Catalysts with mixed ligands on immobilized supports. Electronic and steric advantages.

Article abstract of DOI:10.1021/ol027475a

[reaction: see text] Immobilized dirhodium(II) catalysts having mixed chiral ligands enhance reactivity (AH = azetidinone) and influence stereoselectivity in cyclopropanation and carbon-hydrogen insertion reactions.

Full text of DOI:10.1021/ol027475a

ORGANIC
LETTERS
2003
Vol. 5, No. 4
561-563
Catalysts with Mixed Ligands on
Immobilized Supports. Electronic and
Steric Advantages
Michael P. Doyle* and Ming Yan
Department of Chemistry, UniVersity of Arizona, Tucson, Arizona 85721-0041
Han-Mou Gau
Department of Chemistry, National Chung-Hsing UniVersity, 250, Kuo-Kuang Road,
Taichung City 40227, Taiwan, R.O.C.
Erich C. Blossey
Department of Chemistry, Rollins College, Winter Park, Florida 32789
mdoyle@u.arizona.edu
Received December 16, 2002
ABSTRACT
Immobilized dirhodium(II) catalysts having mixed chiral ligands enhance reactivity (AH ) azetidinone) and influence stereoselectivity in
cyclopropanation and carbon−hydrogen insertion reactions.
The synthesis and applications of immobilized metal catalysts
are receiving increasing attention because of their advantages
for separation and reuse.1-3 However, attachment of a
transition metal to a polymer through a bound ligand adds
several reaction variables beyond those with uses of homo-
geneous catalysts. The structure of the polymer, the point
of attachment of the ligand to the polymer, and the nature
and strength of the metal-ligand association can affect
turnover numbers and rates, recovery and reuse, and intrinsic
catalyst selectivities.4-7 We have recently shown that im-
mobilization of chiral dirhodium(II) tetrakis(methyl 2-oxa-
pyrrolidine-(5S)-carboxylate), Rh2((5S)-MEPY)4, could be
achieved on the NovaSyn Tentagel (TG) hydroxy resin and
the Merrifield resin through an ester linkage to one of the
pyrrolidinone (PY) ligands with yields and selectivities for
cyclopropanation reactions comparable to those with the
homogeneous catalyst (Scheme 1).8
Structurally, neither 2 nor 3 are identical to the homoge-
neous Rh2((5S)-MEPY)4 because one of the ligands is bound
to the polymer, making one rhodium face different from the
other, but the enantioselectivity in cyclopropanation reactions
does not appear to be affected significantly by the alkyl ester
attachment,9 even to recovery and reuse eight times.
Immobilized dirhodium(II) catalysts offer an advantage
beyond the conveniences of recovery and reuse that has not
been previously reported. Mixed ligand systems prepared by
substitution with the use of the polymer-bound ligand (eq
(1) (a) Bergbreiter, D. E. J. Polym. Sci., Chem. 2001, 39, 2351. (b)
Rechavi, D.; Lemaire, M. Chem. ReV. 2002, 102, 3467.
(2) Foder, K.; Kolmschot, S. G. A.; Sheldon, R. A. Enantiomer 1999, 4,
497.
(3) (a) Sherrington, D. C. Supported Catalysts and Their Applications;
Springer: New York, 2001. (b) Chiral Catalyst Immobilization and
Recycling; DeVos, D. E., Vankelecom, I. F. J., Jacobs, P. A., Eds.; Wiley-
VCH: Weinheim, Germany, 2000.
(4) (a) Orlandi, S.; Mandioli, A.; Pini, D.; Salvadori, P. Angew. Chem.,
Int. Ed. 2001, 40, 2519. (b) Reger, T. S.; Janda, K. D. J. Am. Chem. Soc.
2000, 122, 6929. (c) Jafarpour, L.; Heck, M.-P.; Baylon, C.; Lee, H. M.;
Mioskowski, C.; Nolan, S. P. Organometallics 2002, 21, 671.
(5) Thomas, J. M.; Maschmeyer, T.; Johnson, B. F. G.; Shephard, D. S.
J. Mol. Catal. 1999, 141, 139.
(7) (a) Rechavi, D.; Lemaire, M. Org. Lett. 2001, 3, 2493. (b) Rigby, J.
H.; Kondratenko, M. A.; Fiedler, C. Org. Lett. 2000, 2, 3917.
(8) Doyle, M. P.; Timmons, D. J.; Tumonis, J. S.; Gau, H.-M.; Blossey,
E. C. Organometallics 2002, 21, 1747.
(9) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds; Wiley & Sons: New York,
1998.
(6) de Miguel, Y. R. J. Chem. Soc., Perkin Trans. 1 2000, 4213.
10.1021/ol027475a CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/30/2003

