Reactions Involving Multiple Isocyanide Insertions

Abstract

Isocyanides (isonitriles or carbylamine) have been intensively used in organic synthesis to prepare a diverse variety of N‐heterocycles on the basis of the carbene‐like reactivity of their divalent carbon atom. Isocyanides participate in a variety of reactions involving one, two, or more isocyanides. Compared to the popularity of single isocyanide reactions, few examples of reactions involving two or more isocyanides have been reported. In this review, we categorized and classified the literatures of reactions involving two or more isocyanides especially double isocyanide insertions under metal‐catalyzed or metal‐free conditions from 2014 to 2022.

Recent advances in [4 + 4] annulation of conjugated heterodienes with 1,4-dipolar species for the synthesis of eight-membered heterocycles

“…30 Isocyanides have emerged as versatile synthons that are widely applied in synthetic chemistry. 32 Combining two robust synthons in a cascade transformation under phosphine catalysis, Cui, Li and coworkers disclosed that a novel type of furan-fused eightmembered N-heterocyclic ring could be conveniently constructed through a phosphine-mediated [4 + 1]/[4 + 4] cyclization reaction in 2019. 33 Using allenyl ketone 49 and isocyanide 50 as the starting materials, a variety of furo [2,3-b]azocine derivatives 51 were readily generated in moderate to good yields via the cascade annulation in the presence of PPh 3 (Scheme 7).…”

Rh-catalysed divergent synthesis of polysubstituted pyrroles from α,β-unsaturated ketones via selective single or double insertion of isocyanides

“…3 The second insertion can be preceded by successive reactions, such as intramolecular cyclisation or addition of another reactant after the first insertion of the isocyanide, which also provides access to double insertion products. 4 In most cases, the number of inserted isocyanide molecules is specific to the catalytic system, whereas only limited examples of switchable selectivity based on the number of inserted isocyanides have been reported. [5][6][7][8][9] One of the key factors for switching selectivity is the amount of the isocyanide relative to that of another condensation partner.…”

“…3 The second insertion can be preceded by successive reactions, such as intramolecular cyclisation or addition of another reactant after the first insertion of the isocyanide, which also provides access to double insertion products. 4…”

Rapid Access to Fused Tetracyclic N-Heterocycles via Amino-to-Alkyl 1,5-Palladium Migration Coupled with Intramolecular C(sp3)–C(sp2) Coupling

“…As a highly valuable building block, isocyanide has been widely applied in the construction of nitrogen-containing compounds due to the carbene-like reactivity of the divalent carbon atom. 7 In recent decades, its synthetic utilities have mainly been witnessed by transition-metal-catalyzed isocyanide insertions, 8 isocyanide-based multicomponent reactions, 9 and radical isocyanide chemistry. 10 In particular, transition-metalcatalyzed isocyanide chemistry has established a facile paradigm for producing fused N-heterocycles.…”