How to Control the Chemoselectivity of the Catalytic Formation of Chiral γ-Lactams or 2,3-Disubstituted Pyrroles by the Choice of Solvent

rac-1-(4-tert-Butylphenyl)-5-ethyl-4-ferrocenyl-5-hydroxy-1H-pyrrol-2(5H)-one

“…Therefore, a radical mechanism cannot be ruled out for the formation of the title compound, although no addition of any typical initiator is necessary. So overall, depending on the reaction conditions, either chiral 1,3-dihydropyrrolones, chiral 5-hydroxy-1,5-dihydropyrrolones or 2,3-disubstituted pyrrole derivatives might be the main products of the catalytic synthetic methodology developed in our lab (Biletzki & Imhof, 2011;Gillies et al, 2007;Do ¨nnecke & Imhof, 2003).…”

“…In a series of recent publications, we were able to show that the ruthenium-catalysed four-component reaction of an ,unsaturated aldehyde with a primary amine (producing an intermediate imine), carbon monoxide and ethylene produces a library of chiral 1,3-dihydropyrrolones and pyrroles, respectively (Biletzki & Imhof, 2011). The ratio of those two products is highly dependent on the relative permittivity of the solvent used, with the yield of the pyrrole increasing with the polarity of the solvent (Gillies et al, 2007). We were also able to show that the oxidation of the resulting pyrroles with oxygen leads to the formation of derivatives of the title compound (Do ¨nnecke & Imhof, 2003).…”

A Combinatorial Approach towards a Library of Chiral γ-Lactams and 2,3-Disubstituted Pyrroles

“…The product ratio is highly dependent on the relative permittivity of the solvent used; with nonpolar solvents like, for example, hydrocarbons leading to the quantitative and selective formation of racemic lactams 4, whereas use of more polar solvents or the presence of traces of water leads to an enhancement of the yield of the pyrrole 5 (75% in anhyd MeOH). 15 g-Lactams or g-bu-tyric acid derivatives have been investigated with respect to their potential as psychotropic drugs, as agents against Alzheimer's disease, Down's syndrome, osteoporosis, and cancer or as constituents of peptide mimetics exhibiting g-turns. [16][17][18][19][20][21][22] It has also been demonstrated that incorporation of g-amino acids into protein sequences considerably enhances their stability against proteases, which is an essential prerequisite to use those proteins as drugs under physiological conditions.…”