyclobutenones was reported by Auvinet
and Harrity.[16] The activation of cyclobutanones was first
reported by the research group of Murakami (Scheme 2a).[17]
Murakami et al. subsequently reported a catalyzed intra-
molecular insertion of styrene-type olefins into cyclobuta-
nones to give [3.1.2] bicycles.[18,19] More recently, the research
group of Murakami reported a nickel-catalyzed addition of
alkynes and alkenes to cyclobutanones through oxidative
cyclization and b-carbon elimination.[20]
Entry
Ligand
Bite angle [8][a]
Conversion [%][b]
Yield [%][b]
[c]
1
2
3
4
5
6
7
8
PPh3
N/A
N/A
N/A
72
85
91
24
58
40
7
11
14
5
none
[d]
PPh3
dppm
dppe
dppp
dppb
dppb[e]
23
62
5
77
>99
>99
46
88
84
98
98
[a] The bite angle was obtained from Ref. [26]. [b] Determined by
1H NMR spectroscopy using mesitylene as the internal standard.
[c] Wilkinson’s catalyst was used. [d] 24 mol% of PPh3 was used.
[e] ZnCl2 (20 mol%) was added and THF was used as solvent. cod=1,5-
cyclooctadiene, dppm=1,1-bis(diphenylphosphino)methane,
dppe=1,1-bis(diphenylphosphino)ethane, dppp=1,1-bis(diphenyl-
phosphino)propane, dppb=1,1-bis(diphenylphosphino)butane,
N/A=not applicable.
We wanted to explore the feasibility of using such a cut-
and-sew approach to access fused rings by investigating
benzocyclobutenones. The intramolecular insertion of olefins
À
into the C1 C2 s bond of benzocyclobutenones would lead to
benzofused tricycles (Scheme 2b), which are key motifs in
a
number of biologically important natural products
(Scheme 3).[21] However, there are a number of challenges:
entries 2 and 3, is attributed to decomposition of 1a,
presumably in the form of undesired decarbonylation.[18]
A
series of bidentate phosphine ligands were examined. Inter-
estingly, the yields and conversions correlate well with the
bite angle of these ligands (dppb > dppp > dppe > dppm;
Table 1, entries 4–7), and the highest yield (88%) was
obtained using dppb (Table 1, entry 7).[25]
The efficacy of dppb can be tentatively attributed to its
large bite angle because it then engenders a metal complex
that is unsuitable for promoting the undesired decarbon-
ylation pathway, owing to the blockage of potential coordi-
nation sites on the rhodium atom; this feature also promotes
both migratory insertion and reductive elimination.[27] In
contrast, the use of the combination of [Rh(cod)Cl]2 and
dppm gave a conversion and yield that was similar to those
obtained when Wilkinsonꢀs catalyst was used (Table 1,
entry 4); starting material decomposition was observed
when dppe was used (Table 1, entry 5). In addition, the
presence of the Lewis acid, ZnCl2, is compatible with the
carboacylation reaction[28] and a high yield was obtained
(Table 1, entry 8). Furthermore, control experiments indi-
cated that no desired product 2a was formed in the absence of
a rhodium catalyst either in the presence or in the absence of
ZnCl2. The tricyclic product 2a was unambiguously identified
by 1H, 13C NMR, and IR spectroscopy, as well as HRMS and
X-ray crystallography (see the Supporting Information).
With optimized reaction conditions established, we next
investigated the scope of this reaction (Table 2). As expected,
1,1-disubstituted olefins were converted into the correspond-
ing fused-ring products, which contained all-carbon quater-
nary carbon centers, in good to excellent yield (Table 2,
entries 1–7). The presence of both electron-donating and
electron-withdrawing substituents on the benzocyclobute-
nones were tolerated (Table 2, entries 2 and 3). Moreover, the
presence of esters, TBS silyl ethers, and styrene moieties were
Scheme 3. Representative natural products.
