Highly efficient asymmetric hetero-diels-alder reactions of carbonyl compounds catalyzed by Lewis acid platinum complexes of conformationally flexible NUPHOS-type diphosphines

Article abstract of DOI:10.1021/om049392z

Conformationally flexible NUPHOS-type diphosphines have been resolved as their diastereopure platinum BINOLate complexes δ- and λ-[(NUPHOS)Pt{(S)-BINOL}] and the corresponding enantiopure Lewis acids δ- and λ-[(NUPHOS)Pt(OTf)₂], being generated

Full text of DOI:10.1021/om049392z

Organometallics 2004, 23, 6127-6133
6127
Highly Efficient Asymmetric Hetero-Diels-Alder
Reactions of Carbonyl Compounds Catalyzed by Lewis
Acid Platinum Complexes of Conformationally Flexible
NUPHOS-Type Diphosphines
Simon Doherty,*,† Julian G. Knight,*,‡ Christopher Hardacre,† He-Kuan Lou,†
Colin R. Newman,† Rakesh K. Rath,† Sarah Campbell,† and
Mark Nieuwenhuyzen†
Centre for the Theory and Applications of Catalysis, School of Chemistry,
The Queen’s University of Belfast, David Keir Building, Stranmillis Road,
Belfast BT9 5AG, U.K., and School of Natural Sciences, Chemistry, Bedson Building,
The University of Newcastle upon Tyne, Newcastle upon Tyne NE1 7RU, U.K.
Received August 5, 2004
Conformationally flexible NUPHOS-type diphosphines have been resolved as their
diastereopure platinum BINOLate complexes δ- and λ-[(NUPHOS)Pt{(S)-BINOL}] and the
corresponding enantiopure Lewis acids δ- and λ-[(NUPHOS)Pt(OTf)2], being generated by
protonation with trifluoromethanesulfonic acid, act as highly efficient catalysts for the hetero-
Diels-Alder reaction of nonactivated conjugated dienes with aryl glyoxals and glyoxylate
esters, giving ee’s as high as 99%.
Advances in the area of platinum-group asymmetric
catalysis have traditionally been guided by the premise
that conformationally rigid enantiopure diphosphines
are required to achieve high selectivities.1 Recently,
though, numerous reports have appeared that use either
achiral or meso ligands to convey asymmetry in enan-
tioselective catalysis.2 In this approach an enantiopure
ligand (L*), sometimes referred to as a chiral activator,
interacts with an achiral or meso ligand (L) and causes
the latter to preferentially adopt one of its chiral
conformations, which is ultimately responsible for the
transmission of asymmetry in an enantioselective trans-
formation. One such ligand is 2,2′-bis(diphenylphosphi-
no)biphenyl (BIPHEP),3 a biaryl diphosphine whose
axial chiral conformations cannot be resolved due to
rapid off-metal rotation about the biaryl axis; such
ligands are now commonly termed tropos.4
Mikami and Noyori were first to demonstrate that
BIPHEP could replace its atropisomeric counterpart
BINAP in the highly enantioselective ruthenium-
catalyzed asymmetric hydrogenation of ketones.5 In this
approach, the 1:1 mixture of S/S,S and R/S,S diastere-
oisomers that formed as a result of addition of (S,S)-
1,2-diphenylethylenediamine ((S,S)-DPEN) to rac-[(DM-
BIPHEP)RuCl2(dmf)n] (DM-BIPHEP ) 2,2′-bis((3,5-
dimethylphenyl)phosphino)biphenyl) slowly equilibrated
to a 1:3 thermodynamic mixture which catalyzed the
hydrogenation of 1′-acetonaphthone to give an ee of 84%,
a marked improvement on the performance of the
corresponding catalyst generated from rac-BINAP. In
this case, effective catalysis relied on the combination
of BIPHEP and another enantiopure ligand defining the
chiral environment at the metal. Shortly after, Gagne´
demonstrated that BIPHEP could be used as the sole
source of chirality to achieve high ee’s in platinum group
asymmetric catalysis.6 This was possible, since coordi-
* To whom correspondence should be addressed.
† The Queen’s University of Belfast.
‡ The University of Newcastle upon Tyne.
(1) (a) Seyden-Penne, J. Chiral Auxiliaries and Ligands in Asym-
metric Catalysis: Wiley: New York, 1995. (b) Noyori, R. Asymmetric
Catalysis in Organic Synthesis; Wiley: New York, 1994. (c) Ojima, I.,
Ed. Catalytic Asymmetric Synthesis, 2nd ed.; Wiley-VCH: New York,
2000.
(2) For a recent comprehensive and informative review see: (a)
Walsh, P. J.; Lurain, A. E.; Balsells, J. Chem. Rev. 2003, 103, 3297.
For additional relevant reviews see: (b) Mikami, K.; Terada, M.;
Korenaga, T.; Matsumoto, Y.; Ueki, M.; Angelaud, R. Angew. Chem.,
Int. Ed. 2000, 39, 3532. (c) Mikami, K.; Terada, M.; Korenaga, T.;
Matsumoto, Y.; Matsukawa, S. Acc. Chem. Res. 2000, 33, 391. For
selected examples see: (d) Mikami, K.; Matsukawa, S. Nature 1997,
385, 613. (e) Matsukawa, S.; Mikami, K. Tetrahedron: Asymmetry
1997, 8, 815. (f) Ding, K.; Ishii, A.; Mikami, K. Angew. Chem., Int. Ed.
1999, 38, 497. (g) Balsells, J.; Walsh, P. J. J. Am. Chem. Soc. 2000,
122, 1802. (h) Davis, T. J.; Balsells, J.; Carroll, P. J.; Walsh, P. J. Org.
Lett. 2001, 3, 2161. (i) Garcia, C.; LaRochelle, L. K.; Walsh, P. J. J.
Am. Chem. Soc. 2002, 124, 10970.
(4) For an insightful account see: Mikami, K.; Aikawa, K.; Yukinori,
Y.; Jodry, J. J.; Yamanaka, M. Synlett 2002, 1561.
