Asymmetric Catalysis with Chiral-at-Metal Ruthenium and Iridium Complexes
Transition metal catalyzed C-H functionalization represents an efficient and reliable strategy for the construction of carbon-carbon and carbon-heteroatom bonds in organic synthesis. This thesis deals with enantioselective C-H functionalization related to ruthenium nitrenoid intermediates and the sy...
|PDF Full Text
No Tags, Be the first to tag this record!
|Transition metal catalyzed C-H functionalization represents an efficient and reliable strategy for the construction of carbon-carbon and carbon-heteroatom bonds in organic synthesis. This thesis deals with enantioselective C-H functionalization related to ruthenium nitrenoid intermediates and the synthesis of a new chiral-at-iridium complex as well as its application in asymmetric catalysis.
1) An enantioselective intramolecular C(sp3)-H amination of N-benzoyloxycarbamates catalyzed by a chiral-at-metal ruthenium catalyst (Λ-RuCF3) was developed. The C-N bond formation afforded chiral 2-oxazolidinones in high yields (up to 99%) and with up to 97% ee. The amination occurred smoothly at benzylic, allylic, propargylic and unactivated alkyl C(sp3)-H bonds under mild conditions. Control experiments support a stepwise nitrene insertion mechanism through hydrogen atom transfer (HAT) of a ruthenium nitrenoid intermediate followed by a radical-radical recombination (Chapter 2).
2) A chiral-at-metal ruthenium complex (RuTES) catalyzed intramolecular catalytic C(sp3)-H oxygenations to furnish cyclic carbonates or 1,2-diols. Especially, this is the first
demonstration that easily accessible transition metal nitrenoids can be used for controlled direct intramolecular C(sp3)-H oxygenations. The here developed methodology can be applied to the chemoselective C-H oxygenation of benzylic, allylic, and propargylic C-H bonds. Control experiments and density functional theory (DFT) calculations indicate that the mechanism involves a radical pathway. In addition, the reaction can be performed in an enantioselective fashion. This work provides a new reaction mode for the regiocontrolled and stereocontrolled conversion of C(sp3)-H into C(sp3)-O bonds (Chapter 3).
3) An enantioselective intramolecular C(sp2)-H aminooxygenation of alkenes with functionalized hydroxylamines by using a chiral-at-metal ruthenium catalyst (Λ-RuH) was
reported. The ring-closing products were obtained with extremely high diastereoselectivity (>20:1 d.r.) and excellent enantioselectivity (up to 99% ee). The reaction is proposed to proceed through a ruthenium nitrenoid intermediate that depending on the nature of the substrate undergoes either an aminooxygenation (1,2-disubstituted alkenes) or stops at the stage of the aziridination (trisubstituted alkenes), which can then be ring-opened with benzoic acid. The resulting chiral cyclic carbamates can be converted to chiral 2-amino-1,3-diols after hydrolysis under basic conditions (Chapter 4).
4) A new member of the family of chiral-at-metal biscyclometalated iridium(III) catalysts featuring exclusively metal centered chirality is introduced, which emphasizes the simplicity of the organic ligand design. The catalyst is built from readily available 1,3-bis(ptolyl)imidazolium chloride, which, upon double deprotonation, serves as a cyclometalated Nheterocyclic carbene. The resulting configurationally stable, enantiomerically pure Λ- and Δ- iridium complexes show excellent catalytic properties for the asymmetric Michael addition of nitromethane to α,β-unsaturated 2-acyl imidazoles, providing the C-C bond adducts with up to 98 % yield and 99 % ee (Chapter 5).