Rhodium-catalyzed ring opening of vinyl epoxides with alcohols and aromatic amines

Article abstract of DOI:10.1021/ol0060782

(equation presented) [Rh(CO)₂Cl]₂ is an effective catalyst for the ring opening of vinyl epoxides with alcohols and aromatic amines under neutral conditions at room temperature. The reaction occurs with excellent diastereo- and regioselectivity (>20:1) giving the trans-1,2-amino alcohols or alkoxy alcohols for a wide range of substrates. The regio- and stereochemistry of these reactions is complementary to that typically obtained with palladium-catalyzed ring openings of vinyl epoxides.

Full text of DOI:10.1021/ol0060782

ORGANIC
LETTERS
2000
Vol. 2, No. 15
2319-2321
Rhodium-Catalyzed Ring Opening of
Vinyl Epoxides with Alcohols and
Aromatic Amines
Keith Fagnou and Mark Lautens*
Lash Miller Laboratories, Department of Chemistry, UniVersity of Toronto,
Toronto, Ontario, Canada M5H 3H6
mlautens@alchemy.chem.utoronto.ca
Received May 18, 2000
ABSTRACT
[Rh(CO)2Cl]2 is an effective catalyst for the ring opening of vinyl epoxides with alcohols and aromatic amines under neutral conditions at room
temperature. The reaction occurs with excellent diastereo- and regioselectivity (>20:1) giving the trans-1,2-amino alcohols or alkoxy alcohols
for a wide range of substrates. The regio- and stereochemistry of these reactions is complementary to that typically obtained with palladium-
catalyzed ring openings of vinyl epoxides.
Vinyl epoxides are commonly used starting materials in
organic synthesis.1 Among their most important applications
are as electrophiles in transition metal catalyzed reactions.
The most frequently used catalysts are palladium based
which permit coupling with a wide variety of nucleophiles.2
A common trend in all of these reactions is a preference for
the nucleophilic addition to occur in a 1,4-manner syn to
the leaving group. This results from a net SN2′ addition with
retention of configuration arising from a double inversion
pathway.
Transition metal catalyzed reactions giving 1,2-addition
products are far fewer in number. To obtain 1,2-addition with
palladium, the nucleophile is typically delivered in an
intramolecular fashion via a tether to give the cis product3,4
(Scheme 1). While trans-1,2-addition products can some-
Scheme 1. Regioselectivity in Vinyl Epoxide Ring Opening
(1) ComprehensiVe Organic Synthesis; Trost, B. M., Flemming, I., Eds.;
Permagon Press: New York, 1991; Vol. 6.
(2) For a review on allylic alkylation, see: Trost, B. M.; Van Vranken,
D. L. Chem. ReV. 1996, 96, 395 and pertinent references therein. For a
review on allylic amination, see: Johannsen, M.; Jorgensen, K. A. Chem.
ReV. 1998, 98, 1689 and pertinent references therein. For a general reference
on the chemistry of palladium, see: Tsuji, J. Palladium Reagents and
Catalysis; Wiley and Sons Ltd.: Toronto, 1995.
(3) For the use of tin alkoxides, see: Trost, B. M.; Tenaglia, A.
Tetrahedron Lett. 1988, 29, 2931. Keinan, E.; Sahai, M.; Roth, Z.;
Nudelman, A.; Herzig, J. J. Org. Chem. 1985, 50, 3558. For the use of
cocatalytic trialkylborates with alcohols, see: Trost, B. M.; McEachern, E.
J.; Toste, F. D. J. Am. Chem. Soc. 1998, 120, 12702. For the use of carbon
monoxide to give cyclic carbonates, see: Trost, B. M.; Angle, S. R. J. Am.
Chem. Soc. 1985, 107, 6123. For the use of aldehydes to give cyclic acetals,
see: Suzuki, S.; Fujita, Y.; Kobayashi, Y.; Sato, F. Tetrahedron Lett. 1986,
27, 69. For the use of isocyanates to give oxazolidinones, see: Trost, B.
M.; Sudhakar, A. R. J. Am. Chem. Soc. 1987, 109, 3792.
times be obtained through stoichiometric or catalytic use of
Brønsted and Lewis acids, these methods suffer from poor
functional group compatibility. In addition, such methods
(4) Very recently, a palladium-catalyzed dynamic kinetic asymmetric
transformation has been reported with phthalimide and vinyl epoxides giving
the 1,2-addition products in good yield and excellent ee’s. See: Trost, B.
M.; Bunt, R. C.; Lemoine, R. C.; Calkins, T. L. J. Am. Chem. Soc. ASAP.
10.1021/ol0060782 CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/28/2000

