Catalyst‐ and Base‐free One‐pot, Multicomponent, De Novo Assembly of Structurally Diverse Morpholine Glycoconjugates

Abstract

A catalyst-, metal-and base-free unprecedented one-pot multicomponent synthetic strategy has been established for the construction of various substituted morpholine glycoconjugates through four-component reactions of glycosyl amino alcohol, chloroacetone, acid, and isocyanides. Unexpectedly, this one-pot approach generates only the cyclized morpholine scaffolds rather than normal Ugi adduct without any external base. This reaction proceeds via in situ formations of Schiff-base followed by an intramolecular halogen displacement process, finally the Joullie-Ugi reaction takes place leading to the corresponding products with a mixture of diastereomers.

Metal‐Free Substituent‐Controlled Direct Synthesis of Unprecedented Iminotetrazoles via One‐pot Ugi‐Azide Reaction

“…Recently, we further took glycosyl amino alcohol to explore its use in a direct method for the synthesis of structurally diverse morpholine glycoconjugates in one pot using four‐component Ugi‐Mumm processes (Scheme 1b) [10b] . Surprisingly, this process could bring out a fruitful pathway to prepare the direct cyclized morpholine scaffolds instead of the expected normal Ugi adduct without any external base.…”

Ugi 5-center-4-component reaction of α-Amino Aldehydes/Deprotection/Cyclization sequence leading to substituted 2-oxopiperazine derivatives

“…Among the known MCRs, the isocyanide-based Ugi reaction [2] has received much attention in medicinal [3,4] and macrocyclic chemistry [5,6,7] chemical biology and bioconjugation [8, 9,10] as well as in natural product synthesis [11,12]. Several variants of this condensation have been developed, the Ugi three-(U-3CR) [13,14] and four-component reactions (U-4CR) [15] being most extensively studied (Scheme 1).…”

Ugi 5-center-4-component reaction of α-amino aldehydes and its application in synthesis of 2-oxopiperazines

“…Among the known MCRs, the isocyanide-based Ugi reaction [ 2 ] has received much attention in medicinal [ 3 , 4 ] and macrocyclic chemistry [ 5 – 7 ], chemical biology and bioconjugation [ 8 – 10 ], as well as in natural product synthesis [ 11 , 12 ]. Several variants of this condensation have been developed, the Ugi three- (U-3CR) [ 13 , 14 ] and four-component reactions (U-4CR) [ 15 ] being most extensively studied (Scheme 1 ).…”