(5) (a) Mikami, K.; Korenaga, T.; Terada, M.; Ohkuma, T.; Pham,
T.; Noyori, R. Angew. Chem., Int. Ed. 1999, 38, 495. For related articles
see also: (b) Korenaga, T.; Aikawa, K.; Terada, M.; Kawauchi, S.;
Mikami, K. Adv. Synth. Catal. 2001, 343, 284. (c) Yamanaka, M.;
Mikami, K. Organometallics 2002, 21, 5847. (d) Aikawa, K.; Mikami,
K. Angew. Chem., Int. Ed. 2003, 42, 5455. (e) Aikawa, K.; Mikami, K.
Angew. Chem., Int. Ed. 2003, 42, 5458.
(3) (a) Mikami, K.; Aikawa, K.; Korenaga, T. Org. Lett. 2001, 3, 243.
(b) Ogasawara, M.; Yoshida, K.; Hayashi, T. Organometallics 2000,
19, 1567. (c) Desponds, O.; Schlosser, M. J. J. Organomet. Chem. 1996,
507, 257.
10.1021/om049392z CCC: $27.50 © 2004 American Chemical Society
Publication on Web 11/19/2004

6128 Organometallics, Vol. 23, No. 26, 2004
Doherty et al.
Chart 1
Scheme 1
nation of BIPHEP to platinum slows atropinterconver-
sion such that the diastereoisomeric complexes δ- and
λ-[(BIPHEP)Pt{(S)-BINOL}] can each be isolated, the
BINOL liberated, and the resulting enantiopure Lewis
acid δ- or λ-[(BIPHEP)Pt(OTf)2] used to catalyze the
Diels-Alder and glyoxylate-ene reactions, with ee’s of
94 and 72%, respectively. Following this, Mikami used
3,3′-dimethyl-2,2′-diamino-1,1′-binaphthyl (DM-DABN)
to resolve palladium complexes of BIPHEP and showed
that the enantiopure Lewis acid (R)-[(BIPHEP)Pd-
(MeCN)2][SbF6]2 catalyzed the Diels-Alder reaction
between 1,3-cyclohexadiene and ethyl glyoxylate, to give
an ee of 82%.7 Most surprisingly, the diastereopure
DABN complex (R)-[(BIPHEP)Pd{(R)-DABN}][SbF6]2
proved to be a highly activated catalyst and gave an ee
of 94% in the same Diels-Alder reaction. Similarly, (R)-
DABN has been used to control axial chirality in Pt,
Pd, and Ni complexes of (diphenylphosphino)ferrocene
(dppf), the (dppf)Ni/(R)-DABN combination giving mark-
edly higher ee’s than their Pd and Pt counterparts in
the glyoxylate-ene reaction.8
We have recently prepared a new class of conforma-
tionally flexible diphosphine, NUPHOS, which bears a
close structural similarity to BIPHEP.9 Indeed, prelimi-
nary studies have shown that both acyclic and mono-
cyclic NUPHOS-type diphosphines (Chart 1) behave in
much the same manner as BIPHEP in that coordination
slows atropinterconversion10 such that enantiopure
conformations can be resolved and the resulting Lewis
acid fragment δ-[(NUPHOS)Pt(OTf)2] used to catalyze
the Diels-Alder reaction between acryloyl-N-oxazolidi-
nones and cyclopentadiene, in some cases with excellent
enantioselectivities.11 On the basis of this similarity, we
have recently begun to explore the applications of this
new class of diphosphine in asymmetric catalysis and
herein report that Lewis acid platinum complexes of
NUPHOS diphosphines are highly efficient catalysts for
a range of hetero-Diels-Alder reactions of nonactivated
conjugated dienes with aryl glyoxals and glyoxylate
esters.
Each of the BINOLate complexes δ/λ-[(NUPHOS)Pt-
{(S)-BINOL}] (2a-d) is typically prepared as a 1:1
mixture of diastereoisomers by reaction of [(NUPHOS)-
PtCl2] with Na2-(S)-BINOL, as previously described.10
Diastereopure samples of these complexes are obtained
either by thermal interconversion followed by crystal-
lization of the diastereoenriched mixture to give the
thermodynamically favored δ-[(NUPHOS)Pt{(S)-BINOL}]
(δ-2a-d) or, in the case of 1a, by fractional crystalliza-
tion of a 1:1 diastereoisomeric mixture to give the
thermodynamically less favored λ-[(Me4-NUPHOS)Pt-
{(S)-BINOL}] (λ-2a). Compounds δ-2a-d/λ-2a are typi-
cally deep golden yellow or red-orange air- and moisture-
stable solids that can be stored in the atmosphere for
several months without noticeable decomposition. Thus,
although δ-2a-d/λ-2a can be converted into the corre-
sponding enantiopure dichlorides by reaction with
hydrogen chloride, it is far more convenient to store the
catalyst as its BINOLate complex and generate the
active species, δ-3a-d/λ-3a, in situ by liberating the
BINOL with a strong acid of a weakly coordinating
anion: e.g., trifluoromethanesulfonic acid (Scheme 1).
Moreover, solutions of δ-2a-d/λ-2a are considerably
more stable with respect to atropinterconversion than
their dichloride counterparts, which begin to racemize
within hours at room temperature.
(6) (a) Becker, J. J.; White, P. S.; Gagne´, M. R. J. Am. Chem. Soc.
2001, 123, 9487. (b) Tudor, M. D.; Becker, J. J.; White, P. S.; Gagne´,
M. R. Organometallics 2000, 19, 4376.
(7) (a) Mikami, K.; Aikawa, K.; Yusa, Y.; Hatano, M. Org. Lett. 2002,
4, 91. (b) Mikami, K.; Aikawa, K.; Yusa, Y. Org. Lett. 2002, 4, 95.
(8) Mikami, K.; Aikawa, K. Org. Lett. 2002, 4, 99.
(9) (a) Doherty, S.; Knight, J. G.; Robins, E. G.; Scanlan, T. H.;
Champkin, P. A.; Clegg, W. J. Am. Chem. Soc. 2001, 123, 5110. (b)
Doherty, S.; Robins, E. G.; Nieuwenhuyzen, M.; Knight, J. G.; Champ-
kin, P. A.; Clegg, W. Organometallics 2002, 21, 1383. (c) Doherty, S.;
Newman, C. R.; Hardacre, C.; Nieuwenhuyzen, M.; Knight, J. G.
