Rh-catalyzed enyne cycloisomerization [2]

Full text of DOI:10.1021/ja994220s

6490
J. Am. Chem. Soc. 2000, 122, 6490-6491
to Ru-catalyst and Ti-catalyst systems) at room temperature, (2)
easy variation of the diphosphine ligand in [Rh(diphos)Cl]2 allows
the Rh-catalyst to be fine-tuned with respect to steric and elec-
tronic requirements of substrates, (3) cycloisomerization of enyne
with an allylic ester tether gives an R-methylene γ-butyrolactone.
Rh-Catalyzed Enyne Cycloisomerization
Ping Cao, Bin Wang, and Xumu Zhang*
Department of Chemistry, 152 DaVey Lab
The PennsylVania State UniVersity
UniVersity Park, PennsylVania 16802
Recently, a variety of rhodium(I) complexes have been applied
to catalyze the [4 + 2],7 [5 + 2],8 and Pauson-Khand9 reactions.
Metallacyclopentenes were suggested as key intermediates in these
transformations.7-9 We envisioned that a new Rh-catalyzed Alder
ene reaction might be possible if â-hydride and reductive
eliminations could be controlled after the formation of the
metallacyclopentene intermediate. A key for this reaction is to
generate a highly coordinatively unsaturated environment to bind
the enyne substrate so that the formation of a metallacyclopentene
can proceed smoothly. A related example of such an unsaturated
compound is the Crabtree catalyst [Ir(COD)Py(PCy3)]+.10 The
highly coordinatively unsaturated chelating phosphine modified
Rh(I)-catalyst has been applied in asymmetric hydroacylation11
and enantioselective isomerization of allylamines.12
ReceiVed December 2, 1999
Transition metal-catalyzed carbocyclization of alkenes and
alkynes is one of the most efficient methods for the synthesis of
a variety of carbocyclic and heterocyclic compounds.1 This
strategy has allowed transformations of unsaturated functional
groups in ways which are either difficult or impossible without
the action of transition metal complexes. One excellent example
is the transition metal-catalyzed cycloisomerization of 1,6-enynes
which leads to the formation of 1, 4-dienes (intramolecular Alder-
ene reaction)2 (eq 1). Many transition metals have been applied
To find appropriate conditions to perform the Rh-catalyzed
enyne cycloisomerization reaction, 1a was selected as a prototypi-
cal substrate. Through systematic studies, high yield and clean
transformation was achieved with a cis-olefin Z-1a using 10 mol
% Rh-catalyst with dppb as the ligand (84% yield) (see Supporting
Information). The major adVance in this study was to prepare a
[Rh(dppb)Cl]2 complex as the clean catalyst precursor and the
cationic Rh-catalyst was prepared in situ from the reaction of
[Rh(dppb)Cl]2 dimer with AgSbF6 in the presence of enyne
substrates. Typically, the catalytic reactions were carried out in
1,2-dichloroethane (DCE) with a 0.1 M substrate concentration
at room temperature. On the basis of this important finding, a
number of phosphines were tested for the enyne cycloisomeriza-
tion reaction. Interestingly, the catalytic activity varies consider-
ably by changing phosphine ligands. A Rh complex with a 1,
4-diphosphinite, BICPO,13 is the most active isomerization
catalyst. A Rh-catalyst with the chelating phosphine dppb is more
active than the Rh system with the dppe ligand. Rh complexes
with chelating phosphines such as dppp and dppm are inactive
for the enyne isomerization reaction.
to catalyze this Alder-ene type reaction.3 Both Pd- and Ru-
catalyzed Alder-ene reactions have been developed by Trost.4 The
intramolecular cycloisomerization of 1, 6-enynes has evolved into
a synthetically powerful carbon-carbon bond forming process.5
Recently, a highly selective enyne cycloisomerization has also
been developed by Buchwald using an early transition metal
catalyst [Cp2Ti(CO)2].6 Although Pd-, Ru-, and Ti-catalyzed
Alder-ene type reactions have been extensively studied, new
catalytic systems are still valuable to expand the reaction scope,
activity, and selectivity.
To the best of our knowledge, no Rh-based catalyst systems
have been reported for facilitating Alder-ene type reactions. Herein
we report a highly effective and selective Rh-catalyzed cyclo-
isomerization of 1, 6-enynes to form 1, 4-dienes. The following
attractive features of the Rh-catalyzed Alder-ene type reaction
have been revealed: (1) 1, 4-dienes are formed selectively (similar
To perform effective enyne isomerization, both dppb and
BICPO have been used to prepare active Rh-catalysts. A variety
of enyne substrates were converted to 1, 4-dienes in moderate to
excellent yields. The results with the Rh-dppb catalyst are
summarized in Table 1. In contrast to the titanium-catalyzed
reaction,6 only enyne substrates containing a cis-olefin are
cycloisomerized. trans-Olefins do not react. In this catalytic
system, an ether-tethered enyne gave higher reactivity than other
type of enyne substrates. A cis fused ring system was formed
exclusively when 1g was used as the enyne. The cis configuration
of product 2g was assigned by a 2D NOESY study. An allylic
ester (1h) was converted smoothly to an ene product 2h,
R-methylene-γ-butyrolactone, using the Rh-catalyst. The R-me-
thylene-γ-butyrolactone is common in sesquterpenes and has a
(1) Reviews: (a) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96,
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Trost, B. M.; Mu¨ller, T. J. J. J. Am. Chem. Soc. 1994, 116, 4985. (f) Trost, B.
