Organocatalysed decarboxylative protonation process from Meldrum's acid: enantioselective synthesis of isoxazolidinones

Abstract

An asymmetric organocatalysed decarboxylative protonation reaction allowed a straightforward synthesis of α-substituted isoxazolidin-5-ones from readily available 5-substituted Meldrum's acids. This process is initiated by an anionic formal (3+2) cycloaddition-fragmentation, generated in-situ from a sulfone-amide precursor which also served as a latent source of proton.

Enantioselective Phase‐Transfer Catalyzed α‐Sulfanylation of Isoxazolidin‐5‐ones: An Entry to β2,2‐Amino Acid Derivatives

“…The construction of 3 is based on an innovative domino (3+2)‐annulation‐decarboxylation reaction terminated by the protonation of the potassium enolate 4 a . Actually, an asymmetric version was achieved by means of a chiral Brønsted base …”

“…The PT‐catalyzed sulfanylation (SPh) conditions were then probed, in the presence of 2 mol % of binaphthyl catalyst 9 b , on a range of readily available α‐substituted isoxazolidinones 3 (Table ) . Some of those display pendants found on proteinogenic α‐amino acids.…”

“…The corresponding sulfone 10 was easily formed in 76 % yield by oxidation of the sulfur centre ( 6 o ) by an excess of m CPBA . The N ‐Boc β 2,2 ‐amino acid 11 was synthesized through a straightforward palladium‐promoted hydrogenolysis of precursor 6 a in a high yield of 92 % . The ring‐opening sequence of the sterically hindered 6 a was achieved in the presence of BnNH 2 in refluxing tert‐ butanol allowing the construction of the corresponding β 2,2 ‐amino amide product 12 in 87 % isolated yield.…”

Redox Non‐Innocence of Coordinated 2‐(Arylazo) Pyridines in Iridium Complexes: Characterization of Redox Series and an Insight into Voltage‐Induced Current Characteristics

“…Brière and colleagues recently proposed an alternative decarboxylative protonation approach involving Meldrum's acid derivatives 100 as user‐friendly α‐keto carboxylic acid derivative precursors (Scheme ). In the presence of α‐sulfone amide 101 , the construction of α‐substituted isoxazolidinones 102 , as precursors of biologically important β 2 ‐amino acids, was achieved with good ee values 45. As far as the proposed mechanism is concerned, a mixture of Na 2 CO 3 (1.3 equiv.)…”

C5‐Disubstituted Meldrum's Acid Derivatives as Platform for the Organocatalytic Synthesis of C3‐Alkylated Dihydrocoumarins

“…Although several teams ventured into this convenient enantioselective protonation (EP) strategy, mostly from hemimalonic esters in organocatalysis, only the groups of Brunner, Rouden, Zhang and Song succeeded in getting good er (rarely > 95:5) albeit at the expense of the use of high catalyst loading (up to 1 equiv.). [11] We reasoned that a novel and readily available MA platform 1 (Scheme 2), [12] may undergo the intramolecular nucleophilic addition of the phenol moiety thanks to the electrophilic character of the carbonyl groups. Context of the investigation.…”