Asymmetric Three-Component Radical Alkene Carboazidation by Direct Activation of Aliphatic C–H Bonds

Abstract

Azide compounds are widely present in natural products and drug molecules, and their easy-to-transform characteristics make them widely used in the field of organic synthesis. The merging of transition-metal catalysis with radical chemistry offers a versatile platform for radical carboazidation of alkenes, allowing the rapid assembly of highly functionalized organic azides. However, the direct use of readily available hydrocarbon feedstocks as sp 3 -hybridized carbon radical precursors to participate in catalytic enantioselective carboazidation of alkenes remains a significant challenge that has yet to be addressed. Herein, we describe an iron-catalyzed asymmetric three-component radical carboazidation of electron-deficient alkenes by direct activation of aliphatic C−H bonds. This approach involves intermolecular hydrogen atom transfer between a hydrocarbon and an alkoxy/aryl carboxyl radical, leading to the formation of a carbon-centered radical. The resulting radical then reacts with electron-deficient alkenes to generate a new radical species that undergoes chiral iron-complex-mediated C−N 3 bond coupling. An array of valuable chiral azides bearing a quaternary stereocenter were directly accessed from widely available chemical feedstocks, and their synthetic potential is further demonstrated through more facile transformations to give other valuable enantioenriched building blocks.

Iron-Catalyzed Asymmetric Imidation of Sulfides via Sterically Biased Nitrene Transfer

“…Chiral N , N ′-dioxide ligands have been identified as a class of tetra-oxygen ligands to promote efficient and stable coordination with main group metals, transition metals and rare-earth metals, which have been extensively applied to chiral Lewis acid-catalyzed asymmetric synthesis. − Exploiting their capability of group transfer and redox properties, chiral N , N ′-dioxide/3d metal complexes have exhibited uniqueness in a set of reactions. − Motivated by the significance of chiral sulfimides and iron, we envisaged to explore the potential of chiral N , N ′-dioxide/iron complexes for the nitrene transfer reaction of various sulfides through a sterically biased model. Herein, we wish to disclose our endeavor along this line.…”