Selenium Nucleophiles Research Articles

Mechanochemical synthesis of organoselenium compounds

We disclose herein a strategy for the rapid synthesis of versatile organoselenium compounds under mild conditions. In this work, magnesium-based selenium nucleophiles are formed in situ from easily available organic halides, magnesium metal, and elemental selenium via mechanical stimulation. This process occurs under liquid-assisted grinding (LAG) conditions, requires no complicated pre-activation procedures, and operates broadly across a diverse range of aryl, heteroaryl, and alkyl substrates. In this work, symmetrical diselenides are efficiently obtained after work-up in the air, while one-pot nucleophilic addition reactions with various electrophiles allow the comprehensive synthesis of unsymmetrical monoselenides with high functional group tolerance. Notably, the method is applied to regioselective selenylation reactions of diiodoarenes and polyaromatic aryl halides that are difficult to operate via solution approaches. Besides selenium, elemental sulfur and tellurium are also competent in this process, which showcases the potential of the methodology for the facile synthesis of organochalcogen compounds.

Access to NHC-Boryl Mono- and Bis-Selenide and Utility as Mild Selenium Transfer Reagent Including to the C-F Bond.

Reactions of 5-SIDipp ⋅ BH3 (5-SIDipp=1,3-bis(2,6-diisopropylphenyl)-imidazolin-2-ylidene) (1) with diphenyldiselenide provide access to 5-SIDipp-boryl mono- (5-SIDipp ⋅ BH2 SePh) (2) and bis-selenide (5-SIDipp ⋅ BH(SePh)2 ) (3). The facile cleavage of the B-Se bond makes 2 a neutral source of selenium nucleophiles in substitutions reactions with benzyl bromides, and provide access to the corresponding selenoethers. The direct transformations of one of the C(sp2 )-F bonds of C5 F5 N and C6 F5 CF3 to C-Se bonds have also been achieved by the use of 2 without employing transition-metal catalysts. While it was previously established that C6 F6 could undergo complete defluoroselenation under harsh conditions, we successfully achieved partial defluorination of C6 F6 by employing 2 as a mild selenide transfer reagent. During the formation of C-Se bonds through the cleavage of C-F bonds, the potential by-product NHC ⋅ BH2 F undergoes ring expansion of the NHC, leading to the formation of the six-membered diaazafluoroborinane (7).

Synthesis of α-Seleno Boronates via Diboration of Carbonyl Compounds.

A method has been described for accessing α-seleno alkyl boronates. The selenoboration was achieved via the diboration of carbonyl compounds to give α-oxyl boronates, which then undergo 1,2-metalate rearrangement in the presence of lithium selenolates and trifluoroacetic anhydride (TFAA). A variety of structurally diverse substrates were compatible with this protocol and efficiently provides difunctionalized products from simple starting materials. The presence of the boronic ester in the resulting organoselenium compounds serves as a versatile synthetic handle for various functionalizations. Mechanistic studies revealed that the binding of selenium nucleophile to both the boron centers in α-oxyl boronate esters.

Selenium and Tellurium Derivatives of Corannulene: Serendipitous Discovery of a One-Dimensional Stereoregular Coordination Polymer Crystal Based on Te-O Backbone and Side-Chain Aromatic Array.

Monobromo-, tetrabromo-, and pentachloro-corannulene are subjected to nucleophilic substitution reactions with tolyl selenide and phenyl telluride-based nucleophiles generated in situ from the corresponding dichalcogenides. In the case of selenium nucleophile, the reaction provides moderate yields (52-77 %) of the targeted corannulene selenoethers. A subsequent oxidation of the selenium atoms proceeds smoothly to furnish corannulene selenones in 81-93 % yield. In the case of tellurides, only monosubstitution of the corannulene scaffold could be achieved albeit with concomitant oxidation of the tellerium atom. Unexpectedly, this monotelluroxide derivative of corannulene (RR'Te=O, R=Ph, R'=corannulene) is observed to form a linear coordination polymer chain in the crystalline state. In this chain, Te-O constitutes the polymer backbone around which the aromatic groups (R and R') arrange as polymer side-chains. The polymer crystal is stabilized through intramolecular π-π stacking interactions of the side-chains and intermolecular hydrogen and halogen bonding interactions with the solvent (chloroform) molecules. Interestingly, each diad of the polymer chain is racemic. Therefore, in terms of stereoregularity, the polymer chain can be described as syndiotactic.

