TY - JOUR
T1 - Synthesis of (Arylamido)pyrrolidinone Libraries through Ritter-Type Cascade Reactions of Dihydroxylactams
AU - Wu, Peng
AU - Petersen, Michael Åxman
AU - Petersen, Rico
AU - Ohsten Rasmussen, Martin
AU - Bonnet, Karine
AU - Nielsen, Thomas Eiland
AU - Clausen, Mads Hartvig
PY - 2015
Y1 - 2015
N2 - The Ritter-type reaction of arylnitriles and N-acyliminium ions generated in situ from dihydroxy-γ-lactams gave tetrahydropyrrolo[2,3-d]oxazol-5-ones in excellent yields. A subsequent acidic hydrolysis in EtOH/H2O/TFA (trifluoroacetic acid) yielded new (arylamido)pyrrolidinones with excellent cis diastereoselectivity. A combined one-step Ritter–hydrolysis procedure proved to be of equal efficiency. This versatile method, which was successfully used for the construction of a screening library containing 706 molecules within the European Lead Factory consortium, provides a simple way to access new compounds incorporating an arylamido and a pyrrolidinone moiety, both of which are widely found in marketed drugs and in biologically active molecules.
AB - The Ritter-type reaction of arylnitriles and N-acyliminium ions generated in situ from dihydroxy-γ-lactams gave tetrahydropyrrolo[2,3-d]oxazol-5-ones in excellent yields. A subsequent acidic hydrolysis in EtOH/H2O/TFA (trifluoroacetic acid) yielded new (arylamido)pyrrolidinones with excellent cis diastereoselectivity. A combined one-step Ritter–hydrolysis procedure proved to be of equal efficiency. This versatile method, which was successfully used for the construction of a screening library containing 706 molecules within the European Lead Factory consortium, provides a simple way to access new compounds incorporating an arylamido and a pyrrolidinone moiety, both of which are widely found in marketed drugs and in biologically active molecules.
KW - Ritter reaction
KW - Hydrolysis
KW - Synthetic methods
KW - Nitrogen heterocycles
KW - Amides
KW - Library synthesis
U2 - 10.1002/ejoc.201500712
DO - 10.1002/ejoc.201500712
M3 - Journal article
SN - 1434-193X
VL - 2015
SP - 5633
EP - 5639
JO - Justus Liebigs Annalen der Chemie
JF - Justus Liebigs Annalen der Chemie
IS - 25
ER -