Racemic but tropos (chirally flexible) BIPHEP ligands for Rh(I)-complexes: Highly enantioselective ene-type cyclization of 1,6-enynes

Article abstract of DOI:10.1021/ol048604l

(Chemical Equation Presented) The tropos (chirally flexible) or atropos (chirally rigid) nature of BIPHEP-Rh complexes at room temperature critically depends on the amines complexed. The aliphatic DPEN complex is atropos, whereas the aromatic DABN complex

Full text of DOI:10.1021/ol048604l

ORGANIC
LETTERS
2004
Vol. 6, No. 21
3699-3701
Racemic but Tropos (Chirally Flexible)
BIPHEP Ligands for Rh(I)-Complexes:
Highly Enantioselective Ene-Type
Cyclization of 1,6-Enynes
Koichi Mikami,* Shohei Kataoka, Yukinori Yusa, and Kohsuke Aikawa
Department of Applied Chemistry, Tokyo Institute of Technology,
Tokyo 152-8552, Japan
kmikami@o.cc.titech.ac.jp
Received July 20, 2004
ABSTRACT
The tropos (chirally flexible) or atropos (chirally rigid) nature of BIPHEP
complexed. The aliphatic DPEN complex is atropos, whereas the aromatic DABN complex is tropos. BIPHEP
by DABN at room temperature. The amine-free BIPHEP Rh complex is tropos. At 5 C, even amine-free BIPHEP
and hence can be used as enantiopure catalysts to give high enantioselectivity in ene-type cyclization of 1,6-enynes.
−
Rh complexes at room temperature critically depends on the amines
Rh chirality can thus be controlled
Rh complexes are atropos
−
−
°
−
Despite enantioresolution and synthetic transformation, many
enantiopure atropisomeric (atropos in Greek; a ) not, tropos
) turn)1 ligands are synthesized and used in catalytic
asymmetric reactions.2 In sharp contrast, we have succeeded
in asymmetric catalysis using racemic but chirally flexible
(tropos)1 bis(phosphanyl)biphenyl (BIPHEP) ligand,3,4a of
which the axial chirality can be controlled by a chiral
controller. Thus, the BIPHEPs-Ru and -Pd complexes
afford high enantioselectivity in asymmetric hydrogenation
and Diels-Alder reactions, respectively.4 The complexes
bearing BIPHEPs are inherently tropos, but high levels of
enantioselectivity can be achieved under appropriate condi-
tions depending on the central metals employed. Ru com-
plexes are tropos, but Pd complexes are, by contrast, atropos
at room temperature. Thus, the question arises with BIPHEP-
complexes of Rh in the same row between Ru and Pd: tropos
or atropos at room temperature?5
(1) Mikami, K.; Aikawa, K.; Yusa, Y.; Jodry, J. J.; Yamanaka, M. Synlett
2002, 10, 1561-1578.
(2) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. ComprehensiVe Asym-
metric Catalysis; Springer: Berlin, 1999; Vols. 1-3.
(3) The activation barrier to axial torsion in selectivity deuterated BIPHEP
is measured to be only (22 ( 1) kcal, which suggests that axial rotation
takes place at room temperature or above: Desponds, O.; Schlosser, M.
Tetradedron Lett. 1996, 37, 47-48.
(4) For the BIPHEP-Ru complex: (a) Mikami, K.; Korenaga, T.; Terada,
M.; Ohkuma, T.; Pham, T.; Noyori, R. Angew. Chem., Int. Ed. 1999, 38,
495-497. For the BIPHEP-Pd complex: (b) Mikami, K.; Aikawa, K.;
Yusa, Y.; Hatano, M. Org. Lett. 2002, 4, 91-94. (c) Mikami, K.; Aikawa,
K.; Yusa, Y. Org. Lett. 2002, 4, 95-97. For the BIPHEP-Pt complex:
(d) Tudor, M. D.; Becker, J. J.; White, P. S.; Gagne´, M. R. Organometallics
2000, 19, 4376-4484. (e) Becker, J. J.; White, P. S.; Gagne´, M. R. J. Am.
Chem. Soc. 2001, 123, 9478-9479.
Herein, we report chiral control of tropos BIPHEPs-Rh
complexes at room temperature (25 °C) and their application
as atropos catalysts for highly enantioselective ene-type
cyclization of 1,6-enynes at 5 °C.
(5) A half-life of 1000 s (16.7 min) is considered as the minimum
requirement for atropos molecules; cf. Oki, M. Top. Stereochem. 1983,
14, 1-81.
10.1021/ol048604l CCC: $27.50
© 2004 American Chemical Society
Published on Web 09/23/2004

