Asymmetric synergy between chiral dienes and diphosphines in cationic Rh(I)-catalyzed intramolecular [4 + 2] cycloaddition

Article abstract of DOI:10.1021/ja0650100

High enantioselective [4 + 2] cycloaddition can be achieved by cationic Rh complexes bearing not only chiral phosphine but also chiral diene. This is the first example of asymmetric synergy between chiral dienes and diphosphines. Copyright

Full text of DOI:10.1021/ja0650100

Published on Web 09/09/2006
Asymmetric Synergy between Chiral Dienes and Diphosphines in Cationic
Rh(I)-Catalyzed Intramolecular [4 + 2] Cycloaddition
Kohsuke Aikawa, Susumu Akutagawa, and Koichi Mikami*
Department of Applied Chemistry, Tokyo Institute of Technology, Tokyo 152-8552, Japan
Received July 14, 2006; E-mail: kmikami@o.cc.titech.ac.jp
Transition metal-catalyzed Diels-Alder reactions1 of unactivated
Table 1. Enantioselective [4 + 2] Cycloaddition of 1a by Rh
Catalysts Derived from a Variety of Rh-Diene Precatalysts
dieneynes, such as intramolecular [4 + 2] cycloaddition, are
powerful synthetic methods leading to 5,6- or 6,6-fused rings.2,3
The fused structures thus obtained can be inducted into a variety
of natural products whose syntheses are difficult without use of
transition metals. Therefore a number of catalyst systems, such as
Rh complexes,2 that perform intramolecular [4 + 2] cycloaddition
yield
ee
in excellent yields have been developed in the past 15 years.3,4
entry
Rh cat*
time
(%)c
(%)d
However, the highly enantioselective catalysis is only limited;5 the
chiral Rh catalysts are generally derived from achiral diene-Rh
precatalysts and chiral diphosphine ligands, but the effect of the
dienes on enantioselectivity has been overlooked. Herein we report
a highly efficient catalysis by cationic Rh(I)-chiral diphosphine
complexes in the proper combination of chiral diene-Rh precata-
lysts (eq 1). The intramolecular [4 + 2] cycloaddition of dieneyne
1 catalyzed by the chiral diene-Rh(I)-chiral diphosphine complex
thus provides significantly increased enantioselectivity than that
obtained simply by the Rh(I)-chiral diphosphine complex without
involvement of chiral diene.
1a [Rh(COD2](SbF6)/(S,S)BDPP
48 h
48 h
4 h
18 h
30 min 89
0
0
81
69
2
3
4
[Rh{(S,S)-BDPP}(COD)]SbF6
[Rh{(S,S)-BDPP}(NBD)]SbF6
[Rh{(S,S)-BDPP}]SbF6
0
0
0
0
5b [RhCl(COD)]2/(S,S)-BDPP/AgSbF6
6b [RhCl(COD)]2/(S,S)-CHIRAPHOS/AgSbF6 40 min 87
7b [RhCl(COD)]2/(R,R)-DIOP/AgSbF6
8b [RhCl(COD)]2/(S)-BINAP/AgSbF6
15 min 94 -2e
20 min 70
9
13
0
9b [RhCl(COD)]2/(R,R)-Me-DUPHOS/AgSbF6 5 min
10b [RhCl(NBD)]2/(R,R)Me-DUPHOS/AgSbF6 5 min
99
88
a Rh:BDPP ) 1:1.1. b Rh:ligand:AgSbF6 ) 1:1.1:2. c Isolated yield.
d Enantiopurity was determined by chiral GC analysis on a CP-cyclodextrin-
â-2,3,6-M-19. e Opposite configuration.