methyl styryldiazoacetate, for example, under mild condi-
tions. The azetidinone-ligated resins were prepared by
standard methods8 and then used to replace one of the ligands
of the homogeneous Rh2((5S)-MEPY)4, Rh2((4S)-MPPIM)4,
Rh2((4S)-MEAZ)4, or Rh2((4S)-IBAZ)4 catalysts (eq 2).
Scheme 1. Preparation of Immobilized Chiral Dirhodium
Carboxamidates
Styryldiazoacetates are notably resistant to catalytic diazo
decomposition with dirhodium(II) carboxamidates.12 With
catalysts that include 5 and 6, only the intramolecular dipolar
addition product (e.g., 11) is observed, and this process does
not involve dirhodium catalysis. The exception is catalysts
such as 4 with azetidinone ligands.10 Consequently, we were
surprised when the mixed-ligand catalyst 8 caused rapid
conversion of 9 to 10 without forming 11 (eq 3), whereas
1) are conveniently accessible compared to replacement with
“free ligand,” which gives mixtures, and the steric and
electronic factors imparted on the catalyst with mixed ligands
should be considerably different from those of catalysts with
one ligand structure.
Would only one azetidinone ligand, for example, lengthen
the rhodium-rhodium bond distance to enhance reactivity?
Could the mixed ligand catalyst exhibit selectivities higher
than those of its homogeneous counterparts? The answers
to these questions are definitely yes as demonstrated by
results from the following experiments.
Azetidinone-ligated dirhodium(II) catalysts (e.g., 4) exhibit
high reactivity for diazo decomposition relative to their
counterparts that are constructed from five-membered ring
heterocycles (e.g., 5 and 6).10
11 was the sole product with Rh2((4S)-MPPIM)4 and even
evident with Rh2((4S)-MEAZ)4 (percent isolated yields are
in parentheses). With the analogous phenyldiazoacetate (12),
however, enantioselectivities were lower with 8 than with
either Rh2((4S)-MEAZ)4 or Rh2((4S)-IBAZ)4 alone (eq 4).13
The reason for this is the longer Rh-Rh bond distance for
azetidinone-ligated catalysts, whose origin is the wider bite-
angle of the NCO dirhodium bridge.11 Only these catalysts
cause diazo decomposition of methyl phenyldiazoacetate and
562
Org. Lett., Vol. 5, No. 4, 2003

