Cuprate Addition to a 6‐Substituted Pentafulvene – Preparation of sec‐Alkyl‐Substituted Titanocene Dichlorides and Their Biological Activity

Abstract

AbstractThe copper‐catalysed (10 mol‐% CuBr·SMe2, CuCN·LiCl or CuI/PPh3) addition of RMgBr to the pentafulvene 1‐(cyclopenta‐2,4‐dien‐1‐ylidenemethyl)‐2‐methoxybenzene allows the formation of cyclopentadienyl derivatives with α‐CHR(2‐MeOPh) sidechains (R = Me, Et, nBu, iBu, allyl, Ph) without H– transfer. The deprotonation of these sec‐alkyl‐substituted cyclopentadienyls followed by the addition of TiCl4 allows the isolation of TiCl2{η5‐C5H4CHR(2‐OMePh)} as rac/meso mixtures that show activity against human colon, breast and pancreatic cell lines (GI50 2.3–42.4 μM).