Domino reactions consisting of heterocyclization and 1,2-migration-redox- neutral and oxidative transition-metal catalysis

Article abstract of DOI:10.1002/anie.201103961

Two cats, two paths: Two novel domino reactions starting from 6-hydroxy-2-alkyl-2-alkynylcyclohexanones have been discovered. While redox-neutral platinum catalysis gives rise to furans through a sequence of cyclization, 1,2-shift, and Grob fragmentation, oxidative copper catalysis provides an entry to bicyclic 2,3-dihydrofurans. Upon cyclization and oxidation, an unusual benzilic acid rearrangement can take place in this case. Copyright

Full text of DOI:10.1002/anie.201103961

DOI: 10.1002/anie.201103961
Cyclizations
Domino Reactions Consisting of Heterocyclization and 1,2-
Migration—Redox-Neutral and Oxidative Transition-Metal
Catalysis**
Klaus-Daniel Umland, Adeline Palisse, Timm T. Haug, and Stefan F. Kirsch*
Dedicated to Professor Dieter Enders on the occasion of his 65th birthday
Domino reactions, in which two (or more) distinct reactions
are performed in a single operation without isolation of the
reaction intermediates, possess significant economic and
ecological benefits and have thus emerged as powerful tools
for the creation of architecturally complex structures from
relatively simple starting compounds.[1] A major class of
domino reactions is based on cationic cyclizations; these
include reactions in which the cascade terminates with a
pinacol rearrangement—a particularly useful approach for
the creation of products with challenging quaternary stereo-
genic centers.[2,3]
Recently, carbophilic Lewis acids have been recognized to
activate p systems including alkenes, allenes, and alkynes
toward intermolecular and intramolecular nucleophilic
attack.[4] On the basis of this expedient reactivity, we launched
a program focusing on domino reactions that start with
catalytic alkyne activation and terminate with a pinacol-type
1,2-alkyl migration.[5,6] For example, in 2006 we constructed
Scheme 1. Catalyzed domino reactions with alkynones. a) Synthesis of
valuable 3(2H)-furanones 2 by combining an initial 5-endo
heterocyclization with a pinacol-type rearrangement.[7] To
this end, carbonyl substrates 1 were designed incorporating
both a tertiary hydroxy and an alkynyl substituent at the a-
position (1!2, Scheme 1a). Inspired by this intriguing
reactivity,[8,9] we then expected that alkynone A, which
generates an oxonium ion intermediate in which the hydroxy
group is outside the cycle, could be induced to undergo 1,2-
migration of Ra (Scheme 1b). If the envisaged domino process
is feasible, synthetically challenging 2,3-dihydrofurans should
be accessible through a pathway that departs from traditional
approaches to dihydrofurans;[10] this would significantly
expand the value of pinacol-terminated domino reactions.
Herein we report a novel method for the diastereoselective
3(2H)-furanones through a cyclization/1,2-shift strategy. b) Projected
route to 2,3-dihydrofurans.
construction of bicyclic 2,3-dihydrofurans starting from 5-
hydroxyalkyn-4-ones, and illustrate how oxidative conditions
with copper catalysts are prerequisite to the realization of this
goal: Both alkyne activation and alcohol oxidation are
triggered by copper catalysis. This unique and unexpected
finding is complemented by the observation that the same
starting compounds can be efficiently transformed into furans
through an alternative alkyl shift by replacing oxidative
copper catalysis with redox-neutral platinum catalysis.
In analogy to related heterocyclizations,[11] we reasoned
that the direct cyclization of alkyn-4-ones to give simple
furans must be blocked to facilitate the transformation A!B.
