Aza‐Michael Reaction: A Decade Later – Is the Research Over?

European Journal of Organic Chemistry, Год журнала: 2023, Номер 26(26)

Опубликована: Июнь 14, 2023

Abstract The 1,4‐conjugated addition of nitrogen centered nucleophiles to electron‐deficient alkenes, historically called the aza‐Michael addition, is one most significant and widely used reactions in modern synthetic organic chemistry. In last decade, great progress has been made this field namely development various catalytic systems. Fundamental advances involve use transition metal catalysts, organocatalysts, enzymes, ionic liquids, Brønsted Lewis acids bases. This Review aims critically analyze results research into aliphatic aromatic amines with Michael acceptors.

Язык: Английский

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Pull‐Pull Alkenes in the Aza‐Michael Reaction

Advanced Synthesis & Catalysis, Год журнала: 2022, Номер 364(10), С. 1622 - 1642

Опубликована: Апрель 8, 2022

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

Язык: Английский

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Weak Nucleophiles in the Aza‐Michael Reaction

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(12), С. 1908 - 1925

Опубликована: Май 15, 2023

Abstract The 1,4‐conjugated addition of nitrogen centered nucleophiles to electron‐deficient alkenes is one the most significant and widely used reactions in modern synthetic organic chemistry. To date, various protocols for aza‐Michael reaction have been developed. However, these reports mainly focus on use strong Michael donors. In recent years, conjugate weak acceptors gained increasing popularity. Impressive progress this area has achieved by more efficient catalyst systems. This review aims provide a critical analysis results obtained (azoles, pyrroles, indoles, carbamates, purines, amides, hydrazides, uraciles etc ) with which were reported over past twelve years.

Язык: Английский

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Hydrazine Hydrate in Asymmetric Synthesis: A Bifunctional Squaramide Catalytic Approach toward Fused Pyrazolines

Organic Letters, Год журнала: 2023, Номер 25(38), С. 6993 - 6998

Опубликована: Сен. 20, 2023

A unified strategy has been developed to utilize hydrazine hydrate in asymmetric organic synthesis by overcoming the rapid background reaction with dienone. The H-bond donor ability of cinchona-alkaloid-derived squaramide catalyst unlocks this previously deemed infeasibility. dissymmetric addition symmetrical dienones tolerates various substitutions, resulting formation optically pure fused pyrazoline derivatives under mild conditions. Furthermore, scalability methodology and a successful demonstration postsynthetic transformations have accomplished.

Язык: Английский

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A Concise Enantioselective Synthesis of Fluorinated Pyrazolo-Piperidine GSK3901383A Enabled by an Organocatalytic Aza-Michael Addition

Organic Letters, Год журнала: 2024, Номер 26(8), С. 1533 - 1538

Опубликована: Фев. 16, 2024

A highly enantioselective organocatalytic aza-Michael addition of 4-nitro-pyrazole to ethyl (E)-2,2-difluoro-5-oxopent-3-enoate has been developed. This reaction enabled a concise, four-step, stereoselective synthesis functionalized 3,3-difluoro-4-pyrazolo-piperidine GSK3901383A, key intermediate for the leucine-rich repeat kinase 2 inhibitor API. Computational analysis provided insight into steric requirements catalytic system, enabling rational selection selective catalyst.

Язык: Английский

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The mechanism of the phosphine-catalyzed oxa-Michael reaction: a DFT investigation

Structural Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

Язык: Английский

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Advances in Catalytic Asymmetric Construction of Quaternary Stereogenic Centers by Conjugate Addition to β,β‐Disubstituted Nitroalkenes

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(17), С. 2789 - 2817

Опубликована: Июль 6, 2023

Abstract Quaternary stereogenic centers are of great importance because their prevalence in a series bioactive natural products and pharmaceuticals. Although the catalytic asymmetric construction these highly congested poses formidable challenge, this field has been extensively explored past few decades, several elegant strategies, such as conjugate addition to β,β‐disubstituted nitroalkenes, have developed. The resultant β‐nitro quaternary stereocenters can be conveniently transformed into corresponding β‐amino commonly found compounds. This review summarizes recent advances all‐carbon or hetero‐carbon via metal‐catalyzed organocatalyzed focusing on scope, applications, mechanisms reactions.

Язык: Английский

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Developments and applications of α-bromonitrostyrenes in organic syntheses

RSC Advances, Год журнала: 2024, Номер 14(21), С. 14835 - 14846

Опубликована: Янв. 1, 2024

In this work, we have described the use of α-bromonitrostyrenes in synthesis a wide variety carbocyclic and heterocyclic compounds under organocatalysis, metal catalysis, base-catalysis systems as well catalyst-free reactions.

Язык: Английский

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Asymmetric Phase-Transfer Catalytic aza-Michael Addition to Cyclic Enone: Highly Enantioselective and Diastereoselective Synthesis of Cyclic 1,3-Aminoalcohols

Organic Letters, Год журнала: 2022, Номер 24(8), С. 1647 - 1651

Опубликована: Фев. 17, 2022

The highly enantioselective aza-Michael reaction of tert-butyl β-naphthylmethoxycarbamate to cyclic enones has been accomplished by using a new cinchona alkaloid derived C(9)-urea ammonium catalyst under phase-transfer catalysis conditions with up 98% ee at 0 °C. resulting adducts can be converted versatile intermediates selective deprotection and the 1,3-aminoalcohols diastereoselective reduction 32:1, which have widely used as important pharmacophores in pharmaceutical development.

Язык: Английский

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Sigmatropic [1,5] Carbon Shift of Transient C3 Ammonium Enolates

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(31)

Опубликована: Май 10, 2022

The stereospecific sigmatropic [1,5] carbon shift of C3 ammonium enolates is discovered. According to mechanistic, kinetic and computational experiments, this new rearrangement proceeds via the catalytic generation a transient enolate by intramolecular aza-Michael addition. This intermediate rapidly undergoes migration furnish respective tetrahydroquinoline-4-ones with excellent diastereoselectivities d.r. >99 : 1 in 61-98 % yield.

Язык: Английский

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