Aryl Amidation Routes to Dihydropyrrolo[3,2-e]indoles and Pyrrolo[3,2-f]tetrahydroquinolines:  Total Synthesis of the (±)-CC-1065 CPI Subunit

Abstract

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.

Dialkylbiaryl phosphines in Pd-catalyzed amination: a user's guide

“…The original studies made use of DavePhos ( L8 ) and JohnPhos ( L9 ) for amination reactions 24, 70 and these ligands have found ongoing application in the synthesis of natural products 5, 71–74 and pharmaceuticals, 75–79 including examples in process development. 80, 81 Subsequently, several structural variants have been reported.…”

Biaryl Phosphane Ligands in Palladium‐Catalyzed Amination

“…It was noted that attempts to perform a copper-based coupling on these substrates were unsuccessful. [205] Kerr [206] carried out an intramolecular amination of aryl triflate 112 with a Pd 2 dba 3 / JohnPhos catalyst combination to form a dihydropyrrolo[3,2-e]indole as part of a synthetic studies on the synthesis of the CC-1065 CPI subunit, such natural products have been studied intensively for their antitumor properties (Scheme 47).…”

Synthesis of Novel Pterocarpen Analogues via [3 + 2] Coupling‐Elimination Cascade of α,α‐Dicyanoolefins with Quinone Monoimines

“…Quinone monoimine 2a was prepared according to the known procedure [6o]. Quinone monoimines 2b and 2c were prepared according to the known procedure with little modification . …”