On the basis of this hypothesis, we anticipated that 5-
[*] K.-D. Umland, A. Palisse, T. T. Haug, Prof. Dr. S. F. Kirsch[+]
Department Chemie, Technische Universitꢀt Mꢁnchen
Lichtenbergstrasse 4, 85747 Garching (Germany)
E-mail: stefan.kirsch@ch.tum.de
hydroxyalkyn-4-ones with
a quaternary center at C3
(Rb,Rc ¼ H) could serve as a potentially useful class of
substrates since the corresponding cyclic oxonium ion inter-
mediates cannot undergo competing aromatization or
double-bond isomerization. Accordingly, starting 6-hydrox-
ycyclohexanones 1a–n having 2-alkynyl side chains were
prepared as detailed in the Supporting Information. When
conducting first experiments with these compounds to test
their ability to undergo cyclization–pinacol cascades with
carbophilic Lewis acids, we found that subjecting alkynone 1a
to typical conditions for (Ph3P)Au+-catalyzed reactions
[+] New address: Bergische Universitꢀt Wuppertal
Fachbereich C – Organische Chemie
Gaußstraße 20, 42119 Wuppertal (Germany)
E-mail: sfkirsch@uni-wuppertal.de
[**] The authors thank Deutsche Forschungsgemeinschaft (DFG) and
Fonds der Chemischen Industrie (FCI) for generous support. A.P.
thanks the DAAD for a PhD fellowship. Support from the TUM
Graduate School is gratefully acknowledged.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201103961.
Angew. Chem. Int. Ed. 2011, 50, 9965 –9968
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
9965

Communications
resulted in traces of the unexpected furan 2a (Table 1,
entry 1). Changing the ligand from PPh3 to numerous other
ligands led only to the formation of the furan in varying
yields; not even traces of the desired aldehyde 3a were
detected. We subsequently examined several platinum com-
Table 1: Catalyzed rearrangements of 1a.
Scheme 2. Plausible mechanism for the formation of 2a.
presence of stoichiometric amounts of iPrOH as an external
proton source.
Entry
Catalyst
Conditions
Yield[a] [%]
We next examined the intriguing copper-catalyzed reac-
tion that provides access to complex 2,3-dihydrofurans having
two adjacent quaternary stereogenic centers. When studying
the conversion of cyclohexanone 1a into dihydrofuran 4a, we
encountered major experimental problems with regard to
product purity and reaction reproducibility. Attempts to
isolate the free carboxylic acid 4a resulted in substantial
decomposition; therefore, the intermediate carboxylic acids
were transformed in situ into their methyl esters, which could
be readily purified. In light of our preliminary reaction
conditions (10 mol% of Cu(OTf)2, 808C, wet DMF), we
continued our investigations by testing various solvents under
open-flask conditions (Table 2, entries 1–5). While complete
decomposition of 1a was observed in toluene, dioxane, and
1
2
3
4
5
6
(Ph3P)AuCl/AgSbF6
(Me3P)AuCl/AgSbF6
(Me3P)AuCl/AgSbF6
PtCl2
PtCl4
PtCl4
238C, 1 h, CH2Cl2
238C, 1 h, CH2Cl2
1008C, 1 h, toluene
1008C, 5 h, toluene
1008C, 2 h, toluene
iPrOH, 1008C, 0.5 h,
toluene
238C, 5 h, CH2Cl2
air, 808C, 4 h,
(wet) DMF
traces (2a)[b]
54 (2a)
68 (2a)
74 (2a)
77 (2a)
83 (2a)
7
HBF4
Cu(OTf)2
0[c]
62 (4a)
8[d]
[a] Yield of isolated product after complete consumption of 1a.
[b] Identified by gas chromatography. [c] No conversion of 1a was
detected. [d] 10 mol% of catalyst was used.
plexes and were pleased to find that PtCl4 (5 mol%) catalyzed
the formation of furan 2a in toluene at 1008C in 77% yield
(Table 1, entry 5). To our delight, the addition of iPrOH
markedly decreased the time required for full conversion
(Table 1, entry 6). Although we did not find conditions for the
direct formation of bicyclic aldehyde 3a, we finally found that
the reaction of cyclohexanone 1a with 10 mol% of Cu(OTf)2
in wet DMF at 808C in an open flask provided acid 4a, which
has the desired carbon core, in 62% yield (Table 1, entry 8).
