J. Am. Chem. Soc. 1997, 119, 5075-5076
Scheme 1
5075
The Remarkable Catalytic Activity of Alkali-Metal
Alkoxide Clusters in the Ester Interchange Reaction
Matthew G. Stanton and Michel R. Gagn e´ *
Department of Chemistry, UniVersity of North Carolina at
Chapel Hill, Chapel Hill, North Carolina 27599
ReceiVed February 21, 1997
Despite the fact that the transesterification reaction stands
out as one of the most fundamental reactions in organic
chemistry, there are no general methods for carrying out this
transformation under mild conditions. We wish to report that
a variety of alkali-metal alkoxides show high activity as catalysts
for the ester interchange reactionsa coupled transesterification
6
process (eq 1). These alkoxide clusters are at least 10 times
more active than the known lanthanide isopropoxide catalysts
1
recently reported by Okano (M(OiPr)3; M ) La, Nd, Gd, Yb).
Although alkali-metal alkoxides have been used for decades as
strong bases, to our knowledge, these complexes have been
observation is not consistent with the simple scenario in Scheme
since NaOMe should be immediately generated and precipi-
2
1
overlooked as catalysts for the ester metathesis reaction. We
present herein preliminary experiments which document the
remarkable rate-accelerations that alkali-metal alkoxides (M )
tated from the solution. Isolation of this slowly precipitated
1
solid and quenching with DCl/D2O followed by H NMR
analysis indicates that the aggregate is composed of a 3:1 ratio
of NaOMe and NaOtBu.
An examination of the known solution5,6 and solid-state7
structures of Mtert-butoxides suggests that higher order clusters
+
+
+
+
Li , Na , K , Rb ) affect on the ester metathesis reaction.
(
tetramers or hexamers) are reasonable intermediates and may
be intimately involved in catalyst turnover. In a related
transesterification reaction, Jackman has clearly demonstrated
that tetrameric and/or hexameric aggregates are the primary
The high activity of these complexes became evident as we
attempted to measure the rate at which the substrates in eq 1
reached equilibrium. In the presence of 5 mol % NaOtBu, this
reaction reaches equilibrium in <10 s. To establish equilibrium
this catalyst completes at least 400 turnoVers in <10 s!! Such
fast rates make aliquot quenching techniques coupled with GC
analysis inappropriate for kinetic studies. However, more
convenient rates were observed with tert-butyl acetate, and thus
8
reactants in THF and dioxolane.
Literature precedence coupled with the reported data leads
to the preliminary hypothesis that our catalysts are also alkoxide
clusters, perhaps tetramers (A-C), and that high reactivity
(
relative to NaOEt) is at least partially due to the enhanced
solubility imparted by the tert-butoxy ligands in organic
solvents. In essence, the in situ-derived clusters are solubilized
forms of NaOMe and NaOEt resulting from the partial replace-
the process in eq 2 was adopted for more detailed mechanistic
studies.3
9
ment of the tert-butoxy groups in the cluster B. As tert-butoxy
groups continue to be substituted by methoxy or ethoxy
substituents, the clusters lose their solubility and precipitate from
1
0
solution. In hexane/ester mixtures, the insolubility of the
trimethoxy/mono-tert-butoxy cluster suggests that for the process
in eq 2, A, B, and the cluster derived from 2-OMe and 2-OtBu
Since Mtert-butoxides are soluble in common organic solvents
and are easily purified by sublimation, they serve as ideal
catalyst precursors. At a first-order level of analysis, the
mechanism for the equilibration undoubtedly involves a series
of coupled transesterification reactions (Scheme 1). This
scenario invokes the intermediacy of NaOMe or NaOEt,
suggesting that these materials should be equally competent
catalysts for this process. Control experiments, however, show
that, in fact, NaOEt is a poor catalyst for eq 2, presumably due
to its insolubility in the reaction medium. Careful studies of
the reaction in eq 2 using 5 mol % of NaOtBu as catalyst show
that clean first-order relaxation kinetics are observed for at least
1
1
groups constitute the active catalysts. The presence of more
than one active catalyst may also be responsible for the apparent
(
5) For a partial list of references to the solution structures of alkali-
metal alkoxides, see: (a) Arnett, E. M.; Moe, K. D. J. Am. Chem. Soc.
1991, 113, 7288-7293. (b) Jackman, L. M.; Smith, B. D. J. Am. Chem.
Soc. 1988, 110, 3829-3835, and references therein. (c) Schmidt, P.;
Lochmann, L.; Schneider, B. J. Mol. Struct. 1971, 9, 403-411. (d) Bauer,
W.; Lochmann, L. J. Am. Chem. Soc. 1992, 114, 7482-7489. (e) Hartwell,
G. E.; Brown, T. L. Inorg. Chem. 1966, 5, 1257-1259.
(6) For general references on the solution and solid-state structures of
metal-enolates, see: (a) Seebach, D. Angew. Chem., Int. Ed. Engl. 1988,
4
a single half-life (∼10-20 turnovers). However, the solutions
2
2
7, 1624-1654. (b) Jackman, L. M.; Lange, B. C. Tetrahedron 1977, 33,
begin to cloud after this period of time, and the reaction rates
speed up despite precipitation of the catalyst. Clearly, such an
737-2769.
(7) (a) Chisolm, M. H.; Drake, S. R.; Naiini, A.; Streib, W. E. Polyhedron
991, 10, 337-345. (b) Davies, J. E.; Kopf, J.; Weiss, E. Acta. Crystallogr.
1
(
1) Okano, T.; Hayashizaki, Y.; Kiji, J. Bull. Chem. Soc. Jpn. 1993,
863-1864.
2) Encyclopedia of Organic Reagents; Paquette, L. A., Ed.; potassium
tert-butoxide; John Wiley and Sons: 1995; Vol. 6, pp 4189-4195.
1982, B38, 2251-2253. (c) Weiss, E.; Alsdorf, H.; K u¨ hr, H. Angew. Chem.,
1
Int. Ed. Engl. 1967, 6, 801-802.
(
(8) Jackman, L. M.; Petrei, M. M.; Smith, B. D. J. Am. Chem. Soc. 1991,
113, 3451-3458.
(
3) Using methyl alkanoates and tert-butyl acetate as substrates also
(9) Consistent with this proposal is the detection (GC) of substoichio-
metric quantities of tert-butyl esters (eq 1) from the addition of tert-butoxide
to the starting esters.
sufficiently slows down the rate of reaction that comparisons of different
alkyl groups are possible. In these studies, the relative reactivities are nPr
(
100) > Ph(36) > iPr(6) > tBu(<1).
(10) Alkali-metal methoxides form highly insoluble sheet-like structures,
see: (a) Weiss, E.; Aldsorf, H. Z. Anorg. Allg. Chem. 1970, 206-213. (b)
Weiss, E.; Aldsorf, H. Z. Anorg. Allg. Chem. 1964, 197-203.
(11) It is certainly reasonable to suggest that aggregates of higher order
than four may characterize materials with high OMe/OtBu ratios. Our
experiments have not addressed this issue as of yet.
(4) Reaction kinetics were determined by monitoring the conversion (by
GC) of methyl benzoate to a ∼50:50 mixture of methyl benzoate and tert-
butyl benzoate. The rate constants kobs ) (k1 + k-1) were obtained from a
plot of ln([tert-butyl benzoate]equil - [tert-butyl benzoate]t) versus timesthe
slope of the line is -kobs.
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