1) achieving the desired regioselectivity is not trivial, because,
À
in general, cleavage of the C1 C8 bond of benzocyclobute-
nones is kinetically favored and therefore catalyzed trans-
À
formations that involve the cleavage of the C1 C2 bond
remain elusive; 2) the scope of olefins that can undergo
carboacylation is often limited.[22] Herein, we describe the
development of a rhodium-catalyzed regioselective olefin
carboacylation reaction of benzocyclobutenones for rapid
access to polyfused rings.[23]
To convert benzocyclobutenone 1a[24] into tricyclic ketone
2a, Wilkinsonꢀs catalyst was investigated initially (Table 1,
entry 1). To our delight, the desired product was isolated
albeit with low conversion, thus showing that activation had
À
occurred at the unusual C1 C2 bond. The yield was slightly
higher when Wilkinsonꢀs catalyst was generated in situ by
mixing [Rh(cod)Cl]2 and PPh3 (Table 1, entry 3). When
[Rh(cod)Cl]2 was used in the absence of additional ligand,
58% conversion was observed and the product was isolated in
11% yield, thus indicating that the intermediate, that is, the
diene–metal complex, is still reactive although it does not
react very selectively. The discrepancy between the conver-
sion of substrate and the yield of product, as in Table 1,
2
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
Table 2: Substrate scope.
obtained in less than 5% yield; however, when the solvent
was switched to THF, the yield was significantly higher (35%
and 67% brsm; Table 2, entry 8). The carboacylation of 1,2-
disubstituted olefins has only been reported in the context of
strained substrates such as norbornene.[10d,15,22] We were
pleased to find that 1,2-disubstituted olefin 1i gave the
desired insertion product (2i) as a single diastereomer when
ZnCl2 was used as a cocatalyst (Table 2, entry 9).[30] In
addition, the linking of the olefin to the benzocyclobutenones
through an ether moiety is not essential for the reaction,
Entry
Substrate
Product
Condi- Yield
tion[a] [%][b]
1
A
83
2
3
A
74
À
because when they were linked through a C C bond, as in
A
94
substrate 1j, the corresponding tricyclic carbocycle 2k was
obtained in good yield (Table 2, entry 10).
To the best of our knowledge, carboacylation of trisub-
À
stituted olefins through C C bond activation has not been
4
5
6
A
A
B
92
reported.[31] Gratifyingly, the subjection of trisubstituted
olefin 3 to the reaction conditions with ZnCl2 as a cocatalyst
gave the complex tetracycle 4 as a single diastereomer in 69%
yield (88% brsm; Scheme 4).
93
91 (95)
7
B
65 (83)
35 (67)
10 (47)
61 (92)[d]
8
A[c]
Scheme 4. The transformation of trisubstituted olefin 3 into 4. Reac-
tions conditions: [Rh(cod)Cl]2 (5 mol%), dppb (12 mol%), ZnCl2
(10 mol%), THF, 1308C; a second portion of the same catalysts was
added after 12 h. For the X-ray crystal structure of 4, thermal ellipsoids
are shown at 50% probability and hydrogen atoms are omitted for
clarity.
9
B
10
B
A proposed catalytic cycle is depicted in Scheme 5. It is
likely that the olefin serves as a strong directing group[32] and
guides the rhodium catalyst to activate, through oxidative
[a] Conditions A: [Rh(cod)Cl]2 (5 mol%), dppb (12 mol%), toluene,
1308C, 24 h; condition B: [Rh(cod)Cl]2 (2.5 mol%), dppb (6 mol%),
ZnCl2 (10 mol%), THF, 1308C, another portion of the same catalysts
was added after 12 h. [b] Yield upon isolation; the number in paren-
theses represents the yield based on recovered starting material (brsm).
[c] THF was used as solvent. [d] The product was obtained as a mixture
of diastereomers (d.r.=1.3:1). TBS=tert-butyldimethylsilyl.
À
addition, the proximal C1 C2 bond rather than the distal
À
C1 C8 bond. Subsequent migratory insertion would lead to
compatible (Table 2, entries 3, 5, and 7). The conversion of
compound 1 f into the tricycle 2 f, which contains three fused
six-membered rings, was also efficient when the reaction was
conducted in the presence of ZnCl2 (Table 2, entry 6); in
contrast, when the same reaction was conducted in the
absence of ZnCl2 in either toluene or THF as solvent, the
product was obtained in only 10% and 4% yield, respec-
tively.[29] It has been observed previously that alkyl mono-
substituted olefins are challenging substrates for carboacyla-
tion.[10c,22] Indeed, under the original reaction conditions with
toluene as the solvent (condition A), the product was
Scheme 5. Proposed catalytic cycle.
