Selective assembly of saturated aza-heterocycles from β-functionally substituted enoates

Zubkov, Ilya N.; Romanov, Alexey R.; Ushakov, Igor А.; Rulev, Alexander Yu.

doi:10.1016/j.tet.2019.130884

Cited by 7 publications

(10 citation statements)

References 15 publications

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“…An analogous regioselectivity was observed when acrylic acid derivatives bearing a carbonyl group at the β ‐position were treated with primary or secondary amines [17–19] . On the contrary, only β ‐amino acid derivatives were formed in the reactions of amines or N,N‐ and N,O‐binucleophiles with β ‐trifluorocrotonic acid derivatives [20–22] . Finally, the aza‐Michael addition of some primary amines and azoles to unsymmetrical fumaric esters led to the formation of the regioisomers mixture [23] …”

Section: Introductionmentioning

confidence: 72%

“…However, a few articles published during the last decades on the reaction of nucleophiles on such derivatives (Scheme 2) bars generalization. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] It was nevertheless demonstrated that several nitrogen nucleophiles add to β-nitroalkenoates to afford exclusively α-amino esters. [9][10][11][12][13][14][15][16] An analogous regioselectivity was observed when acrylic acid derivatives bearing a carbonyl group at the β-position were treated with primary or secondary amines.…”

Section: Introductionmentioning

confidence: 99%

“…[17][18][19] On the contrary, only β-amino acid derivatives were formed in the reactions of amines or N,N-and N,Obinucleophiles with β-trifluorocrotonic acid derivatives. [20][21][22] Finally, the aza-Michael addition of some primary amines and azoles to unsymmetrical fumaric esters led to the formation of the regioisomers mixture. [23] The paucity of results in this field and the differences between the published reaction conditions make the prediction of the regioselectivity of the addition to unsymmetrical alkenes containing two vicinal EWG groups difficult.…”

Section: Introductionmentioning

confidence: 99%

“…Doubly activated olefins bearing two different electron‐withdrawing groups in vicinal position (so‐called pull–pull olefins) [1b,8] could a priori be regarded as highly reactive compounds because of their global electron depletion. However, a few articles published during the last decades on the reaction of nucleophiles on such derivatives (Scheme 2) bars generalization [9–23] . It was nevertheless demonstrated that several nitrogen nucleophiles add to β ‐nitroalkenoates to afford exclusively α ‐amino esters [9–16] .…”

Section: Introductionmentioning

confidence: 99%

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Regioselectivity of the Conjugate Addition of Amines to Dissymmetrical Pull‐Pull Alkenes

et al. 2021

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The regioselectivity of the conjugate nucleophilic addition of amines to vicinal di-acceptor-substituted alkenes has been studied. A set of results obtained with standard primary and secondary amines gives some clues on the relative acceptor character of classical electron-withdrawing groups (EWG). We have shown in addition that computed inverse local nucleophilicity index can be used to predict the regioselectivity of the nucleophilic attack.

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Section: Introductionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Regioselectivity of the Conjugate Addition of Amines to Dissymmetrical Pull‐Pull Alkenes

et al. 2021

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“…They have been utilized in various ways, such as antibiotics, analgesics, and antidepressants, as well as anticancer, anti-HIV, and anti-HCV agents. [5][6][7][8] Fluorinated organic compounds are of particular interest in the area of functional materials sciences, pharmaceuticals, and agrochemicals, [9][10][11] thanks to the unique characteristics of the fluorine atom, which can alter the properties of organic compounds. 12 Fluorine is undoubtedly one of the elements that has recently attracted high research importance in several aspects of chemistry and drug research.…”

Section: Introductionmentioning

confidence: 99%

Application of Oxidative Ring Opening/Ring Closing by Reductive Amination Protocol for the Stereocontrolled Synthesis of Functionalized Azaheterocycles

Kiss

Ouchakour

Nonn

et al. 2021

Synlett

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The current Account gives an insight into the synthesis of some N-heterocyclic β-amino acid derivatives and various functionalized saturated azaheterocycles accessed from substituted cycloalkenes via ring C=C bond oxidative cleavage followed by ring closing across double reductive amination. The ring-cleavage protocol has been accomplished according to two common approaches: a) Os-catalyzed dihydroxylation/NaIO4 vicinal diol oxidation and b) ozonolysis. A comparative study on these methodologies has been investigated. Due to the everincreasing relevance of organofluorine chemistry in drug research as well as of the high biological potential of β-amino acid derivatives several illustrative examples to the access of various fluorine-containing piperidine or azepane β-amino acid derivatives are also presented in the current Account.1 Introduction2 Olefin-Bond Transformation by Oxidative Ring Cleavage3 Synthesis of Saturated Azaheterocycles via Oxidative Ring-Opening/Ring-Closing Double Reductive Amination3.1 Importance of Fluorine-Containing Azaheterocycles in Pharmaceutical Research3.2 Synthesis of Azaheterocyclic Amino Acid Derivatives with a Piperidine or Azepane Framework through Oxidative Ring Opening/Reductive Amination3.2.1 Synthesis of Piperidine β-Amino Esters3.2.2 Synthesis of Azepane β-Amino Esters3.2.3 Synthesis of Fluorine-Containing Piperidine γ-Amino Esters3.3 Synthesis of Tetrahydroisoquinoline Derivatives through Oxidative Ring Opening/Reductive Amination Protocol3.4 Synthesis of Functionalized Benzazepines through Reductive Amination3.4.1 Synthesis of Benzo[c]azepines3.4.2 Synthesis of Benzo[d]azepines3.5 Synthesis of Various N-Heterocycles via Ozonolysis/Reductive Amination3.5.1 Synthesis of Compounds with an Azepane Ring3.5.2 Synthesis of Piperidine β-Amino Acids and Piperidine-Fused β-Lactams3.5.3 Synthesis of γ-Lactams with a Piperidine Ring3.5.4 Synthesis of other N-Heterocycles4 Summary and Outlook5 List of Abbreviations

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Pull‐Pull Alkenes in the Aza‐Michael Reaction

Rulev

Tyumentsev

2022

Adv Synth Catal

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Aza‐Michael addition is known to be one of the most exploited reactions in organic chemistry. Taking into account the fact that each seventh reaction in pharmaceutical industry involves the formation of at least one C−N bond, it is not surprising that this reaction is especially valuable for the synthesis of bioactive compounds and drugs. Traditionally, only push‐pull alkenes are regarded as starting material for this reaction. The participation of pull‐pull alkenes as Michael acceptors is much less studied. The presence of two vicinal electron‐withdrawing groups makes them highly reactive in nucleophilic reactions especially with nitrogen‐centered nucleophiles. This feature allows them to be excellent building blocks in the synthesis of bioactive molecules and polyfunctional materials. The review considers the most important and sometimes unexpected results obtained over the last two decades on the conjugate addition of nitrogen nucleophiles to pull‐pull alkenes bearing various acceptor moieties (alkoxycarbonyl‐, carbonyl‐, formyl‐, cyano‐, trifluoromethyl‐ or nitro group) in various combinations.

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Selective assembly of saturated aza-heterocycles from β-functionally substituted enoates

Cited by 7 publications

References 15 publications

Regioselectivity of the Conjugate Addition of Amines to Dissymmetrical Pull‐Pull Alkenes

Regioselectivity of the Conjugate Addition of Amines to Dissymmetrical Pull‐Pull Alkenes

Application of Oxidative Ring Opening/Ring Closing by Reductive Amination Protocol for the Stereocontrolled Synthesis of Functionalized Azaheterocycles

Pull‐Pull Alkenes in the Aza‐Michael Reaction

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