Asymmetric hydrogenation of unfunctionalized tetrasubstituted olefins with a cationic zirconocene catalyst [13]

Full text of DOI:10.1021/ja990535w

4916
J. Am. Chem. Soc. 1999, 121, 4916-4917
Table 1. Asymmetric Hydrogenations of Tetrasubstituted Olefins
with (R,R)- or (S,S)-(EBTHI)ZrMe2/[PhMe2NH]+[(BC6F5)4]- a
Asymmetric Hydrogenation of Unfunctionalized
Tetrasubstituted Olefins with a Cationic Zirconocene
Catalyst
Malisa V. Troutman,† Daniel H. Appella, and
Stephen L. Buchwald*
Department of Chemistry
Massachusetts Institute of Technology
Cambridge, Massachusetts 02139
ReceiVed February 22, 1999
The asymmetric hydrogenation of olefins is a powerful method
of generating optically pure compounds.1 Among double bond-
containing substrates that are suitable as targets for asymmetric
reduction, tetrasubstituted olefins are of particular interest because
the products may contain two new stereogenic centers. At the
same time, tetrasubstituted olefins are generally the least reactive
class of olefins in hydrogenation reactions; steric hindrance
compromises their ability to bind to most transition metal
complexes. Asymmetric hydrogenations of tetrasubstituted N-
acylaminoacrylic esters and aryl acrylic acids have been achieved
by using cationic Rh catalysts with bidentate phosphine ligands.2
Coordination of nearby heteroatoms to the Rh is necessary for
these reductions to proceed with high efficiency and enantiose-
lectivity. Crabtree’s catalyst, [Ir(COD)(PCy3)(py)]+[PF6]-, is
highly effective for the hydrogenation of tetrasubstituted olefins,3
but attempts to develop asymmetric versions have, until recently,
not been very successful.4 Pfaltz has recently described a highly
active and enantioselective Ir catalyst for the hydrogenation of
unfunctionalized trisubstituted olefins.5 In this paper, he also
reported the reduction of the tetrasubstituted olefin 2-(p-meth-
oxyphenyl)-3-methyl-2-butene to the corresponding aryl-substi-
tuted alkane with an ee of 81%.
We have previously described a highly selective asymmetric
reduction of unfunctionalized trisubstituted olefins,6 using (S,S)-
(EBTHI)TiH (EBTHI ) ethylenebistetrahydroindenyl) as catalyst.
At 65 °C, under 80-2000 psig H2, the olefins were hydrogenated
to products with ee’s of 83-99%. Even at high pressures the
reductions of some substrates required several days to reach
completion, presumably due to steric hindrance about the trisub-
stituted double bonds. In the case of tetrasubstituted olefins, this
problem would likely be exacerbated.
a Reactions were run at 0.25 M [olefin], at room temperature, for
13-21 h. b The relative stereochemistry was determined for products
in entries 2, 7, and 8. The absolute stereochemistry was assigned for
the product in entry 2. c Yields are the average of two isolated yields
of >95% purity as determined by GC, 1H NMR and, for new
compounds, elemental analysis. d Percent conversion is reported. e Re-
action time was 39 h. f Reaction time was 65 h. g Reaction time was
30 h. h When the hydrogenation was performed at 2000 psig, the major
i
enantiomer was the opposite of that obtained at 80 psig. Yield includes
9% 5,6-dimethyl-1,2,3,4-tetrahydronaphthalene that was present with
the product.
Scheme 1
We have begun investigating cationic titanocene and zir-
conocene complexes as hydrogenation catalysts for tri- and
tetrasubstituted olefins, based on the idea that they should be
particularly effective at binding highly substituted olefins due to
their high electrophilicity. Cationic metallocenes of the type [Cp2-
MMe]+ (M ) Ti, Zr)7 have been extensively investigated in
Ziegler-Natta-type polymerizations.8 Under a hydrogen atmo-
† Present address: Ciba Speciality Chemicals, 540 White Plains Rd.,
Tarrytown, NY 10591.
(1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley: New
York, 1994; pp 16-94. (b) Seyden-Penne, J. Chiral Auxiliaries and Ligands
in Asymmetric Synthesis; Wiley: New York, 1995; pp 367-388.
