An application of electronic asymmetry to highly enantioselective catalytic Diels-Alder reactions

Article abstract of DOI:10.1021/ja003528c

The compounds (R_Ru)-[CyRuCl(S)-BINPO]SbF₆ and [CyRuCl(S)-TolBINPO]SbF₆ (Cy = η⁶-cymene), were synthesized from (CyRuCl₂)₂ and the appropriate non-C₂-symmetric bisphosphine monoxide ligands (S)BINPO and (S)-TolBINPO (BINPO = 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) in the presence of NaSbF₆. When these complexes were mixed with AgSbF₆ the resulting Lewis acids catalyzed the Diels-Alder cycloaddition of cyclopentadiene and methacrolein. The product (2S)-methylbicyclo[2.2.1]hept-5-ene-2-carboxaldehyde was obtained with excellent diastereoselectivity (up to 99%) and enantioselectivity (up to 99%) in several cases. When the complexes containing the analogous C₂-symmetric bisphosphine ligands (S)-BINAP and (S)-TolBINAP were employed as catalysts, the Diels-Alder cycloadducts were obtained with much lower enantioselectivity (19 to 50%) for the opposite antipode. Although some of the effect may arise from chelate ring size change, much of the enhanced stereoselectivity of (R_Ru)-[CyRuCl(S)-BINPO]SbF₆ and [CyRuCl(S)-TOlBINPO]SbF₆ can be attributed to the electronic asymmetry at the stereogenic Ru center.

Full text of DOI:10.1021/ja003528c

J. Am. Chem. Soc. 2001, 123, 2525-2529
2525
An Application of Electronic Asymmetry to Highly Enantioselective
Catalytic Diels-Alder Reactions
J. W. Faller,* Brian J. Grimmond, and Darlene G. D’Alliessi
Contribution from the Department of Chemistry, Yale UniVersity, 225 Prospect Street,
New HaVen, Connecticut 06520
ReceiVed September 28, 2000
Abstract: The compounds (RRu)-[CyRuCl(S)-BINPO]SbF6 and [CyRuCl(S)-TolBINPO]SbF6 (Cy ) η6-cymene),
were synthesized from (CyRuCl2)2 and the appropriate non-C2-symmetric bisphosphine monoxide ligands (S)-
BINPO and (S)-TolBINPO (BINPO ) 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) in the presence of NaSbF6.
When these complexes were mixed with AgSbF6 the resulting Lewis acids catalyzed the Diels-Alder
cycloaddition of cyclopentadiene and methacrolein. The product (2S)-methylbicyclo[2.2.1]hept-5-ene-2-
carboxaldehyde was obtained with excellent diastereoselectivity (up to 99%) and enantioselectivity (up to
99%) in several cases. When the complexes containing the analogous C2-symmetric bisphosphine ligands
(S)-BINAP and (S)-TolBINAP were employed as catalysts, the Diels-Alder cycloadducts were obtained with
much lower enantioselectivity (19 to 50%) for the opposite antipode. Although some of the effect may arise
from chelate ring size change, much of the enhanced stereoselectivity of (RRu)-[CyRuCl(S)-BINPO]SbF6 and
[CyRuCl(S)-TolBINPO]SbF6 can be attributed to the electronic asymmetry at the stereogenic Ru center.
Introduction
ties of the ligands initially attached to the metal. Electronic
effects have also been observed in catalytic systems, such as
the hydroformylation of olefins with Rh-based catalysts, for
which C1-symmetric ligands containing mixed bisphosphines
have been shown to influence linear:branched regioselectivity.6
Also, Achiwa demonstrated how catalyst activity and enanti-
oselectivity were modulated by the choice of phosphine aryl
substituents in mixed bisphosphine systems.7 Electronic asym-
metry has been proposed to account for the improved enanti-
oselectivity in numerous metal-catalyzed organic transforma-
tions, including olefin epoxidation,8 the hydrocyanation of vinyl
arenes,9 olefin hydroformylation,10 aldol reactions,11 and the
hydrogenation of dehydroaminoesters and itaconate esters.12 We
have recently investigated the synthesis of bisphosphine mon-
oxide complexes of Ru and Os where the metal center is
chiral.3,13 Included in this series was the compound (RRu)-
[CyRuCl(S)-BINPO]SbF6 [1; Cy ) cymene, BINPO ) (2-
diphenylphosphino,2′-diphenylphosphineoxide)-binaphthyl] which
was confirmed to be an active in situ Lewis acid cocatalyst for
the Diels-Alder reaction of methacrolein and cyclopentadiene
with moderate enantioselectivity. Recently, several compounds
containing stereogenic metal centers have been identified as
Diels-Alder catalysts, although the degree of enantioselectivity
The implementation of enantiopure organometallic catalysts
is an increasingly versatile methodology in asymmetric organic
synthesis.1 Typically, bidentate C2-symmetric enantiopure ligand
sets are employed as auxiliaries to the metal center to control
the stereochemical assembly of an organic substrate at the
catalyst site. In many instances, optimum stereoselectivity for
a particular asymmetric event is realized when using ligands of
C2-symmetry because the number of diastereomeric transition
states during the stereodetermining step is reduced, relative to
ligands of lower symmetry.2 However, an alternative approach
relies on the employment of non-C2-symmetric heterobidentate
enantiopure ligands which engender electronic asymmetry at
the metal center.3 Perturbation of the metal electronic character
can generate a superior chiral site in cases where catalytic
intermediates do not inherently possess symmetry similar to that
of the chiral ligand.4 For these situations, the selective binding
and orientation of an organic substrate prior to a stereoselective
procedure facilitates manipulation of the catalytic event with
greater stereocontrol.