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
[4] For reviews on the related (3+2) reaction with activated
cyclopropanes and cyclopropenes, see: a) F. De Simone, J.
Waser, Synthesis 2009, 3353; b) M. Yu, B. L. Pagenkopf,
Tetrahedron 2005, 61, 321; c) M. J. Campbell, J. S. Johnson,
A. T. Parsons, P. D. Pohlhaus, S. D. Sanders, J. Org. Chem. 2010,
a seven-membered rhodacycle, which would then undergo
reductive elimination to give the desired fused-ring product.
The operation of a pathway involving syn migratory insertion
and reductive elimination is supported by the relative
stereochemistry in product 4, the structure of which was
confirmed by X-ray crystallography (Scheme 4). We postulate
that the role of the Lewis acid, ZnCl2, in this catalytic cycle is
twofold:[33] it promotes both oxidative addition[34] and reduc-
tive elimination[35] through coordination with the carbonyl
group of the substrate and the rhodacycle intermediate,
respectively, an interaction, which makes both the substrate
and the rhodacycle intermediate electron deficient.
˝
75, 6317; d) P. Binger, H. M. Buch, Top. Curr. Chem. 1987, 135,
77; e) A. Brandi, A. Goti, Chem. Rev. 1998, 98, 589; f) A. Brandi,
S. Cicchi, F. M. Cordero, A. Goti, Chem. Rev. 2003, 103, 1213;
g) M. Rubin, M. Rubina, V. Gevorgyan, Chem. Rev. 2007, 107,
3117; see Refs. [2d] and [2g].
[5] For a recent review, see: H. Nemoto, Chem. Pharm. Bull. 2007,
55, 961; for a book series, see: Small Ring Compounds in Organic
Synthesis I – III (Ed: A. de Meijere), Springer, Berlin, 1986, 1987
and 1988.
[6] For reviews of cyclobutanones and cyclobutenones, see: a) D.
Bellus, B. Ernst, Angew. Chem. 1988, 100, 820; Angew. Chem.
Int. Ed. Engl. 1988, 27, 797; b) T. Seiser, T. Saget, D. N. Tran, N.
Cramer, Angew. Chem. 2011, 123, 7884; Angew. Chem. Int. Ed.
2011, 50, 7740.
In conclusion, we have developed an intramolecular
rhodium-catalyzed olefin-carboacylation reaction of benzo-
cyclobutenones. This method involves the selective cleavage
À
of the usually-less-reactive C1 C2 bond, thus providing
a facile means for accessing polyfused ring systems, the
access to which may be challenging through conventional
methods. Although still in its infancy stage, this cut-and-sew
strategy that employs simple cyclic ketones as substrates
should have broad applications in synthesis. Efforts toward
developing highly enantioselective variants together with
detailed mechanistic study of the reaction to broaden the
reaction scope and facilitate application of this method in the
total synthesis of bioactive natural products are in prog-
ress.[36,37]
[7] N. Cramer, T. Seiser, Synlett 2011, 449.
À
[8] For a catalytic C C bond activation reaction of biphenylene, see:
B. L. Edelbach, R. J. Lachicotte, W. D. Jones, J. Am. Chem. Soc.
1998, 120, 2843.
[9] For leading references, see: a) C.-H. Jun, C. W. Moon, D.-Y. Lee,
Chem. Eur. J. 2002, 8, 2423; b) Y. J. Park, J.-W. Park, C.-H. Jun,
Acc. Chem. Res. 2008, 41, 222.
[10] For leading references, see: a) J. W. Suggs, C.-H. Jun, J. Am.
Chem. Soc. 1986, 108, 4679; b) J. W. Suggs, C.-H. Jun, J. Am.
Chem. Soc. 1984, 106, 3054; c) A. M. Dreis, C. J. Douglas, J. Am.
Chem. Soc. 2009, 131, 412; d) M. T. Wentzel, V. J. Reddy, T. K.
Hyster, C. J. Douglas, Angew. Chem. 2009, 121, 6237; Angew.
Chem. Int. Ed. 2009, 48, 6121; e) H. Li, Y. Li, X.-S. Zhang, K.
