Abstract
This account summarizes our recent results on the direct carbon-hydrogen
bond functionalization of heterocyclic compounds, including arylation,
alkenylation, alkynylation, alkylation, and amination. In the arylation
and alkenylation reactions, we mainly focus on the potential of
less-expensive first transition elements and demonstrate the good
activities of copper and nickel catalysts which are similar to those
of conventional palladium ones. The catalytic systems based on copper
or nickel also enable direct alkynylation with simple terminal alkynes,
as well as with alkynyl halides. On the other hand, a new application
of palladium catalysts in the relatively difficult direct alkylation
is shown. In addition to the development of catalysts, we introduce
chloramines as new, efficient electrophilic amination reagents for
heteroaromatic carbon-hydrogen bonds; these compounds allow
the concise synthesis of amino-substituted azoles that are of great
interest in pharmaceutical and medicinal chemistry.
1 Introduction
2 Direct Arylation and Alkenylation
2.1 Copper-Mediated Arylation with Aryl Iodides
2.2 Nickel-Catalyzed Arylation with Aryl Bromides
2.3 Nickel-Catalyzed Arylation and Alkenylation with Organosilanes
and Organoboron Compounds
3 Direct Alkynylation
3.1 Nickel- and Copper-Catalyzed Alkynylation with Alkynyl Bromides
3.2 Nickel- and Copper-Catalyzed Alkynylation with Terminal Alkynes
4 Direct Alkylation
4.1 Palladium-Catalyzed Benzylation with Benzyl Carbonates
4.2 Palladium- and Nickel-Catalyzed Alkylation with Unactivated
Alkyl Bromides and Chlorides
5 Direct Amination
5.1 Copper-Catalyzed Direct Amination with Chloramines
6 Summary and Outlook
Key words
carbon-hydrogen bond functionalization - copper - heterocycles - nickel - palladium
