17 research outputs found

    Alkynylation of Thiols with Ethynylbenziodoxolone (EBX) Reagents: alpha- or beta- pi-Addition?

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    The alkynylation of thiols with EthynylBenziodoXolone (EBX) reagents is a fast and chemoselective method for the synthesis of thioalkynes. Combined experimental and computational studies are reported, which led to the identification of a new mechanism for this reaction, proceeding via an initial sulfur iodine interaction followed by beta-addition, alpha-elimination, and a 1,2-shift. Depending on the substituent on the alkyne, this mechanism can be favored over the previously disclosed concerted alpha-addition rti pathway

    Indole- and Pyrrole-BX: Bench-Stable Hypervalent Iodine Reagents for Heterocycle Umpolung

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    The one-step synthesis of the bench-stable hypervalent iodine reagents IndoleBX and PyrroleBX using mild Lewis acid catalyzed conditions is reported. The new reagents are stable up to 150 degrees C and were applied in the C-H arylation of unactivated arenes using either rhodium or ruthenium catalysts. A broad range of heterocyclic systems of high interest for synthetic and medicinal chemistry was accessed in high yields. The developed C-H functionalization could not be achieved using reported reagents or methods, highlighting the unique reactivity of Indole- and Pyrrole-BX

    Enantioselective Synthesis of Homoallylic Azides and Nitriles via Palladium-Catalyzed Decarboxylative Allylation

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    Azides and nitriles are important building blocks for the synthesis of nitrogen-containing bioactive compounds. The first example of enantioselective palladiumcatalyzed decarboxylative allylation of alpha-azido and cyano beta-ketoesters is reported. Indanone derivatives were obtained in 50-88% yield/77-97% ee and 46-98% yield/78-93% ee for azide and nitrile substituents, respectively. The required starting materials were synthesized in one step from ketoesters via electrophilic azidation and cyanation using benziodoxole hypervalent iodine reagents. The products could be easily converted into useful nitrogen-containing building blocks, such as triazoles, amides, or alpha- and beta- amino ketones

    Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

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    The C–H indolation of heteroarenes was realized using the benziodoxolone hypervalent iodine reagents indoleBXs. Functionalization of the C–H bond in bipyridinones and quinoline N-oxides catalyzed by a rhodium complex allowed to incorporate indole rings into aza-heteroaromatic compounds. These new transformations displayed complete regioselectivity for the C-6 position of bipyridinones and the C-8 position of quinoline N-oxides and tolerated a broad range of functionalities, such as halogens, ethers, or trifluoromethyl groups

    Gold-catalyzed domino cyclization-alkynylation reactions with EBX reagents: new insights into the reaction mechanism

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    Gold-catalyzed domino processes constitute a useful alternative to C-H functionalization for the synthesis of functionalized (hetero)arenes. Herein, we report computational studies on the gold-catalyzed cyclization alkynylation of keto-allenes with ethynylbenziodoxole (EBX) reagents, which identified a gold(I) picolinate complex as the active catalyst, giving the first mechanistic insights into this transformation

    Development of New Strategies of Umpolung with Cyclic Hypervalent Iodine Reagents

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    Organic chemistry is essential for the development of a modern society and technical progress requires the continuous development of synthetic methodologies Novel, efficient, selective and flexible protocols are employed to access complex frameworks from simple starting materials. However, classical synthetic methods often relies on the intrinsic reactivity of functional groups, reducing the portfolio of available reactions for synthetic chemists. The reversal of classical reactivity of functional groups allows alternative disconnection pathways and can improve synthetic efficiency. The research presented in this thesis was aimed at the development of new strategies of Umpolung with hypervalent iodine reagents. Three new Umpolung methods have been investigated. First a strategy for the synthesis of enantioenriched α-cyano α-allyl ketones has been developed. Second, novel indole- and pyrrole-based hypervalent iodine reagents have been synthesized and applied in the context of metal-catalysis ad metal-free transformations. Third, a new class of umpoled enamides and enol ethers have been prepared from simple starting materials. α-Cyano carbonyls are important structural motifs of bioactive compounds and natural products. Nitriles are also versatile building blocks that undergo a plethora of transformations, which are usually accessed by transfer of the nucleophilic cyanide anion to electrophiles. The reactivity of cyanide can be reversed by the use of hypervalent iodine reagents. Part I focus on the application of umpoled nitriles for the functionalization of carbonyls. With these reagents, a variety of β-keto esters were successfully cyanated in racemic fashion. Inspired by previous results obtained in our group, a decarboxylative asymmetric allylic alkylation strategy was applied for the synthesis of enantioenriched quaternary α-cyano α-allyl ketones embedded in an indanone framework. Cyclic indanone derivatives were accessed in good yields and enantioselectivities. Indole and pyrrole heterocycles are often embedded in relevant drugs, natural products and materials. Their ubiquity inspired decades of intensive research for both their synthesis and functionalizations. Especially functionalization methods mainly focused on their intrinsic nucleophilic properties. The field exploiting their electrophilic derivatization was severely underdeveloped. An alternative strategy to access electrophilic indole and pyrrole synthons takes advantage of the unique properties of hypervalent iodine. In Part II of this thesis, indole- and pyrrole-based benziodoxoles were prepared and used for the metal-catalyzed direct indole transfer on aromatic CâH bonds. A large variety of indole-aryl frameworks, previously elusive or accessed via multi-step syntheses, were accessed in a straightforward manner, starting from simple commercially available building blocks. A direct oxidative metal-free cross-coupling for the synthesis of mixed bi-(hetero)aryl-indoles was then developed. The reaction worked well with our previously synthesized reagents, and a new class of electrophilic indoles (activated at the C2 carbon) was specifically developed for this transformation, further expanding the pool of available benziodoxoles

    Alkynylation of Thiols with Ethynylbenziodoxolone (EBX) Reagents: α- or β- π‑Addition?

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    The alkynylation of thiols with EthynylBenziodoXolone (EBX) reagents is a fast and chemoselective method for the synthesis of thioalkynes. Combined experimental and computational studies are reported, which led to the identification of a new mechanism for this reaction, proceeding via an initial sulfur–iodine interaction followed by β-addition, α-elimination, and a 1,2-shift. Depending on the substituent on the alkyne, this mechanism can be favored over the previously disclosed concerted α-addition pathway
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