Stereoselective synthesis of densely functionalized pyrrolidin-2-ones by a conjugate addition/nitro-Mannich/lactamization reaction.
Copper-catalyzed conjugate addition of diorgano zinc reagents to nitroacrylate 1 followed by a subsequent nitro-Mannich reaction and in situ lactamization leads to an efficient one-pot synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-2-ones (5). The versatility of the reaction is shown for a wide range of N-p-(methoxy)phenyl protected aldimines 3 derived from alkyl, aryl, and heteroaryl aldehydes. The densely functionalized pyrrolidin-2-ones 5 are isolated as single diastereoisomers (40 examples, 33-84% yield). An enantioselective copper-catalyzed conjugate addition of diethylzinc led to highly crystalline products that could be recrystallized to enantiopurity in high yield. A range of successful chemoselective transformations were investigated, which widens the applicability of the pyrrolidn-2-ones as stereochemically pure building blocks for further organic synthesis.
Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK. j.c.anderson@ucl.ac.uk
James C
JC
Anderson
Lisa R
LR
Horsfall
Andreas S
AS
Kalogirou
Matthew R
MR
Mills
Gregory J
GJ
Stepney
Graham J
GJ
Tizzard
D002384:Catalysis; D003300:Copper / Q000737:chemistry; D015394:Molecular Structure; D009574:Nitro Compounds / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry
D009574:Nitro Compounds; D009942:Organometallic Compounds; D011760:Pyrrolidinones; D003300:Copper; D015032:Zinc