Organometallics 2003, 22, 1452.
(10) Doherty, S.; Newman, C. R.; Rath, R. K.; Hardacre, C.;
Nieuwenhuyzen, M.; Knight, J. G. Organometallics 2004, 23, 1055.
(11) (a) Doherty, S.; Newman, C. R.; Rath, R. K.; Hardacre, C.;
Nieuwenhuyzen, M.; Knight, J. G. Org. Lett. 2003, 5, 3863. (b) Doherty,
S.; Goodrich, P.; Hardacre, C.; Luo, H.-K.; Rooney, D. W.; Seddon, K.
R.; Styring, P. Green Chem. 2004, 6, 63.
A single-crystal X-ray study of one of these BINOLate
precursors, [{1,2-bis(1-diphenylphosphinoprop-1-ylidene)-
cyclohexane}Pt{(S)-BINOL}] (δ-2c), has been under-
taken, a perspective view of which is shown in Figure
1. Figure 1 clearly shows that the NUPHOS diphos-
phine coordinates to platinum to form a seven-mem-
bered ring with a δ-skew conformation, typical of this
ligand type, and a dihedral angle between the least-
squares planes containing C(2)C(21)C(3)C(31) and C(4)C-

Pt Complexes of NUPHOS-Type Diphosphines
Organometallics, Vol. 23, No. 26, 2004 6129
The enantiopure Lewis acids δ-[(NUPHOS)Pt(OTf)2]
(δ-3a-d) and λ-[(NUPHOS)Pt(OTf)2] (λ-3a) are highly
efficient catalysts for hetero-Diels-Alder reactions of
nonactivated conjugated dienes with ethyl glyoxylate
and aryl glyoxals. The active catalysts are conveniently
generated in situ by protonation of a dichloromethane
solution of δ-/λ-2a-d prior to addition of the substrates,
which is performed at low temperature to limit racem-
ization of the resulting Lewis acid. In a typical proce-
dure a dichloromethane solution of δ-2a-d and 4 Å
molecular sieves was treated with trifluoromethane-
sulfonic acid at 0 °C for 10 min to generate δ-[(NU-
PHOS)Pt(OTf)2], after which time both substrates were
added and the resulting solution was warmed to room
temperature. After 5 h the reaction mixture was filtered
through a short silica plug with ethyl acetate and the
Diels-Alder adduct purified by column chromatography
and analyzed by 1H NMR spectroscopy and either HPLC
or GC. All reactions were performed in the presence of
4 Å molecular sieves, since it is commonly accepted that
they improve catalyst performance, in particular enan-
tioselectivity, by removing trace amounts of water and
acid impurities.15
The benchmark hetero-Diels-Alder reactions between
1,3-cyclohexadiene and ethyl glyoxylate and aryl gly-
oxals were first to be examined, and the results are
summarized in Table 1. In each case δ-3a-d were found
to be effective and selective catalysts for this transfor-
mation, giving high conversions, near complete endo
selectivities, and good to excellent endo enantioselec-
tivities (81-99%, 1S,3R,4R configuration). Although the
BINOLate precursors offer a practical advantage in
terms of storage and ease of catalyst generation, we
have examined the performance of the Lewis acid δ-4b,
generated by treatment of the corresponding enan-
tiopure δ-[(Ph4-NUPHOS)PtCl2] with silver hexafluo-
roantimonate (eq 1) and obtained an ee of 93% and a
Figure 1. Molecular structure of δ-[(1,4-Et2-2,3-cyclo-
C6H8-NUPHOS)Pt{(S)-BINOL}] (δ-2c), highlighting the
alternating edge-face arrangement of the diphenylphos-
phino phenyl rings. Hydrogen atoms and toluene molecules
of crystallization have been omitted for clarity. Ellipsoids
are at the 30% probability level. Selected bond lengths (Å)
and angles (deg): Pt(1)-P(1), 2.227(3); Pt(1)-P(6), 2.225-
(3); Pt(1)-O(1A), 2.025(7); Pt(1)-O(1B), 2.028(7); C(2)-
C(3), 1.344(14); C(3)-C(4), 1.501(14); C(4)-C(5), 1.312(14);
P(1)-Pt(1)-P(6), 90.51(10); O(1A)-Pt(1)-O(1B), 88.5(3);
P(6)-Pt(1)-O(1A), 176.0(2); P(6)-Pt(1)-O(1B), 93.06(19);
P(1)-Pt(1)-O(1B), 174.5(3); P(1)-Pt(1)-O(1A), 88.24(19);
C(2)-C(3)-C(4), 125.3(9); C(3)-C(4)-C(5), 123.7(8); C(2)-
C(3)-C(31), 122.8(10); C(31)-C(3)-C(4), 111.7(9); C(41)-
C(4)-C(5), 124.0(10); C(3)-C(4)-C(41), 112.0(9).
(41)C(5)C(51) of 55.2°, similar to that reported for a
number of related conformationally restricted diphos-
phines.12 The platinum atom in δ-2c is distorted from
an ideal square-planar geometry with a dihedral angle
of 5.6° between the PtP2 and PtO2 planes. The phenyl
rings of the diphenylphosphino groups adopt the famil-
iar alternating edge-face arrangement with the two
pseudoaxial rings C(61A)-C(66A) and C(11B)-C(16B)
exposing their edges toward the platinum center to form
torsion angles of 18.8 and 11.3°, respectively, and the
equatorial phenyl rings C(61B)-C(66B) and C(11A)-
C(16A) exposing their faces toward platinum to form
torsion angles of 43.5 and 44.1°, respectively. The
endocyclic bond angles of 111.7(9) and 112.0(9)° for
C(31)-C(3)-C(4) and C(3)-C(4)-C(41), respectively,
are significantly smaller than the ideal value of 120°
for an sp2-hybridized carbon and reflect the strong
tendency of this carbon atom to adopt an angle close to
109.5° required by a cyclohexane ring. The Pt(1)-P(1)
and Pt(1)-P(6) bond lengths of 2.227(3) and 2.225(3)
Å, respectively, are essentially the same, as are the Pt-
(1)-O(1A) and Pt(1)-O(1B) distances of 2.025(7) and
2.028(7) Å. The natural bite angle of 90.51(10)° is close
to the ideal value of 90° and is comparable to those in
related complexes, including [(1,4-Ph2-cyclo-C6H8-NU-
PHOS)PtCl2] (92.26(6)°),9b [{(R)-BINAP}PdCl2] (92.69-
(8)°),13 and [Pt(BINAP)2] (92.3(1)°).14
conversion of 99% for the Diels-Alder reaction between
1,3-cyclohexadiene and ethyl glyoxylate (entry 4), which
compares favorably to that obtained using δ-3b (entry
3). Comparable conversions and enantioselectivities
were also obtained with aryl glyoxal substrates (entries
11 and 17).
