Cross-dehydrogenative N-N couplings

Abstract

The relatively high electronegativity of nitrogen makes N-N bond forming cross-coupling reactions particularly difficult, especially in an intermolecular fashion. The challenge increases even further when considering the case of dehydrogenative N-N coupling reactions, which are advantageous in terms of step and atom economy, but introduce the problem of the oxidant in order to become thermodynamically feasible. Indeed, the oxidizing system must be designed to activate the target N-H bonds, while at the same time avoid undesired N-N homocoupling as well as C-N and C-C coupled side products. Thus, preciously few intermolecular hetero N-N cross-dehydrogenative couplings exist, in spite of the central importance of N-N bonds in organic chemistry. This review aims at analyzing these few rare cases and provides a perspective for future developments.

Scheme 1. Examples of compounds potentially accessible by intermolecular N–N bond formation.

Scheme 2. The N–N cross-dehydrogenative coupling approach.

Scheme 3. Seminal work concerning the oxidation of secondary amines and decisive impact of the oxidizing method.

Scheme 4. Cu-mediated N–N dehydrogenative coupling of secondary amines.

Scheme 5. Cu-catalyzed N–N dehydrogenative coupling of secondary amines.

Scheme 6. Formation of di- and tetra-phenylhydrazines.

Scheme 7. Iron-catalyzed oxidative N–N homocoupling of diarylamines.

Scheme 8. Oxidative homocoupling reaction of secondary amines using rare-earth-metals.

Scheme 9. Synthesis of 9,9′-bicarbazoles with KMnO₄ as the oxidant.

Scheme 10. I₂/KI-mediated dehydrogenative N–N bond formation.

Scheme 11. KI/KIO₄-mediated dehydrogenative N–N bond formation.

Scheme 12. Electrochemical dehydrogenative N–N dimerization of carbazoles and carbolines, route to the total synthesis of dixiamycin B.

Scheme 13. Other electrochemical synthesis of tetrasubstituted hydrazines by dehydrogenative N–N bond formation.

Scheme 14. Dehydrogenative anodic oxidation of anilides for N–N bond formation.

Scheme 15. Electrochemical dehydrogenative N–N bond formation of N-aryl aminopyridines.

Scheme 16. Proposed mechanism of the electrochemical oxidative N–N bond formation of N-aryl aminopyridines.

Scheme 17. Cu-catalyzed dehydrogenative hetero N–N bond formation.

Scheme 18. Origin of the N1–N2 hetero-coupling product and proposed oxidative mechanism.

Scheme 19. Metal-free dehydrogenative hetero N–N cross-coupling reactions.

Scheme 20. Electrochemical oxidative hetero N–N coupling reaction.

Scheme 21. Heterodehydrogenative N–N coupling of amides and benzotriazoles.

Scheme 22. Towards atroposelective/enantioselective N–N bond formation.