Iron-catalyzed cross-coupling reactions

Abstract

This thesis concerns the synthesis and study of iron(III) halide complexes supported by amine-bis(phenolate) ligands. These paramagnetic molecules were characterized by a variety of methods including MALDI-TOF mass spectrometry and UV-vis spectroscopy. Two dimeric iron complexes, {FeCl[O₂N]BuMenPr}₂ (1), {FeCl[O₂N]BuMeBn}₂ (5) and one monomeric FeBr₂[O₂NH]BuMenPr (8), where [O₂N]BuMenPr = n-propylamine-N,N-bis(2-methylene-4-methyl-6-tert-butylphenolate) and [O₂N]BuMeBn = benzylamine-N,N-bis(2-methylene-4-methyl-6-tert-butylphenolate), were characterized in the solid state by single crystal X-ray diffraction. The abbreviated nomenclature for these ligands can be generalized by the form [O₂N]RR’R”, where [O₂N] describes the three donor atoms (two oxygens are phenolic and one nitrogen is aminic) of the ligand, R and R' define the substituents at the 2- and 4- positions, respectively, on the phenol group, and R” represents the alkyl group on the central amine donor (such as nPr for n-propyl or Bn for benzyl). Variable temperature magnetic susceptibility data for {FeCl[O₂N]BuMenPr}₂ (1) was also obtained using a SQUID magnetometer. -- The easily synthesized, inexpensive, and relatively air-stable novel iron complex {FeCl[O₂N]BuMenPr}₂ can be used as a mild and efficient catalyst for C-C cross-coupling of aryl Grignards with alkyl halides. Compared to other iron-catalyzed sp³-sp² C-C cross-coupling reactions, it displays several advantages: i) the complex is easy to handle and has the potential for large-scale applications, ii) by employing microwave conditions, hindered Grignard reagents can react with primary alkyl halides bearing β-H atoms and gives excellent yields, iii) secondary alkyl chlorides and benzyl halides can be effectively used as electrophilic substrates, iv) a number of functional groups are tolerated. Cross-coupling products are obtained in good to excellent yield as shown by GC-MS and ¹H NMR analysis. Screening of cross-coupling reactions for over thirty substrate combinations and the effect of microwave heating on reaction yields are described. Mechanistic studies suggest a radical-mediated route to cross-coupling as shown by “radical clock” experiments. -- We also present the ability of FeCl₃ to cleave both C-Cl bonds in CH₂Cl₂ and two C-Cl bonds in CDCl₃ in the presence of Grignard reagents. Different conditions for the catalytic system are explored, and the products are obtained from low to excellent yields. The results are monitored by GC-MS and ¹H NMR. To our knowledge, this is the first time that such transformations have been observed using an iron pre-catalyst, leading to the first efficient double aryl-alkyl coupling of CH₂Cl₂. Hypotheses regarding the mechanism of cross-coupling are presented.