Neither 5 nor 6 caused diazo decomposition of 12 under these
conditions, and unreacted starting material was recovered.
Recovery and reuse of the polymer-linked catalyst through
four cycles afforded the same product yields and selectivities
as those reported ((2%). Catalyst loadings as low as 0.2
mol % were effective for complete conversion. Reactions
in benzene or cyclohexane gave lower enantioselectivities
than those in dichloromethane.
disubstituted lactones. The classic system is insertion reac-
tions of cyclohexyl diazoacetate (16) for which high % ee
values are common, but diastereoselectivities can vary (eq
6).15
Catalyst loading was determined from % Rh elemental
analyses and was 0.1 mmol/g for 8. Coverage of polymer
sites for ligand attachment was 60-90%, and dirhodium(II)
attachment was more complete on the NovaSyn resin than
on the Merrifield resin. However, the factor primarily
responsible for lower yields and irreproducible results was
water inclusion within the immobilized catalyst. Heating the
catalyst at 50 °C under reduced pressure was effective in
conditioning the catalyst for optimum use and reuse.
Another process for which azetidinone-ligated dirhodium-
(II) catalysts are uniquely suited is carbon-hydrogen inser-
tion. In the case of 2-propyl phenyldiazoacetate (14),
enantioselectivities in the range of 24-33% characterized
five homogeneous azetidinone-ligated catalysts (eq 5).14
Similar product yields and selectivities were obtained with
the Merrifield resin-linked dirhodium catalyst 3 (17c:17t )
61:31, % ee 17c > 99, % ee 17t ) 81) and with those where,
in eq 1, B ) (4S)-MPPIM (17c:17t ) 52:48, % ee 17c )
92, % ee 17t ) 57) and B ) (4S)-MEAZ (17c:17t ) 53:47,
% ee 17c ) 97, % ee 17t ) 88). Application of the
immobilized catalysts provides results that show no mean-
ingful decrease in enantiocontrol, but diastereoselectivities
for the trans isomer are clearly increased. To ascertain the
cause of this change in diastereocontrol, we prepared the
octadecyl ester analogue of Rh2((5S)-MEPY)4, Rh2((5S)-
ODPY)4 (4b). When this catalyst, which is soluble in
hydrocarbon solvents, was used, the 17c:17t composition
changed to 76:24, a value between those of Rh2((5S)-MEPY)4
and the immobilized support. Thus, increasing the hydro-
carbon content of the catalyst ester linkage increases dias-
tereoselection for the trans isomer. This was confirmed in
C-H insertion reactions of 1,3-dimethoxy-2-propyl diaz-
oacetate16 where the cis:trans product ratio decreased from
93:7 with 5a to 90:10 with 5b and then to 82:18 with 8 (L′
) (5S)-MEPY). As an example of the effectiveness of these
immobilized catalysts for recovery/reuse, we conducted diazo
decomposition of cyclohexyl diazoacetate with 8 (L′ ) (4S)-
MPPIM) through three cycles without diminution in product
yield or stereoselectivity. Further enhancements with these
immobilized catalysts are currently under investigation.
With 8, where L′ ) (5S)-MEPY, however, selectivity was
increased to a level beyond that with the most selective
azetidinone-ligated homogeneous catalyst, suggesting another
advantage of this catalyst methodology. Similar features of
reaction were observed in reactions with cyclohexyl phenyl-
diazoacetate, which also resulted in exclusive formation of
â-lactone product.
Homogeneous chiral dirhodium(II) carboxamidates have
a characteristic diastereoisomeric preference for intra-
molecular C-H insertion of diazoacetates resulting in cis-
Acknowledgment. This work was supported by grants
from the National Science Foundation, the National Institutes
of Health (M.P.D.), and the National Science Council of
R.O.C (H.M.G.).
(10) Doyle, M. P.; Davies, S. B.; Hu, W. Org. Lett. 2000, 2, 1145.
(11) Doyle, M. P.; Zhou, Q.-L.; Simonsen, S. H.; Lynch, V. Synlett 1996,
697.
(12) Davies, H. M. L.; Antoulinakis, G. Org. React. (N. Y.) 2001, 57, 1.
(13) Doyle, M. P.; Hu, W. AdV. Synth. Catal. 2001, 343, 1.
(14) Doyle, M. P.; May, E. J. Synlett 2001, 967.
Supporting Information Available: Immobilized resin-
catalyst preparation and characterization. This material is
available free of charge via the Internet at http://pubs.acs.org.
(15) (a) Doyle, M. P.; Kalinin, A. V.; Ene, D. G. J. Am. Chem. Soc.
1996, 118, 8837. (b) Doyle, M. P.; Dyatkin, A. B.; Roos, G. H. P.; Can˜as,
F.; Pierson, D. A.; van Basten, A.; Mu¨ller, P.; Polleux, P. J. Am. Chem.
Soc. 1994, 116, 4507.
OL027475A
(16) Doyle, M. P.; Tedrow, J. S.; Dyatkin, A. B.; Spaans, C. J.; Ene, D.
G. J. Org. Chem. 1999, 64, 8907.
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