Rhodium-catalyzed direct C-H addition of 3,4-dihydroquinazolines to alkenes and their use in the total synthesis of vasicoline.
The inter- and intramolecular couplings of unactivated alkenes to 3,4-dihydroquinazolines with a Rh(I) catalyst are reported. Coupling between olefins and NH-3,4-dihydroquinazoline was found to occur consecutively with heterocycle dehydrogenation in the presence of a Rh(I)/PCy3/HCl catalyst. The reaction was used to develop an effective method for the synthesis of 2-substituted quinazolines through an oxidative workup step. The regiocontrolled synthesis and Rh-catalyzed cyclization of alkene-tethered 3,4-dihydroquinazolines are also described. Applying this method, the second total synthesis of vasicoline was achieved. The key Rh-catalyzed cyclization step was made possible by the use of a rigid bicyclic phosphine ligand. The synthesis further demonstrates a challenging Cu-catalyzed amidation of an ortho-substituted aryl chloride.
Department of Chemistry, University of California, Berkeley, California 94720, USA.
Sean H
SH
Wiedemann
Jonathan A
JA
Ellman
Robert G
RG
Bergman
D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D011758:Pyrroles / Q000138:chemical synthesis*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry*
D000475:Alkenes; D011758:Pyrroles; D011799:Quinazolines; C516072:vasicoline; D012238:Rhodium