Chiral diene-phosphine tridentate ligands for rhodium-catalyzed asymmetric cycloisomerization of 1,6-enynes

Article abstract of DOI:10.1021/ol2013236

Asymmetric cycloisomerization of nitrogen-bridged 1,6-enynes proceeded in the presence of a cationic rhodium complex coordinated with a chiral diene/phosphine tridentate ligand to give high yields of chiral 3-azabicyclo[4.1.0]heptenes with high enantiosel

Full text of DOI:10.1021/ol2013236

ORGANIC
LETTERS
2011
Vol. 13, No. 14
3674–3677
Chiral Diene-Phosphine Tridentate
Ligands for Rhodium-Catalyzed
Asymmetric Cycloisomerization of
1,6-Enynes
Takahiro Nishimura,* Yuko Maeda, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo,
Kyoto 606-8502, Japan
tnishi@kuchem.kyoto-u.ac.jp; thayashi@kuchem.kyoto-u.ac.jp
Received May 17, 2011
ABSTRACT
Asymmetric cycloisomerization of nitrogen-bridged 1,6-enynes proceeded in the presence of a cationic rhodium complex coordinated with a
chiral diene/phosphine tridentate ligand to give high yields of chiral 3-azabicyclo[4.1.0]heptenes with high enantioselectivity.
The recent development of transition-metal-catalyzed
cycloisomerization of 1,n-enynes provides a useful metho-
dology for the preparation of diverse polycyclic com-
pounds in a single step.1 Cycloisomerization of heteroatom-
bridged 1,6-enynes is one of the most straightforward
methods for the synthesis of bicyclo[4.1.0]heptene deriva-
tivescontaining heteroatoms, suchasoxygenand nitrogen,
which have potential biological activities.2 Although there
have been several reports on the cycloisomerization cata-
lyzed by π-acidic metals, such as Pt,3 Au,4 Rh,5 and Ir,6,7
asymmetric variants have not been well developed.8 Shi-
bata and co-workers reported the first asymmetric cycloi-
somerization of nitrogen-bridged 1,6-enynes catalyzed by
an iridium/bisphosphine complex under CO.6 A chiral
bisphoshine/NHC- or a chiral monophosphine/cyclome-
talated NHC-platinum complex has been developed by
Marinetti and co-workers.9 Michelet and co-workers re-
ported that the asymmetric cycloisomerization with high
enantioselectivity is catalyzed by chiral gold/bisphoshine
complexes.10,11 Although high enantioselectivity is attained
in some catalytic systems, they are still limited in terms of
substrate scope and catalyst efficiency, and thus develop-
ment of a new catalytic system is desirable. In this context,
we recently reported that a rhodium(I) complex coordi-
nated with triphenylphosphine and a chiral diene ligand12
based on a tetrafluorobenzobarrelene (tfb) skeleton is a
good catalyst for asymmetric cycloisomerization of nitro-
gen- and oxygen-bridged 1,6-enynes, where the active
cationic rhodium species has a stereochemically controlled
(1) For reviews, see: (a) Lloyd-Jones, G. C. Org. Biomol. Chem. 2003,
1, 215. (b) Echavarren, A. M.; Nevado, C. Chem. Soc. Rev. 2004, 33, 431.
€
(c) Bruneau, C. Angew. Chem., Int. Ed. 2005, 44, 2328. (d) Furstner, A.;
Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410. (e) Michelet, V.;
^
Toullec, P. Y.; Genet, J.-P. Angew. Chem., Int. Ed. 2008, 47, 4268. (f)
ꢀ
ꢀ~
Jimenez-Nunez, E.; Echavarren, A. M. Chem. Rev. 2008, 108, 3326. (g)
Shen, H. C. Tetrahedron 2008, 64, 7847.
(2) Micheli, F.; Cavanni, P.; Andreotti, D.; Arban, R.; Benedetti, R.;
Bertani, B.; Bettati, M.; Bettelini, L.; Bonanomi, G.; Braggio, S.;
Carletti, R.; Checchia, A.; Corsi, M.; Fazzolari, E.; Fontana, S.;
Marchioro, C.; Merlo-Pich, E.; Negri, M.; Oliosi, B.; Ratti, E.; Read,
K. D.; Roscic, M.; Sartori, I.; Spada, S.; Tedesco, G.; Tarsi, L.; Terreni,
S.; Visentini, F.; Zocchi, A.; Zonzini, L.; Di Fabio, R. J. Med. Chem.
