Synthesis of indolizidines from optically pure α-amino acids via stereocontrolled rhodium-catalyzed hydroformylation of N-allylpyrroles.

Indolizidine alkaloids have attracted considerable attention because of their vast array of structural diversity and varied biological activity. This article relates the results that we obtained in the field of the total synthesis of indolizidines from α-amino acids, based on the rhodium-catalyzed hydroformylation of N-allylpyrroles intermediates. The formed pyrrolylbutanals undergo an intramolecular cyclodehydration to 5,6-dihydroindolizines, which are fully hydrogenated to indolizidines.

Computational prediction of selectivities in nonreversible and reversible hydroformylation reactions catalyzed by unmodified rhodium-carbonyls.

The regio- and stereoselectivities of the hydroformylation reaction catalyzed by an unmodified Rh catalyst have been investigated at the B3P86/6-31G* level with Rh described by effective core potentials in the LANL2DZ valence basis set for a number of either mono- or (1,1-, 1,2-, 1,3-) di-substituted substrates and compared with a variety of earlier results of ours, supplemented with free energy results when not already available. The computational prediction of regio- and stereoselectivities in nonreversible hydroformylations performed under mild reaction conditions is seemingly possible provided a careful conformational search for TS structures is carried out and all the low energy conformers are taken into account. The internal energy can be used to compute both the regio- and stereoselectivities in the hydroformylation of 1,1- and 1,3-substituted substrates with satisfactory results, whereas for 1,2-substituted substrates the regioselectivity determined from the internal energy is in good agreement with the experiment in the case of aliphatic olefins just for the lowest terms in the series (i.

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

The synthesis of (-)-Indolizidine 167B has been achieved from optically active (R)-3-(pyrrol-1-yl)hex-1-ene. The key step is a highly regioselective hydroformylation reaction and a one-pot intramolecular cyclization providing a general approach to the indolizine nucleus.