Masters of Mediation: MN(SiMe₃)₂ in Functionalization of C(sp³)−H Latent Nucleophiles

Abstract

Organoalkali compounds have undergone a far‐reaching transformation being a coupling partner to a mediator in unusual organic conversions which finds its spot in the field of sustainable synthesis. Transition‐metal catalysis has always been the priority in C(sp3)−H bond functionalization, however alternatively, in recent times this has been seriously challenged by earth‐abundant alkali metals and their complexes arriving at new sustainable organometallic reagents. In this line, the importance of MN(SiMe3)2 (M = Li, Na, K & Cs) reagent revived in C(sp3)−H bond functionalization over recent years in organic synthesis is showcased in this minireview. MN(SiMe3)2 reagent with higher reactivity, enhanced stability, and bespoke cation‐π interaction have shown eye‐opening mediated processes such as C(sp3)−C(sp3) cross‐coupling, radical‐radical cross‐coupling, aminobenzylation, annulation, aroylation, and other transformations to utilize readily available petrochemical feedstocks. This article also emphasizes the unusual reactivity of MN(SiMe3)2 reagent in unreactive and robust C−X (X = O, N, F, C) bond cleavage reactions that occurred alongside the C(sp3)−H bond functionalization. Overall, this review encourages the community to exploit the untapped potential of MN(SiMe3)2 reagent and also inspires them to take up this subject to even greater heights.

Sulfonamides as N-Centered Radical Precursors for C–N Coupling Reactions To Generate Amidines

“…The deprotonation of N-benzyl ketimines to form 2-azaallyl anions is mediated by a base. 16 pleased to find that KN(SiMe 3 ) 2 and KO t Bu afforded product 3aa in 85 and 32% AY, respectively. Other bases did not result in the desired product.…”

“…Among them, CPME provided the target compound 3aa in 23% AY, while other solvents led to a lower AY or no reaction. The deprotonation of N -benzyl ketimines to form 2-azaallyl anions is mediated by a base . We, therefore, conducted a careful survey of various bases [LiN­(SiMe 3 ) 2 , KN­(SiMe 3 ) 2 , LiO t Bu, NaO t Bu, and KO t Bu; entries 10–14] in CPME.…”

Base-Promoted Synthesis of Isoquinolines through a Tandem Reaction of 2-Methyl-arylaldehydes and Nitriles

“…Other impressive examples of the functionalization of toluene derivatives were developed by Kobayashi and co-workers, who introduced an asymmetric addition of toluene-derived benzyl groups to imines . The groups of Guan and Gandhi have also introduced methods for the functionalization of toluenes. Wang and Ma outlined the synthesis of isoquinolone derivatives from 2-methylaryl aldehydes and benzonitriles …”

One-Pot Synthesis of Indolin-3-ones Mediated by LiN(SiMe3)2/CsF

“…We are interested in chemoselectively deprotonative functionalization of benzylic C­(sp 3 )–H bonds over aromatic C­(sp 2 )–H bonds with our bimetallic base systems (MN­(SiMe 3 ) 2 , M = Li, Na/Cs + ). Other groups, such as Guan, Kondo and Shigeno, Kobayashi, Gandhi, Screttas, and others, have also made significant contributions to this field by different and efficient Bro̷nsted base systems. By using these bimetallic systems, a diverse array of transformations based on BnM (M = Li, Na, K, or Cs) has been demonstrated.…”