2010, 53, 4989.
r
10.1021/ol2013236
Published on Web 06/21/2011
2011 American Chemical Society

only be applied to high yielding reactions with high
enantioselectivity. (iii) The chiral tfb ligand is not readily
available in an enantiopure form. To establish a more
efficient and general catalytic system for cycloisomeriza-
tion of 1,6-enynes, we designed new tridentate ligands for
rhodium (Scheme 2).15,16 The designed rhodium catalysts
involve characteristic features as follows: (i) A tridentate
ligand, which has chelating one phosphorus atom and a
chiral diene moiety, strongly coordinates to a rhodium
center, and the in situ generated cationic complex provides
a single vacant site on the square planar geometry of the
rhodium(I) center. (ii) An electron-withdrawing character
of an alkene moiety substituted with an ester group, which
locates trans to the single vacant site of the cationic
complex, is expected to enhance the π-acidity of rhodium
toward electrophilic alkyne activation. (iii) The chiral
diene framework is readily obtained from a natural pro-
duct (R)-R-phellandrene. Here we report the development
of new chiral diene-phosphine tridentate ligands for rho-
dium in asymmetric cycloisomerization of nitrogen-bridged
1,6-enynes giving 3-azabicyclo[4.1.0]heptene derivatives
with high enantioselectivity.
Scheme 1. A Rh/Chiral Diene-Phosphine Catalyst in Asym-
metric Cycloisomerization of 1,6-Enynes
single coordination site13 on the rhodium center for elec-
trophilic activation of the alkyne moiety (Scheme 1).14 The
catalytic system, however, has some drawbacks as follows:
(i) The oligomerization of enynes is sometimes observed,
probably due to the dissociation of nonchelating triphe-
nylphosphine. (ii) The applicable substrates are limited to
enynes substituted with a methyl group at the alkyne
terminus, and limited substituents of alkene moieties can
(3) (a) Blum, J.; Beer-Kraft, H.; Badrieh, Y. J. Org. Chem. 1995, 60,
€
5567. (b) Furstner, A.; Szillat, H.; Stelzer, F. J. Am. Chem. Soc. 2000,
ꢀ
~
ꢀ
122, 6785. (c) Mendez, M.; Munoz, M. P.; Nevado, C.; Cardenas, D. J.;
€
Scheme 2. Concept of New Rh/Chiral Diene-Phosphine Cata-
lysts
Echavarren, A. M. J. Am. Chem. Soc. 2001, 123, 10511. (d) Furstner, A.;
Stelzer, F.; Szillat, H. J. Am. Chem. Soc. 2001, 123, 11863. (e) Nevado,
C.; Ferrer, C.; Echavarren, A. M. Org. Lett. 2004, 6, 3191. (f) Furstner,
€
A.; Davies, P. W.; Gress, T. J. Am. Chem. Soc. 2005, 127, 8244. (g) Cho,
ꢀ
E. J.; Kim, M.; Lee, D. Org. Lett. 2006, 8, 5413. (h) Hercouet, A.; Berree,
F.; Lin, C. H.; Toupet, L.; Carboni, B. Org. Lett. 2007, 9, 1717. (i) Ferrer,
C.; Raducan, M.; Nevado, C.; Claverie, C. K.; Echavarren, A. M.
Tetrahedron 2007, 63, 6306. (j) Olagnier, D.; Costes, P.; Berry, A.; Linas,
M.-D.; Urrutigoity, M.; Dechy-Cabaret, O.; Benoit-Vical, F. Bioorg.
Med. Chem. Lett. 2007, 17, 6075. (k) Xia, J.-B.; Liu, W.-B.; Wang, T.-M.
You, S.-L. Chem.;Eur. J. 2010, 16, 6442.
~
~
(4) (a) Nieto-Oberhuber, C.; Munoz, M. P.; Bunuel, E.; Nevado, C.;
ꢀ
Cardenas, D. J.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43,
2402. (b) Lee, S. I.; Kim, S. M.; Kim, S. Y.; Chung, Y. K. Synlett 2006,
2256. (c) Lee, S. I.; Kim, S. M.; Choi, M. R.; Kim, S. Y.; Chung, Y. K. J.
Org. Chem. 2006, 71, 9366. (d) Kim, S. M.; Park, J. H.; Choi, S. Y.;
Chung, Y. K. Angew. Chem., Int. Ed. 2007, 46, 6172. (e) Chen, Z.; Zhang,
Y.-X.; Wang, Y.-H.; Zhu, L.-L.; Liu, H.; Li, X.-X.; Guo, L. Org. Lett.
2010, 12, 3468.
(5) Costes, P.; Weckesser, J.; Dechy-Cabaret, O.; Urrutigoıty, M.;
Kalck, P. Appl. Organomet. Chem. 2008, 22, 211.