Of primary importance, either 2a or 4a was obtained as the
exclusive product under the conditions tested.
Since they are ubiquitous in bioactive substances, poly-
substituted furans are important target structures, and thus
countless synthetic routes toward furans having a specific
substitution pattern have been designed.[12] However, the title
reaction converting cyclohexanone 1a into furan 2a differs
significantly from other cycloisomerization routes to furans
since the catalyzed ring closure is invariably accompanied by
the opening of the six-membered ring system to install the
aldehyde-containing side chain. The mechanism depicted in
Scheme 2 explains the furan formation. The domino reaction
starts with the activation of the alkyne moiety in 1a through
coordination of the transition-metal catalyst. Nucleophilic
attack of the carbonyl group produces the cyclic oxonium ion
C, which, after a ring-contracting 1,2-shift, rearranges to the
spirocyclic intermediate D.[13] Grob-type fragmentation[14] of
this rather stabilized cation gives rise to the furan heterocycle
and installation of the C4 side chain containing the aldehyde
group. The protodemetalation step required for the regener-
ation of the catalytic species appears to be facilitated by the
Table 2: Optimization of the copper-catalyzed domino reaction.
Entry Catalyst
(mol%)
Conditions
Yield[a] [%]
1
Cu(OTf)2 (10)
air, 808C, DMF
60
2
3
4
5
6
7
8
9
Cu(OTf)2 (10)
Cu(OTf)2 (10)
Cu(OTf)2 (10)
Cu(OTf)2 (10)
Cu(OTf)2 (10)
Cu(OTf)2 (10)
CuSO4 (10)
CuCl2/AgSbF6 (10/5) air, 808C, DMPU
CuOTf (10)
CuCl (10)
air, 808C, DMPU
air, 808C, toluene
air, 808C, dioxane
air, 808C, CH3CN
Ar, 808C, DMPU
73
0[b]
0[b]
0[b]
<10
O2, 808C, (anhydrous) DMPU traces
air, 808C, DMPU
32
50
78
82
10
11
air, 808C, DMPU
air, 808C, DMPU
[a] Yield of isolated product after complete consumption of 1a and
subsequent ester formation by addition of NaH and MeI to the reaction
mixture at room temperature. Unless otherwise indicated, all reactions
were run under open-flask conditions. [b] Decomposition only.
acetonitrile, the substrate was fully consumed in the reaction
in
1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone
(DMPU), affording methyl ester 5a in 73% yield. We found
that the presence of both oxygen and water[15] was essential,
since the use of either argon atmosphere or rigorously dried
solvents resulted in only trace amounts of product (Table 2,
entries 6 and 7). Gratifyingly, this domino reaction also took
9966 www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 9965 –9968

Table 3: Synthesis of furans 2 and 2,3-dihydrofurans 5.
place when copper(I) salts were employed as precatalysts.
The use of CuCl as an inexpensive and nontoxic copper
source improved the yield of ester 5a to 82%, and thus our
optimal reaction conditions (10 mol% CuCl, 808C, air, wet
DMPU; Table 2, entry 11) are of great practicability.[16]
The transformation of alkynone 1a into 2,3-dihydrofuran
4a comprises three distinct steps: 1) oxidation (of the
ꢀ
hydroxy-bearing carbon), 2) C O bond formation (between
the alkyne carbon and carbonyl oxygen atoms), and 3) 1,2-
alkyl migration (in a pinacol-type manner with ring contrac-
tion). Since a mechanism via aldehyde intermediate 3a and
subsequent oxidation can be ruled out,[17] we propose the
mechanism outlined in Scheme 3 for this reaction. By
coordinating to the cationic CuI/II species, alkyne 1a is
activated for intramolecular nucleophilic attack. The
Entry
Substrate 1
Yield[a] [%]
R1
R2 R3 R4
R5
2[b] 5[c]
1
2
3
4
5
6
7
8
a
b
c
d
e
f
g
h
i
Ph
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
nBu
nBu
H
H
H
H
H
H
H
H
H
H
H
H
H
83 82
88 92
56 84
77 95
86 76
41 n.r.