We have successfully used unsymmetrical transition metal
complexes containing stereogenic metal centers as stoichiometric
reagents to functionalize prochiral organic molecules enanti-
oselectively.5 The source of enantioselectivity was attributed
to the preferential orientation of the metal-bound organic
precursor that was determined by the different bonding proper-
(6) Casey, C. P.; Paulsen, E. L.; Beuttenmeuller, E. W.; Proft, B. R.;
Matter, B. A.; Powell, D. R. J. Am. Chem. Soc. 1999, 121, 63.
(7) Inoguchi, K.; Sakurabu, S.; Achiwa, K. Synlett 1992, 169.
(8) Jacobsen, E. N.; Zhang, W.; Guler, M. L. J. Am. Chem. Soc. 1991,
113, 6703.
(9) (a) Rajanbabu, T. V.; Casalnuovo, A. L. J. Am. Chem. Soc. 1996,
118, 6325. (b) Casalnuovo, A. L.; Rajanbabu, T. V.; Ayers, T. A.; Warren,
T. H. J. Am. Chem. Soc. 1994, 116, 9869. (c) Rajanbabu, T. V.; Casalnuovo,
A. L. J. Am. Chem. Soc. 1992, 114, 6265.
(10) Ayers, T. A.; Rajanbabu, T. V. Tetrahedron Lett. 1994, 35, 4295.
(11) Pastor, S.; Togni, A. J. Am. Chem. Soc. 1989, 111, 2333.
(12) Rajanbabu, T. V.; Ayers, T. A.; Casalnuovo, A. L. J. Am. Chem.
Soc. 1994, 116, 4101.
(1) Foote, C. S. Acc. Chem. Res. 2000, 6, 323ff. Entire issue (pp 323-
440) devoted to Catalytic Asymmetric Synthesis.
(2) (a) Trost, B. Chem. ReV. 1996, 96, 395. (b) Brown, J. M. Chem.
Soc. ReV. 1993, 22, 25.
(3) Faller, J. W.; Liu, X.; Parr, J. Chirality 2000, 12, 325. (b) Faller, J.
W.; Patel, B. P.; Albrizzio, M. A.; Curtis, M. Organometallics 1999, 18,
3096
(4) Carmichael, D.; Doucet, H.; Brown, J. M. Chem. Commun. 1999,
261.
(5) (a) Faller, J. W.; Linebarrier, D. L. J. Am. Chem. Soc. 1989, 111,
1937. (b) Faller, J. W.; Mazzieri, M. R. Tetrahedron Lett. 1989, 30, 1769.
(13) (a) Faller, J. W.; Parr, J. Organometallics 2000, 19, 3556. (b) Faller,
J. W.; Parr, J. Organometallics 2000, 19, 1829.
10.1021/ja003528c CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/27/2001

2526 J. Am. Chem. Soc., Vol. 123, No. 11, 2001
Faller et al.
has not yet reached acceptable levels.14 Reported here is our
preliminary study on optimizing the cycloaddition reaction of
cyclopentadiene to R,â-enals with remarkably high (99%)
enantioselectivity with 1 as a catalyst precursor. Identical
catalytic assays with the C2-symmetric ligand equivalent, (S)-
BINAP, resulted in much poorer enantioselectivities, thus
providing an, as yet, rare instance where a transition metal
catalyst relying on the principles of electronic asymmetry
effectively promoted more stereoselective Diels-Alder reac-
tions.
