Rhodium-catalyzed olefin isomerization/enantioselective intramolecular alder-ene reaction cascade

Article abstract of DOI:10.1021/ol201986e

The olefin isomerization/enantioselective intramolecular Alder-ene reaction cascade was achieved by using a cationic rhodium(I)/(R)-BINAP complex as a catalyst. A variety of substituted dihydrobenzofurans and dihydronaphthofurans were obtained from phenol

Full text of DOI:10.1021/ol201986e

ORGANIC
LETTERS
2011
Vol. 13, No. 18
4894–4897
Rhodium-Catalyzed Olefin Isomerization/
Enantioselective Intramolecular Alder-Ene
Reaction Cascade
Ryuichi Okamoto,† Eri Okazaki,† Keiichi Noguchi,‡ and Ken Tanaka*,†
Department of Applied Chemistry, Graduate School of Engineering, and Instrumentation
Analysis Center, Tokyo University of Agriculture and Technology, Koganei,
Tokyo 184-8588, Japan
tanaka-k@cc.tuat.ac.jp
Received July 23, 2011
ABSTRACT
The olefin isomerization/enantioselective intramolecular Alder-ene reaction cascade was achieved by using a cationic rhodium(I)/(R)-BINAP
complex as a catalyst. A variety of substituted dihydrobenzofurans and dihydronaphthofurans were obtained from phenol- or naphthol-linked
1,7-enynes, respectively, with good yields and ee values.
The transition-metal-catalyzed intramolecular Alder-
ene reaction of 1,6-enynes is a valuable method for the
construction of carbocycles and heterocycles.1,2 The Trost
group first reported an enantioselective variant of this
reaction by using palladium catalysts, although the enan-
tioselectivity was moderate.3a The Zhang group realized
the highly enantioselective reaction by using rhodium
catalysts.3b After these pioneering works, a number of
highly efficient enantioselective reactions have been
reported.4 In these reports, 1,6-enynes, in which the pro-
pargyl group and the allyl group are connected with
heteroatoms or malonates, have been most frequently
† Department of Applied Chemistry.
‡ Instrumentation Analysis Center.
(1) For reviews, see: (a) Trost, B. M. Acc. Chem. Res. 1990, 23, 34.
(b) Trost, B. M. Chem.;Eur. J. 1998, 4, 2405. (c) Trost, B. M.; Krische,
M. J. Synlett 1998, 1. (d) Aubert, C.; Buisine, O.; Malacria, M. Chem.
Rev. 2002, 102, 813. (e) Brummond, K. M.; McCabe, J. M. In Modern
Rhodium-Catalyzed Organic Reactions; Evans, P. A., Ed.; Wiley-VCH:
Weinheim, Germany, 2005; p 151. (f) Zhang, Z.; Zhu, G.; Tong, X.; Wang,
F.; Xie, X.; Wang, J.; Jiang, L. Curr. Org. Chem. 2006, 10, 1457.
(3) (a) Trost, B. M.; Lee, D. C.; Rise, F. Tetrahedron Lett. 1989, 30,
651. (b) Cao, P.; Zhang, X. Angew. Chem., Int. Ed. 2000, 39, 4104.
(4) For examples, see: (a) Hatano, M.; Terada, M.; Mikami, K.
Angew. Chem., Int. Ed. 2001, 40, 249. (b) Lei, A.; He, M.; Zhang, X.
J. Am. Chem. Soc. 2002, 124, 8198. (c) Lei, A.; He, M.; Wu, S.; Zhang, X.
Angew. Chem., Int. Ed. 2002, 41, 4104. (d) Lei, A.; Waldkirch, J. P.; He,
M.; Zhang, X. Angew. Chem., Int. Ed. 2002, 41, 4526. (e) Hatano, M.;
Mikami, K. J. Am. Chem. Soc. 2003, 125, 4704. (f) Lei, A.; He, M.;
Zhang, X. J. Am. Chem. Soc. 2003, 125, 11472. (g) Hashmi, A. S. K.;
Haufe, P.; Nass, A. R. Adv. Synth. Catal. 2003, 345, 1237. (h) Hashmi,
A. S. K.; Haufe, P.; Nass, A. R.; Bats, J. W. Adv. Synth. Catal. 2004, 346,
421. (i) Mikami, K.; Kataoka, S.; Yusa, Y.; Aikawa, K. Org. Lett. 2004,
6, 3699. (j) He, M.; Lei, A.; Zhang, X. Tetrahedron Lett. 2005, 46, 1823.
(k) Mikami, K.; Kataoka, S.; Aikawa, K. Org. Lett. 2005, 7, 5777.
(l) Mikami, K.; Kataoka, S.; Wakabayashi, K.; Aikawa, K. Tetrahedron
Lett. 2006, 47, 6361. (m) Nicolaou, K. C.; Edmonds, D. J.; Li, A.; Tria,
G. S. Angew. Chem., Int. Ed. 2007, 46, 3942. (n) Liu, F.; Liu, Q.; He, M.;
Zhang, X.; Lei, A. Org. Biomol. Chem. 2007, 5, 3531. (o) Nicolaou,
K. C.; Li, A.; Ellery, S. P.; Edmonds, D. J. Angew. Chem., Int. Ed. 2009,
48, 6293. (p) Corkum, E. G.; Hass, M. J.; Sullivan, A. D.; Bergens, S. H.
Org. Lett. 2011, 13, 3522.
^
(g) Michelet, V.; Toullec, P. Y.; Genet, J.-P. Angew. Chem., Int. Ed.
2008, 47, 4268.
(2) For examples, see: (a) Trost, B. M.; Lautens, M. J. Am. Chem. Soc.
1985, 107, 1781. (b) Trost, B. M.; Lautens, M.; Chan, C.; Jeberatnam,
D. J.; Mueller, T. J. Am. Chem. Soc. 1991, 113, 636. (c) Trost, B. M.;
Tanoury, G. J.; Lautens, M.; Chan, C.; MacPherson, D. T. J. Am. Chem.
Soc. 1994, 116, 4255. (d) Sturla, S. J.; Kablaoui, N. M.; Buchwald, S. L.
J. Am. Chem. Soc. 1999, 121, 1976. (e) Trost, B. M.; Toste, F. D. J. Am.
Chem. Soc. 2000, 122, 714. (f) Cao, P.; Wang, B.; Zhang, X. J. Am. Chem.
Soc. 2000, 122, 6490. (g) Trost, B. M.; Toste, F. D. J. Am. Chem. Soc.
2002, 124, 5025. (h) Tong, X.; Zhang, Z.; Zhang, X. J. Am. Chem. Soc.
2003, 125, 6370. (i) Tong, X.; Li, D.; Zhang, Z.; Zhang, X. J. Am. Chem.
€
Soc. 2004, 126, 7601. (j) Furstner, A.; Martin, R.; Majima, K. J. Am.
€
Chem. Soc. 2005, 127, 12236. (k) Furstner, A.; Majima, K.; Martin, R.;
Krause, H.; Kattnig, E.; Goddard, R.; Lehmann, C. W. J. Am. Chem. Soc.
2008, 130, 1992. (l) Wang, J.; Xie, X.; Ma, F.; Peng, Z.; Zhang, L.; Zhang,
Z. Tetrahedron 2010, 75, 1281.
r
10.1021/ol201986e
Published on Web 08/25/2011
2011 American Chemical Society