47 decomp.
65 56
n.r. 58
63 n.r.
77 70
93 83[d]
n.r. 83[d]
78 65
4-MeO-C6H4
4-F3CO-C6H4
3-Cl-C6H4
2-thienyl
1-cyclohexenyl
cyclopropyl
nPent
9
tBu
10
11
12
13
14
j
Ph
k
l
4-MeO-C6H4
Ph
Me Me
H
H
m
n
Ph
Ph
Me
Me Me
[a] Yield of isolated product after complete consumption of 1. [b] Con-
ditions: PtCl4 (5 mol%), iPrOH (1.5 equiv), 1008C, toluene (0.05m).
[c] Conditions: 1) CuCl (10 mol%), open-flask, 808C, DMPU (0.3m);
2) NaH, MeI, 238C. [d] d.r.>95:5. n.r.=experiment not run; decom-
p.=decomposition only.
Scheme 3. Plausible mechanism for the formation of 4a.
of the furans under the reaction conditions (in the presence of
Lewis acids) and aerobic purification conditions. When
hydroxyalkynones 1 were treated with 10 mol% of CuCl
under open-flask conditions at 808C in DMPU, substrates
with aryl substituents at the alkyne unit provided dihydrofur-
ans 5 in good yields and as a single diastereoisomer.[19] Alkyl-
substituted alkynes also participated in the domino reaction,
but the yields were lower.[20] The most impressive feature of
the copper-catalyzed domino reaction is that in all cases not
even traces of furan products were detected.
In conclusion, two unprecedented domino reactions
starting from 6-hydroxy-2-alkyl-2-alkynylcyclohexanones
have been disclosed. In one, the starting substrates are
transformed into substituted furans. This sequence is effec-
tively catalyzed by PtCl4 and most likely proceeds through a
heterocyclization followed by a ring-contracting 1,2-shift and
a Grob-type fragmentation. In the second domino reaction,
identical starting compounds are submitted to catalytic
amounts of CuCl under convenient open-flask conditions in
hot DMPU to give 2,3-dihydrofurans with two adjacent
quaternary stereogenic centers. Oxidative copper catalysis
allows for heterocyclization and oxidation and, thus, opens
the way for an alternative 1,2-shift analogous to the benzilic
acid rearrangement. This is a striking example of how to
determine the catalytic reaction pathway by simply switching
between appropriate reaction parameters. Further work in
our laboratory is devoted to extending the use of benzilic acid
domino reaction then commences, passing through cyclic
oxonium ion E which presumably equilibrates with cyclic
hemiacetal F. Crucial for the selective dihydrofuran formation
is that oxonium ion E does not rearrange to a spirocyclic
intermediate analogous to D, possibly because the electron
back-donation capability of copper atoms are weaker than
that of platinum. Instead, oxidation promoted by CuII results
in the formation of carbonyl compound G. If the addition of
water to the carbonyl moiety gives hydrate H, it can rearrange
by ring contraction with conversion into the 2,3-dihydrofuran
4a, which contains a free carboxylic acid. Therefore, this
unique 1,2-alkyl migration resembles the classical benzilic
acid rearrangement,[18] which, in this special case, does not
proceed through the action of hydroxide anions. To our
knowledge, the use of a benzilic acid type rearrangement as
the pivotal step in domino reactions catalyzed by p acids has
not been reported before.
