Synthesis of a γ-lactam library via formal cycloaddition of imines and substituted succinic anhydrides.
Formal cycloaddition reactions between imines and cyclic anhydrides serve as starting point for the synthesis of diverse libraries of small molecules. The synthesis of succinic anhydrides substituted with electron-withdrawing groups is facilitated by new mild conditions for alkylation of aryl-substituted acetyl esters with ethyl bromoacetate. These anhydrides are then used in formal cycloaddition reactions with imines to produce γ-lactams. 2-Fluoro-5-nitrophenylsuccinic anhydride reacts efficiently with imines to provide lactams that are further diversified by conversion of the nitro group to either an aniline and an azide for subsequent reactions with acylating agents and alkynes, respectively. The synthesis of cyanosuccinic anhydride is reported for the first time, and the use of this compound in reactions with imines and subsequent functionalization of the resultant lactams is demonstrated.
Department of Chemistry, University of California, Davis, 95616, United States.
Darlene Q
DQ
Tan
Amy L
AL
Atherton
Austin J
AJ
Smith
Cristian
C
Soldi
Katherine A
KA
Hurley
James C
JC
Fettinger
Jared T
JT
Shaw
D003500:Cyclization; D007097:Imines / Q000737:chemistry*; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000737:chemistry; D013387:Succinic Anhydrides / Q000737:chemistry*
D007097:Imines; D007769:Lactams; D054852:Small Molecule Libraries; D013141:Spiro Compounds; D013387:Succinic Anhydrides