Premium
Synthesis of Sulfonimidamides from Sulfenamides via an Alkoxy‐amino‐λ 6 ‐sulfanenitrile Intermediate
Author(s) -
Briggs Edward L.,
Tota Arianna,
Colella Marco,
Degennaro Leonardo,
Luisi Renzo,
Bull James A.
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201906001
Subject(s) - chemistry , alkoxy group , nucleophile , acetic acid , combinatorial chemistry , carbamate , alkylation , organic chemistry , catalysis , alkyl
Sulfonimidamides are intriguing new motifs for medicinal and agrochemistry, and provide attractive bioisosteres for sulfonamides. However, there remain few operationally simple methods for their preparation. Here, the synthesis of NH‐sulfonimidamides is achieved directly from sulfenamides, themselves readily formed in one step from amines and disulfides. A highly chemoselective and one‐pot NH and O transfer is developed, mediated by PhIO in i PrOH, using ammonium carbamate as the NH source, and in the presence of 1 equivalent of acetic acid. A wide range of functional groups are tolerated under the developed reaction conditions, which also enables the functionalization of the antidepressants desipramine and fluoxetine and the preparation of an aza analogue of the drug probenecid. The reaction is shown to proceed via different and concurrent mechanistic pathways, including the formation of novel S≡N sulfanenitrile species as intermediates. Several alkoxy‐amino‐λ 6 ‐sulfanenitriles are prepared with different alcohols, and shown to be alkylating agents to a range of nucleophiles.