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

European Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 26(26)

Published: June 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.

Language: Английский

---

Pull‐Pull Alkenes in the Aza‐Michael Reaction

Advanced Synthesis & Catalysis, Journal Year: 2022, Volume and Issue: 364(10), P. 1622 - 1642

Published: April 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

Language: Английский

---

Weak Nucleophiles in the Aza‐Michael Reaction

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(12), P. 1908 - 1925

Published: May 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.

Language: Английский

---

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

Structural Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Language: Английский

---

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

Organic Letters, Journal Year: 2023, Volume and Issue: 25(38), P. 6993 - 6998

Published: Sept. 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.

Language: Английский

---

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

Organic Letters, Journal Year: 2024, Volume and Issue: 26(8), P. 1533 - 1538

Published: Feb. 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.

Language: Английский

---

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

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(17), P. 2789 - 2817

Published: July 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.

Language: Английский

---

Synthesis of Multifused Pyrrolo[1,2-a]quinoline Systems by Tandem Aza-Michael–Aldol Reactions and Their Application to Molecular Sensing Studies

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(9), P. 5622 - 5638

Published: March 30, 2023

Herein, we have presented a weak acid-promoted tandem aza-Michael-aldol strategy for the synthesis of diversely fused pyrrolo[1,2-a]quinoline (tricyclic to pentacyclic scaffolds) by construction both pyrrole and quinoline ring in one pot. The described protocol fabricated two C-N bonds C-C bond pyrrole-quinoline rings which been sequentially formed under transition-metal-free conditions extrusion eco-friendly water molecules. A ketorolac drug analogue has synthesized following current protocol, tricyclic fluorophores used detect highly toxic picric acid via fluorescence quenching effect.

Language: Английский

---

1,2-Silyl Shift-Induced Heterocyclization of Propargyl Silanes: Synthesis of Five-Membered Heterocycles Containing a Functionalized Olefin Side Chain

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(19), P. 13857 - 13870

Published: Sept. 22, 2023

Propargyl silanes with a terminal alkyne moiety undergo 1,2-silyl shift when activated electrophiles such as H+, Br+, I+, and PhSe+. A method was developed to trap 1,3-transposed electrophilic centers various internal O-, N-, S-nucleophiles in 5-exo manner. This synthetic procedure provided five-membered heterocycles containing trisubstituted olefin side chain. The scope of the includes access tetrahydrofuran, γ-butyrolactone, 2-isooxazoline, pyrrolidine, thiolane derivatives yields ranging from 25 85% (23 examples total). Reactions TsNBr2 ensured complete (E)-selectivity newly formed olefins. Further functionalization obtained 1-trialkylsilyl-2-bromovinyl chain demonstrated by double-bond geometry-preserving substitution cross-coupling reactions that vinyl moiety.

Language: Английский

---

Reinvigorating aza-Michael reactions under ionic liquid catalysis: a greener approach

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(12), P. 2423 - 2434

Published: Jan. 1, 2024

Cholinium α-amino carboxylates, which debuted in the ionic liquid arena over a decade ago, exhibit superior stability and suitable physical properties relative to other RTILs. Although synthetic pursuits such media, leveraging their dual role as solvents catalysts, have been scarce so far, we herein illustrate catalytic advantage aza-Michael reactions terms of low loading, acceleration improved yields with respect conventional conditions imidazolium-based ILs. These highly structured salts most likely act through multiple cooperative non-covalent interactions. mechanistic features also investigated high-level computational analyses well.

Language: Английский

---