Metalation was first observed in the laboratory by Edward Frankland during a synthesis of diethylzinc in 1849. While this development eventually led to the development of organometallic compounds of other metals, these compounds saw little use in the laboratory because of their expense and (in the case of organozinc compounds) their highly pyrophoric nature. Metalation reactions (particularly in the form of transmetalation) only began to see more widespread use in synthetic laboratories after François Auguste Victor Grignard’s synthesized organomagnesium halides directly from metallic magnesium and organic halides. These newfound organomagnesium reagents extreme versatility in organic synthesis caused metalation to see widespread use in laboratory science. Organolithium reagents were synthesized for the first time in 1917 by Schlenk and Holtz, though these reagents did not see widespread use as metallating agents or reagents in organic synthesis until Karl Ziegler, Henry Gilman, and Georg Wittig — among others — developed synthetic methods that improved upon this initial synthesis. After these improvements in synthesis came to be known, interest in the compounds increased significantly, as they are generally more reactive than organomagnesium compounds. The first use of an organolithium reagent as a metalation reagent occurred in 1928, with Schlenk and Bergmanns metalation of fluorene with ethyllithium.