The reaction of dieneyne 1a was first attempted by use of a
variety of Rh catalyst systems with (S,S)-BDPP6 as a chiral
diphosphine ligand (Table 1, entries 1-5), which have been found
to be effective in the asymmetric ene-type cyclization, including
trisubstituted 1,6-enyne substrates.7 [Rh{(S,S)-BDPP}(COD)] SbF6
(COD ) 1,5-cyclooctadiene) or the combination of [Rh(COD)2]-
SbF6 with (S,S)-BDPP was not active presumably because of the
competition between COD and the diene substrate 1a (entries 1
and 2). In contrast, the Rh-NBD (NBD ) 2,5-norbornadiene)
catalyst was active to give the desired product 2a in 81% yield
(entry 3). The same [Rh{(S,S)-BDPP}(NBD)]SbF6 complex was,
after hydrogenation under hydrogen (1 atm) to remove NBD, not
active enough to catalyze the reaction over 18 h in only 69% yield
(entry 4).5c,7 Intriguingly, the mixture of [RhCl(COD)]2, (S,S)-BDPP,
and AgSbF68 gave 89% yield, within 30 min, of the racemic product
2a (entry 5). A variety of chiral diphosphine ligands (such as DIOP)9
was thus examined (entries 6-9), and (R,R)-Me-DUPHOS10 was
the most effective to give 2a with 13% ee in 99% yield within 5
min (entry 9). In sharp contrast, when [RhCl(NBD)]2 was used
instead of [RhCl(COD)]2, the racemic 2a was obtained (entry 10).
These results imply that the dienes, such as COD and NBD, affect
enantiodiscrimination between the enantiofaces of substrate 1a.
Therefore, we investigated the effect of chiral dienes,11 such as
C1 symmetric dienes 3-5,11b in the combination of chiral diphos-
phine ligands. A remarkable increase in enantioselectivity was
observed by using chiral dienes (Table 2). When [RhCl(3)]2 was
examined without chiral diphosphine ligand, the product 2a was
obtained in 91% yield within 30 min though with low enantiose-
lectivity (26% ee) (entry 1). The combination of diene 3 with
CHIRAPHOS12 gave a low level of enantioselectivity (entry 2).
The use of BINAP13 and sterically more demanding DM-BINAP
even in either enantiomeric form did not influence the sense of
enantioselectivity: The same enantiomer product was obtained with
a similar level of enantioselectivity (26-30% ee), presumably
because the sterically demanding BINAP derivative might be kicked
out (entries 1 vs 3-6). However, the combination of [RhCl(3)]2
with (R,R)-Me-DUPHOS provided an effective catalyst system to
afford the product 2a in high enantioselectivity and yield (entry
7). The use of (R,R)-Me-DUPHOS gave a higher level of enantio-
selectivity than that obtained with only chiral diene or the
combination of (R,R)-Me-DUPHOS with achiral COD (Table 2,
entries 7 vs 1, or Table 1, entry 9). On the other hand, the use of
(S,S)-Me-DUPHOS led to the opposite enantiomer product with
lower enantioselectivity (entry 8). Use of monodentate PPh3 led to
the same enantioselectivity as in entry 1 (entry 9).
These results clearly show that both chirality of chiral dienes
and Me-DUPHOS work synergistically in the right combination in
the enantiodiscriminating step of the intramolecular [4 + 2]
cycloaddition; (R,R)-Me-DUPHOS is the matched pair with the
chiral dienes 3, and hence (S,S)-Me-DUPHOS is the mismatched
9
12648
J. AM. CHEM. SOC. 2006, 128, 12648-12649
10.1021/ja0650100 CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Enantioselective [4 + 2] Cycloaddition of 1a-e
Catalyzed by Diphosphine-Rh Complexes Bearing Chiral Dienes
bidentate fashion, can be eliminated because [Rh{(S,S)-BDPP}-
(COD)]SbF6 or combination of [Rh(COD)2]SbF6 with (S,S)-BDPP
is inactive. Therefore, it can be proposed that chiral dienes
coordinate to rhodium in monodentate fashion in the enantiodis-
criminating step A.
In summary, we have succeeded in a highly enantioselective
intramolecular [4 + 2] cycloaddition catalyzed by cationic chiral
Rh complexes bearing not only chiral phosphine but also chiral
diene. This is the first example of asymmetric synergy between
chiral dienes and diphosphines. Further studies on the synergy effect
on asymmetric catalysis are underway.14
Supporting Information Available: Typical experimental proce-
dures and spectral data for 1, 2, and [RhCl(diene*)]2. This material is
available free of charge via the Internet at http://pubs.acs.org.
entry
substrate
diene*
PP* ligand
time
yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1a
1d
1e
3
3
3
3
3
3
3
3
3
4
5
4
3
3
3
3
30 min
(S,S)-CHIRAPHOS 1 h
91
61
27
51
81
94
90
96
85
82
68
51
91
99
89
97
26
22
30
26
29
28
88
-9d
26
91
87
81
93
95
86
98
References
(S)-BINAP
(R)-BINAP
(S)-DM-BINAP
(R)-DM-BINAP
3 h
3 h
30 min
30 min
(1) (a) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. ComprehensiVe Asymmetric
Catalysis; Springer: Berlin, 1999; Vols. 1-3. (b) Yamamoto, H. Lewis
Acids in Organic Synthesis; Wiley-VCH: New York, 2000; Vols. 1-2.
