Reductive amination without an external hydrogen Source.

Wu X., Neumann H., Beller M.

AbstractPalladium‐catalyzed coupling reactions have become a powerful tool for advanced organic synthesis. This type of reaction is of significant value for the preparation of pharmaceuticals, agrochemicals, as well as advanced materials. Both, academic as well as industrial laboratories continuously investigate new applications of the different methodologies. Clearly, this area constitutes one of the major topics in homogeneous catalysis and organic synthesis. Among the different palladium‐catalyzed coupling reactions, several carbonylations have been developed and widely used in organic syntheses and are even applied in the pharmaceutical industry on ton‐scale. Furthermore, methodologies such as the carbonylative Suzuki and Sonogashira reactions allow for the preparation of interesting building blocks, which can be easily refined further on. Although carbonylative coupling reactions of aryl halides have been well established, palladium‐catalyzed oxidative carbonylation reactions are also interesting. Compared with the reactions of aryl halides, oxidative carbonylation reactions offer an interesting pathway. The oxidative addition step could be potentially avoided in oxidative reactions, but only few reviews exist in this area. In this Minireview, we summarize the recent development in the oxidative carbonylation reactions.

Wu X., Neumann H., Beller M.

Bähn S., Imm S., Neubert L., Zhang M., Neumann H., Beller M.

In this Minireview, the synthesis of amines by the amination of alcohols, by means of the so-called borrowing hydrogen methodology, is presented. Compared to other synthetic methodologies for the synthesis of amines, these transformations are highly attractive because often alcohols are readily available starting materials, some of them on a large scale from renewable sources. In addition, the amination of alcohols produces water as the only by-product, which makes the process potentially environmentally benign. Already today, lower alkyl amines are produced in bulk by the chemical industry with this synthetic method. In particular, the recent progress applying organometallic catalysts based on iridium, ruthenium, and other metals will be discussed. Notable recent achievements include the conversion of challenging substrates such as diols, the development of recyclable catalysts, milder reaction temperatures, and the direct alkylation of ammonia or its equivalents with alcohols.

Wu X., Neumann H., Beller M.

Palladium-catalyzed carbonylative coupling reactions of aromatic halides and related compounds have undergone a rapid development during recent years. Nowadays, a plethora of palladium catalysts are available for the synthesis of ketones, alkynones, chalcones, etc., which are important intermediates in the manufacture of dyes, pharmaceuticals, agrochemicals, and other industrial products. In this critical review, we summarize the development of these carbonylative transformations with carbon nucleophiles (136 references).

Saidi O., Blacker A. ., Farah M., Marsden S., Williams J. .

Saidi O., Blacker A. ., Farah M., Marsden S., Williams J. .

Something borrowed: Amine cross-coupling reactions are catalyzed using [{Cp*IrI2}2] (Cp*=C5Me5) in the absence of a base. A range of anilines were converted into their N-isopropyl derivatives, and the same process was also effective for alkylation of benzylamines and other aliphatic primary amines.

Hamid M.H., Allen C.L., Lamb G.W., Maxwell A.C., Maytum H.C., Watson A.J., Williams J.M.

The alkylation of amines by alcohols has been achieved using 0.5 mol % [Ru(p-cymene)Cl(2)](2) with the bidentate phosphines dppf or DPEphos as the catalyst. Primary amines have been converted into secondary amines, and secondary amines into tertiary amines, including the syntheses of Piribedil, Tripelennamine, and Chlorpheniramine. N-Heterocyclization reactions of primary amines are reported, as well as alkylation reactions of primary sulfonamides. Secondary alcohols require more forcing conditions than primary alcohols but are still effective alkylating agents in the presence of this catalyst.

Hamid M.H., Slatford P., Williams J.M.

Alcohols can be temporarily converted into carbonyl compounds by the metal-catalysed removal of hydrogen. The carbonyl compounds are reactive in a wider range of transformations than the precursor alcohols and can react in situ to give imines, alkenes, and α-functionalised carbonyl compounds. The metal catalyst, which had borrowed the hydrogen, then returns it to the transformed carbonyl compound, leading to an overall process in which alcohols can be converted into amines, compounds containing CC bonds and β-functionalised alcohols.

