Novel intramolecular reactivity of oximes: synthesis of cyclic and spiro-fused imines.
Under conventional heat (135-145 degrees C) or microwave irradiation and 1 equiv of acetic anhydride, ortho-substituted aryl-oximes undergo a novel sp3 C-H activated cyclization to produce the corresponding isoindoles, and aliphatic oximes afford the corresponding dihydropyrroles. The cyclization occurs with various substrates in good yield (46-82%) leading to unique spiro-fused and cyclic imines. An initial mechanistic investigation suggests the reaction occurs via a nitrenium or vinyl nitrene intermediate. [reaction: see text]
Savarin
Cécile G
CG
Department of Process Research, Merck Research Laboratories, Merck & Co., P.O. Box 2000, Rahway, NJ 07065, USA. cecilesavarin@gmail.com
Grisé
Christiane
C
Murry
Jerry A
JA
Reamer
Robert A
RA
Hughes
David L
DL
D000089:Acetic Anhydrides / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D006358:Hot Temperature; D007097:Imines / Q000138:chemical synthesis* / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D008872:Microwaves; D008956:Models, Chemical; D010091:Oximes / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis*; D014753:Vinyl Compounds / Q000737:chemistry
D000089:Acetic Anhydrides; D007097:Imines; D007211:Indoles; D010091:Oximes; D011758:Pyrroles; D013141:Spiro Compounds; D014753:Vinyl Compounds; C017621:phenylnitrene; C031800:acetic anhydride