Table 1. Diels-Alder Reactions of CpH Catalyzed by
[CyRu(S)-BINPO](SbF6)2
catalysta
entry (R) loading (%) (°C) product
temp
conversion de
ee (%)
[config]
(%)
(%)
1 (Me)
2 (Me)
3 (Me)
4 (Me)
5 (Me)b
6 (Et)
7 (Et)
8 (Br)
9 (Br)
10
1
10
1
10
10
10
10
10
-78
-78
-24
-24
-78
-78
-24
-78
-24
4
4
4
4
4
5
5
6
6
100
100
100
100
5
100
100
100
100
93 99 [S-(+)]
91 92 [S-(+)]
99 94 [S-(+)]
95 85 [S-(+)]
3 [S-(+)]
Results and Discussion
The bisphosphine monoxide ligands (S)-BINPO and (S)-
TolBINPO [TolBINPO ) (2-di(p-tolyl)phosphino, 2′-di(p-tolyl)-
phosphineoxide)-binaphthyl] were synthesized according to the
method described by Grushin.15 In a procedure modified from
the original preparation for 1, the complexes (RRu)-[CyRuCl-
(S)-BINPO]SbF6 (1) and [CyRuCl(S)-TolBINPO]SbF6 (2) were
more conveniently produced from the corresponding ligands,
(CyRuCl2)2 and NaSbF6 in CH2Cl2 as shown in eq 1.13b Isolated
99 95
99 93
96 76
88 50
a All reactions except 5 were conducted in CH2Cl2 with the in situ
Lewis acid generated from [CyRuCl(S)-BINPO]SbF6 (11 mol %) and
AgSbF6 (10 mol %). b Assay conducted in the presence of 10 mol %
2,6-lutidine.
methacrolein and cyclopentadiene (10 equiv) was cleanly
converted to 2-methylbicyclo[2.2.1]hept-5-ene-2-carboxaldehyde
(4) with excellent enantioselectivity (94%) for (2S)-4 and exo
diastereoselectivity (99%) by using a 10 mol % catalyst loading
of 1 (11 mol %) and AgSbF6 (10 mol %) (Table 1).18 Cooling
the reaction mixture to -78 °C provided 4 with an enhanced
enantioselectivity of 99% for (2S)-4 under otherwise identical
conditions. As shown in Table 1, when the catalyst loading was
decreased to 1 mol %, there was a noticeable drop in enanti-
oselectivity at -24 °C, although at -78 °C the product 4 was
as analytically pure red solids in excellent yield (85%, 1; 88%,
1
2), characterization by H, 13C{1H}, and 31P{1H}NMR spec-
troscopy revealed that 1 was obtained as a single diastereomer
(RRu, S), as established by X-ray crystallography, whereas 2
contained a 10:1 mixture of diastereomers, presumably with
(RRu, S) as the major component.3b
1
still obtained with satisfactory enantiopurity. H NMR experi-
ments indicated that the reaction was complete after 2 h with
10 mol % catalyst; however, the reaction time was extended to
12 h at a 1 mol % loading to ensure 100% conversion of
methacrolein. When performed on a more preparative scale, 4
could be isolated after 100% conversion as a white solid in 84%
yield after workup (Table 1). As shown in Table 1, the
cycloadduct 2-ethylbicyclo[2.2.1]hept-5-ene-2-carboxaldehyde
(5) was also prepared from 2-ethylpropenal and CpH with
excellent enantioselectivity (95%) and exo diastereoselectivity
(99%) under identical catalytic conditions. Experiments with
the dienophile R-bromoacrolein and cyclopentadiene afforded
the corresponding product 2-bromobicyclo[2.2.1]hept-5-ene-2-
carboxaldehyde (6) with reduced stereoselectivity (76%, Table
1), albeit with complete conversion and satisfactory diastereo-
selectivity. Ku¨ndig has developed a bisphosphinite Ru assembly
that catalytically produced exo-6 with excellent enantioselectivity
when the basic additive 2,6-lutidine was included.19 With
catalyst 3, the inclusion of 2,6-lutidine in the reaction mixture
resulted in catalyst deactivation. Notably, in all experiments with
3, product work up required precipitation of the catalyst residue
from pentane as an orange solid that could then be isolated by
filtration. Spectroscopic examination of the postreaction catalyst
species indicated that the aquo complex, 3, was regenerated after
the catalytic event, available to be recycled for further experi-
ments.20
Compounds 1 and 2 were then investigated as Lewis acid
catalysts for the cycloaddition of CpH (CpH ) cyclopentadiene)
to several R-substitued R,â-enals given the application of some
bicyclo[2.2.1]hept-5-ene-2-carboxaldehydes to prostaglandin
synthesis.16 When a slight excess of 1 (1.1 equiv) was mixed
with AgSbF6, the resulting complex, 3, was activated toward
Lewis acid catalysis. 1H and 31P{1H} NMR spectroscopy
revealed that the resting state of the catalyst complex was the
diastereopure aqua adduct [CyRu(OH2)(S)-BINPO](SbF6)2 (3).