Chen, X. Wang, Z.-J. Shi, J. Am. Chem. Soc. 2011, 133, 15244;
f) Z.-Q. Lei, H. Li, Y. Li, X.-S. Zhang, K. Chen, X. Wang, Z.-J.
Shi, Angew. Chem. 2012, 124, 2744; Angew. Chem. Int. Ed. 2012,
51, 2690; g) K. Chen, K. H. Li, Y. Li, X.-S. Zhang, Z.-Q. Lei, Z.-J.
Shi, Chem. Sci. 2012, 3, 1634.
Received: April 10, 2012
Revised: May 25, 2012
Published online: && &&, &&&&
À
Keywords: annulation · carboacylation · C C activation ·
homogeneous catalysis · fused-ring systems
.
[11] a) R. L. Danheiser, S. K. Gee, J. Org. Chem. 1984, 49, 1672;
b) R. L. Danheiser, A. Nishida, S. Savariar, M. P. Trova,
Tetrahedron Lett. 1988, 29, 4917.
[1] B. M. Trost, Science 1991, 254, 1471.
[2] For recent reviews of cycloaddition, see: a) A. Padwa, Tetrahe-
dron 2011, 67, 8057; b) U. Chiacchio, A. Padwa, G. Romeo, Curr.
Org. Chem. 2009, 13, 422; c) M. Lautens, W. Klute, W. Tam,
Chem. Rev. 1996, 96, 49; d) H.-U. Reissig, R. Zimmer, Chem.
Rev. 2003, 103, 1151; e) M. Murakami, Angew. Chem. 2003, 115,
742; Angew. Chem. Int. Ed. 2003, 42, 718; f) S. E. Gibson, N.
Mainolfi, Angew. Chem. 2005, 117, 3082; Angew. Chem. Int. Ed.
2005, 44, 3022; g) M. Rubin, M. Rubina, V. Gevorgyan, Chem.
Rev. 2007, 107, 3117; h) Z.-X. Yu, Y. Wang, Chem. Asian J. 2010,
5, 1072; i) P.-A. Inglesby, P. A. Evans, Chem. Soc. Rev. 2010, 39,
2791; j) G. Jiang, Y. Wang, Z.-X. Yu in Science of Synthesis:
Stereoselective Synthesis, Vol. 3 (Ed.: P. A. Evans), Thieme,
Stuttgart, 2011, p. 7; k) F. Lꢁpez, J. L. MascareÇas, Chem. Eur. J.
2011, 17, 418; l) P. A. Wender, G. Gamber, T. J. Williams in
Modern Rhodium-Catalyzed Organic Reactions (Ed.: P. A.
Evans), Wiley-VCH, Weinheim, 2005, p. 263; m) B. M. Trost,
Angew. Chem. 1986, 98, 1.
[12] P. Schiess, M. Eberle, M. Huys-Francotte, J. Wirz, Tetrahedron
Lett. 1984, 25, 2201.
[13] For leading references, see: a) L. S. Liebeskind, S. L. Baysdon,
Tetrahedron Lett. 1984, 25, 1747; b) L. S. Liebeskind, L. P. Leeds,
S. L. Baysdon, J. Am. Chem. Soc. 1984, 106, 6451; c) M. A.
Huffman, L. S. Liebeskind, W. T. Pennington, Organometallics
1990, 9, 2194; d) M. A. Huffman, L. S. Liebeskind, W. T.
Pennington, Organometallics 1992, 11, 255; e) M. A. Huffman,
L. S. Liebeskind, J. Am. Chem. Soc. 1990, 112, 8617; f) M. A.
Huffman, L. S. Liebeskind, J. Am. Chem. Soc. 1991, 113, 2771.
[14] L. S. Liebeskind, M. S. South, J. Am. Chem. Soc. 1984, 106, 4181.
[15] a) T. Kondo, Y. Taguchi, Y. Kaneko, M. Niimi, T. Mitsudo,
Angew. Chem. 2004, 116, 5483; Angew. Chem. Int. Ed. 2004, 43,
5369; b) T. Kondo, M. Niimi, M. Nomura, K. Wada, T. Mitsudo,
Tetrahedron Lett. 2007, 48, 2837; For recent reviews, see: c) T.
Kondo, Synlett 2008, 629; d) T. Kondo, T. Mitsudo, Chem. Lett.
2005, 34, 1462.