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10.1021/ja994220s CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/23/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 27, 2000 6491
Table 1. Rhodium-Catalyzed Cycloisomerization of 1,6-Enynesa
Table 2. Rhodium-Catalyzed Cycloisomerization of 1,6-Enynes
with a Phosphinite Ligandsa
a All reactions were carried out in ClCH2CH2Cl with substrate (0.2
mmol, 0.1M)/[Rh(dppb)Cl]2/AgSbF6 ) 1: 0.05:0.1. The catalyst
[Rh(dppb)]+ was prepared by adding AgSbF6 to the [Rh(dppb)C1]2 in
the presence of substrate. b The stereochemistry is relative. c Conversion
based on H NMR (360 MHz), ene product cannot be separated from
the substrate.
a All reactions were carried out in ClCH2CH2Cl with substrate (0.2
mmol, 0.1M). The catalyst [Rh(BICPO)]+ was prepared by adding
AgSbF6 to the [Rh(BICPO)Cl]2 after substates were introduced. b 2m:
2m′ ) 66:34.
1
wide range of biological activity.14 This example is noteworthy
because cycloisomerization of enynes with an allylic ester tether
to yield γ-butyrolactones has not been reported in the corre-
sponding Pd-, Ti-, or Ru-catalyzed enyne isomerizations. The
cyclization of nitrogen containing substrate Z-1i is slow with a
Rh-dppb catalyst. After 12 h at 40 °C, Z-1i was converted to a 1,
4-diene product 2i in around 50% yield (entry 9, Table 1).
However, both 1, 4-diene and 1, 3-diene products were obtained
after an additional 12 h. So far, the enyne substrate 1j containing
a carbon tether does not cyclize with the Rh-dppb catalyst.
We demonstrated a Rh-catalyzed cycloisomerization of 1,
6-enynes to 1, 4-dienes using a 1, 4-bisphosphine as the ligand.
This transformation provides an excellent complement to the
previous catalyst system. However, this cyclization protocol is
limited by the substrate scope in which only ether linked enyne
substrates give high reactivity toward cyclization. To make this
reaction more useful, we were interested in searching for a more
active Rh-catalyst which can promote cyclization of a wide variety
of 1, 6-enynes.
observed with the Rh-BICPO catalyst compared to results
achieved with the Rh-dppb catalyst system. The increase of
activity (catalyst loading lowered to 3 mol %) is found with the
bisphosphinite-Rh catalyst. Cycloisomerization of an array of 1,
6-enyne substrates bearing an O, N, or C in the tether gave 1,
4-dienes in excellent yields (Table 2). Furthermore, this Rh-
BICPO catalyst can promote cyclization of enynes containing
either E- or Z-alkenes Rh-BICPO (entry 4, 5 in Table 2).
Therefore, the substrate scope with the RhBICPO catalyst is
broader than that observed with the Rh-dppb catalyst.
In conclusion, we have demonstrated a Rh-catalyzed enyne
cycloisomerization to make 1, 4-dienes. Our findings illustrate
that the Rh catalytic system has unique reactivity and selectivity
compared to other late transition metal- and Ti-catalyzed pro-
cesses. Work toward developing an asymmetric variant of the
enyne cycloisomerization reaction as well as Rh-catalyzed [4 +
2] and [5 + 2] reactions is underway and will be reported in due
course.
Table 2 summarizes experimental results of Rh-catalyzed
cycloisomerization of 1, 6-enynes with a Rh-bisphosphinite (Rh-
BICPO) catalyst.The enyne cycloisomerization reaction was
performed at room temperature in ClCH2CH2Cl. The catalyst was
prepared from 1.5 mol % [Rh(BICPO)Cl]2 and 3 mol % AgSbF6
in the presence of substrate. Significant improvement has been
Acknowledgment. This work was supported by a Camille and Henry
Dreyfus Teaching-Scholar Award, and a DuPont Young Faculty Award.
We acknowledge a generous loan of precious metals from Johnson
Matthey Inc. and a gift of GC columns from Supelco.
Supporting Information Available: Spectroscopic data, experimental
details and path of reaction discovery (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
(14) (a) Schultz, A. G.; Godfrey, J. D. J. Am. Chem. Soc. 1980, 102,
2414. (b) Kulyyasov, A. T.; Seitembetov, T. S.; Turdybekov, K. M.;
Adekenov, S. M. Chem. Nat. Compd. 1996, 32, 869. (c) Thuring, J. W. J.
F.; Nefkens, G. H. L.; Schaafstra, R.; Zwanenburg, B. Tetrahedron 1995,
51, 5047.
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