gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• series of new α,β-unsaturated amides, both fluorinated and nonfluorinated, were synthesized. Keywords: gem-difluorovinyl Michael acceptors; Michael addition; trifluorovinyl Michael acceptors; α,β-unsaturated amides; Introduction The Michael reaction, characterized by the addition of stable carbon

• using organolithium reagents (Scheme 1), revealing new avenues in fluorinated unsaturated amide synthesis, which are present in numerous natural products, pharmaceuticals, and polymers [34][35][36][37][38]. The obtained α,β-unsaturated amides may represent promising structural motifs for further

• -unsaturated amides. Formation of β-fluorinated and nonfluorinated α,β-unsaturated amides. Michael addition of 1a–d with tert-BuLi. Michael addition of 2a–d with tert-BuLi. Formation of N-methylation products. Optimization of reaction conditions. Supporting Information Supporting Information File 40: Detailed

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• -workers have recently described a method for the one-step, diastereoselective 1,2-difluorination of alkenes, mediated by a hypervalent iodine catalyst [24]. The substrate scope of the Jacobsen method has certain constraints but their original report did include some examples of α,β-unsaturated amides, and

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• gadolinium catalyst and chiral ligand L2 (Scheme 43b) [108]. By altering the radical precursor to α-silyl amines 277 and using α,β-unsaturated amides 278, Yoon et al. found that the reactions could be stopped at the RCA step to give enantioenriched 1,4-addition products 279 using a scandium catalyst and

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• -Bu as the catalytic system. The conditions employed B2(OH)4 as an atom economical source of boron, starting from α,β-unsaturated amides 422, ketones, and esters in MeOH as the solvent (Scheme 68) [131]. The β-amidotrifluoroborates synthesized through this protocol do not encounter the purification

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• values were observed (20–36% ee), whereas no reactivity was observed with α,β-unsaturated amides. Although Pineschi’s conditions were ineffective for amides [49], Harutyunyan and co-workers achieved an important breakthrough by reporting the first enantioselective alkylation of α,β-unsaturated amides [50

• reagents to α,β-unsaturated amides. Cu/Josiphos (L9)-catalyzed ECA of Grignard reagents to polyunsaturated amides. Cu-catalyzed ECA of trimethylaluminium to N-acylpyrrole derivatives. Acknowledgements We are grateful to the Ecole Nationale Supérieure de Chimie de Rennes (ENSCR) and the Centre National de

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• B, natural products that inhibit microtubule function [62]. The enantioselective addition of 4-tert-butyl(thiophenol) to 149 using 5 mol % of (S)-Sm-144 was used to set the C8 stereocenter in the final product (Scheme 34). α,β-Unsaturated amides Lewis acids In 2009, the Shibasaki group reported the

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• condensation followed by diazo-transfer reaction. The chiral dihydrobenzofuran scaffold (5 or 6) could be synthesized by asymmetric intramolecular oxa-Michael reaction (AIOM) of α,β-unsaturated amides 7 or 8. Such reactions are generally considered to be challenging due to low nucleophilicity of the oxygen

• . Conclusion We have developed the first asymmetric catalytic synthesis of the key intermediate for beraprost in 14 steps, via an organocatalyzed AIOM reaction of α,β-unsaturated amides. During the course of this study, it was revealed that a bromo substituent ortho to the phenolic OH group significantly

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• demonstrated in the synthesis of many natural products, materials, and pharmacological agents. In the last three decades, there has been a significant increase in the development of asymmetric variants of this reaction. Unfortunately, conjugate addition reactions using α,β-unsaturated amides and lactams remain

• underdeveloped due to their inherently low reactivity. This review highlights the work that has been done on both diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams. Keywords: α,β-unsaturated amides; α,β-unsaturated lactams; conjugate addition

• expanded to include α,β-unsaturated ketones, aldehydes, lactones, esters, nitroolefins, and to a lesser extent α,β-unsaturated amides and lactams. Review The lack of development in the CA of α,β-unsaturated amides and lactams is not surprising because these substrates are significantly less reactive than

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• MMP inhibitors by Hanessian and co-workers, trans- and cis-aziridines scaffolds were used as peptidomimetics to construct a series of hydroxamic acids analogs such as 17 (Scheme 17) [63]. While the trans-aziridines were prepared by conjugate addition of O-benzylhydroxylamine to α,β-unsaturated amides

Tandem Cu-catalyzed ketenimine formation and intramolecular nucleophile capture: Synthesis of 1,2-dihydro-2-iminoquinolines from 1-(o-acetamidophenyl)propargyl alcohols

• Gadi Ranjith Kumar,
• Yalla Kiran Kumar,
• Ruchir Kant and
• Maddi Sridhar Reddy

Beilstein J. Org. Chem. 2014, 10, 1255–1260, doi:10.3762/bjoc.10.125

• creating initially a leaving group and its subsequent substitution or via activation of the nitrogen atom and direct amination at C-2 while few methods afforded the direct 2-aminoquinoline synthesis from the acyclic precursors. Most recently, we have disclosed a method for the synthesis of E-α,β

• -unsaturated amides from propargyl acetates via copper catalyzed ketenimine formation with sulfonyl azides (Scheme 1) [16]. The reaction was thought to proceed through intramolecular nucleophilic attack on the in situ generated ketenimine. We became curious to know the fate of the reaction in the presence of