Para‐Selective Cyanation of Arenes by H‐Bonded Template

Abstract

The significance of site selective functionalization stands upon the superior selectivity, easy synthesis and diverse product utility. In this work, we demonstrate the para‐selective introduction of versatile nitrile moiety, enabled by a detachable and reusable H‐bonded auxiliary. The methodology holds its efficiency irrespective of substrate electronic bias. The conspicuous shift in the step energetics was probed by both experimental and computational mechanistic tools, which heralds the inception of para‐deuteration. The synthetic impact of the methodology was highlighted with reusability of directing group and post synthetic modifications.

Transition Metals and Transition Metals/Lewis Acid Cooperative Catalysis for Directing Group Assisted para-C–H Functionalization

“…In 2020, Maiti and co-workers reported a para-selective cyanation protocol using their previously developed 2nd gen- eration D-shaped template considering its enormous importance in synthetic chemistry, agrochemicals, and pharmaceuticals. 16 para-Cyanation of toluene derivative, 30a was delivered in 70% yield with 10:1 selectivity (para:others) in presence of Pd(OAc) 2 , Ac-Gly-OH, Ag 2 CO 3 hexafluoroisopropanol (HFIP) solvent and CuCN as cyanating reagent (Scheme 12). Substrate containing electronically distinct functional groups were well tolerated under the reaction conditions to deliver the desired compounds in good to excellent yield with synthetically acceptable selectivity.…”

Decoding Directing Groups and Their Pivotal Role in C−H Activation

“…[288] The resulting biphenyl moiety is turned into a benzyl bromide scaffold after bromination with N-bromosuccinimide with benzoyl peroxide presence. Then, the resulting 4'-(bromomethyl)-[1,1'-biphenyl]-2carbonitrile [291] or the 4'-(bromomethyl)-4,5-dimethoxy-[1,1'-biphenyl]-2-carbonitrile [292] is then treated with magnesium turnings and iodine to afford the corresponding Grignard reagent to react with diisopropylchlorosilane. This intermediate is then brominated with N-bromosuccinimide and subsequently coupled to the phenol substrate.…”

“…[291] Recently, Lu et al demonstrated a palladium-catalyzed para-selective cyanation of phenols in moderate yields. [292] Again, the choice of an electronrich template and HFIP as solvent was founded to crucial for this protocol (Scheme 59). [292] Gervorgyan group envisioned the usage of easily removable silanols for diverse traceless palladium-catalyzed ortho-diversification in phenols.…”

“…[292] Again, the choice of an electronrich template and HFIP as solvent was founded to crucial for this protocol (Scheme 59). [292] Gervorgyan group envisioned the usage of easily removable silanols for diverse traceless palladium-catalyzed ortho-diversification in phenols. [293][294][295] The silanols are obtained from readily Scheme 58.…”

“…Recently, Lu et al . demonstrated a palladium‐catalyzed para ‐selective cyanation of phenols in moderate yields [292] . Again, the choice of an electron‐rich template and HFIP as solvent was founded to crucial for this protocol (Scheme 59).…”