À
[3] For recent reviews of C C bond activation, see: a) B. Rybtch-
[16] A-L. Auvinet, J. P. A. Harrity, Angew. Chem. 2011, 123, 2821;
Angew. Chem. Int. Ed. 2011, 50, 2769.
inski, D. Milstein, Angew. Chem. 1999, 111, 918; Angew. Chem.
Int. Ed. 1999, 38, 870; b) M. Murakami, Y. Ito, Top. Organomet.
Chem. 1999, 3, 97; c) M. E. van der Boom, D. Milstein, Chem.
Rev. 2003, 103, 1759; d) C.-H. Jun, Chem. Soc. Rev. 2004, 33, 610;
e) T. Satoh, M. Miura, Top. Organomet. Chem. 2005, 14, 1; f) C.-
H. Jun, J.-W. Park, Top. Organomet. Chem. 2007, 24, 117; g) D.
Necas, M. Kotora, Curr. Org. Chem. 2007, 11, 1566; h) R. H.
Crabtree, Chem. Rev. 1985, 85, 245; i) W. D. Jones, Nature 1993,
364, 676.
[17] For reviews and leading references, see: a) M. Murakami, M.
Makino, S. Ashida, T. Matsuda, Bull. Chem. Soc. Jpn. 2006, 79,
1315, and ref. [3b]; b) M. Murakami, H. Amii, Y. Ito, Nature
1994, 370, 540; c) M. Murakami, H. Amii, K. Shigeto, Y. Ito, J.
Am. Chem. Soc. 1996, 118, 8285.
[18] M. Murakami, T. Itahashi, Y. Ito, J. Am. Chem. Soc. 2002, 124,
13976.
4
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
[19] The use of a vinyl cyclobutanone in a [6+2] cycloaddition as an
efficient strategy for accessing eight-membered rings was first
developed by Wender, see: P. A. Wender, A. G. Correa, Y. Sato,
R. Sun, J. Am. Chem. Soc. 2000, 122, 7815.
[20] a) M. Murakami, S. Ashida, T. Matsuda, J. Am. Chem. Soc. 2005,
127, 6932; b) M. Murakami, N. Ishida, T. Miura, Chem.
Commun. 2006, 643; c) L. Liu, N. Ishida, M. Murakami,
Angew. Chem. 2012, 124, 2535; Angew. Chem. Int. Ed. 2012,
51, 2485.
[21] For a review on the synthesis of morphine and related alkaloids,
see: N. Chida, Top. Curr. Chem. 2011, 299, 1, and references
therein; for the isolation and related biological studies of
parviflorene J, see: M. Tamaki, S. K. Sadhu, T. Ohtsuki, K.
Toume, T. Koyano, T. Kowithayakorn, M. Hayashi, K.
Komiyama, M. Ishibashi, Heterocycles 2007, 72, 649; for the
isolation and related biological studies of carnosic acid 12-
methyl ether g-lactone and cycloinumakiol, see: a) Z. Djarmati,
R. M. Jankov, A. Djordjevic, B. Ribar, D. Lazar, P. Engel,
Phytochemistry 1992, 31, 1307; b) J. G. Urones, S. S. Marcos, D.
Diez, R. L. Cubilla, Phytochemistry 1998, 48, 1035; c) M. W.
Pertino, C. Theoduloz, J. A. Rodriguez, T. Yanez, V. Lazo, G.
Schmeda-Hirschmann, J. Nat. Prod. 2010, 73, 639; d) K. P.
Devkota, et al., J. Nat. Prod. 2011, 74, 374.
in 12% yield and 6% ee, and 14% yield and 11% ee, respec-
tively; for details, see the Supporting Information.
[26] P. J. Dierkes, J. Chem. Soc. Dalton Trans. 1999, 1519.
[27] For a kinetic study on the effect of bite angle on reductive
elimination, see: J. E. Marcone, K. G. Moloy, J. Am. Chem. Soc.
1998, 120, 8527.
[28] ZnCl2-promoted regioselective oxidative addition of cyclobute-
nones with a cobalt complex was first reported by Liebeskind
and co-workers, see: Ref. [13d]. The use of other Lewis acids,
such as ZnBr2, InCl3, YbCl3, and In(OTf)3 have been attempted,
and ZnCl2 was the most effective.
