Selective Synthesis of Unnatural α‐, β‐ and γ‐Amino Esters

Nugent, Thomas C.; Ghosh, Abhijit

doi:10.1002/ejoc.200700345

Cited by 10 publications

(6 citation statements)

References 51 publications

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“…Two years later, Nugent and co-worker performed the reductive amination of α-, β-, and γ-keto esters with (R)-or (S)-α-methylbenzylamine to unnatural diastereomeric amino esters in good to high de's (72−94%) and moderate to good yields (25−74%) (Scheme 176B). 317 The reactions are optimally performed in the presence of AcOH, while the γketo ester requires [Ti(O i Pr) 4 ]. The Raney Ni catalyst loading had no influence on the diastereoselectivity of the products.…”

Section: Ptmentioning

confidence: 99%

Transition-Metal-Catalyzed Reductive Amination Employing Hydrogen

2020

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The reductive amination, the reaction of an aldehyde or a ketone with ammonia or an amine in the presence of a reducing agent and often a catalyst, is an important amine synthesis and has been intensively investigated in academia and industry for a century. Besides aldehydes, ketones, or amines, starting materials have been used that can be converted into an aldehyde or ketone (for instance, carboxylic acids or organic carbonate or nitriles) or into an amine (for instance, a nitro compound) in the presence of the same reducing agent and catalyst. Mechanistically, the reaction starts with a condensation step during which the carbonyl compound reacts with ammonia or an amine, forming the corresponding imine followed by the reduction of the imine to the alkyl amine product. Many of these reduction steps require the presence of a catalyst to activate the reducing agent. The reductive amination is impressive with regard to the product scope since primary, secondary, and tertiary alkyl amines are accessible and hydrogen is the most attractive reducing agent, especially if large-scale product formation is an issue, since hydrogen is inexpensive and abundantly available. Alkyl amines are intensively produced and use fine and bulk chemicals. They are key functional groups in many pharmaceuticals, agro chemicals, or materials. In this review, we summarize the work published on reductive amination employing hydrogen as the reducing agent. No comprehensive review focusing on this subject has been published since 1948, albeit many interesting summaries dealing with one or the other aspect of reductive amination have appeared. Impressive progress in using catalysts based on earth-abundant metals, especially nanostructured heterogeneous catalysts, has been made during the early development of the field and in recent years.

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Section: Ptmentioning

confidence: 99%

Transition-Metal-Catalyzed Reductive Amination Employing Hydrogen

2020

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“…We previously reported the asymmetric reductive amination of all precursor ketones 1a–e in the presence of Ti(OiPr) 4 , Raney-Ni and hydrogen (8.3 bar, 120 psi) at room temperature in a variety of aprotic solvents [54,58–59]. For the current study we isolated the corresponding imines, as noted above, and reduced them under similar reaction conditions (Scheme 2).…”

Section: Resultsmentioning

confidence: 88%

“…Of further advantage, we were familiar with the phenomenon (mediocre cis / trans N -chiral imine ratios yielding good to excellent amine product diastereomeric ratios) from our previous work with ( R )- or ( S )-PEA-based reductive amination with hydrogen [54,58–60]. …”

Section: Resultsmentioning

confidence: 99%

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

Nugent¹,

Williams²,

Dragan³

et al. 2013

Beilstein J. Org. Chem.

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SummaryThe default explanation for good to high diastereomeric excess when reducing N-chiral imines possessing only mediocre cis/trans-imine ratios (>15% cis-imine) has invariably been in situ cis-to-trans isomerization before reduction; but until now no study unequivocally supported this conclusion. The present study co-examines an alternative hypothesis, namely that some classes of cis-imines may hold conformations that erode the inherent facial bias of the chiral auxiliary, providing more of the trans-imine reduction product than would otherwise be expected. The ensuing experimental and computational (DFT) results favor the former, pre-existing, explanation.

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“…The same group synthesized unnatural amino esters through the ARA of α-, β-, and γ-keto esters with ( R )- or ( S )-α-methylbenzylamine (Scheme ). The reactions for α-, β-keto esters are optimally conducted in the presence of AcOH, whereas the γ-keto ester requires [Ti(O i Pr) 4 ]. The Raney Ni loading does not affect the diastereoselectivity of the products.…”

Section: Intermolecular Aramentioning

confidence: 99%

Recent Progress in Transition-Metal-Catalyzed Asymmetric Reductive Amination

et al. 2021

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Asymmetric reductive amination (ARA) of a prochiral carbonyl compound with an amine using a H2/hydrogen surrogate is a concise and operationally simple method for the synthesis of chiral amines. ARA proceeds via condensation of a carbonyl group with an amine/ammonia followed by the enantioselective reduction of the generated intermediate. The activation of reductant and stereoselective transfer of hydrogen to intermediate imine/enamine is often mediated by a chiral transition metal catalyst. Considering the wide applications of enantiopure amines in pharmaceuticals, agrochemicals, and materials, the development of effective catalysts for ARA has been intensively pursued in the last two decades. Since the first report by Blaser in 1999, this key research area has grown significantly in recent years, as reflected by the advances in catalyst design, diversifying substrate scope and better mechanistic understanding. Several highly efficient and general ARA methodologies applicable to challenging carbonyl and amine partners have been demonstrated, providing ready access to a variety of enantiopure amines. In this Review, we present the recent progress in ARA featuring diverse carbonyl and amine partners employing transition metal-catalysts. This Review provides an organized and critical discussion on catalyst engineering and evolution, expanding susbstrate scope and mechanistic insights. To conclude, the remaining challenges and opportunities in ARA are also highlighted.

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Selective Synthesis of Unnatural α‐, β‐ and γ‐Amino Esters

Cited by 10 publications

References 51 publications

Transition-Metal-Catalyzed Reductive Amination Employing Hydrogen

Transition-Metal-Catalyzed Reductive Amination Employing Hydrogen

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

Recent Progress in Transition-Metal-Catalyzed Asymmetric Reductive Amination

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