Ragaini F., Cenini S., Gallo E., Caselli A., Fantauzzi S.

Tararov V.I., Kadyrov R., Riermeier T.H., Dingerdissen U., Börner A.

Kiss G.

PdX2L2/L/HA (A = weakly coordinating anion, L = phosphine) complexes are active catalysts in the hydroesterification of alkenes, alkynes, and conjugated dienes. Shell, the only major corporate player in the field, recently developed two very active catalyst systems tailored to the hydroesterification of either alkenes or alkynes. The hydroesterification of propyne with their Pd(OAc)2/PN/HA (PN = (2-pyridyl)diphenylphosphine, HA = strong acid with weakly coordinating anion, like methanesulfonic acid) catalyst has been declared commercially ready. However, despite the significant progress in the activity of Pd-hydroesterification catalysts, further improvements are warranted. Thus, for example, activity maintenance still seems to be an issue. Homogeneous Pd catalysts are prone to a number of deactivation reactions. Activity and stability promoters are often corrosive and add to the complexity of the system, making it less attractive. Nonetheless, the versatility of the process and its tolerance toward the functional groups of substrates should appeal especially to the makers of specialty products. Although hydroesterification yields esters from alkenes, alkynes, and dienes in fewer steps than hydroformylation does, the latter has some advantages at the current state of the art. (1) Hydroformylation catalysts, particularly some recently published phosphine-modified Rh systems, can achieve very high regioselectivity for the linear product that hydroesterification catalysts cannot match yet. By analogy with hydroformylation, bulkier ligands ought to be tested in hydroesterification to increase normal-ester selectivity. (2) Hydroformylation is proven, commercial. Hydroesterification can only replace it if it can provide significant economic incentives. Similar or just marginally better performance could not justify the cost of development of a new technology. (3) Hydroesterification requires pure CO while hydroformylation uses syngas, a mixture of CO and H2. The latter is typically more available and less expensive (for industrial applications CO is most often separated from syngas). (4) The acid component of the hydroesterification catalyst makes the process corrosive. It would be desirable to develop new hydroesterification catalysts that do not require acid stabilizer/activity booster. Clearly, any new hydroesterification technology will directly compete with the hydroformylation route. This is especially true for olefin feeds, since both processes add one CO to the olefin, yielding oxygenates that can be converted into identical products. For some niche applications, like the production of MMA from propyne, hydroesterification seems to have an advantage as compared to hydroformylation due to the high activity and selectivity of the Pd(OAc)2/(2-pyridyl)diphenylphosphine catalyst. Since hydroesterification is an emerging technology, it is reasonable to assume that the potential for improvement is greater than in the mature hydroformylation. It is therefore possible that hydroesterification will become competitive in the future; thus, continued effort in the field is warranted.

Eller K., Henkes E., Rossbacher R., Höke H.

Abstract The article contains sections titled: 1. Introduction 2. General Chemical Properties 2.1. Salt Formation 2.2. Conversion to Carboxamides 2.3. Conversion to Sulfonamides 2.4. Reaction with Carbonyl Compounds 2.5. Reaction with Carbon Dioxide and Carbon Disulfide 2.6. Reaction with Epoxides 2.7. Alkylation 2.8. Formation of Isocyanates and Ureas 2.9. Reaction with Acrylonitrile 2.10. Formation of Isonitriles 2.11. Oxidation 2.12. Dealkylation 3. General Production Methods 3.1. Production from Alcohols 3.2. Production from Carbonyl Compounds 3.3. Production from Nitriles 3.4. Production from Alkyl Halides 3.5. Production from Nitro Compounds 3.6. Production from Olefins 3.7. Other Processes 4. Lower Alkylamines 4.1. Physical Properties 4.2. Storage and Transportation 4.3. Quality Specifications and Analysis 4.4. Production 4.5. Uses 4.6. Economic Aspects 5. Cycloalkylamines 6. Cyclic Amines 7. Fatty Amines 7.1. Properties 7.2. Production 7.3. Analysis and Quality Control 7.4. Uses 7.5. Economic Aspects 8. Diamines and Polyamines 8.1. Diamines 8.1.1. 1,2‐Diaminoethane (Ethylenediamine) 8.1.2. Diaminopropanes 8.1.3. Higher Diamines 8.2. Oligoamines and Polyamines 8.2.1. Physical Properties 8.2.2. Chemical Properties 8.2.3. Production, Analysis, and Uses 9. Chiral Amines 10. Toxicology and Occupational Health 10.1. General Aspects 10.2. Toxicology of Specific Amines 10.2.1. Alkylamines, Cyclic Amines, and Polyamines 10.2.2. Fatty Amines 11. Acknowledgment

Tafesh A.M., Weiguny J.

