The synthesis of compounds related to the indole-indoline core of the vinca alkaloids (+)-vinblastine and (+)-vincristine

A series of alpha'-aryl-alpha'-carbomethoxycycloalk-2-en-1 -ones, 16, has been prepared using the Pinhey arylation methodology for introducing the aromatic residue. Subjection of these compounds to Johnson iodination and Pd[0]-catalyzed Ullmann cross-coupling of the resulting alpha-iodocycloalkenones 11 with 2-iodonitrobenzene (5, X=I) then affords alpha,alpha'-diaryl-alpha'-carbomethoxycycloalk-2-en-1 -ones of the general form 10. Reductive cyclization of this last type of compound gives the corresponding indoles 9a-f (n = 1-3), some of which resemble the indole-indoline cores of the clinically important alkaloids (+)-vinblastine (1) and (+)-vincristine (2). (C) 2008 Elsevier Ltd. All rights reserved.