A General Diastereoselective Catalytic Vinylogous Aldol Reaction Among Tetramic Acid-Derived Pyrroles

ABSTRACT: A catalytic diastereoselective aldol reaction has been developed for N1-arylated/C2-O-silylated/C3-methylated and brominated/ C4-O-methylated pyrroles in its reactions with various aldehydes. Syn adducts emerge with regard to the vicinal nitrogen and oxygen heteroatom substituents. The N1-aryl residue undergoes oxidative cleavage, and the C3-bromine atom undergoes palladium-mediated coupling reactions, both without disturbing the newly created stereocenters. Tetramic acid aldolate adducts are known with both synand anti stereochemical arrangements. Natural product examples include tetrapetalone B (1),1 cylindramide A (2),2 militarinone B (3),3 paecilosetin (4),4 and cryptocin (5)5 (Figure 1). Given their occurrence, it was surprising for us to learn that a general diastereoselective aldol method leading to the construction of this motif had not been reported. A chief problem appears to have been selection of the protecting grou