In a limited examination of the catalyst loading for
δ-3b and ethyl glyoxylate, it was found that loadings
as low as 0.2 mol % may be achieved (endo:exo 92:8,
93% ee, conversion 89%); however, 2 mol % catalyst
loadings were routinely used for practical reasons. The
absolute configuration of each cycloadduct was deter-
mined by comparison of samples generated using cata-
lysts formed by activation of [M{(S)-BINAP}Cl2] (M )
Pd, Pt) with AgSbF6, as previously described.16 In this
(12) (a) Schmid, R.; Firicher, J.; Cereghetti, M.; Schonholzer, P. Helv.
Chim. Acta 1991, 74, 370. (b) Schmid, R.; Cereghetti, M.; Schonholzer,
P.; Hansen, H.-J. Helv. Chim. Acta 1988, 71, 897. (c) Schmid, R.;
Broger, E.; Cereghetti, M.; Crameri, Y.; Foricher, J.; Lalonde, M.;
Muller, R. K.; Scalone, M.; Schoettel, G.; Zutter, U. Pure Appl. Chem.
1996, 68, 131. (d) Toriumi, K.; Ito, T.; Takaya, T.; Noyori, R. Acta
Crystallogr. 1982, B38, 807.
(13) Ozawa, F.; Kubo, A.; Matsumoto, Y.; Hayashi, T.; Nishioka, E.;
Yanagi, K.; Moriguchi, K. Organometallics 1993, 12, 4188.
(14) Tominaga, H.; Sakai, K.; Tsubomura, T. J. Chem. Soc., Chem.
Commun. 1995, 2273.
(15) (a) Mikami, K.; Terada, M.; Nakai, T. J. Am. Chem. Soc. 1990,
112, 3949. (b) Mikami, K.; Motoyama, Y.; Terada, M. J. Am. Chem.
Soc. 1994, 116, 2812.
(16) Ghosh, A. K.; Matsuda, H. Org. Lett. 1999, 1, 2157.

6130 Organometallics, Vol. 23, No. 26, 2004
Doherty et al.
Table 1. Asymmetric Hetero-Diels-Alder Reaction
of 1,3-Cyclohexadiene with Ethyl Glyoxylate and
Aryl Glyoxals Catalyzed by δ-3a-d and δ-4b
Scheme 2
(II) bis(oxazoline) catalysts.18 Thus, if δ-NUPHOS diphos-
phines behave in a (S)-BINAP-like manner, the pseu-
doequatorial phenyl ring labeled A will be oriented
above the PtP2 plane and prevent attack of the diene
at the Si face, thus rendering endo-Re face attack to give
cycloaddition with 3R absolute configuration the favored
pathway (Scheme 2). Examination of the results in
Table 1 clearly shows that the performance of NU-
PHOS-type diphosphines approaches that of BINAP-
based catalysts, which suggests that this easy-to-
prepare, relatively inexpensive, and air-stable conforma-
tionally flexible diphosphine could offer a practical
alternative to more expensive and often synthetically
more demanding enantiopure ligands. In this regard,
Gagne´ has recently used palladium catalysts stabilized
by various labile electron-poor benzonitriles and based
on the relatively expensive (S)-MeO-BIPHEP to obtain
ee’s of 99% in the hetero-Diels-Alder reaction of 1,3-
cyclohexadiene with ethyl glyoxylate and phenyl gly-
oxal.19
Lewis acids δ-3a-d also catalyze the hetero Diels-
Alder reactions between 2,3-dimethyl-1,3-butadiene and
ethyl glyoxylate, phenyl glyoxal, and p-tolyl glyoxal, the
results of which are summarized in Table 2. In the case
of ethyl glyoxylate, formation of the dihydropyran was
accompanied by minor amounts of hetero-ene byproduct,
and although the enantioselectivities of the Diels-Alder
product were good to excellent (71-90%, 2R), the ee’s
of the ene product were low (15-36%). The formation
of ene byproduct has previously been observed in hetero-
Diels-Alder reactions with palladium-BINAP17 and
Cu(II)-bis(oxazoline) catalysts.20 In the former, Oi
investigated the effect on enantioselectivity and product
distribution of increasing the size of the glyoxylate ester
substituent and reported that the ee’s of both the hetero-
Diels-Alder product and the ene product increased with
increasing size of the alkyl group. Earlier Jørgensen
reported that the alkyl group of the glyoxylate ester has
a dramatic influence on the hetero-Diels-Alder to ene
product ratio but only a limited influence on the ee of
the reaction.20 Although the enantioselectivities of the
ene byproduct are at best modest, Lewis acid palladium
complexes of enantiopure diphosphines, including (S)-
Tol-BINAP and (S)-MeO-BIPHEP, have been used for
the enantioselective synthesis of R-hydroxy esters via
the glyoxylate-ene reaction of 1,1-disubstituted and