Applying these optimized conditions, we examined the
scope of the two domino reactions (Table 3). To probe the
catalyzed furan formation, hydroxyalkynones 1 were allowed
to react with 5 mol% of PtCl4 in the presence of 1.5 equiv-
alents of iPrOH at 1008C in toluene. The reaction outcome
was predictable in all cases, and products 2 were typically
obtained in good to excellent yields. In a few cases diminished
yields presumably result from the somewhat limited stability
Angew. Chem. Int. Ed. 2011, 50, 9965 –9968
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 9967

Communications
Tang, S. Bhunia, S. Md. A. Sohel, M.-Y. Lin, H.-Y. Liao, S. Datta,
A. Das, R.-S. Liu, J. Am. Chem. Soc. 2007, 129, 15677; d) H.-S.
Yeom, Y. Lee, J. Jeong, E. So, S. Hwang, J.-E. Lee, S. S. Lee, S.
Shin, Angew. Chem. 2010, 122, 1655; Angew. Chem. Int. Ed.
2010, 49, 1611; e) X. Huang, L. Zhang, J. Am. Chem. Soc. 2007,
129, 6398; f) V. N. Korotchenko, M. R. Gagnꢂ, J. Org. Chem.
2007, 72, 4877; g) S. G. Sethofer, S. T. Staben, O. Y. Hung, F. D.
Toste, Org. Lett. 2008, 10, 4315; h) F. Kleinbeck, F. D. Toste, J.
Am. Chem. Soc. 2009, 131, 9178; i) L. Liu, J. Zhang, Angew.
Chem. 2009, 121, 6209; Angew. Chem. Int. Ed. 2009, 48, 6093;
j) M. Alcarazo, T. Stork, A. Anoop, W. Thiel, A. Fꢁrstner,
Angew. Chem. 2010, 122, 2596; Angew. Chem. Int. Ed. 2010, 49,
2542; k) A. S. K. Hashmi, W. Yang, F. Rominger, Angew. Chem.
2011, 123, 5882; Angew. Chem. Int. Ed. 2011, 50, 5762; l) S. M.
Canham, D. J. France, L. E. Overman, J. Am. Chem. Soc. 2010,
132, 7876.
rearrangements in transition-metal-catalyzed domino reac-
tions.
Received: June 10, 2011
Published online: September 7, 2011
Keywords: copper · domino reactions · heterocycles ·
.
homogeneous catalysis · platinum
[1] For selected reviews, see: a) L. F. Tietze, Chem. Rev. 1996, 96,
115; b) L. F. Tietze, G. Brasche, G. Gericke in Domino Reactions
in Organic Synthesis, Wiley-VCH, Weinheim, 2006; c) K. C.
Nicolaou, D. J. Edmonds, P. G. Bulger, Angew. Chem. 2006, 118,
7292; Angew. Chem. Int. Ed. 2006, 45, 7134; d) H. Pellissier,
Tetrahedron 2006, 62, 2143; e) J.-C. Wasilke, S. J. Obrey, R. T.
Baker, G. C. Bazan, Chem. Rev. 2005, 105, 1001; f) S. F. Kirsch,
Synthesis 2008, 3183; g) D. M. DꢀSouza, T. J. J. Mꢁller, Chem.
Soc. Rev. 2007, 36, 1095; h) J. Zhou, Chem. Asian J. 2010, 5, 422.
[2] For a leading review, see: L. E. Overman, L. D. Pennington, J.
Org. Chem. 2003, 68, 7143.
[3] For selected applications in natural product synthesis, see: a) N.
Hanaki, J. T. Link, D. W. C. MacMillan, L. E. Overman, W. G.
Trankle, J. A. Wurster, Org. Lett. 2000, 2, 223; b) A. D. Lebsack,
L. E. Overman, R. J. Valentekovich, J. Am. Chem. Soc. 2001,
123, 4851; c) G. C. Hirst, T. O. Johnson, L. E. Overman, J. Am.
Chem. Soc. 1993, 115, 2992; For related strategies, see: d) M. A.
