Chiral Iron-N4-Complexes for Asymmetric C-H Aminations
Due to iron's low toxicity and abundance on Earth, chiral inexpensive metallic iron catalysts have gained great attention. There are still no examples of the direct use of simple and readily available chiral iron catalysts to catalyse the activation of C-H bonds to enantioselectively form C-N b...
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|Due to iron's low toxicity and abundance on Earth, chiral inexpensive metallic iron catalysts have gained great attention. There are still no examples of the direct use of simple and readily available chiral iron catalysts to catalyse the activation of C-H bonds to enantioselectively form C-N bonds. This thesis is based on the enantioselective catalytic amination of challenging secondary and tertiary C-H bonds via chiral N4 iron catalysts. At the same time, the enantioselective amination produces a series of unnatural α-amino acids. A novel approach for synthesizing α-amino acids is disclosed.
In the first two sections, a series of chiral N4 iron catalysts were synthesized and successfully applied to asymmetric secondary C-H bonds amination reactions. Our method employs abundant and easily accessible carboxylic acids as starting materials, which are connected to a nitrogenation reagent, followed by a highly regio- and enantioselective iron-catalyzed C(sp3)-H amination. This straightforward method displays a broad scope, providing rapid access to optically active α-amino acids with aryl, allyl, and alkyl side chains, and also permits stereocontrolled late-stage amination of carboxylic acid-containing drugs and natural products.
In the third section, A straightforward two-step synthesis of non-racemic α,α-disubstituted α-amino acids by an enantioconvergent 1,3-migratory nitrene C(sp3)-H insertion is reported. Readily available racemic α-branched carboxylic acids are DCC/EDCI-coupled to provide racemic azanyl esters which undergo a rearrangement into non-racemic N-Troc-protected α,α-disubstituted α-amino acids catalyzed by an easy to store and robust chiral iron catalyst. α,α-Disubstituted α-amino acids with one aryl group in α-position are provided in yields of up to 99% and with up to 88% ee. Selected examples demonstrate that recrystallization can improve the enantiomeric excess to 99% ee.