trisubstituted olefins and ee’s as high as 98% have been
obtained, albeit with an ene-specific substrate such as
methylenecyclohexane.21
catalyst conversn endo:exo
endo % ee
(confign)d,e
entrya substrate (mol %)
(%)b
ratioc
1
2
3
4
5
6
7
OEt
OEt
OEt
OEt
OEt
OEt
OEt
λ-3a
99
99
99
99
99
98
99
98:2
98:2
98:2
98:2
98:2
97:3
98:2
98 (1R,3S,4S)d
96 (1S,3R,4R)d
95 (1S,3R,4R)d
93 (1S,3R,4R)d
99 (1S,3R,4R)d
99 (1S,3R,4R)d
93 (1S,3R,4R)d
δ-3a
δ-3b
δ-4b
δ-3c
δ-3d
Pt{(S)-
BINAP}
8
9
Ph
Ph
λ-3a
86
60
62
66
75
88
85
99:1
99:1
99:1
99:1
99:1
99:1
99:1
95 (1R,3S,4S)e
92 (1S,3R,4R)e
93 (1S,3R,4R)e
94 (1S,3R,4R)e
96 (1S,3R,4R)e
99 (1S,3R,4R)e
97 (1S,3R,4R)e
δ-3a
δ-3b
δ-4b
δ-3c
10 Ph
11 Ph
12 Ph
13 Ph
14 Ph
δ-3d
Pt{(S)-
BINAP}
15 4-MeC6H4 λ-3a
16 4-MeC6H4 δ-3b
17 4-MeC6H4 δ-4b
18 4-MeC6H4 δ-3c
18 4-MeC6H4 δ-3d
20 4-MeC6H4 Pt{(S)-
67
71
65
74
69
73
99:1
99:1
99:1
99:1
99:1
99:1
81 (1R,3S,4S)e
91 (1S,3R,4R)e
90 (1S,3R,4R)e
98 (1S,3R,4R)e
94 (1S,3R,4R)e
99 (1S,3R,4R)e
BINAP}
a Reaction conditions: 2 mol % catalyst, 1,3-cyclohexadiene (0.63
mmol) and dienophile (2.93 mmol) in 1.0 mL of CH2Cl2, room
temperature. b Conversions for a 5 h run determined by GLC using
1
Chrompak Chirasil-DEX CB. c Determined by H NMR spectros-
copy. d Enantiomeric excess determined by chiral GLC using a
Chrompak Chirasil DEX CB column. e Enantiomeric excess de-
termined by chiral HPLC using a Diacel Chiracel OD-H column.
Average of three runs.
study, Oi and co-workers showed that palladium cata-
lysts of (S)-BINAP gave the hetero Diels-Alder product
with 3R absolute configuration by reduction to the
corresponding alcohol, followed by reaction with (a,S)-
2′-methoxy-1,1′-binaphthyl-2-carboxylic acid and a single-
crystal X-ray crystal structure determination of the
resulting ester.17 While Lewis acids δ-3a-d all gave the
Diels-Alder cycloadducts with 3R configuration, that
based on λ-3a gave the cycloadduct with opposite
absolute configuration and an enantioselectivity com-
parable to that obtained with δ-3a. In this regard,
NUPHOS-type diphosphines behave in a manner simi-
lar to BINAP in that the absolute stereochemistry is
that expected for a δ-(S)-BINAP like diphosphine,
according to the stereochemical model recently proposed
by Oi to account for the high level of enantiofacial
selection obtained in the palladium (S)-BINAP catalyzed
hetero-Diels-Alder reaction between 1,3-cyclohexadiene
and phenyl glyoxal.17 In this model, the dienophile
coordinates in a bidentate manner through both carbo-
nyl oxygen atoms to form a square-planar adduct, in
much the same manner as the catalyst-substrate
complex formed between ethyl glyoxylate and copper-
(18) Evans, D. A.; Burgey, C. S.; Paras, N. A.; Vojkovsky, T.; Tregay,
S. W. J. Am. Chem. Soc. 1998, 120, 5824.
(19) Becker, J. J.; Van Orden, L. J.; White, P. S.; Gagne´, M. R. Org.
Lett. 2002, 4, 727.
(20) Johannsen, M.; Jørgensen, K. A. J. Org. Chem. 1995, 60, 5757.
(21) (a) Koh, J. H.; Larsen, A. O.; Gagne´, M. R. Org. Lett. 2001, 3,
1233. (b) Hao, J.; Hatano, M.; Mikami, K. Org. Lett. 2000, 2, 4059.
(17) Oi, S.; Terada, E.; Ohuchi, K.; Kato, T.; Tachibana, Y.; Inoue,
Y. J. Org. Chem. 1999, 64, 8660.

Pt Complexes of NUPHOS-Type Diphosphines
Organometallics, Vol. 23, No. 26, 2004 6131
Table 2. Asymmetric Hetero-Diels-Alder Reaction
of 2,3-Dimethyl-1,3-butadiene with Ethyl
Glyoxylate Aryl and Glyoxals Catalyzed by δ-3a-d
Diels-Alder
yield % ee
(%)b (confign)c,d (%)b eef
ene
catalyst
(mol %)
yield
%
entrya substrate
1
2
OEt
OEt
OEt
OEt
OEt
OEt
OEt
Ph
λ-3a
42
44
49
47
41
39
86 (S)c
83 (R)c
71 (R)c
89 (R)c,e
90 (R)c
74 (R)c
90 (R)c
88 (S)d
87 (R)d
82 (R)d
93 (R)d,e
97 (R)d
88 (R)d
96 (R)d
89 (S)d
73 (R)d
93 (R)d
78 (R)d
93 (R)d
14
15
22
ndg
3
18
28
36
32
15
δ-3a
δ-3b
δ-3b
δ-3c
δ-3d
3
4
5
23
21
57
6
7
Pt{(S)-BINAP} 49
Figure 2. Perspective view of the molecular structure of
δ-2c to emphasize the asymmetric environment at plati-
num. The BINOL fragment, hydrogen atoms, and toluene
molecules of crystallization have been omitted for clarity.
Ellipsoids are at the 30% probability level.
