ABSTRACT
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.
Subject(s)
Carbamates/chemistry , Carbamates/chemical synthesis , Cyclohexanes/chemistry , Cyclohexanes/chemical synthesis , Lactams/chemistry , Phthalic Anhydrides/chemistry , Stereoisomerism , Substrate SpecificityABSTRACT
The first total synthesis of (-)-calicoferol B (III) is described. The cyclozirconation product I, prepared in enantiomerically pure form, was converted into the CD ring chiron II. This was coupled with the aromatic A-ring, and then the side chain was constructed with control of relative and absolute configuration to complete the total synthesis of III. The first total synthesis of (-)-calicoferol B (1) is described. The cyclozirconation product 8, prepared in enantiomerically pure form, was converted into the CD ring chiron 6. This was coupled with the aromatic A-ring, and then the side chain was constructed with control of relative and absolute configuration to complete the total synthesis of 1.