(c) Kobayashi, S.; Jørgensen, K. A. Cycloaddition Reaction in Organic
Synthesis; Wiley-VCH: New York, 2002. (d) Lautens, M.; Klute, W.;
Tam, W. Chem. ReV. 1996, 96, 49-92.
(R,R)-Me-DUPHOS 40 min
(S,S)-Me-DUPHOS 60 min
(2) Evans, P. A. Modern Rhodium-Catalyzed Organic Reactions; Wiley-
VCH: New York, 2005.
9a
10
11
12
13
14
15
16
PPh3
30 min
(3) Intramolecular [4 + 2] cycloaddition: (a) Wender, P. A.; Jenkins, T. E.
J. Am. Chem. Soc. 1989, 111, 6432-6434. (b) Jolly, R. S.; Luedtke, G.;
Sheehan, D.; Livinghouse, T. J. Am. Chem. Soc. 1990, 112, 4965-4966.
(c) Wender, P. A.; Jenkins, T. E.; Suzuki, S. J. Am. Chem. Soc. 1995,
117, 1843-1844. (d) Wender, P. A.; Smith, T. E. J. Org. Chem. 1996,
61, 824-825. (e) Gilbertson, S. R.; Hoge, G. S. Tetrahedron Lett. 1998,
39, 2075-2078. (f) Kumar, K.; Jolly, R. S. Tetrahedron Lett. 1998, 39,
3047-3048. (g) Paik, S. J.; Son, S. U.; Chung, Y. K. Org. Lett. 1999, 1,
2045-2047. (h) Wang, B.; Cao, P.; Zhang, X. Tetrahedron Lett. 2000,
41, 8041-8044. (i) Motoda, D.; Kinoshita, H.; Shinokubo, H.; Oshima,
K. Angew. Chem., Int. Ed. 2004, 43, 1860-1862. (j) Yoo, W. J.; Allen,
A.; Villeneuve, K.; Tam, W. Org. Lett. 2005, 7, 5853-5856. (k) Lee, S.
I.; Park, S. Y.; Park, J. H.; Jung, I. G.; Choi, S. Y.; Chung, Y. K. J. Org.
Chem. 2006, 71, 91-96. (l) Saito, A.; Ono, T.; Takahashi, A.; Taguchi,
T.; Hanzawa, Y. Tetrahedron Lett. 2006, 47, 891-895.
(R,R)-Me-DUPHOS 2 h
(R,R)-Me-DUPHOS 50 min
(R,R)-Me-DUPHOS 2.5 h
(R,R)-Me-DUPHOS 5 h
(R,R)-Et-DUPHOS
(R,R)-Et-DUPHOS
(R,R)-Et-DUPHOS
2 h
2 h
1.5 h
a Rh:ligand:AgSbF6 ) 1:2.2:2. b Isolated yield. c Enantiopurity was
determined by chiral GC analysis on a CP-cyclodextrin-â-2,3,6-M-19.
d Opposite configuration.
(4) Intermolecular [4 + 2] cycloaddition: (a) Matsuda, I.; Shibata, M.; Sato,
S.; Izumi, Y. Tetrahedron Lett. 1987, 28, 3361-3362. (b) Murakami, M.;
Ubukata, M.; Itami, K.; Ito, Y. Angew. Chem., Int. Ed. 1998, 37, 2248-
2250. (c) Paik, S. J.; Son, S. U.; Chung, Y. K. Org. Lett. 1999, 1, 2045-
2047.
(5) For the Rh(I) catalysts, see: (a) McKinstry, L.; Livinghouse, T.
