A strategy for the synthesis of biologically relevant 5-hydroxy-imidazolidine-2-thione derivatives is presented. A novel class of α-sulfonylamines have been suitably prepared (46-81% yield) as precursors of formal benzylidenethiourea acceptors; these are generated in situ and intercepted by N-heterocyclic carbene (NHC)-activated aldehydes affording open-chain aza-benzoin-type adducts, which in turn undergo an intramolecular aza-acetalization reaction in a one-pot fashion. A thiazolium salt/triethylamine couple proved to be the more effective system to trigger the domino sequence giving the target heterocycles in good yields (45-97%) and diastereoselectivities (up to 99 : 1 dr). The multigram scale synthesis and elaboration of a selected 5-hydroxy-imidazolidine-2-thione compound is also described.

Synthesis of functionalized imidazolidine-2-thiones Via NHC/base-promoted aza-benzoin/aza-acetalization domino reactions

DI CARMINE, Graziano
Primo
;
RAGNO, Daniele
Secondo
;
DE RISI, Carmela
;
BORTOLINI, Olga;GIOVANNINI, Pier Paolo;FANTIN, Giancarlo;MASSI, Alessandro
Ultimo
2017

Abstract

A strategy for the synthesis of biologically relevant 5-hydroxy-imidazolidine-2-thione derivatives is presented. A novel class of α-sulfonylamines have been suitably prepared (46-81% yield) as precursors of formal benzylidenethiourea acceptors; these are generated in situ and intercepted by N-heterocyclic carbene (NHC)-activated aldehydes affording open-chain aza-benzoin-type adducts, which in turn undergo an intramolecular aza-acetalization reaction in a one-pot fashion. A thiazolium salt/triethylamine couple proved to be the more effective system to trigger the domino sequence giving the target heterocycles in good yields (45-97%) and diastereoselectivities (up to 99 : 1 dr). The multigram scale synthesis and elaboration of a selected 5-hydroxy-imidazolidine-2-thione compound is also described.
2017
DI CARMINE, Graziano; Ragno, Daniele; DE RISI, Carmela; Bortolini, Olga; Giovannini, Pier Paolo; Fantin, Giancarlo; Massi, Alessandro
File in questo prodotto:
File Dimensione Formato  
2017 OBC cascade.pdf

solo gestori archivio

Descrizione: versione editoriale
Tipologia: Full text (versione editoriale)
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 1.62 MB
Formato Adobe PDF
1.62 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
11392_2377456_postprint_De Risi_Carmela.pdf

accesso aperto

Descrizione: Post print
Tipologia: Post-print
Licenza: Creative commons
Dimensione 1.73 MB
Formato Adobe PDF
1.73 MB Adobe PDF Visualizza/Apri

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2377456
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 12
social impact