Asymmetric synthesis of 8-aminoindolizidine from chiral 2-pyrroleimines.
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.
Albano
Vincenzo Giulio
VG
Dipartimento di Chimica G. Ciamician, Università di Bologna, via Selmi 2, 40126 Bologna, Italy.
Gualandi
Andrea
A
Monari
Magda
M
Savoia
Diego
D
D018360:Crystallography, X-Ray; D007097:Imines / Q000737:chemistry*; D054836:Indolizidines / Q000138:chemical synthesis*; D008968:Molecular Conformation; D011758:Pyrroles / Q000737:chemistry; D013237:Stereoisomerism
D007097:Imines; D054836:Indolizidines; D011758:Pyrroles