Divergent access to fused <i>N</i>-heterocycle-thiazolines by solvent-dependent reaction of isoquinolinium thiolates with silylketene acetals

Schifferer, Lukas; Hoppmann, Leon; Groeters, Robin; Mück‐Lichtenfeld, Christian; Daniliuc, Constantin G.; Mancheño, Olga Garcı́a

doi:10.1039/d3cc00781b

Cited by 3 publications

(1 citation statement)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three-dimensional structures of the molecules were drawn and subjected to conformational analysis in ComputeVOA using MMFF94 as force field and the GMMX methodology on a Windows operating system machine. Geometrical optimization and energy calculation of conformers occurring in an energy window (Δ E ) of 0–3 kcal/mol were done in Gaussian 16 software by implementation of B3LYP/DGDZVP due to its high accuracy and cost-effectiveness ratio scaling factor, using the COSMO solvation algorithm due to its algorithmic simplicity and numerical stability, as shown by multiple examples of successful applicability to fused ring heterocycles. − The optimized structures (Tables S4, S5, S6, and S7, Supporting Information) were used to calculate the thermochemical parameters estimated at 298 K and 1 atm. Calculations taking into account the solvent (MeOH) were carried out starting from DFT-optimized structures.…”

Section: Experimental Sectionmentioning

confidence: 99%

Formation of Trideuteromethylated Artifacts of Pyrrole-Containing Natural Products

Orfanoudaki,

Akee,

Martínez-Fructuoso

et al. 2024

J. Nat. Prod.

View full text Add to dashboard Cite

Pyrrole-containing natural products form a large group of structurally diverse compounds that occur in both terrestrial and marine organisms. In the present study the formation of trideuteromethylated artifacts of pyrrole-containing natural products was investigated, focusing on the discorhabdins. Three deuterated discorhabdins, 1, 3, and 5, were identified to be isolation procedure artifacts caused by the presence of DMSO-d 6 during NMR sample preparation and handling. Three additional semisynthetic derivatives, 7−9, were made during the investigation of the mechanism of formation, which was shown to be driven by trideuteromethyl radicals in the presence of water, methanol, TFA, and traces of iron in the deuterated solvent. Generation of trideuteromethylated artifacts was also confirmed for other classes of pyrrolecontaining metabolites, namely, makaluvamines, tambjamines, and dibromotryptamines, which had also been dissolved in DMSO-d 6 during the structure elucidation process. Semisynthetic discorhabdins were assessed for antiproliferative activity against a panel of human tumor cell lines, and 14-trideuteromethyldiscorhabdin L (3) averaged low micromolar potency.

show abstract

Section: Experimental Sectionmentioning

confidence: 99%

Formation of Trideuteromethylated Artifacts of Pyrrole-Containing Natural Products

Orfanoudaki,

Akee,

Martínez-Fructuoso

et al. 2024

J. Nat. Prod.

View full text Add to dashboard Cite

show abstract

Copper(I) Iodide Catalyzed [3 + 3] Annulation of Iodonium Ylides with Pyridinium 1,4-Zwitterionic Thiolates for the Synthesis of 1,4-Oxathiin Scaffolds

et al. 2023

View full text Add to dashboard Cite

The selective assembly of the 1,4-oxathiin nucleus has been treated as a powerful strategy to access this scaffold present in molecules with very interesting properties. In this study, the chameleon-like reactivity of pyridinium 1,4-zwitterionic thiolates is exploited to assemble the 1,4-oxathiin core through a [3 + 3] annulation. The optimal annulation partner has been found to be the iodonium ylide of the cyclic 1,3-diketones. The developed protocol allows the synthesis of a variety of bicyclic 1,4-oxathiin derivatives under very mild conditions under copper(I) iodide catalysis. Access to benzoannulated 1,4-oxathiins has been achieved through iodine-mediated aromatization of the initially obtained bicyclic compounds.

show abstract

Chameleonic Reactivity of Imidoyl Sulfoxonium Ylides: Access to Functionalized Pyrroles and Dihydro-pyridines

Xu,

Yang,

2024

Org. Lett.

View full text Add to dashboard Cite

We have found a chameleonic reactivity of imidoyl sulfoxonium ylides. On the one hand, imidoyl sulfoxonium ylides react with electron-deficient reagents, such as alkynyl esters, to lead to the formation of 1,2-dihydro-pyridines. The methyl group attached to the sulfur atom acts as a methylene donor. On the other hand, imidoyl sulfoxonium ylides react with pyridinium 1,4-zwitterionic thiolates, which leads to the formation of functionalized pyrroles. Both transformations feature mild reaction conditions and good functional group tolerance.S ulfoxonium ylides have experienced significant growth in organic synthesis. 1 Imidoyl sulfoxonium ylides are particularly popular as metal carbene precursors (Scheme 1a). 2,3 In addition, imidoyl sulfoxonium ylides also have chameleonic reactivities: 1 they react with various nucleophiles 4 and electrophiles 5 (Scheme 1b). These methods were powerful in constructing N-heterocycles, such as pyrroles and pyridines (Scheme 1b).We envision that imidoyl sulfoxonium ylides may have more chameleonic reactivity. 1 The methyl group (CH 3 -) connected to the sulfur atom could act as a methylene (CH 2 ) donor under suitable conditions (Scheme 1c). More specifically, when imidoyl sulfoxonium ylides react with a highly electrondeficient reagent, such as alkynyl esters, the methyl group attached to the sulfur atom acts as a methylene donor; this type of reactivity is very unusual. In addition, the electrondeficient alkynyl esters could react with pyridine and elementary sulfur to generate the pyridinium 1,4-zwitterionic thiolates. 6 These zwitterionic thiolates are nucleophilic; they may also react with imidoyl sulfoxonium ylides (Scheme 1c). 7 Herein, we report a chameleonic reactivity of imidoyl sulfoxonium ylides. This protocol offered access to synthetically important pyrroles and 1,2-dihydro-pyridines (Scheme 1c). Moreover, functionalized N-heterocycles, such as pyrroles and dihydro-pyridines, are ubiquitous in natural products, medicines, agrochemicals, and advanced materials. 8 We began our research by employing the reaction of CF 3imidoyl sulfoxonium ylides (TFISY) 1a and pyridinium 1,4zwitterionic thiolates 2 as the model system (Table 1). TFISYs could be easily prepared by the reaction of fluorinated

show abstract

Divergent access to fused N-heterocycle-thiazolines by solvent-dependent reaction of isoquinolinium thiolates with silylketene acetals

Abstract: A solvent-dependent, divergent synthesis of highly functionalized N,S-heterocycles presenting a thiazoline and a isoquinuclidine (DCE as solvent) or tetrahydroisoquinoline (DMF as solvent) scaffolds by cyclization reactions of isoquinolinium 1,4-zwitterionic thiolates...

Cited by 3 publications

References 37 publications

Formation of Trideuteromethylated Artifacts of Pyrrole-Containing Natural Products

Formation of Trideuteromethylated Artifacts of Pyrrole-Containing Natural Products

Copper(I) Iodide Catalyzed [3 + 3] Annulation of Iodonium Ylides with Pyridinium 1,4-Zwitterionic Thiolates for the Synthesis of 1,4-Oxathiin Scaffolds

Chameleonic Reactivity of Imidoyl Sulfoxonium Ylides: Access to Functionalized Pyrroles and Dihydro-pyridines

Contact Info

Product

Resources

About