Cameron H. M. Zheng

This study reports that the well-known Co(III) precursor Co(η⁵-Cp*)I₂(CO) (1) is an effective precatalyst for dehydrocoupling reactions of phosphines. Reaction monitoring by NMR, complemented by ESI-MS and EPR, suggests that Co(III) complexes containing secondary and primary phosphine ligands play an important role in this catalysis but that redox chemistry is also facile for these complexes, resulting in paramagnetic species. Representative examples of the mono(phosphine) complexes Co(η⁵-Cp*)I₂(PR₂H) (2) and Co(η⁵-Cp*)I₂(PRH₂) (4) and bis(phosphine) complexes [Co(η⁵-Cp*)I(PR₂H)₂] I (3) have been prepared. The characterization of these complexes through structural, computational, spectroscopic, and electrochemical analysis is reported and serves as a foundation for considering their mechanistic significance in the observed catalytic dehydrocoupling chemistry.

Naturally occurring and structurally diverse alkene-containing substrates, terpenes, provided a platform for establishing chemo-, regio-, and diastereoselective reactivity in tantalum catalysed hydroaminoalkylation. Naturally derived 1,3-butadienes revealed the unique regio- and diastereoselective (Z)-1,4-addition products accessible from isoprene and β-myrcene by hydroaminoalkylation. Selective terpene functionalisation, within an industrially produced turpentine mixture, demonstrates functionalisation specificity of β-pinene and limonene. Lastly, sesquiterpene functionalisation using β-caryophyllene and humulene provide rare examples of trisubstituted alkene reactivity in hydroaminoalkylation, by leveraging strain-release and stereoelectronic effects to control chemoselectivity. As a result of these reactivity studies using natural substrates, new tools for understanding alkene electronic, strain, and stereoelectronic effects on chemo- and diastereoselectivity outcomes have revealed new mechanistic insights into hydroaminoalkylation.

The prominence of saturated N-heterocycle motifs in pharmaceuticals is undeniable. Challenges associated with the alkylation of saturated N-heterocycle scaffolds to efficiently access new drug analogues are hampered by synthetically laborious routes. Stereocontrolled alkyl-substitutions onto saturated N-heterocycles are particularly difficult to access in high yields by traditional synthetic methods. Alternatively, C–H bond functionalization provides a new and powerful synthetic avenue by directly and selectively functionalizing/alkylating/ arylating the abundantly available C–H bonds of saturated N-heterocycles. This review highlights complementary methods for directly activating and functionalizing C–H bonds of saturated N-heterocycles chemo-, regio-, and or stereoselectively to access alkylated products. This synthetic challenge has required catalyst development to access useful N-heterocyclic building blocks or for late-stage functionalization. Early transition metal, late transition metal, photoredox, and electrochemical methods are discussed. The selective functionalization of α, β, and γ C–H bonds to form new C–C, C–N, C–O, and C–B bonds is presented.1 Introduction2 Early Transition Metal Catalyzed α-Alkylation3 Late Transition Metal Catalyzed α-Functionalization4 Photoredox-Catalyzed α-Functionalization5 Electrochemical α-Functionalization6 C–H Functionalization of β and γ C–H Bonds7 Conclusions/Outlook

Early transition metal-catalyzed hydroaminoalkylation is a powerful single-step method to selectively add amines to polybutadienes, offering an efficient strategy to access amine-functionalized polyolefins. Aryl and alkyl secondary amines were used with a tantalum catalyst to functionalize both 28 wt% (PBD13) and 70 wt% (PBD50) 1,2-polybutadiene polymers. The degree of amination was controlled by modifying amine and catalyst loading in both small- and multigram-scale reactions. The vinyl groups of 1,2-polybutadiene were aminated with ease, and unexpectedly the hydroaminoalkylation of challenging internal alkenes of the 1,4-polybutadiene unit was observed. This unanticipated reactivity was proposed to be due to a directing group effect. This hypothesis was supported with small-molecule model substrates, which also showed directed internal alkene amination. Increasing degrees of amination resulted in materials with dramatically higher and tunable glass transition temperature (T_g) values, due to the dynamic cross-linking accessible to hydrogen-bonding, amine-containing materials. Primary amine-functionalized polybutadiene was also prepared, demonstrating that a broad new class of amine-containing polyolefins can be accessed by postpolymerization hydroaminoalkylation.

Titanium-catalyzed hydroaminoalkylation has emerged as an atom-economical, earth-abundant synthesis of N-containing products. Secondary amines are added to diverse alkenes with branched regioselectivity by a catalytic system that is assembled in one step using Ti(NMe₂)₄ and urea ligand. Both 1,1- and 1,2-disubstituted alkenes are aminated with this titanium catalyst. Sterically enhanced aryl and alkyl amines are installed onto silylether functionalized alkenes to synthesize precursors for biologically active substrates. Regioselective formation of branched amine functionalized materials are prepared from vinyl terminated polypropylene to access aminated materials. Such materials are potentially useful adhesives, compatibilizers, and reactive macromolecules to fabricate functional materials. A life cycle analysis of competing tantalum and titanium catalysts is provided to quantify the environmental impacts and demonstrate how titanium-catalyzed hydroaminoalkylation is a “greener” solution to amine terminated polypropylene synthesis.