ABSTRACT
Enantio- and diastereoselective hydrogenation of ß-keto-γ-lactams with a ruthenium-BINAP catalyst, involving dynamic kinetic resolution, has been employed to provide a general, asymmetric approach to ß-hydroxy-γ-lactams, a structural motif common to several bioactive compounds. Full conversion to the desired ß-hydroxy-γ-lactams was achieved with high diastereoselectivity (up to >98% de) by addition of catalytic HCl and LiCl, while ß-branching of the ketone substituent demonstrated a pronounced effect on the modest to excellent enantioselectivity (up to 97% ee) obtained.
ABSTRACT
The novel preparation of 2-aminopyridoimidazoles and 2-aminobenzimidazoles via the cyclization of (2-aminopyridin-3-yl)urea and (2-aminophenyl)urea substrates in the presence of phosphorus oxychloride is described. This methodology is demonstrated for a range of urea substrates with aminoimidazole products obtained in good yields and with excellent levels of purity.
Subject(s)
Aminopyridines/chemical synthesis , Benzimidazoles/chemical synthesis , Imidazoles/chemical synthesis , Urea/analogs & derivatives , Aminopyridines/chemistry , Catalysis , Cyclization , Imidazoles/chemistry , Molecular Structure , Urea/chemical synthesis , Urea/chemistryABSTRACT
An efficient synthetic approach leading to introduction of the hydroxymethyl group to an aryl moiety via combination of the Bouveault formylation and hydride reduction has been optimized using a rational, mechanistic-based approach. This approach enabled telescoping of the two steps into a single efficient process, readily amenable to scaleup.
Subject(s)
Aldehydes/chemical synthesis , Morpholines/chemical synthesis , Phenylethyl Alcohol/chemical synthesis , Antidepressive Agents/chemistry , Humans , Molecular Structure , Morpholines/chemistry , Phenylethyl Alcohol/analogs & derivatives , Phenylethyl Alcohol/chemistry , StereoisomerismABSTRACT
Absolute stereochemistry of oils and viscous liquids can be difficult to determine. Co-crystallization involves generating a crystalline material consisting of more than one neutral compound. The combination of co-crystallization with both X-ray diffraction and chiral HPLC was particularly powerful in overcoming these difficulties for a series of chiral 3-arylbutanoic acids. Co-crystallization offers advantages over salt formation because co-crystals dissociate in solution, meaning identical HPLC conditions can be used for both the materials of interest and their co-crystals.
