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.
DI CARMINE, Graziano; Ragno, Daniele; DE RISI, Carmela; Bortolini, Olga; Giovannini, Pier Paolo; Fantin, Giancarlo; Massi, Alessandro
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/2377456
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