Aryl amidation routes to dihydropyrrolo[3,2-e]indoles and pyrrolo[3,2-f]tetrahydroquinolines: total synthesis of the (+/-)-CC-1065 CPI subunit.

CC-1065 and the related duocarmycins are members of a structurally unique family of naturally occurring molecules and remain some of the most rigorously studied antitumor compounds to date. Herein we describe a total synthesis of the (+/-)-CC-1065 CPI subunit in an overall yield of 9.3% from commercially available 5-fluoro-2-nitrophenol. The key steps of this synthesis are a Diels-Alder reaction of an o-benzoxy-monoimine quinoid and an intramolecular aryl triflate amidation, which formed the pyrrolo[3,2-f]tetrahydroquinoline intermediate en route to CPI.