Although the use of CO as a reductant had been in the past confined to few reactions, its use in organic synthesis, especially in the reductive carbonylation of nitro aromatics and the oxidative carbonylation of aromatic amines, has increased dramatically. Since the discovery of CO-induced reduction of nitro groups, there has been a wide spread increase of interest in the application and mechanistic understanding of this reaction. In a major review published in 1988 it was noted, that in practice no studies of the mechanism of N-carbonylation of aromatic nitro compounds with alcohols leading to carbamates have been carried out. This review clearly shows a major change since that publication. Indeed, metal-catalyzed reductive carbonylation of nitro aromatics using CO as reducing agent has been in the past 10 years the subject of intense investigation both in academia and in the chemical industry. Several articles and reviews have covered the subject up to the late 1980s. The authors will concentrate on more recent literature, but sometimes older data will be used to establish an understanding of these reactions. 127 refs.

Cornils B., Herrmann W.A., Rasch M.

AbstractOtto Roelen discovered the oxo synthesis (hydroformylation) in 1938, and despite all the problems created by the war years he was able to explore successfully the fundamental aspects related to its application up to the point of building the first plant. At the same time he laid the groundwork for industrial utilization of homogeneous organometallic catalysts. Almost simultaneously, his contemporary, Walter Hieber, was investigating the basic chemistry of the same catalysts, but with no knowledge whatsoever of their potential application. Hydroformylation today constitutes one of the most important industrial examples of a homogeneous catalytic process.For corrigendum see DOI:10.1002/anie.199423481

Cornils B., Herrmann W.A., Rasch M.

Otto Roelen hat 1938 die Oxosynthese (Hydroformylierung) entdeckt, noch wahrend schwieriger Kriegsjahre die Grundzuge des Anwendungsbereiches bis hin zu einer ersten grostechnischen Anlage erarbeitet und damit das Tor zur Nutzung metallorganischer, homogen wirkender Katalysatoren geoffnet. Der gleichaltrige Walter Hieber erforschte fast zeitgleich die chemischen Grundlagen der verwendeten Katalysatoren, ohne von deren Anwendung zu wissen. Die Hydroformylierung zahlt heute zu den bedeutendsten homogenkatalytischen Prozessen der Industrie. Die einmalige Chance einer zielgerichteten Zusammenarbeit von Industrie- und Hochschulchemikern am gleichen Problem einer wichtigen, neuen Synthese wurde damals nicht genutzt, wofur weniger die Zeitumstande als vielmehr Mentalitatsunterschiede zweier schwieriger Charaktere verantwortlich gemacht werden mussen: das alte Problem nicht planbarer Individuen in nicht planbarer Zeit. Eine Reihe von hier erstmals veroffentlichten Zeitdokumenten, vermehrt um die Berichte der Alliierten uber „verborgene Reparationen”, gibt interessante Einblicke in die Art der Entdeckung und den spateren Ablauf der Entwicklung.

Cai Y., Huang H., Tan Z., Yang B., Zhou G., Li Z., Xie S.

González-Rodríguez J., Rudroff F.

Brahmachari G.

Vermeeren B., Van Praet S., Arts W., Narmon T., Zhang Y., Zhou C., Steenackers H.P., Sels B.F.

This review provides a holistic overview of aliphatic amine production, from feedstock to applications. It assesses the feasibility of using biomass as an alternative resource in amine synthesis and their usage in applications of societal importance.

Smirnov I.V., Biriukov K.O., Shvydkiy N.V., Perekalin D.S., Afanasyev O.I., Chusov D.

Mangas-Sánchez J.

Kim W.H., Song S.B., Lee D.E., Goswami P., Chung Y.K., Choi S., Jung W.H., Choi S.U., Ham S., Oh Y., Kim K.H., Huh J., Bae H.Y.

