Directed β C–H Amination of Alcohols via Radical Relay Chaperones

Abstract

A radical-mediated strategy for β C–H amination of alcohols has been developed. This approach employs a radical relay chaperone, which serves as a traceless director that facilitates selective C–H functionalization via 1,5-hydrogen atom transfer (HAT) and enables net incorporation of ammonia at the β carbon of alcohols. The chaperones presented herein enable direct access to imidate radicals, allowing their first use for H atom abstraction. A streamlined protocol enables rapid conversion of alcohols to their β-amino analogs (via in situ conversion of alcohols to imidates, directed C–H amination, and hydrolysis to NH2). Mechanistic experiments indicate HAT is rate-limiting, whereas intramolecular amination is product- and stereo-determining.

Photochemical Transformation of O‐(β‐Arylethyl) Arylimidates into 2,4‐Diaryl‐5‐iodoxazoles with 1,3‐Diiodo‐5,5‐dimethylhydantoin

“…Recently, Nagib et al reported interesting methods for the preparation of β‐amino alcohols through the reactions of (trichloromethyl)imidates prepared from alcohols and trichloroacetonitrile, with NaI and PhI(OAc) 2 under visible‐light irradiation, via the formation of iminyl radicals, their 1,5‐H shift, their cyclization to form oxazolines, and their hydrolysis , [8a] and the preparation of γ‐functionalized β‐amino alcohols from alcohols through the reactions of (trichloromethyl)imidates with NaI and PhI(OAc) 2 under visible light irradiation via the formation of amidyl radicals, their 1,5‐H shift, formation of olefinic group, iodocyclization, and their hydrolysis. [8b] He et al also reported the preparation of β‐amino alcohols from (trichloromethyl)imidates, and 2‐aryloxazolines from arylimidates with NIS or with NIS and Ag 2 O at 110 °C. [8c]…”

“…[8b] He et al also reported the preparation of β‐amino alcohols from (trichloromethyl)imidates, and 2‐aryloxazolines from arylimidates with NIS or with NIS and Ag 2 O at 110 °C. [8c]…”

Exploiting Imine Photochemistry for Masked N‐Centered Radical Reactivity

“…Nitrogen-centered radicals have drawn agreat deal of interest in recent years,l argely driven by photochemical innovation. [24,25] Prominent alternatives to amine radical cations include amidyl or imidyl radicals arising from oxidation of N À Hbonds [26,27] via proton-coupled electron transfer (PCET) [28] or from NÀXb onds via homolysis, [29][30][31] reduction, [32] or even oxidation [33] by employing a-aminoxy carboxylic acid auxiliaries popularized by the groups of Leonori [34,35] and Studer. [36,37] Alternatively,i tw as hypothesized that initiation of our desired fragmentation-cyclization sequence could be accomplished not from a discrete N-centered radical but a temporaneous N-centered radical.…”

Exploiting Imine Photochemistry for Masked N-Centered Radical Reactivity

“…Circumventing this limitation would require another means of accessing open-shell character at nitrogen (see Figure 1B). [24,25] Prominent alternatives to amine radical cations include amidyl or imidyl radicals arising from oxidation of N À Hbonds [26,27] via proton-coupled electron transfer (PCET) [28] or from NÀXb onds via homolysis, [29][30][31] reduction, [32] or even oxidation [33] by employing a-aminoxy carboxylic acid auxiliaries popularized by the groups of Leonori [34,35] and Studer. [24,25] Prominent alternatives to amine radical cations include amidyl or imidyl radicals arising from oxidation of N À Hbonds [26,27] via proton-coupled electron transfer (PCET) [28] or from NÀXb onds via homolysis, [29][30][31] reduction, [32] or even oxidation [33] by employing a-aminoxy carboxylic acid auxiliaries popularized by the groups of Leonori [34,35] and Studer.…”