employed due to their high stability and facile preparation
(Scheme 1). However, 1,6-enynes, possessing the heteroa-
tom-substituted alkene moiety, have not been employed
presumably due to their low stability and troublesome
preparation (Scheme 1).
Table 1. Optimization of Reaction Conditions for Rh-Cata-
lyzed Cascade Reaction of 1,7-Enyne 1aa
Scheme 1
% yieldb (% ee)
conv
entry
ligand
temp
(%)
2a
3a
4a
1
(R)-BINAP
rt
43
100
100
100
100
100
100
45
31
0
10 (97)
0
73
62
26
18
15
5
2
(R)-BINAP
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
11 (97)
3
(R)-Segphos
(R)-H8ÀBINAP
(S,S)-DIOP
0
16 (96)
4
15
32
51
78
43
81
8
45 (97)
On the other hand, our research group recently reported
the cationic rhodium(I)/dppf complex-catalyzed olefin
isomerization5/propargyl Claisen rearrangement cascade
of ether-linked 1,6-enynes A, possessing the 1,1-disub-
stituted alkene moiety, leading to allenyl aldehydes C
(Scheme 2).6 In this cascade reaction, 1,5-enynes B, posses-
sing the enol ether moiety, are generated in situ and
subsequently undergo the propargyl Claisen rearrange-
ment in one pot. We anticipated that if 1,7-enynes D, in
which the CR3R4 moiety of A is replaced with the phenyl
group, are employed, 1,6-enynes E, possessing the trisub-
stituted enol ether moiety, are generated in situ7 and
subsequently undergo the enantioselective intramolecular
Alder-ene reaction to give enantioenriched dihydrobenzo-
furans F in one pot (Scheme 2). Although Mikami and
co-workers reported the enantioselective intramolecular
Alder-ene reactions of trisubstituted olefinic 1,6-enynes,4a,e
those possessing a terminally disubstituted alkene moiety
have been scarcely explored.8 Therefore, the enantioselec-
tive transformation from E to F is challenging. Herein, we
report the asymmetric synthesis of substituted dihydroben-
zofurans by the cationic rhodium(I)/(R)-BINAP complex-
catalyzed olefin isomerization/enantioselective intramole-
cular Alder-ene reaction cascade.9
5
0
6
(S,S)-BDPP
(S,S)-Chiraphos
0
7c
8c
9c
10d
0
(R,R)-Me-Duphos 80 °C
(R,R)-QuinoxP*
0
0
0
80 °C
70 °C
98
0
(R)-BINAP
97
69 (98)
4
a [Rh(cod)2]BF4 (0.010 mmol, 10 mol %), ligand (0.010 mmol,
10 mol %), 1a (0.10 mmol), and (CH2Cl)2 (1.5 mL) were used. b Isolated
yield. As 2a and 3a were isolated as a mixture, their yields were deter-
1
mined by H NMR. c [Rh(nbd)2]BF4 was used. d [Rh(cod)2]BF4 (0.015
mmol, 5 mol %), ligand (0.015 mmol, 5 mol %), 1a (0.30 mmol), and
(CH2Cl)2 (1.5 mL) were used.
(10 mol %). At room temperature for 16 h, the desired
dihydrobenzofuran 3a was obtained with a high ee value
(Table 1, entry 1). However, the reaction was sluggish and
enol ether 2a was generated as a major product. Although
a complete conversion of 1a was observed at 80 °C for
16 h, achiral benzofuran 4a was generated as a major pro-
duct (entry 2). The effect of chiral bisphosphine ligands
(Figure 1) was then examined at 80 °C (entries 2À9), which
revealed that biaryl bisphosphines are effective ligands for
the formation of 3a and 4a (entries 2À4), and (R)-BINAP
showed the highest reaction rate (entry 2). To suppress the
formation of 4a, the reaction conditions were carefully
optimized. Gratifyingly, when the reaction was conducted
using 5 mol % catalyst at 70 °C, 3a was obtained in good
yield with a high ee value (entry 10).
The reaction of 1,7-enyne 1a was first investigated in
the presence of a cationic rhodium(I)/(R)-BINAP complex
(5) For a recent review of the transition-metal-catalyzed olefin iso-
merization, see: Tanaka, K. In Comprehensive Organometallic Chemis-
try III; Crabtree, R. H., Mingos, D. M. P., Ojima, I., Eds.; Elsevier: Oxford,
2007; Vol. 10, p 71.
Scheme 2
(6) Tanaka, K.; Okazaki, E.; Shibata, Y. J. Am. Chem. Soc. 2009,
131, 10822.
(7) In the cationic rhodium(I)/bisphosphine complex-catalyzed
Alder-ene reaction of oxygen-linked 1,6-enynes, the formation of 1,5-
enynes, possessing the enol ether moiety, was observed as the undesired
side reaction. See: ref 3b.
(8) A single example using the 1,6-enyne possessing a terminally
disubstituted alkene moiety has been reported. However, this reaction
is limited to an N-tosylate protected amide. See: ref 4d.
(9) Recently, novel cascade reactions initiated by the transition-
metal-catalyzed olefin isomerization reaction were reported. See: (a)
Sorimachi, K.; Terada, M. J. Am. Chem. Soc. 2008, 130, 14452. (b)
Terada, M.; Toda, Y. J. Am. Chem. Soc. 2009, 131, 6354.
Org. Lett., Vol. 13, No. 18, 2011
4895