Asymmetric Desymmetrization of Oxetanes for the Synthesis of Chiral Tetrahydrothiophenes and Tetrahydroselenophenes

AbstractChiral tetrahydrothiophenes and tetrahydroselenophenes are highly useful structural units. Described here is a new catalytic asymmetric approach for their synthesis. With a suitable chiral Brønsted acid catalyst, an oxetane desymmetrization by a well‐positioned internal sulfur or selenium nucleophile proceeded efficiently to generate all‐carbon quaternary stereocenters with excellent enantioselectivities. Taming the sulfur and selenium nucleophile in the form of a thioester and selenoester, respectively, is crucial to the success of this work. This approach also allows the facile synthesis of chiral tetrahydrothiopyrans. Mechanistic studies, including DFT calculations, suggested an intramolecular acyl‐transfer pathway. Utilities of the chiral products are also demonstrated.

Asymmetric Desymmetrization of Oxetanes for the Synthesis of Chiral Tetrahydrothiophenes and Tetrahydroselenophenes.

Chiral tetrahydrothiophenes and tetrahydroselenophenes are highly useful structural units. Described here is a new catalytic asymmetric approach for their synthesis. With a suitable chiral Brønsted acid catalyst, an oxetane desymmetrization by a well-positioned internal sulfur or selenium nucleophile proceeded efficiently to generate all-carbon quaternary stereocenters with excellent enantioselectivities. Taming the sulfur and selenium nucleophile in the form of a thioester and selenoester, respectively, is crucial to the success of this work. This approach also allows the facile synthesis of chiral tetrahydrothiopyrans. Mechanistic studies, including DFT calculations, suggested an intramolecular acyl-transfer pathway. Utilities of the chiral products are also demonstrated.

Divergent synthesis of 5',7'-difluorinated dihydroxanthene-hemicyanine fused near-infrared fluorophores.

We describe an expedient access to a 5',6',7'-trifluoro dihydroxanthene-hemicyanine fused scaffold in 2 steps and 54% overall yield from the corresponding salicylic aldehyde. A 6'-regioselective nucleophilic aromatic substitution (SNAr) reaction with a wide range of nitrogen, sulfur or selenium nucleophiles then gives access to 16 near-infrared (NIR) fluorophores emitting in the 710-750 nm range. We also report the experimental and theoretical photophysical investigations of these unique optical agents that include the first series of 6'-heavy atom substituted dihydroxanthenes, extending the pool of polyfluorinated markers for biomedical and material applications.

Metal-Free Synthesis of Unsymmetrical Organoselenides and Selenoglycosides.

A one-pot, metal-free procedure has been developed to synthesize unsymmetrical organoselenides. In the first step of the reaction, arylation of potassium selenocyanate (KSeCN) with an iodonium reagent proceeds in the absence of a metal catalyst to produce an arylselenocyanate. In the second step, treatment with sodium borohydride unmasks a second selenium nucleophile that engages an aliphatic electrophile, iodonium reagent, or glycosyl halide. The procedure represents an umpolung approach to the synthesis of aryl-selenides.

