reported,10 the well-defined catalysts of the general form
[Lewis acid]+[Co(CO)4]- developed in our laboratory are
the most active and selective.11 Unfortunately, the high
pressure of CO (200-900 psi) necessary for efficient and
selective carbonylation limits the use of these catalysts in
general laboratory applications. Thus, a catalyst that is
efficient under mild conditions and low pressures of CO
would be a significant advance, enabling the widespread use
of epoxide carbonylation as a route to â-lactones. Herein,
we report a readily synthesized catalyst that is capable of
epoxide carbonylation to produce a functionally diverse set
of â-lactones with minimal side-product formation at CO
pressures as low as 1 atm.
During the examination of catalysts containing different
Lewis acids, we discovered that [(salph)Cr(THF)2]+[Co(CO)4]-
(1, Figure 1, salph ) N,N′-bis(3,5-di-tert-butylsalicylidene)-
When our previously reported catalysts are reacted at CO
pressures below 200 psi, a reduction in activity is observed,
concomitant with the significant production of ketone as a
side product.11d This ketone is likely the result of the non-
carbonylative rearrangement12 of a ring-opened epoxide
intermediate (Scheme 2). Our proposed catalytic cycle for
Figure 1. Catalyst 1 with its crystal structure drawn with 40%
thermal ellipsoids.
Scheme 2. Mechanism for Epoxide Carbonylation (Pathway
A) and Competing Ketone Formation (Pathway B) from a
Common Intermediate (I).
1,2-phenylenediamine) was a highly active catalyst for
epoxide carbonylation under our standard conditions (neat
epoxide, 900 psi CO, 60 °C). Catalyst 1 is readily synthesized
using modified literature procedures.11a,16,17 In screening
reactions at 100 psi CO with several epoxide carbonylation
catalysts, 1 displayed the highest activity and selectivity for
â-lactone formation.18 A CO pressure of 100 psi is note-
worthy as it allows the carbonylation reactions to be
performed in sealed glass reactors18 which are significantly
more practical and less expensive than high-pressure, stain-
less steel reactors. One possible explanation for the differ-
ences between carbonylation catalysts at lower CO pressures
is that 1 allows a faster ring-closing event relative to ketone
formation; further exploration of this postulate is currently
being pursued in our laboratory.
Optimization of the conditions necessary for efficient
carbonylation of epoxides by 1 at 100 psi CO highlighted
two important features. First, the judicious choice of reaction
solvent is necessary to maintain catalyst activity and selectiv-
ity for lactone formation. It was found that weakly coordinat-
ing, polar solvents such as 1,2-difluorobenzene and 1,2-
dimethoxyethane (DME) were optimal. More strongly
coordinating solvents such as THF and acetonitrile drastically
reduced the rate of catalysis. Second, although higher
temperatures increased the rate of reaction, the selectivity
for lactone over ketone formation was compromised. Thus,
subsequent reactions were performed at room temperature
(22 °C) using DME as the solvent to favor efficient and
selective lactone formation.
epoxide carbonylation begins with ring opening to form a
metal-alkoxide/cobalt-alkyl species (I, Scheme 2).11a Under
high-pressure conditions, rapid CO insertion into the cobalt-
alkyl bond followed by ring closing results in â-lactone
formation and regeneration of the catalyst (pathway A).13
However, if intermediate I is sufficiently long-lived (as we
propose is the case under lower CO pressures because of
the reversibility of CO insertion),14 the cobalt-alkyl of I can
undergo â-hydride elimination followed by enolate proto-
nation and tautomerization (pathway B) to afford the
observed ketone.15
(10) (a) Allmendinger, M.; Eberhardt, R.; Luinstra, G. A.; Molnar, F.;
Rieger, B. Z. Anorg. Allg. Chem. 2003, 629, 1347-1352. (b) Allmendinger,
M.; Zintl, M.; Eberhardt, R.; Luinstra, G. A.; Molnar, F.; Rieger, B. J.
Organomet. Chem. 2004, 689, 971-979.
(11) (a) Getzler, Y. D. Y. L.; Mahadevan, V.; Lobkovsky, E. B.; Coates,
G. W. J. Am. Chem. Soc. 2002, 124, 1174-1175. (b) Mahadevan, V.;
Getzler, Y. D. Y. L.; Coates, G. W. Angew. Chem., Int. Ed. 2002, 41, 2781-
2784. (c) Schmidt, J. A. R.; Mahadevan, V.; Getzler, Y. D. Y. L.; Coates,
G. W. Org. Lett. 2004, 6, 373-376. (d) Schmidt, J. A. R.; Lobkovsky, E.
B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426-11435.
(12) Eisenmann, J. L. J. Org. Chem. 1962, 27, 2706.
Encouraged by the high activity and selectivity 1 displayed
for carbonylation at 100 psi CO, we sought to determine
(16) Mart´ınez, L. E.; Leighton, J. L.; Carsten, O. M.; Jacobsen, E. N. J.
Am. Chem. Soc. 1995, 117, 5897-5898.
(17) Catalyst 1 was subjected to crystallographic analysis. CCDC-601862
contains the supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallographic Data
(13) A mechanistic study has been conducted on a closely related catalyst
system. See: Church, T. L.; Getzler, Y. D. Y. L.; Coates, G. W. J. Am.
Chem. Soc. 2006, 128, 10125-10133.
(14) Roe, D. C. Organometallics 1987, 6, 942-946.
(15) Prandi, J.; Namy, J. L.; Menoret, G.; Kagan, H. B. J. Organomet.
Chem. 1985, 285, 449-460.
(18) See Supporting Information.
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Org. Lett., Vol. 8, No. 17, 2006