The aqua complex forms from trace water in the solvent and
exposure of reactants to the atmosphere.17 The reaction is
relatively insensitive to trace water and the use of careful inert
atmosphere technique is neither required nor does it have a
significant effect on selectivities. Small amounts of the chloride
precursor, 1, were also detected owing to the ratio of [Ag]:[1].
This ratio was chosen to avoid the presence of silver ion which
could act as a nonselective catalyst. At -24 °C, a mixture of
(14) (a) Davenport, A. J.; Davies, D. L.; Fawcett, J.; Garratt, S. A.; Lad,
L.; Russell, D. R. Chem. Commun. 1997, 2347. (b) Davies, D. L.; Fawcett,
J.; Garratt, S. A.; Russell, D. R. Chem. Commun. 1997, 1351. (c) Carmona,
D.; Cativiela, C.; Elipe, S.; Lahoz, F. J.; Lamata, M. P.; Lo´pez-Ram de
V´ıu, M. P.; Oro, L. A.; Vega, C.; Viguri, F. Chem. Commun. 1997, 2351.
(15) Grushin, V. V. J. Am. Chem. Soc. 1999, 121, 5831.
(16) Corey, E. J.; Loh, T.-P. J. Am. Chem. Soc. 1991, 113, 8966.
(17) Aqua complexes are frequently observed in nonpolar solvents of
organometallic Lewis acids.14b,c Some specific examples are given in the
following. (a) Cp*Rh: Carmona, D.; Cativiela, C.; Garcia-Correas, R.;
Lahoz, F. J.; Lamata, M. P.; Lopez, J. A.; Viu, M. P. L.-R.; Oro, L. A.;
Jose, E. S.; Viguri, F. J. Chem. Soc., Chem. Commun. 1996, 1247. (b) Tp-
(i-Pr)Ru: Takahashi, Y.; Akita, M.; Hikichi, S.; Moro-oka, Y. Inorg. Chem.
1998, 37, 3186. (c) Tp(i-Pr)Ru: Takahashi, Y.; Hikichi, S.; Akita, M.; Moro-
oka, Y. Chem. Commun. 1999, 1491. (d) (PAN)Ru: Therrien, B.; Ward,
T. R. Angew. Chem., Int. Ed. 1999, 38, 405.
When the compound [CyRuCl(S)-TolBINPO](SbF6) (2) was
employed as the Lewis acid precatalyst for the Diels-Alder
(18) Hashimoto, S.-I.; Komeshima, N.; Koga, K. Chem. Commun. 1979,
437.
(19) Ku¨ndig, E. P.; Saudan, C. M.; Bernardinelli, G. Angew. Chem., Int.
Ed. 1999, 38, 1220.
(20) 31P{1H} NMR (CD2Cl3, 298 K) δ 66.4 (s, P[V]), δ 52.2 (s, P[III]).

Catalytic Diels-Alder Reactions
J. Am. Chem. Soc., Vol. 123, No. 11, 2001 2527
Table 3. [CyRu(S)-BINAP](SbF6)2 and
Table 2. Diels-Alder Reactions of CpH Catalyzed by
[CyRu(S)-TolBINPO](SbF6)2
[CyRu(S)-TolBINAP](SbF6)2 Lewis Acid Catalyzed Reaction of
CpH and Methacrolein
catalysta,b temp.
conversion de
ee (%)
entry (R) loading (%) (°C) product
(%)
(%) [config]
temp
conversion
(%)
de
(%)
ee (%)
[config]
entry (ligand)a (°C) product
1 (Me)
2 (Me)
3 (Et)
4 (Et)
5 (Br)
6 (Br)
10
10
10
10
10
10
-78
-24
-78
-24
-78
-24
4
4
5
5
6
6
15
100
10
100
6
96 98 [S-(+)]
98 93 [S-(+)]
99 91
1 (BINAP)
2 (BINAP)
-24
-78
4
4
4
4
100
100
19
93
82
99
99
50 [R-(-)]
19 [R-(-)]
26 [R-(-)]
24 [R-(-)]
3 (TolBINAP) -24
99 93
4 (TolBINAP) -78
15
86
68 10
a All reactions were conducted in CH2Cl2 with the in situ Lewis acid
generated from the cymeneruthenium dichloride complex (11 mol %)
and AgSbF6 (20 mol %).
a All reactions were conducted in CH2Cl2 with the in situ Lewis acid
generated from [CyRuCl-(S)-TolBINPO]SbF6 (11 mol %) and AgSbF6
(10 mol %). b The [CyRuCl-(S)-TolBINPO]SbF6 contained a 10:1
mixture of diastereomers, but this does not reflect the diastereomeric
composition of the catalytic species.
reaction of the R-alkyl R,â-enals and CpH, excellent product
selectivites were maintained (Table 2). Although a reaction
temperature of -24 °C afforded the cycloadducts 4 (98% de,
(S)-93% ee) and 5 (99% de, 93% ee) with 100% conversion,
the substrate conversion was considerably reduced at - 78 °C.
