Aerobically-initiated C(sp³)–H bond amination through the use of activated azodicarboxylates

Abstract

Significant advancements in C−N bond formation via C−H bond functionalisation have made it a staple in the production of nitrogen-containing compounds in both industry and academia. However, transition metal-free synthesis,...

HFIP in Organic Synthesis

“…An aerobic C–H amination of ethereal compounds was reported which utilized azodicarboxylates as the nitrogen source (Scheme ). Cyclic ethers/acetals, acyclic ethers, and even tetrahydrothiophene or N -Boc pyrrolidine were aminated in up to 94% yield in either HFIP or TFE (Scheme a). Theoretical and experimental studies were conducted to confirm the initial hypothesis that these fluorinated alcohols were indeed activating azodicarboxylates through H-bonding.…”

Visible-Light-Mediated (sp3)Cα–H Functionalization of Ethers Enabled by Electron Donor–Acceptor Complex

“…To check the versatility of the developed protocol, we envisioned whether dialkyl azodicarboxylates could act as a radical acceptor to forge the C–N bond. − To our delight, THF radical was successfully trapped by diisopropylazodicarboxylate ( 4a , see SI) under blue LEDs irradiation to deliver amine product with moderate yield. A series of light sources and reaction times were then screened to check the best-fitted one (See SI for the optimization table, section 4.4).…”

“…Similar to diazo compounds, dialkyl azodicarboxylates were also employed for radical-based amination reactions. − In 2020, the Chudasama and Kokotos groups individually reported HFIP mediated and CFL lamp-promoted C–H amination, respectively (Scheme a). , Very recently, Laulhé et al were able to functionalize the ( sp 3 )­Cα–H bond of aliphatic cyclic ethers in the presence of visible light and traces of oxygen (Scheme a) …”

Functionalisation of ethereal-based saturated heterocycles with concomitant aerobic C–H activation and C–C bond formation

“…These acceptors were selected as they have previously been reported to react with nucleophilic radicals, [53][54][55][56] and the reaction conditions selected were based on our previous work. 29 Dibenzothiophenium salt 2 had poor solubility in the THF : HFIP mixture, which led to no formation of the desired THF acetylene product under the reaction conditions; this was also the case for bromophenylacetylene 3. Iodonium tosylate 4 was more soluble in the reaction conditions and underwent some reaction, forming the acetylenic THF adduct 8a as the only product, but in only 7% yield due to the low conversion of alkyne.…”

“…[18][19][20][21] However, existing approaches, whilst effective, typically employ specialised initiators and/or careful management of reaction conditions to achieve this in a controlled fashion. [22][23][24][25][26] Aerobic C-H activation, utilising oxygen in air to promote radical-based C-H bond cleavage, represents a potentially ideal approach, [26][27][28][29][30] but to date has not been exploited for the formation of C-C bonds on saturated heterocycles. To explore this idea, we initially examined tetrahydrofuran (THF, 1a) as a candidate for aerobic C-H activation as THF derivatives are highly sought after.…”