Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry.

In the current ecological context, use of insect sex pheromones as an alternative to conventional pesticides is in constant growth. In this report, we discuss the recent contributions brought by our groups in the field of iron-catalyzed cross-couplings applied to the synthesis of insect pheromones. The pivotal question of the development of sustainable synthetic procedures involving cheap, non-toxic and efficient additives is also discussed, as well as the mechanistic features guiding the reactivity of such catalytic systems.

The molecular-level effect of alkoxide additives in iron-catalyzed Kumada cross-coupling with simple ferric salts.

The molecular-level role of alkoxide salts, used as alternative additive to N-methylpyrrolidone in iron-catalyzed alkyl-alkenyl/aryl cross-coupling reactions, is investigated. Detailed spectroscopic studies reveal that alkoxides promote the formation of homoleptic organoferrates such as [FeMe3]-, providing an alternative to toxic NMP to access these reactive intermediates.

Mechanistic Facets of the Competition between Cross-Coupling and Homocoupling in Supporting Ligand-Free Iron-Mediated Aryl-Aryl Bond Formations.

In the context of cross-coupling chemistry, the competition between the cross-coupling path itself and the oxidative homocoupling of the nucleophile is a classic issue. In that case, the electrophilic partner acts as a sacrificial oxidant. We investigate in this report the factors governing the cross- versus homocoupling distribution using aryl nucleophiles ArMgBr and (hetero)aryl electrophiles Ar'Cl in the presence of an iron catalyst. When electron-deficient electrophiles are used, a key transient heteroleptic [Ar2Ar'FeII]- complex is formed. DFT calculations show that an asynchronous two-electron reductive elimination follows, which governs the selective evolution of the system toward either a cross- or homocoupling product. Proficiency of the cross-coupling reductive elimination strongly depends on both π-accepting and σ-donating effects of the FeII-ligated Ar' ring. The reactivity trends discussed in this article rely on two-electron elementary steps, which are in contrast with the usually described tendencies in iron-mediated oxidative homocouplings which involve single-electron transfers. The results are probed by paramagnetic 1H NMR spectroscopy, experimental kinetics data, and DFT calculations.