RESUMO
A visible-light-induced photocatalyst-free acylative pyridylation of styrenes with 4-acyl-1,4-dihydropyridines (DHPs) and 4-cyanopyridines has been described, featuring mild reaction conditions, a broad substrate scope, and good functional group tolerance. The reaction could also be performed under sunlight irradiation albeit with a slightly lower conversion. 4-Acyl-1,4-DHPs serve a dual role, acting as both a photoreductant to reduce the cyanopyridine to its radical anion intermediate and a radical precursor to produce the acyl radical. The mechanism was especially elucidated through the Hammett analysis, with the quadratic linear regression analysis by using radical dual parameters, σmb and σjj·. The findings from Hammett analysis further demonstrate that the rate-limiting step of the process is the single electron transfer between 4-acyl-1,4-DHPs and 4-cyanopyridines.
RESUMO
An iridium-catalyzed and phenol-directed deoxygenation of benzylic alcohols comes as an alternative access to 4-alkylphenols, featuring low catalyst loading (S/C up to 20,000, TOF up to 12,400 h-1), high functionality compatibility, and excellent site-selectivity. The applications in late-stage modification of steroids and gram-scale total synthesis of a Gastrodia elata extract are highlighted. Mechanistically, the intermediacy of quinone methide controls the site-selectivity, and the formation of iridium hydride serves as the rate-limiting step.
RESUMO
A direct regioselective C-H cyanation of purines was developed through a sequential triflic anhydride activation, nucleophilic cyanation with TMSCN, followed by a process of base-mediated elimination of triflous acid (CF3SO2H). In most cases, the direct C-H cyanation occurred on the electron-rich imidazole motif of purines, affording 8-cyanated purine derivatives in moderate to excellent yields. Various functional groups, including allyl, alkynyl, ketone, ester, nitro et al. were tolerated and acted as a C8 directing group. The electron-donating 6-diethylamino, as C2-directing group substituent, can switch the regioselectivity of purine from 8- to 2-position, enabling the synthesis of 8- and 2-cyano 6-dialkylaminopurines from corresponding 6-chloropurine in different reaction order. Further functional manipulations of the cyano group allow the conversions of 8-cyanopurines to corresponding purine amides, imidates, imidothioates, imidamides, oxazolines, and isothiazoles.
RESUMO
A metal-free cross-dehydrogenation coupling method was established to synthesize N9 alkylated purine derivatives. Using PhI(OAc)2 as the oxidant, versatile thioethers were successfully employed as alkylation reagents. Under the optimized conditions, a variety of alkylated purine derivatives and other aromatic N-heterocycles were obtained in moderate to good yields. The regioselectivity of this protocol which involves the reaction of unsymmetrical thioethers with purine derivatives was also studied.
RESUMO
A base-free bis-alkyl thiolation reaction of indoles with sulfinothioates under Pummerer-type conditions is described. Sulfinothioates, activated with 2,2,2-trifluoroacetic anhydride, are demonstrated to be an efficient thiolation reagent for wide applications. This approach enabled double C-H thiolation at the C2 and C3 of the indole in one pot. The mechanism studies suggested the thiolation was realized through the sulfoxonium salt rather than sulfenyl carboxylate.
Assuntos
Indóis , Indicadores e ReagentesRESUMO
A visible-light-enabled, photocatalyst-free conjugate addition reaction of dehydroamino acids is disclosed. Employing 4-acyl-1,4-dihydropyridines as both a radical reservoir and reductant, various ß-acyl α-amino acids and their deuterated analogues were obtained in good results. Both late-stage peptide modification and stereoselective synthesis of chiral oxazolidinones are successfully achieved. The protocol is characterized by mild conditions and efficient derivatization, thus unlocking a novel blueprint to access unnatural amino acid derivatives, important building blocks with potential application in the peptidomimetic toolbox.
RESUMO
Herein we report a protocol for the visible-light-mediated alkylation/acylation reaction of benzothiazoles. Alkyl/acyl substituted Hantzsch esters are easily prepared and rationally used as radical precursors. In the presence of BF3·Et2O and Na2S2O8, various benzothiazole derivatives were readily obtained in good yields. Our user-friendly protocol can proceed by simple irradiation with blue LEDs (λ = 465 nm) and without the assistance of external photocatalysts. The reaction is also characterized by mild conditions and scalability, thus offering an alternative and efficient tool for the synthesis of 2-functionalized benzothiazoles.
