The Effect of Lewis Acids on the Stereochemistry in the Ugi Three‐Component Reaction with D‐lyxo‐Pyrroline

Abstract

Keywords: Multicomponent reactions / Diastereoselectivity / Indium(III) chloride / Imines / Nitrogen heterocycles A library of polyhydroxylated pyrrolidines was obtained by performing a tandem Staudinger/aza-Wittig/Ugi three-component reaction on a L-ribose-derived 4-azido aldehyde. In this paper we describe the effect of Lewis acids on the diastereoselectivity of the final Ugi three-component reaction step that the intermediate (D-lyxo-pyrroline) cyclic imine undergoes. When the Ugi reaction was performed in methanol almost exclusively pyrrolidines with a 2,3-cis relationship

Highly Stereoselective Synthesis of Substituted Prolyl Peptides Using a Combination of Biocatalytic Desymmetrization and Multicomponent Reactions

“…The 2,3‐ trans relationship is in agreement with the generally accepted mechanism of the Ugi reaction, in which the stereodetermining step is the direct nucleophilic attack of the isocyanide on the imine (or iminium) carbon. The extraordinarily high selectivity for the 2,3‐ trans isomer is in sharp contrast with other reports, where stereoinduction is poor6a–e or the 2,3‐ cis isomer is preferentially formed 6f,g…”

The Development of an Aza‐C‐Glycoside Library Based on a Tandem Staudinger/Aza‐Wittig/Ugi Three‐Component Reaction

“…The configuration of the new chiral center, introduced during the Ugi‐3CR, was previously reported by us4b,4c for D ‐ lyxo ‐pyrrolidine aza‐C‐glycosides and for the new examples described here it was established by 1 H‐ and NOESY‐NMR experiments (Figure 2).…”

“…L ‐Ribose 4 was transformed into 4‐azidopentanal 5 according to our previous report 4b. In our previous work4c we had also found that the outcome in stereochemical terms of an Ugi‐3CR involving the D ‐ lyxo ‐pyrroline that emerges upon treatment of 5 with trimethylphosphane can be influenced by including indium trichloride in the reaction mixture. In agreement with our previous6c finding, performing the Ugi‐3CR in methanol in the absence of InCl 3 yields predominantly the 2,3‐ cis adducts ( 13 , 15 and 17 ) 14.…”

Diversity oriented and chemoenzymatic synthesis of densely functionalized pyrrolidines through a highly diastereoselective Ugi multicomponent reaction

“…7,12-15 Only very few high inducing chiral imines have been reported so far. 12, 16 For our purposes we selected imines 4 and ent-4, on the basis of two considerations: a) the already demonstrated possibility to attain a complete diastereoselection during the MCR, thanks to the conformational rigidity of this bicyclic system; 17 b) the presence of the acetonide moiety, which can be regarded as an additional source of diversity in the final compounds. As far as it concerns the first point, it is worth noting that the obtainment of complete stereoselection in the Ugi reaction of chiral pyrrolines is not general: in more flexible systems, even with a stereogenic centre a to the imine carbon, diastereoselectivity is poor or incomplete.…”