Improved Ruthenium‐Catalyzed Amination of Alcohols with Ammonia: Synthesis of Diamines and Amino Esters

Imm, Sebastian; Bähn, Sebastian; Zhang, Min; Neubert, Lorenz; Neumann, Helfried; Klasovsky, Florian; Pfeffer, Jan; Haas, Thomas; Beller, Matthias

doi:10.1002/anie.201103199

Cited by 222 publications

(107 citation statements)

References 60 publications

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“…hydride) liberated in the first step -the oxidation of the alcohol to the ketone -are directly consumed in the second interconnected step -reductive amination of the ketone. A number of chemo-catalytic hydrogen-borrowing methods have recently been developed using ruthenium as well as iridium catalysts (11,12). Nevertheless, the required reaction conditions (e.g.…”

mentioning

confidence: 99%

Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades

Mutti

Knaus

Scrutton

et al. 2015

Science

373

277

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Abstractα-Chiral amines are key intermediates for the synthesis of a plethora of chemical compounds on industrial scale. Here we present a biocatalytic hydrogen-borrowing amination of primary and secondary alcohols that allows for the efficient and environmentally benign production of enantiopure amines. The method relies on the combination of an alcohol dehydrogenase (ADHs from Aromatoleum sp., Lactobacillus sp. and Bacillus sp.) enzyme operating in tandem with an amine dehydrogenase (AmDHs engineered from Bacillus sp.) to aminate a structurally diverse range of aromatic and aliphatic alcohols (up to 96% conversion and 99% enantiomeric excess). Furthermore, primary alcohols are aminated with high conversion (up to 99%). This redox selfsufficient network possesses high atom efficiency, sourcing nitrogen from ammonium and generating water as the sole by-product.Amines are amongst the most frequently used chemical intermediates for the production of APIs (active pharmaceutical ingredients), fine chemicals, agrochemicals, polymers, dyestuffs, pigments, emulsifiers and plasticizing agents (1). However, the requisite amines are scarce in nature and their industrial production mainly relies upon the metal-catalysed hydrogenation of enamides (i.e. obtained from related ketone precursors), a process requiring transition metal complexes, which are expensive and increasingly unsustainable (2). Moreover, the asymmetric synthesis of amines from ketone precursors requires protection and deprotection steps that generate copious amounts of waste. As a consequence, various chemical processes for the direct conversion of alcohols into amines have been developed during the last decade. The intrinsic advantage of the direct amination of an Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts alcohol is that the reagent and the product are in the same oxidation state and therefore, theoretically, additional redox equivalents are not required.However, many of these methods have low efficiency and high environmental impact (e.g. Mitsunobu reaction) (3). The amination of simple alcohols such as methanol and ethanol, via heterogeneous catalysis, requires harsh conditions (>200 °C) and more structurally diverse alcohols are either converted with extremely low chemoselectivity or not converted at all (4). Furthermore, most of the work in this field involves non-chiral substrates whereas 40% of the commercial optically active drugs are chiral amines (2). Increasingly, biocatalytic methods are applied for the production of optically active amines, e.g. the lipase catalysed resolution of racemic mixtures of amines or the ω-transaminase process with a most recent example employing an engineered enzyme applied to the industrial manufacture of the diabetes medication Januvia® (sitagliptin) (5,6,7).Multi-step chemical reactions in one pot avoid the need for isolation of intermediates and purification steps. This approach leads to economic as well as environmental benefits since time-consuming intermediate work-ups are not...

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mentioning

confidence: 99%

Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades

Mutti

Knaus

Scrutton

et al. 2015

Science

373

277

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“…Nevertheless, a couple of issues need to be addressed in order to improve the yield of the diamine end products and to make the enzymatic reaction competitive with chemical synthesis routes [47].…”

Section: Hplc Analysis After Fmoc Derivatization Of the Amine Reactiomentioning

confidence: 99%

Engineering of alanine dehydrogenase from Bacillus subtilis for novel cofactor specificity

Lerchner

Jarasch

Skerra

2015

Biotech and App Biochem

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The l-alanine dehydrogenase of Bacillus subtilis (BasAlaDH), which is strictly dependent on NADH as redox cofactor, efficiently catalyzes the reductive amination of pyruvate to l-alanine using ammonia as amino group donor. To enable application of BasAlaDH as regenerating enzyme in coupled reactions with NADPH-dependent alcohol dehydrogenases, we alterated its cofactor specificity from NADH to NADPH via protein engineering. By introducing two amino acid exchanges, D196A and L197R, high catalytic efficiency for NADPH was achieved, with k /K = 54.1 µM Min (K = 32 ± 3 µM; k = 1,730 ± 39 Min ), almost the same as the wild-type enzyme for NADH (k /K = 59.9 µM Min ; K = 14 ± 2 µM; k = 838 ± 21 Min ). Conversely, recognition of NADH was much diminished in the mutated enzyme (k /K = 3 µM Min ). BasAlaDH(D196A/L197R) was applied in a coupled oxidation/transamination reaction of the chiral dicyclic dialcohol isosorbide to its diamines, catalyzed by Ralstonia sp. alcohol dehydrogenase and Paracoccus denitrificans ω-aminotransferase, thus allowing recycling of the two cosubstrates NADP and l-Ala. An excellent cofactor regeneration with recycling factors of 33 for NADP and 13 for l-Ala was observed with the engineered BasAlaDH in a small-scale biocatalysis experiment. This opens a biocatalytic route to novel building blocks for industrial high-performance polymers.

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“…Based on previous studies by our group, [10] we initially used [Ru 3 (CO) 12 ]asthe catalyst in combination with different phosphines.O nly traces of the desired product were observed under ligand-free conditions,w hereas the use of different mono-and bidentate phosphines afforded 4-phenyloxazolidin-2-one (3a)s electively in moderate yields (20-52 %). Based on these first results,weperformed am ore detailed optimization of the best ligand system (dppf = 1,1'-bis(diphenylphosphino)ferrocene).…”

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confidence: 99%

(Enantio)selective Hydrogen Autotransfer: Ruthenium‐Catalyzed Synthesis of Oxazolidin‐2‐ones from Urea and Diols

2016

Self Cite

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An ovel strategy for the synthesis of oxazolidin-2-ones from vicinal diols and urea is described. In this heterocycle synthesis,t wo different CÀOa nd CÀNb onds are sequentially formed in ad omino process consisting of nucleophilic substitution and alcohol amination. The use of readily available starting materials and the good atom economy render this process environmentally benign. While this transformation is already highly chemo-and regioselective, we also developed the first asymmetric version of this method using (R)-(+ +)-MeO-BIPHEP as the chiral ligand.

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Improved Ruthenium‐Catalyzed Amination of Alcohols with Ammonia: Synthesis of Diamines and Amino Esters

Cited by 222 publications

References 60 publications

Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades

Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades

Engineering of alanine dehydrogenase from Bacillus subtilis for novel cofactor specificity

(Enantio)selective Hydrogen Autotransfer: Ruthenium‐Catalyzed Synthesis of Oxazolidin‐2‐ones from Urea and Diols

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