Journal of Organic Chemistry 2008-11-07

Asymmetric synthesis of 8-aminoindolizidine from chiral 2-pyrroleimines.

Vincenzo Giulio Albano, Andrea Gualandi, Magda Monari, Diego Savoia

Index: J. Org. Chem. 73(21) , 8376-81, (2008)

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Abstract

1-Allyl-2-pyrroleimines obtained from (S)-valinol and (S)-phenylglycinol underwent highly diastereoselective addition of allylmagnesium chloride, used in excess amounts, to give the corresponding secondary amines with concomitant allyl to (Z)-1-propenyl isomerization of the 1-pyrrole substituent. Transformation of the 2-amino alcohol moiety to an oxazolidinone, or its cleavage and subsequent N-protection, followed by ring-closing metathesis of the two alkene groups gave the unsaturated bicyclic compound. Full hydrogenation of the alkene function and the aromatic rings afforded the indolizidine derivative as a mixture of two or three diastereomers with a ratio which was dependent on the nature of both the N-substituent and the catalyst. The two prevalent diastereomers were isolated, and their configuration was determined by X-ray crystallographic analysis.