(6) Shibata, T.; Kobayashi, Y.; Maekawa, S.; Toshida, N.; Takagi,
K. Tetrahedron 2005, 61, 9018.
(7) Sim, S. H.; Lee, S. I.; Park, J. H.; Chung, Y. K. Adv. Synth. Catal.
We focused on carboxylic acid (1R,4R,7R)-2,17 which is
readily preparedfrom(R)-R-phellandrene, asa chiraldiene
framework for the synthesis of new chiral diene-monopho-
sphine tridentate ligands (Scheme 3). The ligands were
simply prepared by esterification of 2 with 2-(diarylpho-
sphino)phenols. Thus, carboxylic acid 2 was treated with
oxalyl chloride, and the resulting acid chloride was reacted
2010, 352, 317.
(8) For a recent example of asymmetric cycloisomerization of enynes
ꢀ
via 5-endo cyclization, see: Martınez, A.; Garcıa-Garcıa, P.; Fernandez-
(15) Nishimura, T.; Maeda, Y.; Hayashi, T. Angew. Chem., Int. Ed.
2010, 49, 7324.
(16) For selected examples of the use of phosphine/alkene hybrid
Rodriıguez, M. A.; Rodrıguez, F.; Sanz, R. Angew. Chem., Int. Ed. 2010,
49, 4633.
(9) (a) Brissy, D.; Skander, M.; Retailleau, P.; Marinetti, A. Orga-
nometallics 2007, 26, 5782. (b) Brissy, D.; Skander, M.; Retailleau, P.;
Frison, G.; Marinetti, A. Organometallics 2009, 28, 140. (c) Brissy, D.;
Skander, M.; Jullien, H.; Retailleau, P.; Marinetti, A. Org. Lett. 2009,
11, 2137.
(10) Chao, C.-M.; Beltrami, D.; Toullec, P. Y.; Michelet, V. Chem.
Commun. 2009, 6988.
(11) For an example of gold-catalyzed asymmetric cycloisomeriza-
tion for the synthesis of the triple reuptake inhibitor, see: Deschamps,
N. M.; Elitzin, V. I.; Liu, B.; Mitchell, M. B.; Sharp, M. J.; Tabet, E. A. J.
Org. Chem. 2011, 76, 712.
ligands in the symmetric reactions, see: (a) Maire, P.; Delbon, S.; Breher,
€
€
€
€
F.; Geier, J.; Bohler, C.; Ruegger, H.; Schonberg, H.; Grutzmacher, H.
Chem.;Eur. J. 2004, 10, 4198. (b) Shintani, R.; Duan, W.-L.; Nagano,
T.; Okada, A.; Hayashi, T. Angew. Chem., Int. Ed. 2005, 44, 4611. (c)
ꢀ
Kasak, P.; Arion, V. B.; Widhalm, M. Tetrahedron: Asymmetry 2006, 17,
3084. (d) Defieber, C.; Ariger, M. A.; Moriel, P.; Carreira, E. M. Angew.
~
Chem., Int. Ed. 2007, 46, 3139. (e) Mariz, R.; Briceno, A.; Dorta, R.
ꢁ
ꢁ
ꢁ
ꢁ ꢀ
Organometallics 2008, 27, 6605. (f) Stepnicka, P.; Cısarova, I. Inorg.
Chem. 2006, 45, 8785. (g) Stemmler, R. T.; Bolm, C. Synlett 2007, 1365.
(h) Minuth, T.; Boysen, M. M. K. Org. Lett. 2009, 11, 4212. (i) Liu, Z.;
Du, H. Org. Lett. 2010, 12, 3054.
(12) Forreviewsofchiraldieneligands, see:(a)Shintani, R.;Hayashi, T.
€
(17) (a) Okamoto, K.; Hayashi, T.; Rawal, V. H. Org. Lett. 2008, 10,
4387. (b) Okamoto, K.; Hayashi, T.; Rawal, V. H. Chem. Commun. 2009,
4815. (c) Shintani, R.; Tsutsumi, Y.; Nagaosa, M.; Nishimura, T.;
Hayashi, T. J. Am. Chem. Soc. 2009, 131, 13588. (d) Shintani, R.; Soh,
Y.-T.; Hayashi, T. Org. Lett. 2010, 12, 4106. (e) Shintani, R.; Hayashi, T.
Org. Lett. 2011, 13, 350. (f) Pattison, G.; Piraux, G.; Lam, H. W. J. Am.
Chem. Soc. 2010, 132, 14373.
Aldrichimica Acta 2009, 42, 31. (b) Defieber, C.; Grutzmacher, H.;
Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47, 4482.
