New Strategies for the Transition-Metal Catalyzed Synthesis of Aliphatic Amines

Abstract

Transition-metal catalyzed reactions that are able to construct complex aliphatic amines from simple, readily available feedstocks have become a cornerstone of modern synthetic organic chemistry. In light of the ever-increasing importance of aliphatic amines across the range of chemical sciences, this review aims to provide a concise overview of modern transition-metal catalyzed approaches to alkylamine synthesis and their functionalization. Selected examples of amine bond forming reactions include: (a) hydroamination and hydroaminoalkylation, (b) transition-metal catalyzed C­(sp3)–H functionalization, and (c) transition-metal catalyzed visible-light-mediated light photoredox catalysis.

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

“…Significantly, the formation of the key conjugated N -acyliminium intermediate using these photoredox conditions can be seen as complementary to the well-developed electrophilic activation modes of allenamides. We are currently examining the full mechanism of this transformation, expanding the scope of substrates that can be used in the radical addition step, and alternative fates for the α- N -acyl radical 13 [ 58 – 60 ].…”

Site‐Selective C(sp3)−H and C(sp2)−H Functionalization of Amines Using a Directing‐Group‐Guided Strategy

“…γ-CÀ H activation is one of the most explored DG assisted functionalizations of amines. [30] This is due to the ease of forming five membered metallocycles using coordination to the nitrogen, especially if it is first converted into an amide or imine. Both sp 2 and sp 3 carbon centers have been used for the functionalization but special attention has been given to C(sp 3 )À H bonds due to its increased challenge, as well as their presence in numerous complex moieties and biologically active molecules.…”

“…[20,[27][28][29] Though conceptually interesting, CÀ H activation strategies for aliphatic and aromatic amines are challenging because of their nature to easily get oxidized in the presence of transition metals. [30] On top of that 1°, 2°, and 3°amines make the process even more demanding due to the difference in their reactivity. Apart from the nitrogen coordination to the metal and forming Buchwald type inactive moieties, site-selective CÀ H activation is also a major problem that determines the outcome of the protocol (Figure 2).…”

The Hydrogenation Problem in Cobalt‐based Catalytic Hydroaminomethylation

“…One of the first reports of the HAM reaction was described in 1950, in which ethene, ammonia, CO, and H 2 in the presence of a large amount of metallic cobalt were converted into primary and secondary propylamines under very harsh conditions (170-262°C, 470-755 atmospheres). [1] Since then, the HAM reaction has been studied extensively using rhodium- [2][3][4][5][6][7] and ruthenium-based homogeneous catalysts. [2,[8][9][10][11][12][13][14][15] In general, rhodium and ruthenium form poor isomerization catalysts, and in most cases a terminal alkene is used as substrate to form the linear N-alkylated amine.…”

“…[1] Since then, the HAM reaction has been studied extensively using rhodium- [2][3][4][5][6][7] and ruthenium-based homogeneous catalysts. [2,[8][9][10][11][12][13][14][15] In general, rhodium and ruthenium form poor isomerization catalysts, and in most cases a terminal alkene is used as substrate to form the linear N-alkylated amine. [6][7][8][9][10][11][12][13][14][15] A secondary amine is used in these HAM reactions to prevent overalkylation of the amine.…”