α-Secondary alkyl amines are structural motifs frequently encountered in a wide variety of natural products and pharmaceuticals. The N-benzyloxycarbonyl (Cbz) compound is a widely used precursor, acknowledged for its efficacy in implementing a masked amine strategy to access a privileged moiety. Although reductive amination is conducted as a crucial portion of the pharmaceutical industry, direct catalytic access to alkyl Cbz-amine is still rare due to the low reactivity of carbamate. Here, we show a superacid organocatalyst enabled direct access to bioactive Cbz-protected α-secondary alkyl amines using general ketones as the starting material. Through the highly selective and robust catalytic process, a wide substrate scope including drug precursor scaffolds in preparative scalability (up to >99% yield) with practical pharmaceutical syntheses is achieved. The obtained N-Cbz products are found to possess strong cytotoxicities in in vitro bioactivity evaluations, indicating their potential as promising candidates for new anticancer drug discovery.

Podyacheva E., Balalaeva A.I., Afanasyev O.I., Runikhina S., Chusova O., Kozlov A., Liao S., Chusov D.

Syngas (a mixture of H2 and CO) is a synergistic reducing agent working much better than its components independently. In particular it allows to aminate carbonyl compounds with unstable functional groups furnishing the potential fungicides.

Runikhina S.A., Afanasyev O.I., Kuchuk E.A., Perekalin D.S., Jagadeesh R.V., Beller M., Chusov D.

From waste to value. An efficient and convenient ruthenium-catalyzed reduction of aromatic nitro compounds using converter gas as a reducing agent to produce valuable pharmaceuticals has been developed.

Kim T., Park D.I., Kim S., Yadav D., Hong S., Kim S.H., Yoon H.J., Jin K.

Reductive amination has been widely used for manufacturing carbon-nitrogen-containing building blocks. Despite its versatility, the requirements for a chemical reductant or harmful hydrogen gas have limited its further utilization in...

Kozlov A.S., Afanasyev O.I., Losev M.A., Godovikova M.I., Chusov D.

A representative set of amines and N-heterocycles was applied as additives in the CO-assisted Ru-catalyzed reductive amination of p-anisaldehyde with p-anisidine. Among the tested ligands, pyridine caused a strong activation for low active aliphatic substrates while bidentate heterocyclic ligands possess significant inhibition of catalyst for the majority of substrates.

Ouyang L., Miao R., Yang Z., Luo R.

Our Ir-catalyzed reductive amination of carboxylic acids with amines produces structurally diverse N-alkylated amines in good to excellent yields (up to 60 examples). This protocol is advantageous of mild conditions, convenient operations, and excellent functionality tolerance. The synthetic values are highlighted through the synthesis of two pharmaceutical molecules-Cinacalcet and (R)-Fendiline.

Li X., Hu Y., Alenad A.A., Zhou B., Ma Z., Gao J., Rajenahally J., Beller M.

A mild and convenient reductive amination protocol for the synthesis of structurally diverse secondary and tertiary amines as well as N-methylated products under metal-free conditions is presented.

Kliuev F., Kuznetsov A., Afanasyev O.I., Runikhina S.A., Kuchuk E., Podyacheva E., Tsygankov A.A., Chusov D.

NaH2PO2 was found to promote reductive amination. Being nontoxic, stable, environmentally benign, and available in bulk amounts, this reducing agent showed a powerful potential to compete with classical reductants applied in the target process. An E factor of 1 was achieved for the substrate scope. Different carbonyl compounds reacted with amines under the developed conditions. The reaction demonstrated a great compatibility with a wide range of functional groups. Reaction conditions were scaled up to 200-fold.

Nandhu C.T., Aneeja T., Anilkumar G.

• This review discusses the recent developments in the rhodium-catalyzed reductive amination reactions. • Use of various rhodium sources. • Development of reusable and recyclable rhodium sources for reductive amination reactions. • Emphasis on both synthesis and mechanism. Rhodium catalyzed reductive amination has gained much attention in recent times. Nowadays, rhodium complexes are employed as catalysts in various reactions due to their high reaction efficiency and good regio- stereo- and enantioselectivity. This review summarizes the recent advances in rhodium-catalyzed reductive amination covering literature up to 2021. .