Synthesis of (–)-Indolizidine 167B based on domino hydroformylation/cyclization reactions

• Giuditta Guazzelli,
• Raffaello Lazzaroni and
• Roberta Settambolo

Beilstein J. Org. Chem. 2008, 4, No. 2, doi:10.1186/1860-5397-4-2

• describe here a new synthesis of optically active (–)-Indolizidine 167B based on regioselective hydroformylation/intramolecular cyclization reactions which provides a general approach to the indolizine nucleus. It is a multi-step domino process which starts with the interconversion of the isomeric rhodium

• under H2 50 atm, after CO and H2 removal, 80% yield; iii 10 atm H2, Rh/C (5%), r.t. 45 min, 75% yield; iv H2 10 atm, Rh/C (5%), r.t., 60 min, 64% yield. Stereospecific interconversion of the rhodium-alkyl intermediates as the key for regioselective formation of the linear aldehyde 2a. Supporting