Slower conversion rates to 4 and 5 (10-15%) were observed
with the catalyst derived from 2 at low temperatures because
of the inductive effect of the p-tolyl aryl groups. Electron
donation to the Ru center moderated its Lewis acidity and
catalytic activity, although 4 and 5 were still obtained with high
optical yield (Table 2) indicating that the stereodifferentiation
of the chiral catalyst remained effective. The modified catalyst,
2, in fact proved to be a poor catalyst candidate for the synthesis
of the bromo analogue, 6, in all regards. The pronounced
sensitivity of the ruthenium center’s Lewis acidity to the
substitution pattern of the peripheral phosphino aryl substituents
shown here suggested that Lewis acidity can be predictably
manipulated. Presumably, catalytic activation of otherwise inert
organic substrates could be attained by appending phosphines
containing electron-deficient groups to the Lewis acid center.19
It was proposed that 1 and 2 were found to be effective
catalysts for the enantioselective synthesis of the bicyclic
moieties 4-6 by virtue of the stereogenic metal center. The
importance of electronic asymmetry to the degree of catalytic
asymmetric induction was then evaluated by investigation of
the cations produced by abstracting the halides from [CyRuCl-
(S)-BINAP]Cl (7) and [CyRuCl(S)-TolBINAP]Cl (8) as Diels-
Alder Lewis acid catalysts. In these instances, the Ru center
was not stereogenic and chiral induction during the catalytic
event relied on the influence of the C2-symmetric chiral
auxiliaries (S)-BINAP and (S)-TolBINAP. Precatalysts 7 and 8
were prepared according to literature protocols and catalytically
activated upon addition of 1.9 equiv of AgSbF6.21 Each catalyst
candidate was then screened and successfully promoted the
cycloaddition of methacrolein and CpH to 4 under conditions
identical to those previously described for the bisphosphine
monoxide analogues. As shown in Table 3, both 7 and 8
displayed moderate enantioselectivity (19-50%) at best for the
opposite antipode (R)-4, when compared to the superior
performance of the bisphosphine monoxide congeners (93-99%
(S)-4). Although some of the difference may arise from chelate
ring size effects, this stark contrast in reactivity clearly indicated
that the excellent catalytic stereoselectivity noted for 1 and 2
can be attributed to the use of the bisphosphine monoxide
ligands to generate an electronically asymmetric stereogenic
Lewis acidic Ru center.
Figure 1. Sterically encumbered (a) and stable (b) conformations of
a Ru-methacrolein intermediate.
interactions of stereogenic Ru centers with η1-coordinated
carbonyl π-systems have been previously shown to align
aldehyde ligands in the solid and solution state.22 The differential
bonding of the d orbitals aligned along the Ru-P and Ru-O
bonds with the carbonyl π and π* orbitals of the bound aldehyde
confines the enal to two orientations. That is, the P-Ru-OdC
dihedral angle is restricted to two values (∼0 and 180°). Steric
interactions then determine which of these two conformations
will be the most stable. As shown in Figure 1, conformation a
arranges the bulk of the methacrolein ligand toward the PPh2
functional group, generating significant steric hindrance between
those two moieties. Alternatively, conformer b orients the
methacrolein ligand toward the cavity created by the Ph2PdO
group of the bisphosphine monoxide ligand where there is
considerably less steric hindrance with the remote arylphosphino
groups. It is likely, therefore, that b is the actual conformation
adopted in solution given the ability of the sterically modest
PdO group to accommodate the methacrolein ligand. Fixed in
this key conformational state, the trajectory of a reagent toward
the methacrolein CR Re-diastereoface would be blocked by the
binaphthyl and aryl rings, whereas the CR Si-diastereoface would
remain exposed. The culmination of these effects organizes a
well-defined catalyst-substrate structure that facilitates a
controlled approach of CpH to the methacrolein CR Si-
diastereoface giving the (S)-4 enantiomer (Figure 2). For the
simpler bisphosphine analogues, 7 and 8, this implies that the
interface between chiral catalyst and prochiral substrate is less
well-defined in terms of both conformational selectivity and
alignment of the η1-bound aldehyde. This ultimately leads to
poorer enantioselectivity, as observed experimentally.
In conclusion, we have developed some novel chiral Lewis
acid complexes as effective catalysts for enantioselective Diels-
Alder reactions. The electronic asymmetry associated with the
stereogenic Ru center was found to be a critical factor in catalyst
stereorecognition. Future work will be concerned with expanding
(21) Mashima, K.; Kusano, K.; Ohta, K.; Noyori, R.; Takaya, H. Chem.