8
λ-3a
δ-3a
δ-3b
δ-3b
δ-3c
δ-3d
77
74
79
74
74
66
9
Ph
10
11
12
13
14
15
16
17
18
19
Ph
Ph
Ph
Ph
ruthenium-catalyzed asymmetric hydrogenations22 as
well as platinum group catalyzed Diels-Alder reac-
tions,11b,23 and the effect of ionic liquids on enantiose-
lective reactions has recently been reviewed.24 Interest-
ingly, in these reactions the rate is slower in ionic
liquids than in dichloromethane. This may be associated
with strong hydrogen bonding of the dienophile with the
cation, which lowers its reactivity. In contrast, in the
Diels-Alder reactions reported to date, large increases
in the reaction rate are commonly observed in ionic
liquid compared with the rates in organic solvents and
water.
Ph
Pt{(S)-BINAP} 65
4-MeC6H4 λ-3a
4-MeC6H4 δ-3b
4-MeC6H4 δ-3c
4-MeC6H4 δ-3d
67
72
70
71
4-MeC6H4 Pt{(S)-BINAP} 68
a
Reaction conditions: 2 mol % catalyst, 2,3-dimethyl-1,3-
butadiene (0.32 mmol) dienophile (0.25 mmol) in 1.0 mL of CH2Cl2,
room temperature. b Conversion for a 5 h run measured by GC.
c Enantiomeric excess determined by chiral GLC using a Chrompak
Chirasil-DEX CB column. Average of three runs. d Enantiomeric
excess determined by chiral HPLC using a Daicel Chiralpak AD
column. e Reaction conducted at -20 °C for 15 h. f Not determined.
g None detected.
In summary, enantiopure Lewis acid platinum metal
complexes of conformationally flexible NUPHOS-type
diphosphines are highly efficient catalysts for the het-
ero-Diels-Alder reaction between nonactivated dienes
and glyoxylate esters and aryl glyoxals. This study has
shown that the performance of NUPHOS-based cata-
lysts approaches and can even rival that of BINAP, and,
since bidentate phosphines are central to platinum
group catalysis, it could be possible to apply this strat-
egy to a range of asymmetric transformations. More-
over, NUPHOS diphosphines could also replace BINAP
and related ligands in achiral transformations, for in-
stance, in the palladium-catalyzed carbonylation of he-
teroaromatic chlorides26 and the rhodium-catalyzed
chemo- and regioselective intramolecular cyclotrimer-
ization of alkynes,27 two recent examples in which the
optimum catalyst was based on a BINAP-like diphos-
phine.
In contrast, we found no evidence for the ene byprod-
uct in the hetero-Diels-Alder reaction of 2,3-dimethyl-
1,3-butadiene with phenyl or p-tolyl glyoxal catalyzed
by δ-3a-d, and reactions with these substrates gave
good conversions (68-77%) and excellent enantioselec-
tivities (73-96%, 2R). As expected, λ-3a gave the Diels-
Alder adduct of opposite absolute stereochemistry (2S)
with an enantioselectivity comparable to that obtained
with δ-3a (entries 7 and 8) consistent with the BINAP-
like stereoinduction model depicted in Figure 2. The
effect of temperature on the performance of catalyst
δ-3b was also investigated, since it consistently gave
the lowest enantioselectivities in the hetero-Diels-Alder
reactions with 2,3-dimethyl-1,3-butadiene. As expected,
enantioselectivity improved at lower temperatures, and
at -20 °C the ee’s of 89 and 93% for ethyl glyoxlate and
phenyl glyoxal, respectively, were significantly higher
than those of 71 and 82%, respectively, obtained at room
temperature.
Experimental Section
Finally, for selected substrate combinations ionic
liquids appear to provide a marked enhancement in
enantioselectivity. For instance, the Diels-Alder reac-
tion of 2,3-dimethyl-1,3-butadiene with phenyl and
p-tolyl glyoxal catalyzed by δ-3b gave ee’s of 82 and 73%,
respectively, in dichloromethane at room temperature
and 89 and 84%, respectively, in [emim][NTf2]. It should
be noted that an enhancement in enantioselectivity was
not obtained for all substrate combinations; however,
in such cases enantioselectivities were comparable to
those obtained in dichloromethane. Enhancement of
enantioselectivity has previously been reported for
General Procedures. All manipulations involving air-
sensitive materials were carried out in an inert-atmosphere
(22) Jessop, P. G.; Stanley, R. A.; Brown, R. A.; Eckert, C. A.; Liotta,
C. L.; Ngo, T. T.; Pollet, P. Green Chem. 2003, 5, 123.
(23) Mercacz, I.; Oh, T. Tetrahedron Lett. 2003, 44, 6465.
(24) Baudequin, C.; Baudoux, J.; Levillain, J.; Cahard, D.; Gaumont,
A.-C.; Plaquevant, J.-C. Tetrahedron: Asymmetry 2003, 14, 3081.
(25) Bonhoˆte, P.; Dias, A. P.; Papageorgiou, N.; Kalyanasundram,
K.; Gra¨tzel, M. Inorg. Chem. 1996, 32, 1168.
(26) Riley, H. A.; Gray, A. R. In Organic Syntheses; Blatt, A. H.,
Ed.; Wiley: New York, 1943; Collect. Vol. 2, p 59.
(27) Albaneze-Wlaker, J.; Bazaral, C.; Leavey, T.; Dormer, P. G.;
Murry, J. A. Org. Lett. 2004, 6, 2097.
(28) Tanaka, K.; Shirasaka, K. Org. Lett. 2003, 5, 4697.

6132 Organometallics, Vol. 23, No. 26, 2004
Doherty et al.
glovebox or using standard Schlenk line techniques under an
atmosphere of nitrogen or argon in oven-dried glassware.
Diethyl ether was distilled from potassium/sodium alloy and
dichloromethane from calcium hydride, and [emim][NTf2] was
prepared following the method of Bonhoˆte et al.25 (S)-BINAP
was purchased from Strem. Unless otherwise stated, com-
mercially purchased materials were used without further
purification. Deuteriochloroform was predried with calcium
hydride, vacuum-transferred, and stored over 4 Å molecular
sieves. The platinum complexes [(NUPHOS)Pt{(S)-BINOL}]
(2a-e) and [Pt{(S)-BINAP)Cl2]17 were prepared as previously
described. Ethyl glyoxylate and phenyl glyoxal were purchased
from Lancaster, and p-tolyl glyoxal was prepared as described
in the literature;26 all were distilled immediately prior to use.