Scheme 1
The reaction of racemic BIPHEP-Rh complex6 in non-
polar solvents such as dichloromethane under hydrogen (1
atm) gave a dimeric BIPHEP-Rh complex (Scheme 1). The
dimer complexes7 consisted of homo- and hetero-chiral ones
in a 40:60 ratio, but the hetero-chiral complex isomerized
slowly to the homo-chiral one at room temperature over 48
h.8
Figure 1. Solvent effect on chiral control of BIPHEP-Rh/DABN
complex. The diastereomeric ratios were determined by 31P and
1H NMR at room temperature.
The complexation of the BIPHEP-Rh complex and an
equimolar amount of (R,R)-DPEN (1,2-diphenylethylene-
diamine) as a chiral controller was examined to give a
mixture of diastereomers in a 50:50 ratio (eq 1). Unfortu-
nately, no change was observed in the diastereomeric ratio
at room temperature regardless of solvents.
Next, an equimolar amount of (R)-DABN (2,2′-diamino-
1,1′-binaphthyl) was added under a similar condition, to give
a mixture of diastereomers in a R,R/S,R 46:54 ratio (eq 2).
However, the isomerization proceeded slowly in dichloro-
methane at room temperature, leading eventually to the single
R,R diastereomer after 17 days (Figure 1). As a solvent effect,
the complexation in polar solvents such as methanol gave a
different diastereomer ratio R,R/S,R 56:44, and the isomer-
ization was found to be faster to afford the single R,R
diastereomer within 72 h. The single R,R diastereomer could
also be obtained at 80 °C in dichloroethane within 5 h.
However, isomerization was not observed at 5 °C in either
solvent.
It is thus clarified that the tropos or atropos nature of
BIPHEP-Rh complexes at room temperature critically
depend on the amines complexed. The aliphatic DPEN
complex is atropos, whereas the aromatic DABN complex
is tropos. Furthermore, the amine-free BIPHEP-Rh com-
plexes are tropos, as proven after amine complexation.
However, at 5 °C or below, even amine-free BIPHEP-Rh
complexes are atropos and hence can be used as chiral
catalysts.
The enantiopure Rh-complexes obtained via heat pretreat-
ment (80 °C in dichloroethane for 5 h) could be used as
asymmetric catalysts for ene-type cyclization9 of 1,6-enyne
substrate 1 by addition of TfOH to protonate diamines off
the Rh metal center (Table 1). BIPHEP-Rh gave the desired
cyclic product 2 in good yield but in moderate enantio-
selectivity at room temperature (entry 1). Without TfOH,
the reaction was very slow (12.5 h) (entry 2). Using DM-
BIPHEP (DM ) 3,5-dimethy-phenyl) instead of BIPHEP,
(6) Crystal data for BIPHEP-Rh complex in X-ray analysis: formula
C46H44F6P2RhSbCl2, monoclinic, space group P21/n (No. 14), a ) 14.065-
(4) Å, b ) 13.737(4) Å, c ) 21.407(56) Å, â ) 89.5260(1)°, V ) 4097.9-
(21) Å3, Z ) 4, and D ) 1.732 g cm-3. X-ray diffraction data were collected
on a Rigaku Saturn 70 CCD system with graphite-monochromated Mo KR
(λ ) 0.71070 Å) at -100 °C and the structure was solved by direct methods
(SIR92). The final cycle of full-matrix least-squares refinement on F2 was
based on 12097 observed reflections and 542 variable parameters and
converged to R ) 0.076 and Rw ) 0.179. Goodness of fit ) 1.084, shift/
error ) 0.006. Crystallographic data (excluding structure factors) for the
structure reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no. CCDC-
241306. Copies of the data can be obtained free of charge on application
to CCDC, 12 Union Road, Cambridge CB21EZ, U.K. Fax: (+44)1223-
336-033; E-mail: deposit@ccdc.cam.ac.uk.
(7) For the BINAP-Rh complex: Takaya, H.; Miyashita, A.; Souchi,
T.; Noyori, R. Tetrahedron 1984, 40, 1245-1253. For the X-ray analysis
of DPPE-Rh complex: Halpern, J.; Rily, D. P.; Chan, A. S. C.; Pluth, J. J.
J. Am. Chem. Soc. 1977, 8055-8057.
(8) 31P NMR (162 MHz, CD2Cl2): heterochiral δ 39.8 (dd, J ) 193.3,
49.6 Hz), 43.3 (dd, J ) 209.5, 49.6 Hz); homochiral δ 40.8 (dd, J ) 192.3,
48.8 Hz), 44.6 (dd, J ) 209.5, 48.8 Hz). For the homochiral dimer (R)-
BINAP-Rh complex: 31P NMR (162 MHz, CD2Cl2) δ 42.7 (dd, J ) 195.5,
43.6 Hz), 46.4 (dd, J ) 211.4, 43.6 Hz).
3700
Org. Lett., Vol. 6, No. 21, 2004