Commun. 1989, 1208.
(22) (a) Schilling, B. E. R.; Hoffmann, R.; Faller, J. W. J. Am. Chem.
Soc 1979, 101, 592. (b) Faller, J. W.; Ma, Y.; Smart, C. J.; Diverdi, M. J.
J. Organomet. Chem. 1991, 420, 237. (c) Garner, C. M.; Mendez, N. Q.;
Kowalczyk, J. J.; Fernancez, J. M.; Emerson, K.; Larsen, R. D.; Gladysz,
J. A. J. Am. Chem. Soc. 1990, 112, 5146. (d) Huang, Y. H.; Gladysz, J. A.
J. Chem. Educ. 1988, 65, 298.
The sense of stereochemical induction observed when using
catalysts derived from 1 and 2 can be best understood when
considering the two possible anti-s-trans conformations in the
η1-bound Ru-methacrolein intermediate. The preferential orbital

2528 J. Am. Chem. Soc., Vol. 123, No. 11, 2001
Faller et al.
reaction mixture was allowed to warm to ambient temperature and
stirred for 4 h. The dark red solution was filtered through Celite, with
washing of the Celite cake with CH2Cl2 (20 mL) until colorless. The
resultant red solution was concentrated (2 mL) and layered with Et2O
(20 mL). On standing, a red precipitate was isolated by syringe filtration
of the remaining orange solution. The sample was dried in vacuo to
give [CyRuCl(S)-TolBINPO]SbF6 (10:1 mixture of diastereomers) as
a dark red powder (0.36 g, 88% yield). 31P{1H} NMR (CDCl3, 298 K,
162 MHz): major diastereomer δ 53.5 (s, P[V]), 44.1 (s, P[III]); minor
1
diastereomer δ 53.9 (s, P[V]), 44.4 (s, P[III]). H NMR (CDCl3, 298
Figure 2. Proposed trajectory of CpH during reaction with [CyRu-
(S)-BINPO-OCHCMeCH2](SbF6)2 to give 2-(S)-exo-(4). The binaphthyl
and aryl rings block the methacrolein CR Re-diastereoface, leaving the
exposed Si-face open to attack from CpH.
K, 500 MHz): δ 8.02-6.44 (m, 28 H, Ar-H), 6.08 (d, J ) 6.0 Hz, 1
H, Cy-H), 5.90 (d, J ) 6.2 Hz, 1H, Cy-H), 5.63 (d, J ) 8.8 Hz, 1 H,
Ar-H), 5.37 (d, J ) 6.2 Hz, 1H, Cy-H), 4.56 (d, J ) 6.0 Hz, 1 H,
Cy-H), 2.56 (s, 3 H, Tol CH3), 2.49 (s, 3 H, Tol CH3), 2.47 (obs spt,
J ) 6.9 Hz, 1 H, Cy CHCH3), 2.01 (s, 3 H, Tol CH3), 1.98 (s, 3 H, Tol
CH3), 1.30 (s, 3 H, Cy CH3), 1.14 (d, J ) 6.9 Hz, 3 H, Cy CHCH3),
0.93 (d, J ) 6.9 Hz, 3 H, Cy CHCH3). 13C{1H} NMR (CDCl3, 298 K,
126 MHz): δ 145.11, 142.21, 142.01, 141.27, 141.13, 137.24, 137.17,
134.62-125.99, 110.73, 100.45, 97.04, 90.38, 83.90, 71.69, 31.19,
22.46, 22.26, 22.06, 21.73, 21.52, 21.09, 18.29. Anal. Calcd for C58H54-
OP2ClRuSbF6: C, 57.99; H, 4.53. Found: C, 58.58; H, 4.79.
General Catalytic Synthesis of exo-2-Methylbicyclo[2.2.1]hept-
5-ene-2-carboxaldehyde (4). A vial was charged with methacrolein
(0.15 g, 2.1 mmol) and CH2Cl2 (1 mL) followed by cooling for 0.5 h
at -24 °C. A centrifuge tube was charged with [CyRuCl(S)-BINPO]-
SbF6 (0.031 g, 0.023 mmol) and CH2Cl2 (1 mL). A sample of AgSbF6
(0.007 g, 0.021 mmol) was added to the reaction mixture under an N2
atmosphere and the walls of the tube were washed with CH2Cl2 (1
mL). The contents of the flask were mixed and a fine precipitate was
obtained after 10 min. The tube was centrifuged to provide a clear red
solution and a white precipitate. The catalyst solution was transferred
by syringe to the vial containing the methacrolein solution and the
reaction mixture was then allowed to cool for 0.5 h. An aliquot of
freshly distilled CpH (1.7 g, 21 mmol), which had been precooled at
-24 °C for at least 2 h, was then added by syringe to the reaction
mixture giving a clear red solution. After 12 h, the solution was
transferred to a flask where the solvent was removed under reduced
pressure to give an orange residue. The residue was extracted with
pentane (2 × 20 mL) and the pentane solution filtered through Celite
to provide a clear, colorless solution. The volatiles were removed under
reduced pressure to provide the target compound as white glassy solid
(0.235 g, 84% yield).