1H and 31P{1H} and 13C{1H} NMR spectra were recorded on a
JEOL LAMBDA 500 or Bruker AC 200, AMX 300, and DRX
500 machines. Purification of reaction products was carried
out by column chromatography on reagent silica gel (60-200
mesh). Analytical high-performance liquid chromatography
(HPLC) was performed on an Agilent 110 Series HPLC
equipped with a variable-wavelength detector using either a
Daicel Chiralcel OD-H or a Chiralpak AD column. Chiral GLC
was performed on a Agilent 6890N series GC using a Chrompak
Chirasil DEX CB column. Enantiomeric excesses were calcu-
lated from the HPLC and GC profiles.
δ-[{1,4-bis(diphenylphosphino)-1,2,3,4-tetraphenyl-1,3-
butadiene}PtCl2] (δ-4b). A solution of enantiopure δ-[{1,4-
bis(diphenylphosphino)-1,2,3,4-tetraphenyl-1,3-butadiene}-
platinum{(S)-BINOL}] (λ-2b; 1.1 g, 0.91 mmol) in dichloro-
methane (20 mL) was treated with a diethyl ether solution of
HCl (2.5 mL, 2.5 mmol, 1.0 M solution in diethyl ether).
Addition of HCl resulted in an immediate color change from
deep yellow to near colorless. After 10 min the solution was
filtered, the solvent removed under vacuum, and the resulting
residue washed with diethyl ether (5 × 10 mL) and hexane (5
× 10 mL). Crystallization of the product by slow diffusion of a
dichloromethane solution layered with hexane at room tem-
perature gave pale yellow λ-4b in 67% yield (0.61 g). 31P{1H}
NMR (121.5 MHz, CDCl3, δ): 1.9 (t, JPtP ) 3607 Hz, PPh2).
1H NMR (500.13 MHz, CDCl3, 232 K, δ): 9.57 (br m, 4H, C6H5),
7.9 (br m, 6H, C6H5), 7.2 (m, 6H, C6H5), 6.88, (m, 4H, C6H5),
6.7 (t, J ) 7.3 Hz, 2H, C6H5), 6.65 (m, 6H, C6H5), 6.54 (t, J )
7.9 Hz, 4H, C6H5), 6.18 (br, 4H, C6H5), 6.11 (d, J ) 7.3 Hz,
4H, C6H5). Anal. Calcd for C52H40Cl2P2Pt: C, 62.91; H, 4.06.
Found: C, 63.23; H, 4.44. [R]D ) -9.07 (c 1.0, CHCl3).
General Procedure for Platinum-Catalyzed Enantio-
selective Hetero-Diels-Alder Reactions between Ethyl
Glyoxylate and 1,3-Cyclohexadiene with Catalyst Pre-
cursors 2a-d. A flame-dried Schlenk flask charged with δ-2b
(0.0154 g, 0.0127 mmol) and 4 Å molecular sieves (ca. 0.025
g) was cooled to 0 °C and dichloromethane added (1 mL). The
resulting solution was treated with trifluoromethanesulfonic
acid (2.1 µL, 0.024 mmol) to give an immediate color change
from deep red-orange to near colorless. After the mixture was
stirred for 5 min, freshly distilled ethyl glyoxylate (0.390 mL,
2.93 mmol) was added, followed by 1,3-cyclohexadiene (0.060
mL, 0.63 mmol). The resulting mixture was warmed to room
temperature and stirred for a further 5 h, after which time
the solution was filtered through a short plug of silica with
ethyl acetate, the solvent removed, and the residue purified
by column chromatography over silica gel (60-200 mesh, 25%
ethyl acetate/75% hexane). The endo/exo ratio was obtained
from 1H NMR spectroscopy, and the enantiomeric excess was
determined by GC using a Chrompak Chirasil DEX CB column
(90 °C for 7 min ramp to 125 °C at 4 °C/min; hold 15 min,
pressure 11 psi). The retention times of the enantiomers of
endo- and exo-ethyl 2-oxabicyclo[2.2.2]oct-5-ene-3-carboxylate
were 13.81 min (exo1), 14.12 min (exo2), 14.67 min (endo3S),
15.13 min (endo3R). The absolute configuration of the endo
cycloadduct was assigned by comparison with the retention
times of samples prepared from [{(S)-BINAP}PtCl2].
General Procedure for Platinum-Catalyzed Enantio-
selective Hetero-Diels-Alder Reactions between Ethyl
Glyoxylate and 2,3-Dimethyl-1,3-butadiene using Cata-
lyst Precursors 2a-d. Catalyst mixtures were prepared as
described above for 1,3-cyclohexadiene. After 5 h the solution
was filtered through a short plug of silica with ethyl acetate,
the solvent removed, and the resulting residue purified by
column chromatography over silica gel (60-200 mesh, 20%
ethyl acetate/80% hexane) to give the Diels-Alder and ene
products as colorless oils. The enantiomeric excess was deter-
mined by GC using a Chrompak Chirasil-DEX CB column (90
°C for 7 min ramp to 125 °C at 4 °C/min; hold 15 min, pressure
11 psi). The retention times of the Diels-Alder product ethyl
4,5-dimethyl-3,6-dihydro-2H-pyran-2-carboxylate were 17.02
min (2R) and 17.49 min (2S), and those of the ene product
ethyl 2-hydroxy-5-methyl-4-methylene-5-hexenoate were 17.14
and 18.16 min.
