Hydrogen-free reductive amination using iron pentacarbonyl as a reducing agent

We developed solvent-free reductive amination without an external hydrogen source using iron pentacarbonyl as a reducing agent. Neither a catalyst nor any other additives were employed. Various types of substrates are suitable for the reaction, including those with low reactivity, e.g. benzophenone. Among others, the protocol tolerates bromo-, cyano-, benzyloxy-, pyrimidyl and styryl moieties. © 2017 The Royal Society of Chemistry

Hydrogen-free reductive amination using iron pentacarbonyl as a reducing agent

We developed solvent-free reductive amination without an external hydrogen source using iron pentacarbonyl as a reducing agent. Neither a catalyst nor any other additives were employed. Various types of substrates are suitable for the reaction, including those with low reactivity, e.g. benzophenone. Among others, the protocol tolerates bromo-, cyano-, benzyloxy-, pyrimidyl and styryl moieties. © 2017 The Royal Society of Chemistry

Dichotomy of reductive addition of amines to cyclopropyl ketones vs pyrrolidine synthesis

An interesting catalytic dichotomy was discovered: switching between simple ligand-free catalysts leads to fundamentally different outcomes of reductive reaction between amines and α-carbonylcyclopropanes. Whereas a rhodium catalyst leads to the traditional reductive amination product, ruthenium catalysis enables a novel reaction of pyrrolidine synthesis via ring expansion. The protocols do not require an external hydrogen source and employ carbon monoxide as a deoxygenative agent. The developed methodologies are perfectly compatible with a number of synthetically important functionalities such as ester, carboxyl, bromo, and Cbz moieties. © 2016 American Chemical Society

Dichotomy of reductive addition of amines to cyclopropyl ketones vs pyrrolidine synthesis

An interesting catalytic dichotomy was discovered: switching between simple ligand-free catalysts leads to fundamentally different outcomes of reductive reaction between amines and α-carbonylcyclopropanes. Whereas a rhodium catalyst leads to the traditional reductive amination product, ruthenium catalysis enables a novel reaction of pyrrolidine synthesis via ring expansion. The protocols do not require an external hydrogen source and employ carbon monoxide as a deoxygenative agent. The developed methodologies are perfectly compatible with a number of synthetically important functionalities such as ester, carboxyl, bromo, and Cbz moieties. © 2016 American Chemical Society

Reductive Amination in the Synthesis of Pharmaceuticals

Reductive amination plays a paramount role in pharmaceutical and medicinal chemistry owing to its synthetic merits and the ubiquitous presence of amines among biologically active compounds. It is one of the key approaches to C-N bond construction due to its operational easiness and a wide toolbox of protocols. Recent studies show that at least a quarter of C-N bond-forming reactions in the pharmaceutical industry are performed via reductive amination. This Review concisely compiles information on 71 medical substances that are synthesized by reductive amination. Compounds are grouped according to the principle of action, which includes drugs affecting the central nervous system, drugs affecting the cardiovascular system, anticancer drugs, antibiotics, antiviral and antifungal medicines, drugs affecting the urinary system, drugs affecting the respiratory system, antidiabetic medications, drugs affecting the gastrointestinal tract, and drugs regulating metabolic processes. A general synthetic scheme is provided for each compound, and the description is focused on reductive amination steps. The green chemistry metric of reaction mass efficiency was calculated for all reactions. © 2019 American Chemical Society

Ruthenium-Catalyzed Reductive Amidation without an External Hydrogen Source

A catalytic reaction between aldehydes and primary amides that leads to N-alkylated amides was investigated. The developed protocol employs carbon monoxide as a deoxygenative agent and, therefore, avoids the use of an external hydrogen source. Cyclopentadienyl ruthenium complexes provided excellent catalytic efficiency and could be used with loadings as low as 0.5–1 mol-%. A representative number of secondary amides were successfully prepared in yields of 70–84 %. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Ruthenium-Catalyzed Reductive Amidation without an External Hydrogen Source

A catalytic reaction between aldehydes and primary amides that leads to N-alkylated amides was investigated. The developed protocol employs carbon monoxide as a deoxygenative agent and, therefore, avoids the use of an external hydrogen source. Cyclopentadienyl ruthenium complexes provided excellent catalytic efficiency and could be used with loadings as low as 0.5–1 mol-%. A representative number of secondary amides were successfully prepared in yields of 70–84 %. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Indenyl rhodium complexes. Synthesis and catalytic activity in reductive amination using carbon monoxide as a reducing agent

Indenyl-ligated rhodium(III) catalyst [(η5-indenyl)RhX2]n (1) is reported for the synthesis of alkylated amines via catalytic reductive amination using carbon monoxide as a reducing agent. Water as a solvent was found to be the best media for the reaction. Complex 1 was synthesized via a high-yielding procedure based on the reaction of bis(ethylene) derivative (η5-indenyl)Rh(C2H4)2 with iodine. © 2017 Elsevier B.V

Indenyl rhodium complexes. Synthesis and catalytic activity in reductive amination using carbon monoxide as a reducing agent

Indenyl-ligated rhodium(III) catalyst [(η5-indenyl)RhX2]n (1) is reported for the synthesis of alkylated amines via catalytic reductive amination using carbon monoxide as a reducing agent. Water as a solvent was found to be the best media for the reaction. Complex 1 was synthesized via a high-yielding procedure based on the reaction of bis(ethylene) derivative (η5-indenyl)Rh(C2H4)2 with iodine. © 2017 Elsevier B.V

Reductive amination catalyzed by iridium complexes using carbon monoxide as a reducing agent

Development of novel, sustainable catalytic methodologies to provide access to amines represents a goal of fundamental importance. Herein we describe a systematic study for the construction of a variety of amines catalyzed by a well-defined homogeneous iridium complex using carbon monoxide as a reducing agent. The methodology was shown to be compatible with functional groups prone to reduction by hydrogen or complex hydrides. © The Royal Society of Chemistry 2017