(13) Feducia, J. A.; Campbell, A. N.; Doherty, M. Q.; Gagne, M. R.
ꢀ
J. Am. Chem. Soc. 2006, 128, 13290.
(14) Nishimura, T.; Kawamoto, T.; Nagaosa, M.; Kumamoto, H.;
Hayashi, T. Angew. Chem., Int. Ed. 2010, 49, 1638.
Org. Lett., Vol. 13, No. 14, 2011
3675

with2-(diarylphosphino)phenolsinthepresenceoftriethy-
lamine to give diene-phosphine ligands 3aꢀd in high yields
(90ꢀ95%) bearing several substituents on the two benzene
rings of the phosphino group. Rhodium complexes coor-
dinated with the ligands 3aꢀd were also prepared by the
reactions with [RhCl(C2H4)2]2, and they were isolated in
high yields (95ꢀ99%) by column chromatography on
silica gel.
Table 1. Rhodium-Catalyzed Cycloisomerization of 4aa
1H NMR (CDCl3) of the complex [RhCl((R)-3a)] dis-
played two nonequivalent alkenic protons at 3.81 and 4.61
ppm, which are shifted from 3.28 and 7.15 ppm, respec-
tively, of ligand (R)-3a. Four alkenic carbons showing the
entry
ligand (L*)
conversion (%)b
yield (%)b
ee (%)c
1
3a
3b
3c
3d
3d
82
98
100
56
100
33
0
73
87
90d
52
90d
27
0
81
82
91
90
89
83
ꢀ
Scheme 3. Synthesis of Ligands and Their Rhodium Complexes
2
3
4
5e
6
f
1/PPh3
6g
7
g,h
8
6/PPh3
25
50
0
11
49
0
41
55
ꢀ
9
10i
7
3c
a For detailed reaction conditions, see Supporting Information.
b Determined by 1H NMR. c Determined by HPLC. d Isolated yield.
e For 72 h. f [RhCl(PPh3)((S,S)-1)] (2 mol %). g [RhCl((R)-6)]2 (2 mol %
of Rh). h PPh3 (2 mol %). i Without NaBArF
.
4
and the ee value of 5a obtained here are higher than those
obtained with ligand 1 shown in Scheme 1.14 Thus, the
reaction catalyzed by [RhCl(PPh3)((S,S)-1)] (2 mol %)
gave a 27% yield of 5a with 83% ee under the same
reaction conditions (entry 6). Ligand 6,17b which lacks a
phosphorus group, displayed no catalytic activity (entry 7).18
The use of triphenylphosphine as a second ligand com-
bined with ligand 6 displayed low catalytic activity and
enantioselectivity (entry 8). The use of diene-phosphine
ligand 7, where an o-(diphenylphosphino)phenyl group is
tetheredby anether functionality instead of the ester oneof
3a, gave 5a in 49% yield 55% ee (entry 9). This result
indicates that high catalytic activity of the rhodium/3a
complex (entry 1 vs entry 9) is due to its high π-accepting
ability caused by the electron-deficient alkene moiety located
trans to the coordination site toward 4a. Facile formation
coupling with the rhodium center (50.4, 55.4, 84.1, and
109.1 ppm) were also observed in the 13C NMR spectrum,
and 31P NMR displayed a doublet peak at 34.1 ppm
(1JRhꢀP = 173 Hz). These results indicate that the rhodium
center is coordinated with both the diene moiety and the
phosphorus atom in solution.
To evaluate the designed rhodium catalysts, the reac-
tion of 1,6-enyne 4a was carried out in the presence of
[RhCl((R)-L*)] (2 mol %) and NaBArF4 (4 mol %) (ArF =
3,5-bis(trifluoromethyl)phenyl) in 1,2-dichloroethane at
40 °C for 24 h (Table 1). The use of a rhodium complex
coordinated with (R)-3a gave a 73% yield of the cycloi-
somerization product 5a, whose enantiomeric excess was
81% (entry 1). The substituent of the phosphorus atom on
the ligand had a significant effect on the catalytic activity
and enantioselectivity (entries 2ꢀ5). Thus, chiral ligand 3b
substituted with p-tolyl groups on the phosphorus atom
improved both the yield and enantioselectivity of 5a (87%
yield, 82% ee) (entry 2). Ligand 3c having a bulky tert-
butyl group at the para-position displayed the highest
catalytic activity and enantioselectivity to give 5a in 90%
yield with 91% ee (entry 3). High enantioselectivity was
also observed by use of ligand 3d bearing bulkier aromatic
groups (3,5-di-tert-butyl-4-methoxyphenyl), although the
reaction was slow (entry 4), and a prolonged reaction time
(72 h) was required for the complete conversion of 4a
giving 5a in 90% yield with 89% ee (entry 5). Both the yield
of the cationic rhodium species with the aid of NaBArF
4
was also essential in the present reaction (entry 10). The
absolute configuration of 5a obtained with (R)-3 was
determined to be (1S,6R,7R)-(þ) by comparison of its
specific rotation with the value reported previously.14
The substrate scope of the present rhodium-catalyzed
asymmetric cycloisomerization of nitrogen-bridged 1,6-
enynes 4 was fairly broad as shown in Scheme 4. The reac-
tion was carried out by use of [RhCl((R)-3c)] or [RhCl((R)-
3d)] as a precursor of the active cationic rhodium species,
(18) The use of a chiral tetrafluorobenzobarrelene ligand substituted
with a methyl and a 2-(diisopropylamido)phenyl group, which is an
efficient tridentate ligand in the rhodium-catalyed asymmetric cyclo-
propanation of styrene (ref 15), gave no cycloisomerization product 5a.
