Synthesis Of Ferrocenel Tertiaryalcohol

Ferrocenel tertiary alcohol, as a powerful anti-cancer drug core structural motif and central module of biosensors, has been found a number of applications in medicine chemistry, as well as in materials science. In view of the major application of these two aspects, the synthesis of ferrocenel tertiary alcohol will become an important subject in application for industrial production. The synthesis methods in previous research have been reported were alkylation to ferrocenylketones with alkyllithium or Grignard reagents. However those protocols have several disadvantages such as these organometallic reagents often cause the enolization of substrates and give undesired reduction products, self-aldol condensation products or undesired alkylated tertiary alcohols. Besides, the reaction condition is inconvenience and experimental operation is complicated. In addition, alkyllithium is expensive and not suitable for industrialized mass production. Owing to ferrocenylketones' tereo-hindrance, the alkylation reactions with only Grignard reagents existing often demonstrate to be ineffective with undesired reduction products up to 30% yields and corresponding alkylating adducts only obtained in 20% yields. In light of this, we developed a highly efficient alkylation of ferrocenylketones with trialkylzinc(II) ate complexes (R3ZnMgCl) derived from Grignard reagents (3 equiv) and zinc chloride (1 equiv) in situ and found the desired tertiary alcohols were obtained in much improved yields due to the minimization of background reactions. For instance isopropylation of ferrocenylketones is one of the most difficult alkylations, because sec-RMgX often prefers reduction to the desired alkylation. we conducted the isopropylation to ferrocenylketone with i-PrMgBr and found the corresponding alkylation products obtained 20% yields when single Grignard reagent(1.1 equiv) was used, however, dramatic results were observed with zinc(â…¡) ate reagents, prepared in situ from Grignard reagents (3 equiv) and ZnCl2 (1 equiv) at room temperature within one hour, where the yields were dramatically improved from 20% to 90% and the reactions proceeded smoothly with the yield of the reduced byproducts significantly minimized from 36% to 0%.It demonstrates that high alkylation to ferrocenylketones via trialkylzinc(â…¡) ate reagents is more effective than organolithium reagents and Grignard reagents and this stoichiometric alkylation system should be highly useful for both laboratory and industrial applications.