generally fail with amine nucleophiles as a result of their
high basicity.5 Given the synthetic utility of the 1,2-addition
products, particularly 1,2-alkoxy alcohols and 1,2-amino
alcohols, the development of a mild and selective method
for their preparation from vinyl epoxides would be a desirable
goal.
We now report a very mild rhodium-catalyzed reaction
of vinyl epoxides that occurs at room temperature. The
reaction can be conveniently run in an open flask without
any special precautions. Both alcohols and aromatic amines
are effective nucleophiles, giving the trans-1,2-addition
products in greater than 20:1 diastereo- and regioselectivity
(Scheme 2). Because of the mildness of the reaction
our attention on rhodium complexes. Neither the catalyst
shown to induce reaction in our oxabicyclic alkene studies
(entry 1) nor the modified Wilkinson’s catalyst used by P.
A. Evans in the allylic alkylation,7 amination,8 and etheri-
fication9 studies (entry 4) showed any reactivity. [Rh-
(CO)2Cl]2 in the absence of any added ligand (entry 6),
however, produced the best results, giving the trans-1,2-
addition product in 94% isolated yield with >20:1 diastereo-
and regiselectivity.10
The reactivities of other alcohol nucleophiles with this
substrate were examined. Both primary and secondary
alcohols are effective. Phenol gives lower yields and benzyl
alcohol is ineffective, giving very little desired product. The
reaction is general for a wide range of vinyl epoxides (Table
2). When the ring-opened products contained a primary
Scheme 2. Rhodium-Catalyzed Alcoholysis and Aminolysis of
Vinyl Epoxides
Table 2. Reaction of Various Vinyl Epoxides with Alcohols
conditions, we believe that this methodology represents an
attractive alternative to the traditional Brønsted and Lewis
acid mediated routes, especially when substrates contain acid-
labile functionalities.
Our initial experiments focused on finding an active
catalyst system with alcohol nucleophiles (Table 1). As a
Table 1. Effect of the Rhodium Source on Reactivity
alcohol, a significant amount of dimeric and oligomeric
byproducts were produced. By running the reactions in neat
alcohol, however, the isolated yields were increased to
>90%. These reactions are very mild, occurring under neutral
conditions and at room temperature.
The compatibility of amine nucleophiles was also inves-
tigated. We were gratified to find that aromatic amines are
highly reactive nucleophiles providing the trans-1,2-amino
alcohols with selectivities exceeding 20:1.10 The reaction
occurs with a
consequence of our ongoing studies on the asymmetric ring
opening (ARO) reaction of oxabicyclic alkenes,6 we focused
(5) For use of diethylaluminum amides, see: Overman, L. E.; Flippin,
L. A. Tetrahedron Lett. 1981, 195. For use of amino silanes and stannanes,
see: Papini, A.; Ricci, A.; Taddei, M. J. Chem. Soc., Perkin Trans. 1 1984,
2261. Fiorenza, M.; Ricci, A.; Taddei, M.; Tassi, D. Synthesis 1983, 640.
For the use of lithium, magnesium, and zinc salts, see: Chini, M.; Crotti,
P.; Macchia, F. Tetrahedron Lett. 1990, 31, 4661. For the use of amino
lead reagents, see: Yamada, J.; Yumoto, M.; Yamamoto, Y. Tetrahedron
Lett. 1989, 30, 4255. For the use of cobalt-catalyzed aminolysis, see: Iqbal,
J.; Pandey, A. Tetrahedron Lett. 1990, 31, 575. For the use of lanthanide
catalysts, see: Fu, X.-L.; Wu, S.-H. Synth. Commun. 1997, 27, 1677.
(6) Lautens, M.; Fagnou, K.; Rovis, T. J. Am. Chem. Soc. 2000, 122,
5650. Lautens, M.; Fagnou, K.; Taylor, M. Org. Lett. 2000, 2, 1677.
(7) Evans, P. A.; Nelson, J. D. J. Am. Chem. Soc. 1998, 120, 5581.
(8) Evans, P. A.; Robinson, J. E.; Nelson, J. D. J. Am. Chem. Soc. 1999,
121, 6761.
(9) Evans, P. A.; Leahy, D. J. Am. Chem. Soc. 2000, 122, 5012.
(10) For the establishment of regio- and relative stereochemistry, see
Supporting Information.
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Org. Lett., Vol. 2, No. 15, 2000

