Synthesis of Nitrogen-Containing Heterocycles Using Conjugate Addition Reactions of Nucleophiles to α,β-Unsaturated Imines

Hachiya, Iwao; Mizota, Isao; Shimizu, Makoto

doi:10.3987/rev-12-726

Cited by 12 publications

(1 citation statement)

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“…Despite the construction of α,β-unsaturated imines mainly relies on condensation of ene-aldehydes and amines in the current stage 46,47 , the low-boiling points of simple ene-aldehydes and the tedious preparation procedures for functionalized ene-aldehydes have partly limited its practicability [48][49][50] . Taking this in account, together with the widespread application of α,β-unsaturated imines in a number of C-C/N bond formations [51][52][53][54] , searching for supplementary methods for the efficient synthesis of structurally diverse α,β-unsaturated imines, for example the dehydrogenation of abundant N-containing compounds, is highly desirable. However, several inherent challenges accompany with this dehydrogenation hypothesis.…”

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A facile synthesis of α,β-unsaturated imines via palladium-catalyzed dehydrogenation

Zhao,

Gao,

et al. 2024

Nat Commun

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The dehydrogenation adjacent to an electron-withdrawing group provides an efficient access to α,β-unsaturated compounds that serving as versatile synthons in organic chemistry. However, the α,β-desaturation of aliphatic imines has hitherto proven to be challenging due to easy hydrolysis and preferential dimerization. Herein, by employing a pre-fluorination and palladium-catalyzed dehydrogenation reaction sequence, the abundant simple aliphatic amides are amendable to the rapid construction of complex molecular architectures to produce α,β-unsaturated imines. Mechanistic investigations reveal a Pd(0)/Pd(II) catalytic cycle involving oxidative H–F elimination of N-fluoroamide followed by a smooth α,β-desaturation of the in-situ generated aliphatic imine intermediate. This protocol exhibits excellent functional group tolerance, and even the carbonyl groups are compatible without any competing dehydrogenation, allowing for late-stage functionalization of complex bioactive molecules. The synthetic utility of this transformation has been further demonstrated by a diversity-oriented derivatization and a concise formal synthesis of (±)-alloyohimbane.

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