Stereoselective Synthesis of 2-Thio-3-Chloroacrylamides and Investigation of their Reactivity

The stereoselective transformation of 2-thioamides to 2-thio-3-chloroacrylamidesand the investigation of the scope of this transformation, includingextension to ester and nitrile derivatives, is described. Thesehighly functionalised acrylamide derivatives are synthetically versatile,and their reactivity has been investigated in a wide range of transformations,including chemoselective oxidation to the racemic sulfoxide or sulfone,and enantioselective and -diastereoselective oxidationto the sulfoxides. The 2-thio-3-chloroacrylamides were found tobe very effective Michael acceptors in nucleophilic addition/substitutionreactions, dienophiles in Diels-Alder cycloadditions, anddipolarophiles in 1,3-dipolar cycloadditions. The level of oxidationat sulfur was found to strongly influence the reactivity. This accountsummarises synthetic and mechanistic aspects of the research programmefocussed on the synthesis and reactivity of 2-thio-3-chloroacrylamidesin our research group over the past decade. 1 Introduction - Discovery of 2-Thio-2-chloroacrylamides andInitial Observations 2 Synthesis of the β-Chloroacrylamides and Investigationof their Mechanistic Pathway 3 Extension of the Methodology to β-Haloacrylamides, β-Acrylates,and β-Acrylonitriles 4 Oxidation of the β-Chloroacrylamides 4.1 Chemoselective Sulfur Oxidation 4.2 Enantioselective Sulfur Oxidation 4.3 Diastereoselective Sulfur Oxidation 5 Nucleophilic Addition/Substitution Reactions of the β--Chloroacrylamides 5.1 Addition of Carbon Nucleophiles 5.2 Addition of Nitrogen Nucleophiles 5.3 Addition of Oxygen Nucleophiles 5.4 Addition of Sulfur and Selenium Nucleophiles 5.5 Summary of Nucleophilic Additions 6 Reactivity of the β-Chloroacrylamides in Diels-Alder -CycloadditionReactions 6.1 Cycloadditions with Cyclopentadiene 6.2 Cycloadditions with 2,3-Dimethyl-1,3-butadiene 6.3 Summary of Diels-Alder Cycloadditions 7 Reactivity of the β-Chloroacrylamides in 1,3-Dipolar -CycloadditionReactions 7.1 Cycloadditions with Diazoalkanes 7.2 Cycloadditions with Nitrile Oxides and Nitrones 8 Conclusion

A general phosphoric acid-catalyzed desymmetrization of meso-aziridines with silylated selenium nucleophiles

The first example of meso-aziridine desymmetrization with selenium nucleophiles is reported. The reaction, promoted by VAPOL-hydrogen phosphate using (phenylseleno)trimethylsilane as the nucleophile, proves to be very general and highly enantioselective (84-99% ee).

Addition-substitution reactions of 2-thio-3-chloroacrylamides with carbon, nitrogen, oxygen, sulfur and selenium nucleophiles

Synthetically versatile conjugate addition of a range of carbon, nitrogen, oxygen, sulfur and selenium nucleophiles to the highly functionalised 2-thio-3-chloroacrylamides is described. The stereochemical and synthetic features of this transformation are discussed in detail. In most instances, the nucleophile replaces the chloro substituent with retention of stereochemistry. With the oxygen nucleophiles, a second addition can occur leading to acetals, while with the nitrogen nucleophiles, E-Z isomerism occurs in the resulting enamine derivatives. The ratio of the E/Z isomers can be rationalised on the basis of the substituent and the level of oxidation.

5C + 1C/N/S/Se] Annulations of α-Alkenoyl-α-carbamoylketene Dithioacetals: A Facile and Convenient Synthesis of Salicylamide, Nicotinamide and Thio/Selenopyran-3-carboxamide Derivatives

Rapid access to pharmaceutically important scaffolds, including salicylamides, dihydronicotinamides and dihydrothio/dihydroselenopyran­-3-carboxamides, are described. The [5+1]-annulation­ reactions of α-alkenoyl-α-carbamoylketene dithioacetals with carbon, nitrogen, sulfur and selenium nucleophiles give the title­ compounds in high yields under mild conditions.