wide variety of aromatic amines, varying in both steric bulk
and in basicity (e.g., both p-anisidine and p-nitroaniline are
compatible nucleophiles) (Table 3).
In the presence of the more basic amine, the aromatic amine
addition pathway is shut down, indicating that the rhodium
is being sequestered from the catalytic cycle.
There are two possible roles that rhodium might be
playing; it can act as a mild Lewis acid, or it can insert into
the carbon-oxygen bond to produce a π-allyl or enyl7
rhodium intermediate. Preliminary mechanistic studies have
shown that the presence of an olefin is required for the
reaction to occur since cyclohexene oxide does not react
under these conditions. Furthermore, styrene oxide does not
react even after prolonged reaction times, indicating that the
rhodium is likely not acting as a Lewis acid.
Table 3. Reaction of Vinyl Epoxides with Aromatic Amines
When vinyl epoxides possessing a terminal olefin are used,
a mixture of 1,4- and 1,2-addition products is produced,
analogous to the results obtained by Evans with anilines in
the allylic amination of allyl carbonates.8 In contrast to
previous reports on rhodium-catalyzed allylic alkylation,
amination, and etherification that occur with retention of
absolute configuration, [Rh(CO)2Cl]2 promotes the ring
opening of vinyl epoxides with inversion of stereochemistry
at the allylic position undergoing nucleophilic attack. In our
studies of ARO reactions of oxabicyclic alkenes inversion
is also observed, but the reaction proceeds via a net SN2′
displacement contrary to the net SN2 reaction that occurs
with vinyl epoxides. Current studies are focused on elucidat-
ing the source of these intriguing differences.
In conclusion, we have demonstrated that [Rh(CO)2Cl]2
is an effective catalyst for the ring opening of vinyl epoxides
with alcohols and aromatic amines under neutral conditions
at room temperature. The reaction occurs with excellent
diastereo- and regioselectivity (>20:1) giving the trans-1,2-
addition products for a wide range of substrates. This regio-
and stereoselectivity is complementary to that typically
observed with palladium catalysis. The simplicity and
mildness of this methodology make it an attractive option
whenever substrates possess acid-sensitive groups.
Aliphatic amines fail to react under these reaction condi-
tions. This is likely due to the amine binding strongly to the
rhodium metal, resulting in catalyst poisoning. Since aromatic
amines are less basic than aliphatic amines, this mode of
binding would be significantly reduced. Evidence for this
hypothesis is obtained by performing the reaction with 5
equiv of both N-methylaniline and benzylamine (Scheme 3).
Acknowledgment. We thank NSERC, the ORCDF, and
the University of Toronto for valuable support of our research
programs. K.F. thanks NSERC and AstraZeneca for an
Industrial NSERC postgraduate scholarship.
Scheme 3. Effect of Added Aliphatic Amine on Aromatic
Amine Addition
Supporting Information Available: Full characterization
details including proton NMR, carbon NMR, IR, HRMS,
and proof of regio- and stereochemistry. This material is
available free of charge via the Internet at http://pubs.acs.org
OL0060782
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