Palladium-Catalyzed β-C(sp³)–H Nitrooxylation of Ketones and Amides Using Practical Oxidants

Abstract

Herein, we report a Pd­(II)-catalyzed β-C­(sp3)–H nitrooxylation of ketones and native amides. The fine-tuned removable aminooxyamide auxiliary enabled β-C­(sp3)–H functionalization of various aliphatic ketones. Practical iron­(III) nitrate nonahydrate was used as the nitrate source and a single-electron oxidant for Pd­(II)/Pd­(III)/Pd­(IV) catalysis. For amide substrates, N-iodosuccinimide (NIS) was applied as a bystanding two-electron oxidant in combination with silver nitrate for β-C­(sp3)–H nitrooxylation. Palladacycle intermediates were isolated and characterized to elucidate the reaction mechanism for the C­(sp3)–H activation of ketones with the L,X-type imino-amide directing group.

Palladium-catalyzed C(sp3)–H nitrooxylation of masked alcohols

“…of tetrabutyl ammonium hydrogen sulfate (TBAHS) improved the yield to 68% (entry 12). Other phase transfer catalysts were also screened as additives for the reaction, but none of them showed better performance than TBAHS (Table 1, entries [13][14][15].…”

“…Based on our previous work and literature reports, 12,13,15 b we have proposed a putative Pd( ii )/Pd( iv ) catalytic cycle for the nitrooxylation reaction (Scheme 3). Substrate coordination followed by C–H bond cleavage gives the bicyclic palladacycle A .…”

“…12 Recently, we reported a palladium-catalyzed β-C(sp 3 )-H nitrooxylation of ketones and amides using practical oxidants (Scheme 1b). 13 As far as we know, the direct C(sp 3 )-H nitrooxylation of alcohols has never been reported via C-H activation. 9b Alcohols are common and ubiquitous structural motifs found in small molecules to complex natural products and materials.…”

“…12 Recently, we reported a palladium-catalyzed β-C(sp 3 )–H nitrooxylation of ketones and amides using practical oxidants (Scheme 1b). 13 As far as we know, the direct C(sp 3 )–H nitrooxylation of alcohols has never been reported via C–H activation. 9 b…”

Palladium-catalyzed intramolecular C–H amination using aluminum nitrate as the oxidant

“…5 c Nevertheless, the selectivity between the methyl sp 3 C–H bonds and the aryl sp 2 C–H bonds has always caused an issue in these methods. Herein, we report a simple and efficient reaction for the synthesis of oxindoles promoted by in situ directing group (DG) modification using Al(NO 3 ) 3 ·9H 2 O as a readily available oxidant 8 (Scheme 1c). The oxindole products can be efficiently converted into novel polycyclic compounds involving the DG.…”