Enantioselective synthesis of benzyl (1S,2R,4R)-4-(tert-butoxycarbonylamino)-2-(hydroxymethyl)cyclohexylcarbamate using an iodolactamization as the key step.
An efficient enantioselective synthesis of benzyl (1S,2R,4R)-4-(tert-butoxycarbonylamino)-2-(hydroxymethyl)cyclohexylcarbamate 2, an essential intermediate for a series of potent CCR2 antagonists, is described. The key step in the sequence is an iodolactamization to yield the highly functionalized (1R,2S,4S,5S)-tert-butyl 2-(benzyloxycarbonylamino)-4-iodo-7-oxo-6-azabicyclo[3.2.1]octane-6-carboxylate 11. An examination of the reaction mechanism within the 2-step iodolactamization sequence led to the discovery of a single-pot transformation of increased efficiency.
Campbell
Carlton L
CL
AMRI, 26 Corporate Circle, P.O. Box 15098, Albany, New York 12212, USA.
Hassler
Carla
C
Ko
Soo S
SS
Voss
Matthew E
ME
Guaciaro
Michael A
MA
Carter
Percy H
PH
Cherney
Robert J
RJ
D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry*; D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry*; D010796:Phthalic Anhydrides / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity
D002219:Carbamates; D003510:Cyclohexanes; D007769:Lactams; D010796:Phthalic Anhydrides; C552386:benzyl (1S,2R,4R)-4-(tert-butoxycarbonylamino)-2-(hydroxymethyl)cyclohexylcarbamate; C043103:phthalic anhydride