Iron- and Cobalt-Catalyzed Asymmetric Hydrofunctionalization of Alkenes and Alkynes.

Abstract

Transition metal catalyzed asymmetric hydrofunctionalization of readily available unsaturated hydrocarbons presents one of the most straightforward and atom-economic protocols to access valuable optically active products. For decades, noble transition metal catalysts have laid the cornerstone in this field, on account of their superior reactivity and selectivity. In recent years, from an economical and sustainable standpoint, first-row, earth-abundant transition metals have received considerable attention, due to their high natural reserves, affordable costs, and low toxicity. Meanwhile, the earth-abundant metal catalyzed hydrofunctionalization reactions have also gained much interest and been investigated gradually. However, since chiral ligand libraries for earth-abundant transition-metal catalysis are limited to date, the development of highly enantioselective versions remains a significant challenge.This Account summarizes our recent efforts in developing suitable chiral ligands for iron and cobalt catalysts and their applications in the highly enantioselective hydrofunctionalization reactions (hydroboration and hydrosilylation) of alkenes and alkynes. In ligand design, we envisioned that chiral unsymmetric NNN-tridentate (UNT) ligand scaffolds could promote these enantioselective transformations with earth-abundant metals. Therefore, several types of chiral UNT ligands were designed and prepared in our laboratory, utilizing readily available natural amino acids as chiral sources. In the very beginning, chiral oxazoline iminopyridine (OIP) ligands were proposed and investigated through the rational combination of nitrogen-containing ligand scaffolds. After a systematic survey of the ligand effects, the imine moiety in the rigid OIP ligands was replaced by a conformationally more flexible amine unit, leading to the construction of reactive oxazoline aminoisopropylpyridine (OAP) ligands. Subsequently, imidazoline iminopyridine (IIP) and thiazoline iminopyridine (TIP) ligands were prepared by altering the oxygen atom of oxazoline with nitrogen and sulfur linkers, respectively. To further expand the chiral ligand library, other tridentate ligands containing a twisted pincer, anionic, and nonrigid backbone were also designed and synthesized, including iminophenyl oxazolinyl phenylamine (IPOPA) and imidazoline phenyl picolinamide (ImPPA). The efficacy of these chiral UNT ligands for asymmetric induction in iron and cobalt catalysis has been demonstrated through asymmetric hydrofunctionalization of alkenes and asymmetric sequential hydrofunctionalization of alkynes, which exhibit excellent reactivity as well as high chemo-, regio-, and stereoselectivity with broad functional group tolerance. Notably, highly regio- and enantioselective hydrofunctionalization of challenging substrates, such as 1,1-disubstituted aryl alkenes and terminal aliphatic alkenes, was also achieved. Furthermore, the development of asymmetric sequential isomerization/hydroboration of internal alkenes and sequential hydrofunctionalization of alkynes further demonstrates the synthetic power of these catalytic systems. The chiral enantioenriched products obtained by these methodologies could be potentially utilized in organic synthesis, medicinal chemistry, and materials science. We believe that our continuous efforts in this field would be beneficial to the development of asymmetric earth-abundant metal catalysis.