[29] When [Rh(cod)Cl]2 (5 mol%), dppb (12 mol%), and ZnCl2
(20 mol%) were added in one portion (instead of two) to
a THF solution of the substrate, the yield was 60% (71% brsm).
[30] The relatively low yields (brsm) of products 2h and 2i is
presumably attributable to their unstable nature: decomposition
was observed when they were isolated using silica gel chroma-
tography.
[31] For a single example of a carbocyanation of acyclic trisubstituted
olefins, see: Y. Nakao, S. Ebata, A. Yada, T. Hiyama, M. Ikawa,
S. Ogoshi, J. Am. Chem. Soc. 2008, 130, 12874.
À
[32] For an example of an olefin-directed C C bond cleavage
reaction, see: Ref. [18].
[22] J. P. Lutz, C. M. Rathbun, S. M. Stevenson, B. M. Powell, T. S.
Boman, C. E. Baxter, J. M. Zona, J. B. Johnson, J. Am. Chem.
Soc. 2012, 134, 715; see also Refs. [10c], [10d], [18], and [20].
[23] For representative examples of other rhodium-catalyzed reac-
tions that give 6-membered rings, see: a) P. A. Wender, T. E.
Jenkins, S. Suzuki, J. Am. Chem. Soc. 1995, 117, 1843; b) D. J. R.
OꢀMahony, D. B. Belanger, T. Livinghouse, Org. Biomol. Chem.
2003, 1, 2038; c) K. Aikawa, S. Akutagawa, K. Mikami, J. Am.
Chem. Soc. 2006, 128, 12648; d) D. Shu, X. Li, M. Zhang, P. J.
Robichaux, W. Tang, Angew. Chem. 2011, 123, 1382; Angew.
Chem. Int. Ed. 2011, 50, 1346; e) G.-J. Jiang, X.-F. Fu, Q. Li, Z.-
X. Yu, Org. Lett. 2012, 14, 692; f) S. I. Lee, J. H. Park, Y. K.
Chung, S.-G. Lee, J. Am. Chem. Soc. 2004, 126, 2714; g) L. Jiao,
M. Lin, L.-G. Zhuo, Z.-X. Yu, Org. Lett. 2010, 12, 2528; h) C. Li,
H. Zhang, J. Feng, Y. Zhang, J. Wang, Org. Lett. 2010, 12, 3082.
[24] Readily prepared from resorcinol; for details, see the Supporting
Information.
[33] For the use of Lewis acids in promoting alkene carbocyanation,
see: M. P. Watson, E. N. Jacobsen, J. Am. Chem. Soc. 2008, 130,
12594, Ref. [31], and references therein.
À
[34] For examples of Lewis acid promoted C C bond cleavage, see:
´
ˇ
M. Tursky, D. Necas, P. Drabina, M. Sedlꢂk, M. Kotora,
Organometallics 2006, 25, 901, and Ref. [13d].
[35] For some recent examples of Lewis acid promoted reductive
elimination, see: a) Q. Shen, J. F. Hartwig, J. Am. Chem. Soc.
2007, 129, 7734; b) T. Yamamoto, M. Abla, Y. Murakami, Bull.
Chem. Soc. Jpn. 2002, 75, 1997; c) J. Huang, C. M. Haar, S. P.
Nolan, Organometallics 1999, 18, 297.
[36] As requested by a referee, two alkyne substrates were examined;
however, no desired product was obtained and instead a complex
mixture was obtained.
[37] CCDC 875239 (2a) and 875240 (4) contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
[25] The use of (R)-binap and (R)-tol-binap ligands in the reactions
has been investigated and resulted in the product being obtained
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
À
C C Activation
T. Xu, G. Dong*
&&&& — &&&&
Rhodium-Catalyzed Regioselective
À
Carboacylation of Olefins: A C C Bond
Activation Approach for Accessing Fused-
Ring Systems
Cut and sew: A rhodium-catalyzed regio-
selective carboacylation reaction of ben-
zocyclobutenones was developed (see
scheme). Directed by the pendant olefins,
alkene insertion leads to complex fused-
ring systems. This reaction provides facile
access to natural-product-like polycyclic
structures in a chemoselective and atom-
economic fashion.
À
the C1 C2 bond is selectively cleaved
À
rather than the C1 C8 bond. Subsequent
6
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!