Control of the Chemoselectivity of Metal N-Aryl Nitrene Reactivity: C–H Bond Amination versus Electrocyclization

Abstract

A mechanism study to identify the elements that control the chemoselectivity of metal-catalyzed N-atom transfer reactions of styryl azides is presented. Our studies show that the proclivity of the metal N-aryl nitrene to participate in sp-C-H bond amination or electrocyclization reactions can be controlled by either the substrate or the catalyst. Electrocyclization is favored for mono-β-substituted and sterically noncongested styryl azides, whereas sp-C-H bond amination through an H-atom abstraction-radical recombination mechanism is preferred when a tertiary allylic reaction center is present. Even when a weakened allylic C-H bond is present, our data suggest that the indole is still formed through an electrocyclization instead of a common allyl radical intermediate. The site selectivity of metal N-aryl nitrenes was found to be controlled by the choice of catalyst: Ir(I)-alkene complexes trigger electrocyclization processes while Fe(III) porphyrin complexes catalyze sp-C-H bond amination in substrates where Rh(II) carboxylate catalysts provide both products.

Recent Advances in Iron‐Catalyzed C—H Bond Amination via Iron Imido Intermediate

“…Driver found that the [Fe(OEP)Cl]-catalyzed reactions of styryl azides having tertiary allylic C-H bonds show selectivity toward allylic C-H bond amination (Scheme 8). [61] The lowered ratio of 2H-indole/indole (2 : 1) formed in a deuterium-labeling experiment is consistent with the proposal that the two products are formed from the different reaction routes of C-H amination and electrocyclization, respectively. For styryl azides that do not contain tertiary C(sp 3 )-H bond, their [Fe(OEP)Cl]-catalyzed reactions could also produce formal C-H amination products that have the newly formed C-N bond on the original β-carbon position of the styryl azides (Scheme 8).…”

“…Another interesting study of heme-type iron catalyzed-C-H bond amination reaction is Driver's exploration on *Fe(OEP)Cl+catalyzed conversion of styryl azides. [61] Transition-metal-catalyzed intramolecular N-group transfer reactions of styryl azides might give allylic C-H bond amination or electrocyclization products (Scheme 8). Driver found that the [Fe(OEP)Cl]-catalyzed reactions of styryl azides having tertiary allylic C-H bonds show selectivity toward allylic C-H bond amination (Scheme 8).…”

Design and Synthesis of Novel Orexin Antagonists via Structural Simplification of the Morphinan Skeleton

“…Scheme 1 shows the synthetic route to designed compound 2. 1-Boc-4-piperidone (5) was condensed with dimethyl carbonate to give 6 16 and then reacted with methyl vinyl ketone to synthesize 7. 17 Robinson annulation of 7 was carried out in the presence of pyrrolidine and acetic acid, 17 following which demethoxycarbonylation was performed via hydrolysis of the resulting ester 8 with a 1 M aqueous NaOH solution to obtain 9.…”

Catalyst‐Controlled Chemoselective Nitrene Transfers

“…While [Ir(cod)(OMe)] 2 selectively promoted electrocyclization, an iron porphyrin catalyst favored C−H amination ( Scheme 12). [54] …”