Copper Hydride Catalyzed Hydroamination of Alkenes and Alkynes

Abstract

Over the past few years, CuH-catalyzed hydroamination has been discovered and developed as a robust and conceptually novel approach for the synthesis of enantioenriched secondary and tertiary amines. The success in this area of research was made possible through the large body of precedent in copper(I) hydride catalysis and the well-explored use of hydroxylamine esters as electrophilic amine sources in related copper-catalyzed processes. This mini-review details the background, advances, and mechanistic investigations in CuH-catalyzed hydroamination.

Copper-catalyzed asymmetric addition of olefin-derived nucleophiles to ketones

“…By employing a class of electrophilic aminating reagents established by Johnson (17) to intercept these organometallic intermediates, our laboratory (18) and Miura and Hirano (19–21) have independently developed a CuH-catalyzed approach for the enantioselective hydroamination of olefins (22). Based on these studies and notable contributions from other groups in the area of copper-catalyzed enantioselective reductive aldol reactions (6,7, 23–26), we envisioned the development of CuH chemistry as a general platform for the use of simple olefins as latent carbon nucleophiles in carbonyl addition (Fig.…”

Copper-Catalyzed Enantioselective Addition of Styrene-Derived Nucleophiles to Imines Enabled by Ligand-Controlled Chemoselective Hydrocupration

“…In 2013, our group initiated a research program aimed at developing copper(I) hydride catalysis 9,10 as a general platform for accessing enantiomerically enriched organocopper intermediates from easily available olefin precursors. By capturing the catalytically generated organocopper species with electrophilic aminating reagents, our laboratory 10 and Hirano and Miura 11 have independently developed a new approach for the enantioselective hydroamination of olefins.…”

“…By capturing the catalytically generated organocopper species with electrophilic aminating reagents, our laboratory 10 and Hirano and Miura 11 have independently developed a new approach for the enantioselective hydroamination of olefins. More recently, we have also demonstrated the feasibility of engaging organocopper intermediates in carbon–carbon bond-forming processes.…”

“…12a In contrast, the use of other ligands led to the formation of a significant amount of reduction product 4 . For example, our optimal catalyst for hydroamination, based on DTBM-SEGPHOS (L1), 10 provided only 9% product 3 and 85% reduced amine 4 . In addition, bulky phenyl substituents on the phospholane moiety of the BPE ligand proved essential not only for achieving high levels of enantioselectivity but also for enabling the desired chemoselectivity (entries 4–6).…”

Copper-Catalyzed Enantioselective Hydroamination of Alkenes

“…Additional limitations of copper–hydride-catalyzed hydroamination, along with many more successful examples, are described in a recent mini-review. 12 …”