Beaulieu, C. Sabot, N. Achache, K. C. Guꢂrard, S. Canesi, Chem.
Eur. J. 2010, 16, 11224; e) L. E. Overman, J. P. Wolfe, J. Org.
Chem. 2002, 67, 6421; f) A. Armstrong, Y. Bhonoah, S. E.
Shanahan, J. Org. Chem. 2007, 72, 8019.
[4] For selected reviews on p activation with carbophilic Lewis
acids, see: a) A. Fꢁrstner, P. W. Davies, Angew. Chem. 2007, 119,
3478; Angew. Chem. Int. Ed. 2007, 46, 3410; b) H. C. Shen,
Tetrahedron 2008, 64, 3885; c) A. Corma, A. Leyva-Perez, M. J.
Sabater, Chem. Rev. 2011, 111, 1657; d) N. D. Shapiro, F. D.
Toste, Synlett 2010, 675; e) D. J. Gorin, B. D. Sherry, F. D. Toste,
Chem. Rev. 2008, 108, 3351; f) Z. Li, C. Brouwer, C. He, Chem.
Rev. 2008, 108, 3239; g) A. S. K. Hashmi, Chem. Rev. 2007, 107,
3180; h) S. Dꢃez-Gonzꢄlez, N. Marion, S. P. Nolan, Chem. Rev.
2009, 109, 3612; i) E. Jimꢂnez-NfflÇez, A. M. Echavarren, Chem.
Rev. 2008, 108, 3326; j) A. S. K. Hashmi, Angew. Chem. 2010,
122, 5360; Angew. Chem. Int. Ed. 2010, 49, 5232.
[9] For selected examples of heterocyclization combined with 1,2-
migrations, see: a) C. R. Smith, E. M. Bunnelle, A. J. Rhodes, R.
Sarpong, Org. Lett. 2007, 9, 1169; b) H. Gao, X. Zhao, Y. Yu, J.
Zhang, Chem. Eur. J. 2010, 16, 456; c) W. Li, Y. Li, J. Zhang,
Chem. Eur. J. 2010, 16, 6447; d) E. M. Bunnelle, C. R. Smith,
S. K. Lee, W. S. Singaram, A. J. Rhodes, R. Sarpong, Tetrahedron
2008, 64, 7008; e) D. J. Gorin, N. R. Davis, F. D. Toste, J. Am.
Chem. Soc. 2005, 127, 11260.
[10] For a leading reference, see: a) Q.-F. Wang, H. Hou, L. Hui, C.-
G. Yan, J. Org. Chem. 2009, 74, 7403, and references therein; For
a recent phosphine-induced approach to bicyclic 2,3-dihydrofur-
ans, see: b) J. Ma, P. Xie, C. Hu, Y. Huang, R. Chen, Chem. Eur.
J. 2011, 17, 7418.
[11] For furan syntheses through direct heterocyclization of alkyn-4-
ones and related processes, see: a) A. S. K. Hashmi, L. Schwarz,
J.-H. Choi, T. M. Frost, Angew. Chem. 2000, 112, 2382; Angew.
Chem. Int. Ed. 2000, 39, 2285; b) S. Labsch, S. Ye, A. Adler, J.-M.
Neudçrfl, H.-G. Schmalz, Tetrahedron: Asymmetry 2010, 21,
1745; c) T. Yao, X. Zhang, R. C. Larock, J. Am. Chem. Soc. 2004,
126, 11164.
[12] For selected reviews, see: a) X. L. Hou, Z. Yang, H. N. C. Wong
in Progress in Heterocyclic Chemistry, Vol. 15 (Eds.: G. W.
Gribble, T. L. Gilchrist, Pergamon, Oxford, 2003, p. 167; b) H.-
K. Lee, K.-F. Chan, C.-W. Hui, H.-K. Yim, X.-W. Wu, H. N. C.
Wong, Pure Appl. Chem. 2005, 77, 139; c) R. C. D. Brown,
Angew. Chem. 2005, 117, 872; Angew. Chem. Int. Ed. 2005, 44,
850; d) S. F. Kirsch, Org. Biomol. Chem. 2006, 4, 2076; e) X. L.