3676
Org. Lett., Vol. 13, No. 14, 2011

moiety (R2) proceeded to give the corresponding bicyclic
compounds 5dꢀ5h in high yields, the enantioselectivity
ranging between 90 and 99% ee. 1,6-Enynes substituted
with a propyl group (4i), a silyloxymethyl group (4j) on the
alkene moiety (R2), and unsubstituted 4k (R2 = H) also
gave the corresponding cycloisomerization products 5iꢀ5k
in 64ꢀ97% yields over 88% ee. The enynes 4l and 4m
substituted with propyl and phenyl at the alkyne terminus
(R4) were also good substrates to give 5l and 5m with 88%
and 67% ee, respectively.19 In the reactions of 1,6-enynes 4n
and 4o bearing trisubstituted alkene moieties, although the
yields of the cycloisomerization products were modest be-
cause of the formation of oligomeric compounds, enantios-
electivities of the products were high (91% ee for 5n and 88%
ee for 5o). High enantioselectivities were also observed in the
reactions of 1,6-enynes 4pꢀ4t possessing an exomethylene
part (R2 = R3 = H) giving the corresponding products in
high yields with high enantioselectivity (86ꢀ92% ee).20
Scheme 4. Rhodium-Catalyzed Cycloisomerization of
1,6-Enyne 4a
Scheme 5. Transformations of 5a
The bicyclic compound 5a obtained here with 91% ee is
readily converted into functionalized compounds without loss
of enantiomeric purity (Scheme 5). For example, oxidative
cleavage of an alkene moiety of 5a with ozone gave highly
functionalized cyclopropane 8 in 55% yield. The allylation of
5a by treatment with allyltrimethylsilane in the presence of
trifluoroacetic acid gave allylation product 9 in 94% yield.
In summary, we have developed a rhodium-catalyzed
asymmetric cycloisomerization of nitrogen-bridged 1,6-
enynes giving 3-azabicyclo[4.1.0]heptenes in high yields
with high enantioselectivity. The reaction was realized by
use of a cationic rhodium complex coordinated with a
chiral diene/phosphine tridentate ligand, which is readily
prepared in an enantiopure form.
a For detailed reaction conditions, see Table S1 in the Supporting Infor-
mation. bPerformed with [RhCl((R)-3c)]. cPerformed with [RhCl((R)-3d)].
where the ligand, displaying high catalytic activityand ena-
ntioselectivity, was selected depending on the enynes.
Asymmetric cycloisomerization can be applied to the
enynes bearing not only a p-toluenesulfonyl group (Ts; 4a)
on the nitrogen atom but also a 4-nitrobenzenesulfonyl (p-
Ns; 4b) and 2-nitrobenzenesulfonyl group (o-Ns; 4c) to
give the corresponding bicyclic compounds 5aꢀ5c in high
yields with 91, 87, and 76% ee, respectively. The reaction
of 1,6-enynes 4dꢀ4h bearing aryl groups on the alkene
Acknowledgment. This work has been supported by a
Grant-in-Aid for Scientific Research (19105002 and
22750090) from the MEXT, Japan.
Supporting Information Available. Experimental pro-
cedures and data for the substrates and products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(19) The reaction of an oxygen-tethered analogue of 4m under the
same reaction conditions did not give the corresponding oxabicyclo-
[4.1.0]heptene derivative due to oligomerization of the starting 1,6-
enyne.
(20) The relative and absolute configurations of 5p obtained with (R,
R)-3c were determined to be (1S,6S) by X-ray crystallographic analysis
(CCDC 816724).
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