Table 2. Rh-Catalyzed Olefin Isomerization/Enantioselective
Intramolecular Alder-Ene Reaction Cascade of 1,7-Enynes
1aÀka
Figure 1. Structures of chiral bisphosphine ligands.
With the optimized reaction conditions in hand, we
explored the scope of the cationic rhodium(I)/(R)-BINAP
complex-catalyzed olefin isomerization/enantioselective
intramolecular Alder-ene reaction cascade (Table 2). Var-
ious aryl (entries 1À4), alkenyl (entry 5), and alkyl sub-
stituents (entries 6À8) could be incorporated at the alkyne
terminus. This study revealed that the electronic nature of
the aromatic substituents at the alkyne terminus showed a
modest impact on the product yields [electron-deficient
aryl (entries 3 and 4) > electron-rich aryl (entries 1 and
2)].10 On the other hand, the ee values of aryl-, cyclohex-
enyl-, and cyclohexyl-substituted products were higher
than those of primary alkyl-substituted ones (entries 1À6
vs entries 7 and 8). With respect to the substituents at the
alkene moiety, phenyl-substituted enyne 1i could be trans-
formed into the corresponding dihydrobenzofuran 3i with
a high ee value, although the product yield was low (entry
9).11 In these reactions, the major olefin geometries were in
an E configuration (entries 1À9). However, the products
obtained from naphthyl-linked 1,7-enynes 1j and 1k were
Z isomers (entries 10and 11).12 The absolute configuration
of dihydronaphthofuran (À)-3k was unambiguously de-
termined to be S by the anomalous dispersion method
(Figure 2).
The reactions of 1,7-enynes 1l and 1m, possessing the
1,2-disubstituted alkene moiety, were also examined
(10) In the reactions of 1c and 1d, the formation of the corresponding
benzofurans was suppressed.
(11) The corresponding benzofuran 4i was also generated in ca. 13%
yield.
(12) Importantly, the benzene or naphthalene linkage in 1,7-enynes is
necessary to gain high product yield. The reaction of ethylene-linked 1,7-
enyne 1n proceeded in low yield, although the product 3n could not be
isolated in a pure form due to the formation of an unidentified mixture of
byproduct. In addition, the reaction of tosylamide-linked 1,7-enyne 1o
was sluggish.
a Reactions were conducted using [Rh(cod)2]BF4 (0.015 mmol, 5 mol
%), (R)-BINAP (0.015 mmol, 5 mol %), and 1aÀk (0.30 mmol) in
(CH2Cl)2 (1.5 mL). b Isolated yield. c Isolated as a mixture of 2a and 3a.
Pure 2a and 3a were isolated by GPC. d Catalyst: 10 mol %. e Isolated as
a mixture of 3b and 4b. Pure 3b was isolated by GPC.
(Scheme 3). Although the desired chiral dihydrobenzofur-
ans were not obtained at all, the corresponding benzofur-
ans 4l and 4m were obtained in moderate yields.
4896
Org. Lett., Vol. 13, No. 18, 2011