For the reactions carried out with 10 mol % catalyst, the concentra-
tion of the catalyst in CH2Cl2 was held constant and the same
experimental procedure was followed. The amount of the reactants was
decreased by a factor of 10. Reaction times were typically 12 h, although
1H NMR spectroscopy indicated that the reaction was over after 2 h.
Trace amounts of (CpH)2 were removed by filtration of the product
through a silica plug.
Analysis of ee and de. Conversion of acroleins to the corresponding
Diels-Alder product was determined by 1H NMR analysis of the crude
reaction mixture. The diastereomeric excess (de) was determined by
1H NMR spectroscopy by integration of the exo and endo aldehyde
proton resonances. The de provided in Tables 1-3 refers to the excess
of the exo diastereomer.
the scope of asymmetric organic reactions with such catalysts
to cases where conventional C2-symmetric catalysts fail to
provide products with satisfactory enantiomeric purity.
Experimental Section
The reactions were carried out by using standard inert atmosphere
techniques where necessary. The solvent CH2Cl2 and pentane were
distilled from CaH2 prior to use and degassed by 2 freeze-pump-
thaw cycles where necessary. The compounds NaSbF6 (Strem),
methacrolein, 2-ethylpropenal, AgSbF6, and reagent grade Et2O (Al-
drich) were used without purification. Cyclopentadiene was cracked
from dicyclopentadiene (Aldrich) prior to use; bromoacrolein16 and
23
(CyRuCl2)2 were prepared according to literature procedures. The
compounds (S)-BINPO and (S)-TolBINPO were prepared from (S)-
BINAP and (S)-TolBINAP (Strem), respectively, based on the literature
procedures.15 The 1H, 31P{1H}, and 13C{1H} NMR spectra were recorded
on a Bruker 400 or 500 MHz spectrometer at 25 °C unless stated
otherwise. The chiral shift experiments to determine product ee were
determined with use of Eu(hfc)3 (Aldrich).
Synthesis of [CyRuCl(S)-BINPO]SbF6 (1). A Schlenk tube was
charged with (CyRuCl2)2 (0.32 g, 0.52 mmol), NaSbF6 (0.27 g, 1.00
mmol), and (S)-BINPO (0.70 g, 1.10 mmol). The vessel was evacuated
and backfilled with N2 before immersion in a N2 bath. An aliquot of
CH2Cl2 (20 mL) was introduced by syringe giving a pale orange matrix
that was degassed by 2 freeze-pump-thaw cycles. The reaction
mixture was allowed to warm to ambient temperature and stirred for 4
h. The dark red solution was filtered through Celite, washing the Celite
cake with CH2Cl2 (20 mL) until colorless. The resultant red solution
was concentrated (3 mL) and layered with Et2O (20 mL). On standing,
a red precipitate was isolated by syringe filtration of the remaining
orange solution. The sample was dried in vacuo to give [CyRuCl(S)-
BINPO]SbF6 as a dark red powder (1.21 g, 85% yield). 31P{1H} NMR
(CDCl3, 298 K, 162 MHz): δ 53.0 (s, P[V]), 45.3 (s, P[III]). 1H NMR
(CDCl3, 298 K, 400 MHz): δ 8.06-6.58 (m, 30 H, Ar-H), 6.54 (d, J
) 8.7 Hz, 1 H, Ar-H), 6.13 (d, J ) 6.0 Hz, 1 H, Cy-H), 5.99 (d, J )
6.2 Hz, 1H, Cy-H), 5.68 (d, J ) 8.7 Hz, 1 H, Ar-H), 5.44 (d, J ) 6.2
Hz, 1H, Cy-H), 4.58 (d, J ) 6.0 Hz, 1 H, Cy-H), 2.48 (spt, J ) 6.9
Hz, 1 H, Cy CHCH3), 1.26 (s, 3 H, Cy CH3), 1.15 (d, J ) 6.9 Hz, 3
H, Cy CHCH3), 0.93 (d, J ) 6.9 Hz, 3 H, Cy CHCH3).13C{1H} NMR
(CDCl3, 298 K, 126 MHz): δ 137.40, 137.31, 134.76, 134.12, 133.38,
133.28, 133.07, 132.64, 131.78, 131.59, 131.32, 130.81, 130.53, 130.44,
130.23, 130.11, 129.97, 129.00, 128.88, 128.70, 128.61, 128.19, 127.73,
127.57, 127.11, 126.85, 126.51, 126.18, 110.96, 100.58, 97.29, 90.73,
84.27, 71.57, 31.27, 22.45, 22.34, 18.19. Anal. Calcd for C54H46OP2-
ClRuSbF6: C, 56.64; H, 4.05. Found: C, 56.14; H, 4.34.
