Recent developments in enantio- and diastereoselective hydrogenation of N-heteroaromatic compounds

Abstract

The enantioselective and diastereoselective hydrogenation of N-heteroaromatic compounds is an efficient strategy to access chirally enriched cyclic heterocycles, which often possess highly bio-active properties. This strategy, however, has only been...

A recyclable rhodium catalyst anchored onto a bipyridine covalent triazine framework for transfer hydrogenation of N-heteroarenes in water

“…Although catalytic hydrogenation with molecular hydrogen gas is a very atom-efficient strategy, high pressures and temperatures are generally required to break the aromaticity in the substrates. [11][12][13] Hence, specialized reaction equip-ment and safety procedures must be in place for handling and storing of the highly flammable hydrogen gas. As an alternative, catalytic transfer hydrogenation with H 2 -surrogates, such as isopropanol or formic acid, offers a mild yet powerful method due to its operational simplicity and the widespread availability of suitable reducing agents.…”

Translating Planar Heterocycles into Three‐Dimensional Analogs by Photoinduced Hydrocarboxylation**

“…[6][7][8] Indeed, heteroarene hydrogenation reactions are regularly employed to deliver medicinallyrelevant saturated or partially-saturated heterocyclic motifs from widely available heteroaromatic starting materials. [9][10][11] In principle, heteroarene hydrofunctionalization constitutes a deceptively simple class of complementary dearomatization reactions (Figure 1A). These transformations disrupt planarity while also installing a new molecular vector.…”

“…We suspect this sharp sensitivity to the nitrogen protecting group may be a consequence of the highly polarized CO 2 *À nucleophile. However, the reaction is otherwise insensitive to indole electronics; substrates decorated with a variety of electron-donating and electronwithdrawing groups each underwent the desired transformation in high yields (5)(6)(7)(8)(9)(10)(11). These studies also revealed that dearomative hydrocarboxylation is favored over undesired side reactions at diverse medicinally relevant but potentially sensitive functional groups, such as carbamates (4, 11), aryl fluorides (5), thioethers (7), amides (9, 20), amines (10)(11), and pyridines (12-16, 18, 19).…”

“…Dearomatization reactions unlock an approach to directly convert these synthetically accessible planar scaffolds into more C(sp 3 )‐rich congeners [6–8] . Indeed, heteroarene hydrogenation reactions are regularly employed to deliver medicinally‐relevant saturated or partially‐saturated heterocyclic motifs from widely available heteroaromatic starting materials [9–11] . In principle, heteroarene hydrofunctionalization constitutes a deceptively simple class of complementary dearomatization reactions (Figure 1A).…”

Solvent-free mechanochemical grinding facilitates clean synthesis of N-substituted amines

“…25,26 In the list of FDA-approved pharmaceuticals, piperazine is the third most prevalent saturated N-heterocycle. 27 On this point, we executed and optimized solvent-free mechanochemical procedures for obtaining a library of N-substituted amines under milder reaction conditions in a short reaction time with excellent yields without any further purification. The optimized protocol was also well demonstrated for other heteroaromatic compounds.…”