The Elusive 1,4‐Diazabutatrienes: Lurking in the Shadows

Abstract

Isocyanides are isomers of cyanides in which the terminal carbon atom can exist in a divalent state. Their ambivalent electronic nature as nucleophile or electrophile and wide reactivity make the isocyanide scaffold a valuable synthon for the synthesis of structurally complex molecules, in particular azacycles. Although they are known to polymerize easily, the dimerization of isocyanides affording head‐to‐head dimers, namely 1,4‐diazabutatrienes R1‐N=C=C=N–R1, has been scarcely explored. Nowadays the experimental isolation of this kind of heterocumulenes is still a challenge. In this minireview, covering a period of sixty years, we highlight the role of 1,4‐diazabutatienes as putative reaction intermediates in the homo‐ and heterodimerization of different types of isocyanides. Furthermore, we revise a set of reported reactions in which the formation of a transient 1,4‐diazabutatriene intermediate has not been proposed but could be considered as a plausible alternative.

De Novo Synthesis of 2,2′-Bipyridines and Related Bis-azines via Cascade Coupling and Double Pyridannulation of Isocyanides

“…A good yield was restored when performing the reaction on a 10 mmol scale, and 1.18 g of 2a was isolated (Scheme ). In line with literature precedent − and our previous studies, , the mechanism involves the formation of a key 1,4-diazabutatriene intermediate I , which engages in “head-to-head” coupling of the terminal carbon atom of isocyanide 1a , and then I undergoes spontaneous 6π-electrocyclization/aromatization to furnish the 3,3′-diphenyl 2,2′-bipyridiyl 2a .…”

“…14 The dimerization processes that are initiated by "head-to-head" coupling of two isocyano groups provide a dependable method for the construction of azaheterocycles. 15 The dimerization of two isocyanides was first reported in 1977 by Hofle and Lange for the synthesis of 4,4′-bis-quinazoline as a serendipitous result (1 example in 32% yield). 16 After that, 2,2′-biquinolines, 17 fused imidazo[1,2-a]pyridines, 18 2-(isoquinolin-1-yl)oxazoles, 19 and benzo [b][1,4]oxazin-2-ones 20 accordingly prepared by utilizing this reaction.…”

“…Because of the unique reactivity, isocyanides have been explored as versatile building blocks for chemical synthesis . The dimerization processes that are initiated by “head-to-head” coupling of two isocyano groups provide a dependable method for the construction of azaheterocycles . The dimerization of two isocyanides was first reported in 1977 by Höfle and Lange for the synthesis of 4,4′-bis-quinazoline as a serendipitous result (1 example in 32% yield) .…”

In Search of 1,4-Diazabutatrienes, the Elusive Isocyanide Homodimers: The Superchameleonic F–NC

“…Notwithstanding, such heterocumulenes have been proposed as putative reaction intermediates, not only in homodimerizations but also in heterodimerizations (two different reacting partners leading to R 1 –NCCN–R 2 ) of diverse isocyanides − and have been additionally postulated as plausible molecular wires. , Whereas the C–C coupling of two molecules of hydrogen isocyanide affording ethenediimine (R = H) has been studied by theoretical methods, − no previous reports deal with computational studies on the dimerization of N -substituted isocyanides 1 , a lack that might be reasonably associated with its challenging preparation. Motivated by this absence, by our long-standing interest in the chemistry of nitrogenated heterocumulenes, − and by the fascinating but elusive nature of 1,4-diazabutatrienes, we present here a computational study aimed to estimate which N -substituents have better opportunities for favoring the homodimerization of isocyanides 1 toward species 2 (Figure b). With such a purpose, and also bearing in mind future attempts for the preparation of 2 by the herein discussed reactions, we combined commercial or synthetically accessible isocyanides bearing groups of a different electronic nature: H atom; electron donating groups (EDGs) as Me, NH 2 , and NMe 2 ; and electron withdrawing groups (EWGs) such as CF 3 , CHO, and F. Although the preparation of F–NC is still unknown, we incorporated it in our study for evaluating the influence of the most electronegative element (F).…”