(2) (a) Hayashi, T.; Kawamura, N.; Ito, Y. J. Am. Chem. Soc. 1987, 109,
7876. (b) Burk, M. J.; Gross, M. F.; Martinez, J. P. J. Am. Chem. Soc. 1995,
117, 9375. (c) Sawamura, M.; Kuwano, R.; Ito, Y. J. Am. Chem. Soc. 1995,
117, 9602. (d) Imamoto, T.; Watanabe, J.; Wada, Y.; Masuda, H.; Yamada,
H.; Tsuruta, H.; Matsukawa, S.; Yamaguchi, K. J. Am. Chem. Soc. 1998, 120,
1635.
sphere these complexes can be converted into cationic metallocene
hydrides.9 The chiral zirconocene (EBTHI)ZrMe2 (1), in the
presence of methylaluminoxane or [PhMe2NH]+[Co(C2B9H11)2]-,
has been applied to the asymmetric reduction of 1,1-disubstituted
olefins; the ee’s of the products did not exceed 36%.10 We now
(8) (a) Jordan, R. F. AdV. Organomet. Chem. 1991, 32, 325. (b) Marks, T.
J. Acc. Chem. Res. 1992, 25, 57. (c) Kesti, M. R.; Coates, G. W.; Waymouth,
R. M. J. Am. Chem. Soc. 1992, 114, 9679. (d) Bochmann, M. J. Chem. Soc.,
Dalton Trans. 1996, 255. (e) Kaminsky, W.; Arndt, M. AdV. Polym. Sci. 1997,
127, 143.
(9) Jordan, R. F.; Bajgur, C. S.; Dasher, W. E.; Rheingold, A. L.
Organometallics 1987, 6, 1041.
(10) (a) Waymouth, R.; Pino, P. J. Am. Chem. Soc. 1990, 112, 4911. (b)
Grossman, R. B.; Doyle, R. A.; Buchwald, S. L. Organometallics 1991, 10,
1501.
(3) Crabtree, R. Acc. Chem. Res. 1979, 12, 331.
(4) Cabeza, J. A.; Cativiela, C.; Diaz de Villegas, M. D.; Oro, L. A. J.
Chem. Soc., Perkin Trans. 1 1988, 1881.
(5) Lightfoot, A.; Schnider, P.; Pfaltz, A. Angew. Chem., Int. Ed. 1998,
37, 2897.
(6) Broene, R. D.; Buchwald, S. L. J. Am. Chem. Soc. 1993, 115, 12569.
(7) (a) Hlatky, G. G.; Turner, H. W.; Eckman, R. R. J. Am. Chem. Soc.
1989, 111, 2728. (b) Chien, J. C. W.; Tsai, W.-M.; Rausch, M. D. J. Am.
Chem. Soc. 1991, 113, 8570.
10.1021/ja990535w CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/11/1999

Communications to the Editor
J. Am. Chem. Soc., Vol. 121, No. 20, 1999 4917
Scheme 2
report a catalyst generated from 1 and [PhMe2NH]+[B(C6F5)4]-
(2) that can reduce tetrasubstituted olefins with very high
enantioselectivities.
The hydrogenations were carried out at room temperature in
aromatic hydrocarbon solvents using (R,R)- or (S,S)-1 and 2 at
either 80 or 1000-2000 psig H2. In some cases, the rate and
enantioselectivity of the reaction depended markedly on H2
pressure. As shown in Table 1, under the appropriate reaction
conditions, products with ee’s over 90% could be obtained in
most instances.
The relative stereochemistry of two of the products, 1,2-
dimethylindane from 2,3-dimethylindene (Table 1, entry 2) and
1,2-dimethyl-1,2,3,4-tetrahydronaphthalene from 3,4-dimethyl-
1,2-dihydronaphthalene (entry 8), were determined to be cis by
comparison to spectral data;11 the stereochemistry of 2-methyl-
1-phenylindane from 2-methyl-3-phenylindene (entry 7) was
determined to be cis by nOe studies.12 The other indane products
are assumed to also be cis by analogy. The absolute configurations
of most of the products are not known since these hydrocarbons
have not been previously synthesized with a high degree of
enantiopurity. However, we were able to assign the absolute
configuration of the 1,2-dimethylindane product, obtained from
the reduction of 2,3-dimethylindene using (R,R)-1, as (S,S) based
on the crystal structure of the Cr(CO)3 complex of the indane
product.12
The mechanism for the hydrogenation is thought to be
analogous to that previously proposed for the hydrogenation of
trisubsituted olefins.6 In this scenario, the carbon-carbon double
bond inserts into the zirconium hydride to form intermediate A
(Scheme 1).13 Intermediate A then undergoes hydrogenolysis,9
giving the product and regenerating the zirconium hydride. This
mechanism predicts a cis configuration for products from the
reduction of cyclic substrates.
