Stereoselective cyclopropanation of serine- and threonine-derived oxazines to access new morpholine-based scaffolds.
A general strategy for the synthesis of novel, orthogonally protected scaffolds based on the unique 2-oxa-5-azabicyclo[4.1.0]heptane structure is presented. The described reaction sequence takes advantage of easily available starting materials such as serine and threonine and leads to stereochemically dense structures in few, high-yielding synthetic steps. We show how the stereochemistry can be easily tuned by starting from different beta-hydroxy-alpha-amino acids and also by means of a transition metal-catalyzed cyclopropanation step. The compounds find application as constrained templates for the construction of geometrically diversified libraries of compounds.
Sladojevich
Filippo
F
Department of Organic Chemistry Ugo Schiff, University of Florence, Polo Scientifico e Tecnologico, Via della Lastruccia 13, I-50019, Sesto Fiorentino (FI), Italy.
Trabocchi
Andrea
A
Guarna
Antonio
A
D002384:Catalysis; D003521:Cyclopropanes / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry; D012694:Serine / Q000737:chemistry; D013237:Stereoisomerism; D013912:Threonine / Q000737:chemistry
D003521:Cyclopropanes; D009025:Morpholines; D013912:Threonine; D012694:Serine; D006859:Hydrogen; C037574:morpholine