2-Methylbicyclo[2.2.1]hept-5-ene-2-carboxaldehyde (4). 1H NMR
(CDCl3, 298 K, 500 MHz): δ 9.69 exo-CHO (major); δ 9.39 endo-
CHO (minor). The shift reagent Eu(hfc)3 was used to determine the
enantioselectivity of the exo diastereomer. It was observed that the
signal for the (S)-enantiomer was consistently shifted further downfield
than the signal for the (R)-enantiomer. When [CyRuCl(S)-BINPO]SbF6
and [CyRuCl(S)-TolBINPO]SbF6 were used as precatalysts, the (S)-
enantiomer was obtained as the major enantiomer. This was established
by comparison of the sign of the optical rotation to the literature
values.18 The enantioselectivity was then determined by line fitting
analysis (Peakfit 4.0, Jandel Scientific) of the two signals.
Synthesis of [CyRuCl(S)-TolBINPO]SbF6 (2). A Schlenk tube was
charged with (CyRuCl2)2 (0.10 g, 0.17 mmol), NaSbF6 (0.09 g, 0.34
mmol), and (S)-TolBINPO [0.35 g, 0.50 mmol; 31P{1H} NMR (CDCl3,
298 K, 162 MHz) δ 30 (s, P[V]), -15 (s, P[III])]. The vessel was
evacuated and backfilled with N2 before immersion in a N2 bath. An
aliquot of CH2Cl2 (10 mL) was introduced by syringe giving a pale
orange matrix that was degassed by 2 freeze-pump-thaw cycles. The
1
2-Ethylbicyclo[2.2.1]hept-5-ene-2-carboxaldehyde (5). H NMR
(CDCl3, 298 K, 500 MHz): δ 9.70 exo-CHO (major); δ 9.40 endo-
CHO (minor). Use of the chiral europium shift reagent failed to
distinguish the enantiomers. The enantioselectivity of the exo diaste-
reomer was determined by derivatization with (2R,4R)-2,4-pentanediol
(23) Bennett, M. A.; Huang, T.-N.; Methson, T. W.; Smith, A. K. Inorg.
Synth. 1982, 21, 75.

Catalytic Diels-Alder Reactions
J. Am. Chem. Soc., Vol. 123, No. 11, 2001 2529
to the corresponding diastereomeric acetals. Integration or line fitting
analysis (Peakfit 4.0, Jandel Scientific) of the resonances for the CHO2
protons δ 4.85 and 4.82 was used to determine the enantioselectivity.
When [CyRuCl(S)-BINPO]SbF6 and [CyRuCl(S)-TolBINPO]SbF6 were
used as precatalysts, the signal at δ 4.85 corresponded to the major
enantiomer. The configuration of the major enantiomer was not
determined, but is presumed to be the same as that found for the major
isomer found for methacrolein, i.e., (S).
tivity was then determined by line fitting analysis of the two signals.
The configuration of the major enantiomer was not determined.
Catalyst Studies of Cations Derived from 7 and 8. [CyRuCl(S)-
BINAP]Cl (7) and [CyRuCl(S)-TolBINAP]Cl (8) were prepared
according to published procedures.21 A mole ratio of 1.9:1 of AgSbF6
was added to CH2Cl2 solutions of 7 and 8 to produce, in situ, the
catalytically active species [CyRu(S)-BINAP](SbF6)2 and [CyRu(S)-
TolBINAP](SbF6)2, respectively. These catalyst solutions (10 mol %
loading) were transferred by syringe to cold methacrolein solutions and
the catalytic procedure described above was carried out.
2-Bromobicyclo[2.2.1]hept-5-ene-2-carboxaldehyde (6). 1H NMR
(CDCl3, 298 K, 500 MHz): δ 9.55 exo-CHO (major); δ 9.33 endo-
CHO (minor). The shift reagent Eu(hfc)3 was used to determine the
enantioselectivity of the exo diastereomer. When [CyRuCl(S)-BINPO]-
SbF6 and [CyRuCl(S)-TolBINPO]SbF6 were used as precatalysts, the
major enantiomer of the exo product corresponded to the signal that
was shifted furthest downfield by the shift reagent. The enantioselec-
Acknowledgment. This research was supported by a grant
from the National Science Foundation (CHE-9726423).
JA003528C