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

The copper‐catalysed (10 mol‐% CuBr · SMe 2 , CuCN · LiCl or CuI/PPh 3 ) 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, n Bu, i Bu, allyl, Ph) without H – transfer. The deprotonation of these sec ‐alkyl‐substituted cyclopentadienyls followed by the addition of TiCl 4 allows the isolation of TiCl 2 {η 5 ‐C 5 H 4 CHR(2‐OMePh)} as rac / meso mixtures that show activity against human colon, breast and pancreatic cell lines (GI 50 2.3–42.4 μ M ).