Tetrahedron 1994, 50, 6145-6154. (b) O’Mahony, D. J. R.; Belanger,
D. B.; Livinghouse, T. Synlett 1998, 443-445. (c) Gilbertson, S. T.; Hoge,
G. S.; Genov, D. G. J. Org. Chem. 1998, 63, 10077-10080. (d) Heath,
H.; Wolfe, B.; Livinghouse, T.; Bae, S. K. Synthesis 2001, 2341-2347.
For the Ir(I) catalysts, see: (e) Shibata, T.; Takasaku, K.; Takesue, Y.;
Hirata, N.; Takagi, K. Synlett 2002, 1681-1682.
(6) Bakos, J.; To´th, I.; Heil, B.; Marko´, L. J. Organomet. Chem. 1985, 279,
23-29.
(7) Mikami, K.; Yusa, Y.; Hatano, M.; Wakabayashi, K.; Aikawa, K. Chem.
Commun. 2004, 98-99.
(8) (a) Lei, A.; He, M.; Wu, S.; Zhang, X. Angew. Chem., Int. Ed. 2002, 41,
3457-3460. (b) Lei, A.; He, M.; Zhang, X. J. Am. Chem. Soc. 2002,
124, 8198-8199. (c) Lei, A.; Waldkirch, J. P.; He, M.; Zhang, X. Angew.
Chem., Int. Ed. 2002, 41, 4526-4529.
Figure 1. Plausible reaction mechanism.
pair. The enantioselectivity was increased to 91% ee by 4 instead
of 3 (entry 10). In the case of 5, the enantioselectivity slightly
decreased (entry 11). A variety of Rh complexes bearing a achiral
diene, such as COD or NBD, have been used for catalytic
cycloadditions.3-5,7,8 However, there has been no report on the effect
of dienes in detail.
Dieneyne substrates 1b-e with aromatic terminal substituents
were further examined under the optimized conditions. The reactions
were shown to be effective with both electron-withdrawing and
-donating aromatic substituents. Specifically, CF3 substituents 1e
gave the highest level of enantioselectivity by use of (R,R)-Et-
DUPHOS (97%, 98% ee) (entry 16).
In a plausible mechanism (Figure 1), the substrate-coordinated
intermediate A forms, and then oxidative cyclization3a,b,h of dieneyne
substrate 1 affords the metallacyclopentane. Subsequently, allyl
rearrangement and, finally, the reductive elimination produces the
desired cyclization product 2. Another possible intermediate B,
where both chiral diene and diphosphine coordinate to Rh in
(9) Dang, T. P.; Kagan, H. B. J. Chem. Soc., Chem. Commun. 1971, 481-
482.
(10) Burk, M. J. J. Am. Chem. Soc. 1991, 113, 8518-8519.
(11) Recently, chiral dienes have successfully been applied as effective ligands
for asymmetric reactions. In our case, the C1 symmetrical chiral dienes,
which were reported by Carreira et al., were selected due to easy
preparation from a commercially available carvone: (a) Hayashi, T.;
Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125,
11508-11509. (b) Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E. M.
J. Am. Chem. Soc. 2004, 126, 1628-1629. (c) La¨ng, F.; Breher, F.; Stein,
D.; Gru¨tzmacher, H. Organometallics 2005, 24, 5148-5158.
(12) Fryzuk, M. D.; Bosnich, B. J. Am. Chem. Soc. 1977, 99, 6262-6267.
(13) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, T.; Ito, K.; Souchi, T.;
Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932-7934.
(14) (a) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am.
Chem. Soc. 1995, 117, 2675-2676. (b) Noyori, R.; Ohkuma, T. Angew.
Chem., Int. Ed. 2001, 40, 40-73. (c) Matsukawa, S.; Mikami, K.
Tetrahedron: Asymmetry 1995, 6, 2571-2574. (d) Matsukawa, S.; Mikami,
K. Enantiomer 1996, 1, 69-73. (e) Mikami, K.; Matsukawa, S. Nature
1997, 385, 613-615. (f) Mikami, K.; Terada, M.; Korenaga, T.;
Matsumoto, Y.; Ueki, M.; Angelaud, R. Angew. Chem., Int. Ed. 2000,
39, 3532-3556. (g) Mikami, K.; Aikawa, K.; Yusa, Y.; Jodry, J. J.;
Yamanaka, M. Synlett 2002, 10, 1561-1578.
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