Regioselective Difunctionalization and Annulation of Ynamide

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(30)

Published: April 8, 2023

Abstract The use of ynamides in organic synthesis has gained significant attention due to their ability provide access complex molecular structures through transformations such as 1,2‐difunctionalization and annulation reactions. These reactions enable the formation highly functionalized N‐bearing olefins unusual heterocycles. In this minireview, we present a systematic overview regioselective difunctionalization ynamides. We discuss multi‐component reactions, radical‐triggered functionalizations across carbon–carbon multiple bonds bifunctional reagents ynamides, highlighting potential expanding substrate scope. Furthermore, insights into mechanistic breakthroughs that have been achieved recent years development these Finally, emphasize promising future prospects versatile building blocks for architectures.

Language: Английский

---

Recent Advances in the Gold-Catalyzed Reactions of Propargyl Esters

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(12), P. 1406 - 1420

Published: June 6, 2023

ConspectusLate-transition-metal-based complexes represent an indispensable catalytic tool in chemical synthesis due to their ability increase molecular complexity rapidly and efficiently from readily accessible substrates a single operation. Added this is the exquisite control of product chemo-, diastereo-, enantio-, site-selectivities achieved by systems transition-metal salts that have been developed mediate wide range functional group transformations. Within venerable synthetic toolbox, Au(I) Au(III) emerged recent years as invaluable addition result potent σ- π-Lewis acidities stabilize cationic reaction intermediates. The insights provided mechanistic studies examining various electronic, steric, stereoelectronic factors at play organogold species are expected be formed chemistry complex also pivotal understanding exploring potential utility. Illustrative this, for example, contribution made gold-catalyzed cycloisomerization propargyl esters strategies variety bioactive natural products compounds current pharmaceutical materials interest. This Account summarizes our efforts over past decade toward realizing new single-step carbocyclic heterocyclic relied on reactions esters. It outlines methods exploited unique reactivities gold-carbene typically generated [2,3]-sigmatropic rearrangement compound class containing terminal or electron-deficient alkyne moiety exposure salt. describes realization initiated 1,3-acyloxy migration with electronically unbiased disubstituted C≡C bond delivers corresponding allenyl ester primed further reactivity activation 11 metal complex. part ongoing overarching program within was focused determining gold catalysis would enable application recognizable disconnections retrosynthetic analysis. They were additionally aimed evaluating opportunities offered relativistic effects possessed complex, most pronounced among d-block elements thus catalyst choice chemistry, generate space. For instance, we demonstrated several 1,3- 1,4-enyne reliable strategy situ formation 1,4-cyclopentadienyl derivatives. Their appropriately placed second starting material then shown afford targets five-membered ring structure. An example assembly member 1H-isoindole family found exhibit TNF-α (tumor necrosis factor-α) inhibitor activity.

Language: Английский

---

HFIP-Mediated, Regio-, and Stereoselective Hydrosulfenylation of Ynamides: A Versatile Strategy to Access Ketene N,S-Acetals

Organic & Biomolecular Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Herein, we report an HFIP-mediated, versatile, sustainable, atom-economical, and regio- stereoselective hydro-functionalization of ynamides with various S-nucleophiles (1 equiv.) such as thiols, thiocarboxylic acids, carbamates, xanthates, O,O-diethyl S-hydrogen phosphorothioate to access a wide variety stereodefined trisubstituted ketene N,S-acetals under mild conditions. This protocol requires only HFIP, which plays multiple roles, acting Brønsted acid protonate the ynamide regioselectively at beta carbon generate reactive keteniminium intermediate, stabilizing intermediate solvent through H-bonding. After nucleophilic attack S-nucleophile on deprotonation, HFIP is regenerated in most cases can be easily recovered recycled, revealing high sustainability protocol. Remarkably, all reactions are highly efficient furnish excellent yields many pure products were obtained just by washing crude reaction mixture pentane. Significantly, green chemistry metrics found excellent.

Language: Английский

---

Three Component syn‐1,2‐Arylmethylation of Internal Alkynes**

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(12)

Published: Jan. 26, 2023

A Pd-catalyzed three-component syn-1,2-arylmethylation of internal alkynes (ynamides/yne-acetates/alkynes) is described. The readily available and bench stable coupling partners iodo-arenes, methyl boronic acid are successfully used in this strategy to access the methyl-containing tetra-substituted olefins; scope broad showing excellent functional-group tolerance. Notably, transformation regio- as well stereoselective. biologically relevant motifs (BRM) bearing iodo-arenes ynamides also for late-stage alkynes. Aryl-alkylation, aryl-trideuteriomethylation, alkynyl-methylation, alkenyl-methylation presented. Me-substituted alkenes further transformed into synthetically important β-amino-indenones α-fluoro-α'-methyl ketones.

