Twisted amide reduction under Wolff-Kishner conditions: synthesis of a benzo-1-aza-adamantane derivative.
A synthesis of 4,5-benzo-1-aza-tricyclo[4.3.1.1(3,8)]undecane (1), a benzo-1-aza-adamantane derivative, is described and features a previously unknown application of the Wolff-Kishner reduction of a nonresonance stabilized or "twisted" amide. An intermediate amino ester is converted to a severely "twisted amide", which, when exposed to hydrazine in alcohol, provides the corresponding "twisted" amino hydrazone. Wolff-Kishner conditions (KOH/ethylene glycol, 200 degrees C) provide the reduced target 1 without hydrolysis to amino acid derivatives. These operations are conveniently performed in a single flask in high yield.
Bashore
Crystal G
CG
Pfizer Global Research and Development, Groton Laboratories, Pfizer Inc., Groton, CT 06340, USA.
Samardjiev
Ivan J
IJ
Bordner
Jon
J
Coe
Jotham W
JW
D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000577:Amides / Q000737:chemistry*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D015394:Molecular Structure; D010084:Oxidation-Reduction
D000577:Amides; D001372:Aza Compounds; D000218:Adamantane