Scheme 4
Figure 2. ORTEP diagram of (S)-(À)-3k with ellipsoids at 30%
Scheme 5
probability.
Scheme 3
Scheme 6
We propose the following mechanism (Scheme 4). In the
first step, the olefin isomerization13 proceeds to afford 1,6-
enyne 2. Enyne 2 reacts with rhodium to afford rhodacy-
clopenteneG. β-Hydride elimination followed by reductive
elimination affords dihydrobenzofuran (E)-3. In the case
of dihydronaphthofurans, Z isomers were obtained pre-
sumably through the rhodium-catalyzed isomerization of
E isomers in order to release the steric hindrance.14 Sub-
sequent rhodium-catalyzed olefin isomerization affords
benzofuran 4.15
Indeed, isolated 2a was transformed into 3a and 4a at
70 °C in the presence of the cationic rhodium(I)/(R)-
BINAP catalyst (Scheme 5). Furthermore, heating of 3a
in (CH2Cl)2 in the absence of the Rh catalyst did not
furnish 4a (Scheme 6).
In conclusion, the olefin isomerization/enantioselective
intramolecular Alder-ene reaction cascade was achieved
by using a cationic rhodium(I)/(R)-BINAP complex as a
catalyst. A variety of substituted dihydrobenzofurans and
dihydronaphthofurans were obtained from phenol- or
naphthol-linked 1,7-enynes, respectively, with good yields
and ee values. Further utilization of the cationic rhodium-
(I) complex for various cascade reactions is underway in
our laboratory.
Acknowledgment. This work was supported partly by a
Grant-in-Aid for Scientific Research (No. 20675002) from
MEXT, Japan. We thank Takasago International Cor-
poration, for the gift of H8-BINAP and Segphos, and
Umicore, for generous support in supplying a rhodium
complex.
(13) For the cationic rhodium(I)/bisphosphine complex-catalyzed
ꢀ
isomerization of allyl ethers to enol ethers, see: (a) Fatig, T.; Soulie, J.;
Lallemand, J.-Y.; Mercier, F.; Mathey, F. Tetrahedron 2000, 56, 101. (b)
Hiroya, K.; Kurihara, Y.; Ogasawara, K. Angew. Chem., Int. Ed. Engl.
1995, 34, 2287.
(14) For the cationic rhodium(I)/bisphosphine complex-catalyzed E/
Z isomerization of alkenes, see: Tanaka, K.; Shoji, T.; Hirano, M. Eur. J.
Org. Chem. 2007, 2687.
(15) For the cationic rhodium(I)/bisphosphine complex-catalyzed
isomerization of R-alkylidenecycloalkanones to cycloalkenones, see:
Takeishi, K.; Sugishima, K.; Sasaki, K.; Tanaka, K. Chem.;Eur. J.
2004, 10, 5681.
Supporting Information Available. Experimental pro-
cedures, compound characterization data, and an X-ray
crystallographic information file. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
Org. Lett., Vol. 13, No. 18, 2011
4897