S(N)2-type nucleophilic opening of beta-thiolactones (thietan-2-ones) as a source of thioacids for coupling reactions.
Beta-thiolactones monosubstituted in the 3-position by alkyl and carbamoyl groups undergo nucleophilic ring opening by arenethiolates through a process involving an S(N)2-type attack at the 4-position leading to 3-arylthiopropionates substituted in the 2-position. These thiocarboxylates can be trapped in situ by Mukaiyama's reagent or Sanger's reagent through a nucleophilic aromatic substitution process leading to highly activated thioesters that are then allowed to react further with primary or secondary amines leading, overall, to one-pot, three-component syntheses of 3-arylthiopropionamides carrying various substituents in the 2-position. Alternatively, the trapping combination of an electron deficient aryl halide and an amine may be replaced by a 2,4-dinitrobenzenesulfonamide, resulting in the formation of the same products overall with the incorporation of the latent amine in the sulfonamide into the final amide product. In another embodiment, the thiocarboxylate intermediate is allowed to react with a sulfonyl azide, resulting overall in N-arenesulfonyl 3-arylthiopropionamide derivatives.
Crich
David
D
Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, USA. dcrich@icsn.cnrs-gif.fr
Sana
Kasinath
K
D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D007783:Lactones / Q000737:chemistry*; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D000577:Amides; D000588:Amines; D002264:Carboxylic Acids; D007783:Lactones; D013438:Sulfhydryl Compounds; C034666:propionamide