Site-Selective Aliphatic C–H Bromination Using N-Bromoamides and Visible Light

Abstract

Transformations that selectively functionalize aliphatic C-H bonds hold significant promise to streamline complex molecule synthesis. Despite the potential for site-selective C-H functionalization, few intermolecular processes of preparative value exist. Herein, we report an approach to unactivated, aliphatic C-H bromination using readily available N-bromoamide reagents and visible light. These halogenations proceed in useful chemical yields, with substrate as the limiting reagent. The site selectivities of these radical-mediated C-H functionalizations are comparable (or superior) to the most selective intermolecular C-H functionalizations known. With the broad utility of alkyl bromides as synthetic intermediates, this convenient approach will find general use in chemical synthesis.

Visible‐Light Photocatalysis as an Enabling Tool for the Functionalization of Unactivated C(sp3)‐Substrates

“…In 2014, the Tan [90] and Alexanian [91] groups disclosed two varied approaches for the bromination of C(sp abstraction. Although useful yields were obtained in most cases for model substrates, the use of more challenging radical precursors resulted in low levels of conversion and, in some cases, complex product mixtures.…”

Remote Oxidation of Aliphatic C–H Bonds in Nitrogen-Containing Molecules

“…No N -demethylation was observed with imide 14e (57%) and both 4-nitrophthalimide 14g and unsubstituted phthalimide 14h were oxidized in useful yields ( 15g 58%; 15h 46%). 13 Underscoring the medicinal relevance of this reaction, oxidation of thalidomide analog 14i afforded 15i in good yield (54%). Imides are oxidatively stable and inductively deactivating motifs that promote remote oxidations.…”

Diverse sp3 C−H functionalization through alcohol β-sulfonyloxylation

“…Although radical-mediated halogenations of unactivated aliphatic substrates efficiently provide secondary and tertiary chlorides and bromides [33][34][35] , they generally do not give the more reactive primary products and the site selectivity is normally controlled by the inherent steric/electronic bias of the substrates. The palladium-catalysed oxazoline-and amide-directed C−H halogenation, pioneered by Yu and co-workers [36][37][38] and Sahoo and coworkers 39 , can exclusively form primary alkyl halides, albeit restrained to neopentyl-type electrophiles.…”