Language: Английский

---

Palladium-Catalyzed Regioselective Arylalkenylation of Ynamides

Organic Letters, Journal Year: 2022, Volume and Issue: 24(7), P. 1524 - 1529

Published: Feb. 14, 2022

A cationic palladium-catalyzed arylalkenylation of ynamides is presented. The putative keteniminium arylpalladium intermediate likely dictates the regioselective carbopalladation ynamide to form a vinylpalladium species. capture this complex by olefin yields linear conjugated β-alkenyl aminodienes (especially with trans selectivity). transformation features broad scope labile functional group tolerance and makes 42 unusual molecular scaffolds structural diversity. DFT studies provide valuable insights into reaction mechanism.

Language: Английский

---

Gold‐Catalyzed Reaction of Anthranils with Alkynyl Sulfones for the Regioselective Formation of 3‐Hydroxyquinolines

Advanced Synthesis & Catalysis, Journal Year: 2022, Volume and Issue: 364(7), P. 1233 - 1238

Published: March 2, 2022

Abstract The gold‐catalyzed regioselective formation of 3‐hydroxyquinoline is accessed by combining anthranils and alkynyl sulfones. selective scission the epoxide intermediate stems from thermodynamic stability difference resultant cation according to quantum chemical calculations. subsequent semi‐pinacol rearrangement leads 1,2‐shift an aryl or alkyl group originating sulfone. A gram‐scale synthesis further manifests viability protocol for preparation this important scaffold. magnified image

Language: Английский

---

Gold‐Catalyzed Annulation of Ynamides with Aminocarbonyls as a Route to 2‐Aminoquinolines Diversely Substituted at the 4^th‐Position

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(14), P. 2428 - 2434

Published: July 3, 2023

Abstract Gold‐catalyzed interplay between ynamides and aminocarbonyls comprises a route to 2‐aminoquinolines. This modular annulation proceeds under relatively mild conditions (Ph 3 PAuCl/AgNTf 2 5 mol %, DCE, 60–80 °C), number of functionalities were compatible (42 examples; 25–98% yields). In contrast group other gold‐catalyzed methods employing the ynamide/amine combinations for assembly 2‐aminoquinolines, developed approach utilizes diversity aminocarbonyl substrates and, in particular, allows variation substituents 4 th quinoline position. The synthetic potential obtained heterocyclic products was illustrated by post‐modifications backbone peripheral substituents.

Language: Английский

---

TMSOTf-Catalyzed [4 + 2] Annulation of Ynamides and β-(2-Aminophenyl)-α,β-ynones for the Synthesis 2-Aminoquinolines

Organic Letters, Journal Year: 2024, Volume and Issue: 26(17), P. 3503 - 3508

Published: April 25, 2024

A metal-free TMSOTf-catalyzed [4 + 2] annulation of ynamides with β-(2-aminophenyl)-α,β-ynones enables the regiospecific and facile assembly 2-aminoquinoline frameworks. The catalyst TMSOTf presented a remarkable advancement compared to previously reported transition-metal catalysts. wide range 3-aryl/alkyl-substituted 2-aminoquinolines were generated in moderate excellent yields due mild conditions.

Language: Английский

---

TMSOTf/TfOH-Promoted [4 + 2] Annulation of Ynamides with 2-Aminoarylnitriles To Construct 2,4-Diaminoquinolines

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 9, 2025

An effective strategy to synthesize 2,4-diaminoquinoline compounds has been efficaciously developed via a TMSOTf/TfOH-promoted [4 + 2] annulation of ynamides with 2-aminoarylnitriles. Compared the reported transition-metal catalysts, this metal-free promotion system presented remarkable advancement, enabling facile and regiospecific assembly frameworks wide functional group compatibility moderate excellent yields.

Language: Английский

---

Gold-Catalyzed Synthesis of (Dihydro)quinolones by Cyclization of Benzaldehyde-Tethered Ynamides and Anilines

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

Published: March 12, 2025

2-Quinolones represent a versatile class of compounds that are prevalent in natural and medicinally relevant molecules. Here we report new approach to the selective formation these structures. By gold catalysis, range benzaldehyde-tethered ynamides reacted with anilines, leading 4-amino-3,4-dihydro-2-quinolones high efficiency excellent diastereoselectivity dichloromethane. Interestingly, methyl acetate as solvent, same reaction produced 3-aryl 2-quinolones major products. The use substoichiometric amount aniline could also promote this transformation.

Language: Английский

---