Synthesis and Reactivity of Unsymmetrical Azomethine Imines Formed Using Alkene Aminocarbonylation

Abstract

Complex cyclic azomethine imines possessing a β-aminocarbonyl motif can be accessed readily from simple alkenes and hydrazones. This alkene aminocarbonylation approach allows formation of ketone-derived azomethine imines of unprecedented complexity. Since unsymmetrical hydrazones are used, two stereoisomers are formed: the reactivity of chiral derivatives is explored in both intra- and intermolecular systems.

A Practical Approach to Semicarbazone and Hydrazone Derivatives via Imino-isocyanates

“…Evaporation of solvent gave the desired product (1.21g, 98%) as a white solid. Rf 0.4 (100% CH2Cl2); Phenyl 2-(thiophen-2-ylmethylene)hydrazinecarboxylate (4j -substrate for Figure 24) Synthesized according to literature, 65 with minor modifications. Phenyl carbazate (0.304 g, 2.00 mmol), thiophene-2-carbaldehyde (0.224 g, 2.00 mmol), acetic acid (0.04 mL) and methanol (5 mL) were combined and left to stir for 1 h at room temperature.…”

Hydrazones as substrates for cycloaddition reactions

“…4) by the reaction of hydrazone derivatives 113 bearing ester or amide moieties at the N-atom with alkenes (aminocarbonylation) in the absence of a solvent or in a,a,a-trifluorotoluene (Scheme 46). 144,149,150 The generation of N,N H -cyclic azomethine imines from hydrazones and alkenes is a thermal concerted reaction proceeding via the formation of an imino isocyanate intermediate the existence of which was confirmed by quantum chemical calculations. 150 …”

“…142,149 Apparently, this reaction initially occurs to form the azomethine imine 157, the Z-isomer of which is further transformed into the cyclopenta [4,5] …”

A Cascade Synthesis of Aminohydantoins Using In Situ‐Generated N‐Substituted Isocyanates

“…In contrast to normal ( C ‐substituted) isocyanates, the reactivity of N ‐substituted isocyanates has received little attention from the synthetic community 5. Recently, we reported that amphoteric amino‐ and imino‐isocyanates can be formed in situ under mild conditions and engage in high‐yielding alkene cycloadditions6a–c and nucleophilic additions,6d,e despite their known tendency to dimerize or oligomerize 7. 8 Hydrazones6b–d and hydrazides6a,e are bench‐stable, convenient “blocked” N ‐substituted isocyanate precursors9 that form the desired isocyanates via an equilibrium induced under mild conditions, and then react with nucleophiles such as amines, alcohols, and thiols 6d–e.…”