Hou, H. Y. Cheung, T. Y. Hon, P. L. Kwan, T. H. Lo, S. Y. Tong,
H. N. C. Wong, Tetrahedron 1998, 54, 1955.
[13] For processes proceeding through spirocyclic intermediates
somewhat related to cation D, see references [8k,9b,c]. In
those works, a ring-enlarging rearrangement of spirocyclic
oxonium ions was proposed.
[14] For a leading review, see: K. Prantz, J. Mulzer, Chem. Rev. 2010,
110, 3741.
[15] Nearly identical yields for 5a were obtained with DMPU/H2O
ratios ranging from 2:1 to 50:1. Most reactions were conducted
with reagent-grade DMPU under open-flask conditions without
added water.
[16] Reaction temperatures from 60 to 1008C were found to be best
for optimal conversion. Lower temperatures led to dramatically
reduced yields while higher temperatures resulted in decom-
position.
[5] a) B. Crone, S. F. Kirsch, Chem. Eur. J. 2008, 14, 3514; b) A.
Duschek, S. F. Kirsch, Angew. Chem. 2008, 120, 5787; Angew.
Chem. Int. Ed. 2008, 47, 5703.
[6] a) S. F. Kirsch, J. T. Binder, B. Crone, A. Duschek, T. T. Haug, C.
Liꢂbert, H. Menz, Angew. Chem. 2007, 119, 2360; Angew. Chem.
Int. Ed. 2007, 46, 2310; b) H. Menz, J. T. Binder, B. Crone, A.
Duschek, T. T. Haug, S. F. Kirsch, P. Klahn, C. Liꢂbert,
Tetrahedron 2009, 65, 1880; c) B. Baskar, H. J. Bae, S. E. An,
J. Y. Cheong, Y. H. Rhee, A. Duschek, S. F. Kirsch, Org. Lett.
2008, 10, 2605; d) A. Lange, W. Heydenreuther, H. Menz, S. F.
Kirsch, Synlett 2009, 2987; e) T. T. Haug, T. Harschneck, A.
Duschek, C.-U. Lee, J. T. Binder, H. Menz, S. F. Kirsch, J.
Organomet. Chem. 2009, 694, 510.
[7] a) S. F. Kirsch, J. T. Binder, C. Liꢂbert, H. Menz, Angew. Chem.
2006, 118, 6010; Angew. Chem. Int. Ed. 2006, 45, 5878; b) J. T.
Binder, B. Crone, S. F. Kirsch, C. Liꢂbert, H. Menz, Eur. J. Org.
Chem. 2007, 1636; c) B. Crone, S. F. Kirsch, J. Org. Chem. 2007,
72, 5435.
[17] A number of test reactions on the model substrate 1a that
support the proposed mechanism are detailed in the Supporting
Information.
[18] a) S. Yamabe, N. Tsuchida, S. Yamazaki, J. Org. Chem. 2006, 71,
1777; b) A. Schaltegger, P. Bigler, Helv. Chim. Acta 1986, 69,
1666.
[8] For selected examples of carbocyclization combined with 1,2-
migrations, see: a) E. Jimꢂnez-NfflÇez, C. K. Claverie, C. Nieto-
Oberhuber, A. M. Echavarren, Angew. Chem. 2006, 118, 5578;
Angew. Chem. Int. Ed. 2006, 45, 5452; b) J. P. Markham, S. T.
Staben, F. D. Toste, J. Am. Chem. Soc. 2005, 127, 9708; c) J.-M.
[19] The cis configuration was established by extensive NOE studies.
[20] Our attempts to react acyclic alkynones were not successful.
9968 www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 9965 –9968