A variety of C-2 and C-5 difunctionalized indolizines have been prepared through the reaction of 1-ester-substituted indolizines with organometallic bases followed by a reaction with different electrophiles. Metalation takes place under mild conditions allowing the isolation of a number of difunctionalized indolizines in good yields. The regioselectivity of the reaction appears to be governed by the nature of the base and electrophile.

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Directed Metalation of 1-Ester-Substituted Indolizines: Base/Electrophile--Controlled Regioselective Functionalization. -1-Ester-substituted indolizines are metallated and then functionalized by trapping with various electrophiles including iodine, dimethylformamide, aldehydes or trimethylsilyl chloride, or by Negishi cross--coupling partners. The transformation provides regioselectively the C-5 functionalized products if lithium diisopropylamide is used as the base. In contrast, mixtures of C-2 and C-5 isomers are delivered under electrophile-controlled reaction conditions via organomagnesium intermediates, and the major products in form of the C-2 functionalized indolizines are isolated if more reactive electrophiles are used and the C-5 functionalized counterparts are isolated upon reaction with less reactive electrophiles. -(AMARAL, M. F. Z. J.; BAUMGARTNER, A. A.; VESSECCHI, R.; CLOSOSKI*, G. C.; Org. Lett. 17 (2015) 2, 238-241, http://dx.