Bioinspired, base- and metal-free, mild decarboxylative aldol activation of malonic acid half thioesters under phase-transfer reaction conditions

Sean P. Bew, G. Richard Stephenson, Jacques Rouden, Polly Anna Ashford, Manuel Bourane, Agathe Charvet, Virginie M D Dalstein, Raphael Jauseau, G. D. Hiatt-Gipson, Luis A. Martinez-Lozano

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13 Citations (Scopus)


Utilizing ‘off the shelf’ commercially available, cheap, small synthetic molecules that mimic the efficient mediation of important bioreactions utilized by Nature is not only highly sought after but also currently highly topical. This paper details our preliminary efforts at developing a unique base- and metal-free phase-transfer-mediated malonic acid thioester (MAHT) ‘activation protocol’ that efficiently generates (±)-β-thioesters. Our bioinspired aldol process is exceptionally mild, conducted under near neutral pH reaction conditions, does not require an inert, oxygen-free atmosphere or anhydrous reaction conditions and is highly atom-economic. Exemplifying the utility of our protocol, the synthesis of an array of structurally and functionally diverse (±)-β-hydroxy thioesters equipped with highly prized functionality, i.e., chlorine, bromine, fluorine, nitrile and nitro groups, is reported, as is the diastereoselective potential of this important reaction.
Original languageEnglish
Pages (from-to)1245-1257
Number of pages13
JournalAdvanced Synthesis & Catalysis
Issue number6
Early online date25 Mar 2015
Publication statusPublished - 13 Apr 2015


  • aldol reaction
  • base-free conditions
  • decarboxylation
  • metal-free conditions
  • phase-transfer process

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