NHC-Catalyzed Allylation of Aldehydes with MBH Carbonates and Their Michael Addition–Elimination-Cope Rearrangement Cascade: A Route to rac-Sacubitril DOI

Tushar B. Kale,

Sayali G. Jagtap,

Santosh B. Mhaske

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: May 28, 2025

We report herein a novel NHC-catalyzed transition-metal-free chemoselective allylation of aldehydes with Morita-Baylis-Hillman (MBH) carbonates using an inorganic base. Fascinatingly, the use organic base follows different mechanism, leading to highly functionalized 1,5-dienes via Michael addition-elimination reaction followed by [3,3]-sigmatropic Cope rearrangement. The described method harnesses new Csp2-Csp3 bond access α-methylene-γ-oxo-γ-substituted ester derivatives paving way facile synthesis potent natural products and active pharmaceutical ingredients (APIs). A broad range aromatic aliphatic MBH was employed provide variety interesting butanoate dienyl ketone scaffolds in good excellent yields. This chemistry has been extended efficient syntheses rac-sacubitril API γ-butyrolactone scaffold, which is privileged core present many APIs.

Language: Английский

Enal Transfer via Piano-Stool Rh-Enalcarbenoids: Rapid Construction of Enal-Functionalized Isoquinolones, Application Toward Benzo[c]phenanthridinone Scaffolds DOI
Pratap Kumar Mandal, Sudhir Muduli, Sreenivas Katukojvala

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Herein, we disclosed a Rh-catalyzed site-selective enal transfer reaction of benzamides with diazoenals leading to multisubstituted enal-functionalized isoquinolone derivatives. The involves arene ortho C–H activation, migratory insertion new class N-heterocyclic Piano-stool Rh-enalcarbenoid, and metal-templated cyclization. synthetic utility isoquinolones has been demonstrated by the short synthesis valuable benzo[c]phenanthridinone scaffolds, which are present in many naturally occurring alkaloids broad pharmacological properties an analogue oxyavicine natural product used for ophthalmic disorders.

Language: Английский

Citations

0
N-Heterocyclic carbene-catalyzed enantioselective (dynamic) kinetic resolution for the assembly of inherently chiral macrocycles DOI Creative Commons
Zhipeng Li,

Jingyang Zhang,

Wanmeng Zhu

et al.

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

We have successfully achieved the highly enantioselective synthesis of inherently chiral macrocycles through NHC-catalyzed asymmetric esterification heterocalixaromatics.

Language: Английский

Citations

0
NHC-Catalyzed and Brønsted Acid Copromoted E → Z Isomerization Mode of Breslow Intermediates Leading to Ralfuranones DOI

Qingyun Wang,

Xuyang Liang,

Mingyi Pan

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: May 12, 2025

Different Z/E-isomers of functional molecules display distinct chemical and biological activities. The E → Z isomerization reaction is a contra-thermodynamic direction presents long-standing challenge in synthetic transformation. To date, organic catalysis methods for manipulating E/Z are still under development. Here we show new N-heterocyclic carbene (NHC)-catalyzed mode. E-isomer enedial undergoes to give Z-isomer Breslow intermediate via NHC catalysis, an intramolecular hydrogen bond can greatly stabilize this conformation. Subsequently, the Brønsted acid promotes further redox-neutral reaction. desired ralfuranone products obtained from our method be readily transformed various molecules.

Language: Английский

Citations

0
Historical and recent advances in enantioselective NHC-catalyzed radical reactions DOI
Jia Song, Shi‐Chao Ren, Yingguo Liu

et al.

Chem Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 101398 - 101398

Published: May 1, 2025

Language: Английский

Citations

0
N-Heterocyclic Carbene/Organic Photoredox-Cocatalyzed Acyl Azolation of Alkenes with Acyl Azoles DOI

Kanata Togishi,

Yamato Goto, Sho Murakami

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: May 27, 2025

We have developed the N-heterocyclic carbene/organic photoredox-cocatalyzed acyl azolation of styrenes using azoles. The cooperative action organic photoredox catalysis and NHC enabled C-N bond cleavage azole insertion C-C double in styrene with complete regioselectivity. radical cation species, generated by single electron oxidation alkene, subsequently reacted nitrogen nucleophile ketyl intermediate to accomplish alkene into bond.

Language: Английский

Citations

0
Reductive N-Heterocyclic Carbene Catalysis via Hydride Transfer: Generating Homoenolates from Unsaturated Esters DOI

Mingyi Pan,

Qingyun Wang,

Pengcheng Zheng

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: May 27, 2025

In N-heterocyclic carbene (NHC) catalysis, the reduction of NHC-bound acyl azolium species is achieved with progress limited to generation ketyl radical intermediates. Here, we report a novel NHC-catalyzed reductive mode for intermediates, which accept hydride generate Breslow intermediate. Then, reaction intermediate chalcone results in formation cyclopentene, demonstrating classic umpolung transformation. We expect that this catalytic will open new avenues synthetic transformations.

Language: Английский

Citations

0
NHC-Catalyzed Allylation of Aldehydes with MBH Carbonates and Their Michael Addition–Elimination-Cope Rearrangement Cascade: A Route to rac-Sacubitril DOI

Tushar B. Kale,

Sayali G. Jagtap,

Santosh B. Mhaske

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: May 28, 2025

We report herein a novel NHC-catalyzed transition-metal-free chemoselective allylation of aldehydes with Morita-Baylis-Hillman (MBH) carbonates using an inorganic base. Fascinatingly, the use organic base follows different mechanism, leading to highly functionalized 1,5-dienes via Michael addition-elimination reaction followed by [3,3]-sigmatropic Cope rearrangement. The described method harnesses new Csp2-Csp3 bond access α-methylene-γ-oxo-γ-substituted ester derivatives paving way facile synthesis potent natural products and active pharmaceutical ingredients (APIs). A broad range aromatic aliphatic MBH was employed provide variety interesting butanoate dienyl ketone scaffolds in good excellent yields. This chemistry has been extended efficient syntheses rac-sacubitril API γ-butyrolactone scaffold, which is privileged core present many APIs.

Language: Английский

Citations

0