General Procedure for Platinum-Catalyzed Enantio-
selective Hetero-Diels-Alder Reactions between Aryl
Glyoxals and 1,3-Cyclohexadiene using Catalyst Precur-
sors 2a-d. A flame-dried Schlenk flask charged with 2c
(0.0126 g, 0.0127 mmol) and 4 Å molecular sieves (ca. 0.025
g) was cooled to 0 °C and dichloromethane added (1 mL). The
resulting solution was treated with trifluoromethanesulfonic
acid (2.1 µL, 0.024 mmol) to give an immediate color change
from golden yellow to near colorless. After the mixture was
stirred for 5 min, freshly distilled phenyl glyoxal (0.032 mL,
0.25 mmol) was added, followed by 1,3-cyclohexadiene (0.031
mL, 0.33 mmol). The reaction mixture was warmed to room
temperature and stirred for a further 5 h, after which the
solution was filtered through a short plug of silica with ethyl
acetate, the solvent removed, and the resulting residue purified
by column chromatography over silica gel (60-200 mesh, 10%
ethyl acetate/90% hexane). The endo/exo ratio was obtained
from 1H NMR spectroscopy, and the enantiomeric excess was
determined from the HPLC profile using a Daicel Chiralcel
OD-H column (0.75 mL/min flow rate, hexane/propan-2-ol 90/
10). The retention times of the enantiomers of endo-3-benzoyl-
2-oxabicyclo[2.2.2]oct-5-ene were 11.61 min (endo3S) and 12.70
min (endo3R), while those of 3-(4′-methylbenzoyl)-2-oxabicyclo-
[2.2.2]oct-5-ene were 10.96 min (endo3S) and 12.72 min (endo3R).
The absolute configuration of the endo cycloadduct was as-
signed by comparison with the retention times of samples
prepared from (R)- and [{(S)-BINAP}PtCl2].
General Procedure for Platinum-Catalyzed Enantio-
selective Hetero-Diels-Alder Reactions between Aryl
Glyoxals and 2,3-Dimethyl-1,3-butadiene using Catalyst
Precursors 2a-d. Catalyst mixtures were prepared as
described above for 1,3-cyclohexadiene and the products puri-
fied by column chromatography over silica gel. The enantio-
meric excess was determined by HPLC using a Chiralpak AD
column (1 mL/min flow rate, hexane/propan-2-ol 95/5). The
retention times of the two enantiomers of 2-benzoyl-4,5-
dimethyl-3,6-dihydro-2H-pyran were 9.30 min (endo2S) and
12.47 min (endo2R), and those of 4,5-dimethyl-2-(4′-methyl-
benzoyl)-3,6-dihydro-2H-pyran were 12.05 min (endo2S) and
17.27 min (endo2R).
General Procedure for Platinum-Catalyzed Enantio-
selective Hetero-Diels-Alder Reactions between Aryl
Glyoxals and 2,3-Dimethyl-1,3-butadiene using Catalyst
Precursors [{(S)-BINAP)PtCl2]. A solution of [{(S)-BINAP)-
PtCl2] (0.0111 g, 0.0125 mmol) and 4 Å molecular sieves (0.025
g) in dichloromethane (2 mL) was treated with silver hexafluo-
roantimonate (0.0086 g, 0.025 mmol) and stirred for 30 min.
The resulting catalyst solution was cooled to 0 °C, and freshly
distilled phenyl glyoxal (0.057 mL, 0.625 mmol) was added,
followed by 1,3-cyclohexadiene (0.078 mL, 0.825 mmol). The
reaction mixture was warmed to room temperature and stirred
for a further 5 h, after which the solution was filtered through
a short plug of silica with ethyl acetate, the solvent removed,
and the resulting residue purified by column chromatography

Pt Complexes of NUPHOS-Type Diphosphines
Organometallics, Vol. 23, No. 26, 2004 6133
Table 3. Summary of Crystal Data and Structure
Determination Details for Compound 2c
Crystal Structure Determinations of 2c. Data were
collected on a Bruker-AXS SMART diffractometer using the
SAINT-NT software with graphite-monochromated Mo KR
radiation using ψ/ω scans. A crystal was mounted onto the
diffractometer at room temperature (ca. 297 K). Crystal
stabilities were monitored via re-collection of the first set of
frames. There were no significant variations (<(1%). Lorentz
and polarization corrections were applied. The structures were
solved using direct methods and refined with the SHELXTL
program package, and the non-hydrogen atoms were refined
with anisotropic thermal parameters. Table 3 gives further
details. Hydrogen atoms were added at idealized positions, and
a riding model was used for subsequent refinement. The
formula
C70H66O2P2Pt
Mr
1196.26
yellow
0.30 × 0.26 × 0.25
297(2)
orthorhombic
P212121
17.095(8)
17.629(8)
19.234(9)
90
cryst color
cryst size (mm)
temp, K
cryst syst
space group
a, Å
b, Å
c, Å
R
â
γ
90
90
2
2
function minimized was ∑[w(|Fo| - |Fc| )] with reflection
V, Å3
Z
5795(5)
4
2
2
weights w-1 ) [σ2 |Fo| + (g1P)2 + (g2P)], where P ) [max |Fo|
2
+ 2|Fc| ]/3. Additional material available from the Cambridge
Crystallographic Data Center comprises relevant tables of
atomic coordinates, bond lengths and angles, and thermal
parameters.
Dcalcd (g cm-3
F(000)
)
1.371
2440
µ(Mo KR) (mm-1
θmax, deg
)
2.521
23.38
no. of rflns measd
no. of unique rflns
Rint (on F2)
49 429
8395
0.1166
639
0.0515
0.1163
1.059
Acknowledgment. We gratefully acknowledge the
EPSRC (R.K.R.), CenTACat (HKL), and the McClay
Trust (C.R.N.) for funding and Johnson Matthey for
loans of palladium salts.
no. of params
Ra (F2 > 2σ(F2))
Rwb (all data)
GOFc (S)
Supporting Information Available: For 3c, tables of
crystal data and structure solution and refinement details,
atomic coordinates, bond distances, bond angles, and aniso-
tropic thermal parameters. This material is available free of
charge via the Internet at http://pubs.acs.org. Observed and
calculated structure factor tables are available from the
authors upon request.
max, min diff map, e Å-3
0.735, -1.523
a Conventional R ) ∑||Fo| - |Fc||/∑|Fo| for “observed” reflections
2
2
2
having Fo > 2σ(Fo2). b Rw ) [∑w(Fo - Fc )2/∑w(Fo2)2]1/2 for all
2
2
data. c GOF ) [∑w(Fo - Fc )2/((no. of unique rflns) - (no. of
params))]1/2
.
over silica gel. The product was analyzed by 1H NMR spec-
troscopy and either GC or HPLC as described above.
OM049392Z