inserts into the Zr-H bond as shown in Scheme 2. In the transition
state that would lead to (R,R) product, unfavorable steric
interactions between the aromatic ring of the indene and the
tetrahydroindenyl portion of the ligand would disfavor this
reaction pathway. The reduction of 3-ethyl-2-methylindene (entry
6) proceeded with decreased enantioselectivity compared to the
reduction of 2,3-dimethylindene. This result is in accord with
Scheme 2; the larger ethyl substituent in the benzylic position
should increase unfavorable steric interactions in the preferred
transition state of the reduction. Intriguingly, the sense of
enantioselectivity in the reduction of 2-methyl-3-phenylindene
(entry 7) depended on hydrogen pressure,14 indicating that the
mechanism of hydrogenation may be quite complex and substrate
dependent.
In conclusion, the combination of 1 and 2 is a highly
enantioselective catalyst for hydrogenation of unfunctionalized
tetrasubstituted olefins. Previous attempts to use (EBTHI)ZrH+
for the asymmetric hydrogenation of disubstituted olefins have
resulted in low levels of enantioselectivity.10 The increased steric
hindrance of tetrasubstituted olefins most likely allows the catalyst
to discriminate more effectively between the enantiotopic faces
of the double bond. The cationic nature of these catalysts renders
them sufficiently electrophilic to overcome the reluctance of most
metal complexes to bind to such hindered olefins. Further work
to examine the scope and mechanism of this catalyst system is
in progress.
Acknowledgment. M.V.T. was supported by an NSF fellowship,
D.H.A. is an NIH postdoctoral fellow. We gratefully acknowledge
William M. Davis for solving the crystal structure of the chromium
tricarbonyl complex of (S,S)-1,2-dimethylindane, and Donna G. Black-
mond for helpful discussion. We also gratefully acknowledge Boulder
Scientific and Exxon Corporation for gifts of (()-(EBI)ZrCl2 and
[PhMe2NH]+[B(C6F5)4]-, respectively.
If the mechanism proceeds as described in Scheme 1, the
product configuration from the reduction of 2,3-dimethylindene
indicates that this olefin reacts at the re face. In the transition
state that leads to (S,S) product, the double bond of the indene
Supporting Information Available: Preparation and characterization
of 1 and all substrates and products (PDF) and crystallographic data for
chromium tricarbonyl complex of (S,S)-1,2-dimethylindane (CIF format).
This material is available free of charge via the Internet at http://pubs.acs.org.
(11) (a) cis-1,2-dimethylindane: Beckwith, A. L. J.; Gerba, S. Aust. J.
Chem. 1992, 45, 289. (b) cis-1,2-dimethyl-1,2,3,4-tetrahydronaphthalene:
Morin, F. G.; Horton, W. J.; Grant, D. M.; Dalling, D. K.; Pugmire, R. J. J.
Am. Chem. Soc. 1983, 105, 3992.
JA990535W
(14) For other examples of reversals in reaction enantioselectivity with
changes in reaction conditions, see: (a) Ojima, I.; Kogure, T.; Yoda, N. J.
Org. Chem. 1980, 45, 4728. (b) Sun, Y.; Landau, R. N.; Wang, J.; LeBlond,
C.; Blackmond, D. G. J. Am. Chem. Soc. 1996, 118, 1348. (c) Sun. Y.; Wang,
J.; LeBlond, C.; Reamer, R. A.; Laquidara, J.; Sowa, J. R., Jr.; Blackmond,
D. G. J. Organomet. Chem. 1997, 548, 65. (d) Otera, J.; Sakamoto, K.;
Tsukamoto, T.; Orita, A. Tetrahedron Lett. 1998, 39, 3201.
(12) See Supporting Information for details.
(13) Prior to insertion, coordination of the aromatic portion of the substrate
to the Zr cation could direct the regioselectivity of the insertion. Coordination
-
of a phenyl group of BPh4 to a cationic zirconocene complex has been
observed: Horton, A. D.; Frijns, J. H. G. Angew. Chem., Int. Ed. Engl. 1991,
30, 1152.