Modular Synthesis of Chiral N-Protected β-Seleno Amines and Amides via Cleavage of 2-Oxazolidinones and Application in Palladium-Catalyzed Asymmetric­ Allylic Alkylation

A set of chiral β-seleno amines have been efficiently synthesized via the ring-opening reaction of chiral N-acyl oxazolidin-ones by selenium nucleophiles. These compounds could be transformed into β-seleno amides by reaction with acid chlorides. The present method is applicable to the synthesis of β-chalcogeno amides containing selenium, sulfur and tellurium atoms in good yields. Additionally, these new compounds were evaluated as ligands in the palladium-catalyzed asymmetric allylic alkylation, giving the corresponding alkylated products in up to 98% ee.

Synthesis of Hexylselenol and Hexylselenides from Hexylthiol Involving Hexylthiolanium Salts.

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Synthesis of Hexylselenol and Hexylselenides from Hexylthiol Involving ­Hexylthiolanium Salts

Selenium nucleophiles react regioselectively at the endo­cyclic or exocyclic carbon of hexylthiolanium salts depending upon the nature of the salt.

Efficient Synthesis of Chiral β-Seleno Amides via Ring-Opening Reaction of 2-Oxazolines and Their Application in the Palladium-Catalyzed Asymmetric Allylic Alkylation

[structure: see text] A set of chiral beta-seleno amides have been efficiently synthesized via the ring-opening reaction of chiral 2-oxazolines by selenium nucleophiles. The present method is applicable to the synthesis of beta-seleno amides containing thioether, alcohol, and ether moieties in good yields. As an application, the synthesis of a selenocysteine derivative has been accomplished. Additionally, these new compounds were evaluated in the palladium-catalyzed asymmetric allylic alkylation, giving the alkylated products in up to 98% ee.

Synthesis of Primary‐Alkyl Selenols and Selenides from Primary‐Alkyl Thiols Involving Diphenyl Sulfonium Salts.

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Synthesis of primary-alkyl selenols and selenides from primary-alkyl thiols involving diphenyl sulfonium salts

Hexyl thiol has been transformed to hexyl selenol and related selenides and selenocyanate by substitution of the corresponding hexyldiphenylsulfonium tetrafluoroborate with selenium nucleophiles.

Recent New Developments on the Michael Addition of Sulfur and Selenium Nucleophiles

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Allylferrocenylselenide and the synthesis of the first seleno-substituted allenylidene complex: synthesis, spectroscopy, electrochemistry and the effect of electron transfer from the ferrocenylselenyl subunit

Allylferrocenylselenide ( 2) is prepared from diferrocenyldiselenide ( 1Se) which was characterized along with its sulfur analog 1S by X-ray structure analysis. In the crystal lattice the packing is determined by ‘point-to-face’ CH⋯π interactions with close contacts between the CH π donors and cyclopentadienyl rings as the π acceptors. Compound 2 is then used in the trapping of the primary butatrienylidene intermediate trans-[ClRu(dppm) 2CCCCH 2] +. The isolated product, trans-[Cl(dppm) 2RuCCC(SeFc)(C 4H 7)] + ( 3) (Fc=ferrocenyl), represents the first seleno-substituted allenylidene complex to be reported to date. Compound 3 is formed in a sequence involving regioselective addition of the selenium nucleophile to C γ followed by hetero-Cope-rearrangement of the allyl vinyl substituted SeR 3 + cation. Its spectroscopic properties place 3 at an intermediate position between sulfur and arene substituted all-carbon allenylidene complexes of the same metal fragment. The selenoallenylidene complex 3 contains a redox active ferrocenyl substituent attached to the heteroatom giving rise to reversible electrochemistry. ESR spectroscopy proves that electron transfer occurs from this site and its effect on the spectroscopic properties of 3 is probed by combining electrochemistry and IR or UV–vis/NIR spectroscopy by in situ techniques. In contrast, the reversible reduction primarily involves the allenylidene ligand as ascertained by ESR spectroscopy. In situ spectro-electrochemical techniques reveal how the reduction affects the bonding within the unsaturated ligand.