title: Stereocontrolled synthesis of vicinal diamines by organocatalytic asymmetric Mannich reaction of N-protected aminoacetaldehydes: formal synthesis of (-)-agelastatin A.
abstract: The 1,2-diamine (vicinal diamine) motif is present in a number of natural products with interesting biological activity and in many chiral molecular catalysts. The efficient and stereocontrolled synthesis of enantioenriched vicinal diamines is still a challenge to modern chemical methodology. We report here both syn- and anti-selective asymmetric direct Mannich reactions of N-protected aminoacetaldehydes with N-Boc-protected imines catalyzed by proline and the axially chiral amino sulfonamide (S)-3. This organocatalytic process represents the first example of a Mannich reaction using Z- or Boc-protected aminoacetaldehyde as a new entry of α-nitrogen functionalized aldehyde nucleophile in enamine catalysis. The obtained optically active vicinal diamines are useful chiral synthons as exemplified by the formal synthesis of (-)-agelastatin A.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Kano
authors.forename: Ryu
authors.initials: R
authors.lastname: Sakamoto
authors.forename: Matsujiro
authors.initials: M
authors.lastname: Akakura
authors.forename: Keiji
authors.initials: K
authors.lastname: Maruoka
mesh_terms: D000079:Acetaldehyde / Q000138:chemical synthesis / Q000737:chemistry*; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003959:Diamines / Q000138:chemical synthesis* / Q000737:chemistry; D007097:Imines / Q000138:chemical synthesis / Q000737:chemistry; D008958:Models, Molecular; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry; D011392:Proline / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D003959:Diamines; D007097:Imines; D023303:Oxazolidinones; C464968:agelastatin A; D011392:Proline; D000079:Acetaldehyde