Pure Appl. Chem., Vol. 76, No. 3, pp. 557–564, 2004. © 2004 IUPAC 557 Stereochemistry of epoxide carbonylation using bimetallic Lewis acid/metal carbonyl complexes* Yutan D.Y. L. Getzler, Viswanath Mahadevan, Emil B. Lobkovsky, and Geoffrey W. Coates ‡ Baker Laboratory, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301, USA Abstract: The stereochemistry of epoxide carbonylation using bimetallic [Lewis acid] + [Co(CO) 4 ] – complexes is reported. The achiral complex [(salph)Al(THF) 2 ][Co(CO) 4 ] stereospecifically carbonylates cis- and trans-2-butene oxide to the trans- and cis-β-lac- tones, respectively. Preliminary experiments regarding the carbonylative kinetic resolution of racemic trans-2-butene oxide using the enantiomerically pure complex [(R,R-salcy)Al(THF) 2 ][Co(CO) 4 ] are also reported. INTRODUCTION β-Lactones are highly attractive synthetic targets due to their versatility in organic synthesis [1] as well as their presence in natural products with biological activity [2]. They are also useful monomers for the synthesis of poly(β-hydroxyalkanoate)s, a naturally occurring class of biodegradable polyesters [3]. One route to β-lactones which is drawing considerable recent interest, is the selective carbonylation of epoxides [4–14]. An early important advance in this field was the report that Co 2 (CO) 8 in combination with 3-hydroxypyridine formed an active catalyst for the carbonylation of epoxides of ethylene and propylene; depending on the reaction conditions, either β-lactones [7] or poly(β-hydroxyalkanoate)s [9,15] were formed. Recently, Alper and Lee reported the regioselective carbonylation of epoxides and aziridines using a catalyst system consisting of a mixture of [Ph 3 P=N=PPh 3 ][Co(CO) 4 ] and BF 3 Et 2 O [9]. Our research has focused on the development of a class of discrete bimetallic catalysts of the gen- eral formula [Lewis acid] + [Co(CO) 4 ] – [10–12], catalysts which exhibit high selectivities as well as ex- cellent activity for a range of epoxide and aziridine carbonylations. In developing these bimetallic Lewis acid/metal carbonyl catalysts, we envisioned a mechanism (Scheme 1) whereby the cationic Lewis acid coordinates and activates the substrate for attack by an an- ionic metal carbonyl. Following migratory insertion of CO into the metal alkyl bond and recoordination of CO, an intramolecular attack of the metal alkoxide on the metal acyl forms the β-lactone [10,11]. Rieger and coworkers have recently reported density functional theory (DFT) calculations which sup- port this mechanism [14]. In our search for further experimental evidence in support of this mechanism, we noted the stereochemistry of epoxide carbonylation could serve as a mechanistic probe. Based on the mechanism in Scheme 1, cis-epoxide should be converted to a trans-β-lactone upon carbonylation. We therefore initiated research regarding the carbonylation of epoxides of 2-butene, and the preliminary results of these studies employing [Cp 2 Ti][Co(CO) 4 ] were recently published [11], supporting our pro- *Plenary and invited lectures presented at the 12 th IUPAC International Symposium on Organometallic Chemistry Directed Towards Organic Synthesis (OMCOS-12), Toronto, Ontario, Canada, 6–10 July 2003. Other presentations are published in this issue, pp. 453–695. ‡ Corresponding author