Non-heme iron(II) complexes catalyzed asymmetric cIs-dihydroxylation of alkenes and alkylation of N-heteroaromatics

Abstract

Asymmetric catalysis based on non-heme iron complexes has drawn increasing attention in recent years due to the low cost and environmentally benign character of iron. This thesis focuses on the development of chiral iron complexes supported by tetradentate N4 ligands and their applications in asymmetric cis-dihydroxylation of alkenes and Friedel-Crafts alkylation of N-heteroaromatics. In Chapter 2, a series of novel chiral iron(II) complexes were prepared by reacting various bis(quinolyl)-diamines bearing different chiral diamine backbones with [Fe(OTf)2•(CH3CN)2] in good to high yields. Five of these complexes were structurally characterized by X-ray crystallography. Complexes 2.4c, 2.4e, 2.4f, and 2.4h were found to adopt cis-α topology, while 2.4d adopts cis-β conformation. In Chapter 3, we have developed a highly enantioselective cis-dihydroxylation of trisubstituted alkenes with H2O2 catalysed by cis-α-[Fell(Me2BQPN)(OTf)2] 2.4f (Me2BQPN = N,N’-dimethyl-N,N’-bis(2-methyl-8-quinolyl)-1,2-diphenylethane-1,2-diamine). Under “[Fell(Me2BQPN)(OTf)2] 2.4f + H2O2” protocol, a broad range of trisubstituted alkenes including (E)-and (Z)-alkenes and cyclic alkenes were converted to desired cis-diols in high yield (up to 98%) and excellent enantioselectivity (up to 99.9% ee). For (Z)-trisubstituted olefins such as phenyl angelates which are challenging substrates for asymmetric cis-dihydroxylation, iron complex 2.4f gave higher enantioselectivity than Sharpless cis-dihydroxylation of similar substrates. Mechanistic studies by 18O-labeling experiments together with high resolution ESI-MS analysis and low-temperature UV-vis measurements revealed that both the cis-diol oxygen atoms derived from H2O2 rather than H2O and the reaction catalyzed by 2.4f with H2O2 proceed via chiral intermediate LFeIII(OOH) as active oxidant. In Chapter 4, we have developed enantio- and regio-selective N1, C2, and C3 alkylation reactions of indoles with α,β-unsaturated carbonyl compounds catalyzed by cis-β Fe(II)/bis(quinolyl)-diamine complex [Fe(Cp2BQCN)(OTf)2] 2.4d (Cp2BQCN = N,N’-bis(2,3-dihydro-1H-cyclopenta[b]quinolin-5-yl)-N,N’-dimethylcyclohexane-1,2-diamine). In this reaction, iron complex 2.4d served as a Lewis acid to activate the C=C bond for nucleophilic addition through an N,O-bidentate coordination with iron complex. A range of indoles reacted with various α,β-unsaturated 2-acyl imidazoles to give diverse chiral indoles in high yields and with high enantio- and regio-selectivity (up to 98% yield and with >99% ee). The thus obtained products can be converted to a variety of chiral indole derivatives with potential synthetic and biological interest. Mechanistic studies by ESI-MS analysis and DFT calculations revealed that the “chiral-at-metal” cis-β configuration of the iron complex and a secondary π-π interaction in the transition state are responsible for the high enantioselectivity of the reaction. In addition, the iron catalyst is also applicable to alkylation of pyrroles and anilines with α,β-unsaturated 2-acyl imidazoles (Chapter 5). With 2.4d or 2.4h as catalyst, a variety of C2- and C3-alkylated products were obtained in 87-96% yields and 61-99% ee. In the presence of 2.4f, the alkylation of N,N-disubstituted anilines with α,β-unsaturated 2-acyl imidazoles provided a range of para-alkylated anilines as sole product in 87-96% yields and with enantioselectivity of up to 98% ee.