A Simple Conversion of Alcohols into Amines

Fabiano, Emmanuel; Golding, Bernard T.; Sadeghi, Morteza

doi:10.1055/s-1987-27887

Cited by 100 publications

(57 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Mutti

Knaus

Scrutton

et al. 2015

Science

358

277

View full text Add to dashboard Cite

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...

show abstract

mentioning

confidence: 99%

“…The reaction was tested at various concentrations of ammonium ions in order to ascertain the impact on the conversion. Under the following reaction conditions [(S)-1a = 20 mM, NAD + 1 mM and NH 4 + /NH 3 2 M], the conversion of alcohol to amine reached 85% after 24…”

mentioning

confidence: 99%

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

Mutti

Knaus

Scrutton

et al. 2015

Science

358

277

View full text Add to dashboard Cite

show abstract

“…[5] Few classical methods are known for the stepwise, one-pot conversion of alcohols into primary amines. [6][7][8][9] An attractive method for the preparation of secondary and tertiary linear amines by hydroaminomethylation of internal olefins was reported. [10] Amines are also prepared by the reduction of amides, generally under harsh conditions to result in a mixture of products.…”

mentioning

confidence: 99%

Selective Synthesis of Primary Amines Directly from Alcohols and Ammonia

2008

View full text Add to dashboard Cite

show abstract

“…As a first approach, we used diol cis-1 as starting material. [12] Different conditions such as Mitsunobu reaction or alcohol activation through O-tosylation were tried, but unfortunately these protocols did not work out. Hence, we employed a slightly modified method proposed by Delcros and co-workers, [13] starting from commercially accessible cis-1,4-dichlorobut-2-ene (cis-4, Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

But‐2‐ene‐1,4‐diamine and But‐2‐ene‐1,4‐diol as Donors for Thermodynamically Favored Transaminase‐ and Alcohol Dehydrogenase‐Catalyzed Processes

et al. 2016

View full text Add to dashboard Cite

Abstract. cis-and trans-But-2-ene-1,4-diamine have been prepared and efficiently applied as sacrificial cosubstrates in enzymatic transamination reactions. The best results were obtained with the cis-diamine. The thermodynamic equilibrium of the stereoselective transamination process is shifted to the amine formation due to tautomerization of 5H-pyrrole into 1H-pyrrole, achieving high conversions (78-99%) and enantiomeric excess (up to >99%) by using a small excess of the amine donor. Furthermore, when the reaction proceeded, a strong coloration was observed due to polymerization of 1H-pyrrole.A structurally related compound, cis-but-2-ene-1,4-diol, has been utilized as cosubstrate in different alcohol dehydrogenase (ADH)-mediated bioreductions. In this case high conversions (91-99%) were observed due to a lactonization process. Both strategies are convenient from both synthetic and atom economy points of view in the production of valuable optically active products.

show abstract

A Simple Conversion of Alcohols into Amines

Cited by 100 publications

References 0 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

Selective Synthesis of Primary Amines Directly from Alcohols and Ammonia

But‐2‐ene‐1,4‐diamine and But‐2‐ene‐1,4‐diol as Donors for Thermodynamically Favored Transaminase‐ and Alcohol Dehydrogenase‐Catalyzed Processes

Contact Info

Product

Resources

About