to acylation in CH
solvents was maintained over time as the acetic acid
byproduct does not significantly influence the Lewis acidity
3
CN, the rate of reaction in nonpolar
two different forms and oxidation states. A question arises
as to why metal carbonyl anions are acylation catalysts for
alcohols in solvents such as CH CN but not in toluene or
3
BTF. In toluene, we propose the acetic acid byproduct (and
possibly the alcohol reactant) may be strongly hydrogen
bonded to the metal carbonyl anions, thus diminishing their
+
+ 10
of the metal ions (Na , K ). In further support of our
mechanistic hypothesis (Scheme 1), we obtained IR evidence
+
for chelation of Na to benzoic anhydride (complex 3, R )
Ph).11 The two characteristic carbonyl bands in BTF (1792
3
reactivity. In CH CN, the alcohol should be largely hydrogen-
-
1
7a
and 1730 cm ) merged gradually into one band of inter-
bonded to the solvent, leaving the anion free to react. Thus,
an acylation involving only aprotic materials may proceed
by nucleophilic catalysis in nonpolar solution.
-
1
mediate wavenumber (1779 cm ) during addition of NaB-
p-Ph-CF . Note that chelation of other Lewis acids to
anhydrides is precedented.
Alternatively, in aprotic or coordinating solvents such as
THF, CH CN, or anisole, the reaction pathway becomes
(
3 4
)
12
To test our hypothesis rationally, we sought an acylation
process in which neither the reactant nor the product could
donate hydrogen bonds. An optimal example would be the
Staudinger reaction, namely the acylation of imines by
ketenes to form â-lactams, involving only aprotic starting
3
nucleophilic in nature (Scheme 1, path a). As expected, the
addition of 15-crown-5 had no effect on the rate of reaction
4
,5
in THF or CH
anion (but not the anion of NaB(p-Ph-CF )
3
CN. Under these conditions, the cobaltate
) is catalytically
materials. Our approach to making this reaction catalytic
for the first time involves using a much less nucleophilic
imine through attachment of electron-withdrawing groups
onto the imine nitrogen and R to the imine unit. We
3 4
active and the Lewis basic environment results in effective
sequestration of the cationic counterion. To provide support
for the proposed nucleophilic mechanism, we first determined
that a cobalt acyl species was a plausible intermediate. A
solution of acetic anhydride and 1a was mixed in BTF, and
17
determined that electron-deficient R-imino ester 7 does not
18a
react with diphenylketene 8 at room temperature. However,
we found that 5 mol % of 1d catalyzes the addition of 7 to
8 to afford â-lactam 10 in 85% yield after only 5 min in
the resulting complex 2 (R ) CH
3
) was characterized by
1
3
18b
IR. The spectral data were indicative of an acyl cobalt
BTF at room temperature (Scheme 3).
-1
14a
species (IR stretch at 1729 cm ) consistent with precedent.
Consequently, when complex 2 was dissolved in a solution
of cyclopentanol, the stoichiometric acylation reaction was
complete in a matter of minutes. We obtained further
evidence supporting nucleophilic catalysis in polar solvents
Scheme 3
by employing 1 equiv of Collman’s reagent (Na
1
2 4
Fe(CO)
b), a more basic nucleophile than 1a.14b In this case no
catalyzed reaction took place under the standard conditions,
an outcome that disfavors a purely base-catalyzed pathway.
The substrates used in this study, as outlined in Table 2,
include primary and secondary alcohols.
Especially intriguing is the use of the complex salt
cobaltocenium cobaltate 1d as an acylation catalyst (Figure
1
5
1
). As expected, in toluene and BTF the cobaltocenium
A catalytic nucleophile entering the picture can do two
things: either it can add to the ketene to form metalloenolate
9
, thus effectively reversing the polarity of the reaction, or
it can reversibly add to 7 and restore its nucleophilicity.
(
13) Under an inert atmosphere, 0.1 mmol of NaCo(CO)4 was added to
Figure 1. Cobaltocenium cobaltate 1d.
1
1
mmol of acetic anhydride in 3 mL of BTF and the solution was refluxed
h. Excess reagents were removed under vacuum, and the residue was
transferred into an IR cell.
14) (a) Haasz, F.; Bartik, T.; Galamb, V.; Palyi, G. Organometallics
990, 9, 2773. (b) For a review of this reagent, see: Collman, J. P. Acc.
(
cation is responsible for the catalytic acetylation of cyclo-
1
pentanol, whereas in CH
3
CN it is the cobaltate anion. For
(1c) is an active catalyst in toluene
CN.16 Thus, cobalt is the catalytic agent in
Chem. Res. 1975, 8, 342.
+
-
example, Cp
2
Co PF
6
(15) Bockman, T. M.; Kochi, J. K. J. Am. Chem. Soc. 1989, 111, 4669.
(16) By use of 10 mol % of 1c in 2 mL of toluene and CH3CN,
respectively, the acylation of benzyl alcohol with acetic anhydride (1 mM
each) was complete in toluene after 24 h. In CH3CN, however, no product
formation was observed.
(17) Tschaen, D. H.; Turos, E.; Weinreb, S. M. J. Org. Chem. 1984, 49,
5058.
but not in CH
3
(
10) Remarkably, KCo(CO)4 showed essentially the same reactivity as
+
+
its Na analogue, demonstrating that K is also a competent Lewis acid
under the specified conditions.
(
11) (a) Shambayati, S.; Crowe, W. E.; Schreiber, S. L. Angew. Chem.,
Int. Ed. Engl. 1990, 29, 256.
12) Viard, B.; Poulain, M.; Grandjean, D.; Amaudrut, J. J. Chem. Res.
983, 853.
(18) (a) Lund, E. A.; Kennedy, I. A.; Fallis, A. G. Can. J. Chem. 1996,
12, 2401. (b) Using catalyst 1a gave comparable results in this reaction.
Upon addition of 1 equiv of 15-crown-5, the reaction was not inhibited,
indicating that catalysis is primarily nucleophilic in nature.
(
1
Org. Lett., Vol. 1, No. 12, 1999
1987