Table 1. Enantioselective Ene-Type Cyclization of
1,6-Enyne 1a
Table 2. Enantioselective Ene-Type Cyclization of 1,6-Enynesa
entry
R1
R2
time (h)
yieldb (%)
eed (%)
yieldc (%)
1
2
3
4
H (4a )
Me
Me
Me
Et
14
14
14
19
99 (5a )
20c (5b)
84 (5c)
81 (5d )
94 (-)
94 (-)
88 (-)
89 (-)
OMe (4b)
Cl (4c)
H (4d )
entry
P-P
T (°C)
time
2
3
eed (%)
1
2b
3
4
(R)-BIPHEP
(R)-BIPHEP
(R)-DM-BIPHEP
(R)-DM-BIPHEP
25
25
25
5
30 min
12.5 h
5 min
3 h
84
74
70
83
59 (-)
56 (-)
85 (-)
96 (-)
a All reactions were examined after preheating at 80 °C for 5 h. b Yield
of isolated product. c Most of 1,6-enyne substrate 4b was decomposed.
d Enantiopurity was determined by HPLC analysis.
23
5
a All reactions were examined after preheating at 80 °C for 5 h. b The
reaction was examined without TfOH. c Yield of isolated product. d Enan-
tiopurity was determined by chiral GC analysis on a CP-Cyclodextrin-â-
2,3,6-M-19 column.
As expected, at room temperature, enantioselectivity was
decreased from 94% ee after 1 min to 86% ee after 1 h.
However, at 5 °C, enantioselectivity (94% ee) did not change
at all throughout the reaction time. Furthermore, the ene-
product of 94% ee did not racemize under the reaction
conditions even at room temperature.
both the activity and enantioselectivity of the Rh catalyst
increased, however, along with the formation of achiral
conjugated 1,3-diene 3 in 23% yield (entry 3). At lower
temperature (5 °C), DM-BIPHEP-Rh complex exhibited
high enantioselectivity and chemical yield of 2 (96% ee,
83%) with only 5% yield of undesired 3 (entry 4). After the
ene-type reaction, the enantiopure form of the amine-free
BIPHEP-Rh complex was confirmed by adding (R)-DABN.
Because racemization of the DM-BIPHEP-Rh complex
might proceed during the reaction, the change in enantiomeric
excess (% ee) was examined with progress of the reaction
by choosing substrate 4a not to give a 1,3-diene product.
Therefore, 1,6-enyne substrates 4a-d with aromatic
terminal substituents were examined at 5 °C (Table 2). All
of the reactions were shown to be effective with both
electron-withdrawing and -donating substituents except for
low yield obtained with MeO-substrate (4b).
In conclusion, we have established the high levels of
enantioselectivity in ene-type cyclization of 1,6-enynes
catalyzed by BIPHEPs-Rh complexes despite the racemic
and tropos ligands, through chiral control. Further applica-
tions of BIPHEPs-Rh complexes in asymmetric catalysis and
chiral control of other metal complexes bearing BIPHEP
ligands are now in progress.
(9) For reviews on ene-type cycloisomerization: (a) Trost, B. M. Acc.
Chem. Res. 1990, 23, 34-42. (b) Ojima, I.; Tzamarioudaki, M.; Li, Z.;
Donovan, R. J. Chem. ReV. 1996, 96, 635-662. (c) Trost, B. M. Chem.
Eur. J. 1998, 4, 2405-2412. (d) Trost, B. M.; Krische, M. J. Synlett 1998,
1-16. (e) Aubert, C.; Buisine, O.; Malacria, M. Chem. ReV. 2002, 102,
813-834. (f) Mendez, M.; Victor, M.; Fu¨rstner, A. Chemtracts Org. Chem.
2003, 16, 397-425. (g) He, M.; Zhang, X. J. Am. Chem. Soc. 2002, 124,
8198-8199. (h) Lei, A.; He, M.; Wu, S.; Zhang, X. Angew. Chem., Int.
Ed. 2002, 41, 3457-3460. (i) Lei, A.; Waldkirch, J. P.; He, M.; Zhang, X.
Angew. Chem., Int. Ed. 2002, 41, 4526-4529. (j) Mikami, K.; Hatano, M.
Proc. Natl. Acad. Sci. U.S.A. 2004, 20, 5767-5769. (k) Hatano, M.; Mikami,
K. J. Am. Chem Soc. 2003, 125, 4704-4705. (l) Mikami, K.; Yusa, Y.;
Hatano, M.; Wakabayasi, K.; Aikawa, K. Chem. Commun. 2004, 98-99.
Supporting Information Available: Typical experimen-
tal procedures and spectral data for BIPHEPs-Rh complexes
and 1-5, including CIF files. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL048604L
Org. Lett., Vol. 6, No. 21, 2004
3701