One step access to oxindole-based β-lactams through Ugi four-center three-component reaction

Abstract

A multicomponent Ugi reaction involving isatin, isocyanide and β-amino acid components has been developed.

Accessing New 5‐α‐(3,3‐Disubstituted Oxindole)‐Benzylamine Derivatives from Isatin: Stereoselective Organocatalytic Three Component Petasis Reaction

“…Initially the 5‐arylboronate‐3‐substituted oxindole derivative (1a) , salicylaldehyde (2a) (successfully applied in the PR due to the boron‐activating hydroxyl group[8a], ) and morpholine (3a) were selected as model reagents to explore and optimize the reaction conditions. We choose to use the 3‐oxo acetal protected version, as the 5‐arylboronate‐non‐protected 3‐carbonyl group (that could potentially participate in this reaction as is the case of Zhang's methodology[15a] or in some Ugi 4‐centre‐3‐component reactions), failing to give the desired product. The corresponding racemic 5‐α‐(3,3‐dimethoxy‐substituted‐oxindole)‐benzylamine derivative (4aaa) was obtained in 90 % yield (Scheme ).…”

A Ugi Straightforward Access to Bis‐β‐lactam Derivatives

“…These methods based on Ugi reaction open access to these families of important heterocycles without the traditional use of [2+2] cycloaddition processes . Further improvements could be probably brought in the first Ugi step of the sequence using water[4d] or, as recently disclosed, trifluoroethanol as solvent . The observed activity of some compounds against Gram‐positive bacteria, although poor, would set the starting point to further improvements such as the use of an N ‐benzyl removable group followed by deprotection and functionalization towards potentially more active monobactams.…”

Synthesis of Lactams via Isocyanide-Based Multicomponent Reactions

“…Silvani and co-workers 33 developed a strategy for the synthesis of -lactam-core-linked oxindoles 43 via an Ugi-3CR using isatins 41, isocyanides, and -amino acids 42 in a one-pot manner (Scheme 8). When chiral -amino acids 42a and 42b were used, enantiomerically pure -lactam diastereoisomers 43a (dr = 63:37) and 43b (dr = 65:35) were obtained as the products, the relative stereochemistries of which were determined by X-ray analysis.…”