RESUMO
A catalyst-free cross-dehydrogenative coupling reaction of purines and some azoarenes with dialkyl disulfides has been developed. This procedure provided a novel strategy to construct unsymmetrical disulfides through the α-heterocyclic functionalization of symmetrical dialkyl disulfides. The S-S bond was successfully tolerated in this transformation. The mild conditions and the broad scope of azoarenes indicated the potential application of this procedure.
RESUMO
A phenyltrimethylammonium tribromide-mediated nucleophilic substitution/oxygen transformation reaction of benzyl halides with DMSO has been developed. In this transition-metal-free reaction, DMSO acts as not only a solvent but also a "S(O)Me" source, thus providing a convenient method for the efficient and direct synthesis of various benzyl methyl sulfoxides.
RESUMO
Various functionalized thietanes were prepared from thiiranes via an electrophilic ring expansion with rhodium carbenoids as electrophiles generated from safe and readily accessible dimethylsulfonium acylmethylides. The reaction appears to proceed through electrophilic metallocarbenoid-induced activation of thiiranes, nucleophilic ring-opening of the activated thiiranes with dimethyl sulfide as a transient nucleophile, and nucleophilically intramolecular cyclization. The Umpolung from the nucleophilic ylides to the electrophilic carbenoids plays an important role in both the activation and ring opening of thiiranes and subsequent cyclization. The current method provides a new strategy for the efficient preparation of functionalized thietanes from readily available thiiranes.
RESUMO
Synthesis of α-heterosubstituted ketones was achieved through sulfur mediated difunctionalization of internal alkynes in one pot. The reaction design involves: phenyl substituted internal alkyne attacking triflic anhydride activated diphenyl sulfoxide to give a sulfonium vinyl triflate intermediate, hydrolysis to give an α-sulfonium ketone, and then substitution with various nucleophiles. This method provides a unified route to access α-amino ketones, α-acyloxy ketones, α-thio ketones, α-halo ketones, α-hydroxy ketones, and related heterocyclic structures, in a rapid fashion.
RESUMO
A sulfur-mediated electrophilic cyclization reaction of aryl-tethered internal alkynes has been developed. Triflic anhydride-activated sulfoxides induced the electrophilic cyclization and then demethylation with triethylamine in one pot, affording 3-sulfenyl-1,2-dihydronaphthalenes and related types of products in yields of ≤96%.
RESUMO
Polysubstituted furans were prepared in moderate to good yields from various sulfur ylides and alkyl acetylenic carboxylates. The direct reactions of dimethylsulfonium acylmethylides with dialkyl acetylenedicarboxylates afforded dialkyl furan-3,4-dicarboxylates through a tandem sequence of Michael addition, intramolecular nucleophilic addition, 4π ring opening, intramolecular Michael addition, and elimination. The method was extended to synthesize furan-3-carboxylate, -2,4-dicarboxylates, and -2,3,4-tricarboxylates as well. The current method provides a direct and simple strategy in the synthesis of structurally diverse polysubstituted furans with mono to tricarboxylate groups from safe and readily available dimethylsulfonium acylmethylides and different alkyl acetylenic carboxylates.
RESUMO
The efficient synthesis of 2-substituted thiazoles and benzothiazoles has been accomplished employing readily available cysteine esters and 2-aminobenzenethiols as N and S sources. The reaction proceeds under an I2/TBHP system and involves a one-pot tandem cyclization and oxidation sequence. A diverse range of aldehydes is amenable for this transition-metal-free protocol, which provides an alternative method to rapidly access thiazole-containing molecules.
RESUMO
Stereochemical models and mechanistic insights are proposed for [2t + 2i + 2i] annulations of thioketenes and imines on the basis of experimental and computational investigations. In the [2t + 2i + 2i] annulations involving cyclic imines, the zwitterionic intermediates generated from monosubstituted thioketenes and the cyclic imines undergo a stepwise nucleophilic endo-addition/Si-face attack pathway with a second imines molecule, giving initially (2,4)-cis-(4,5)-cis-[2t + 2i + 2i] annuladducts, which completely epimerize into the corresponding (2,4)-cis-(4,5)-trans-annuladducts under basic reaction conditions. The annuloselectivity of thio-Staudinger cycloadditions is dependent on the substituents of both thioketenes and imines. The reactivities and annuloselectivities of Staudinger, thio-Staudinger, and sulfa-Staudinger intermediates are compared.
Assuntos
Etilenos/química , Iminas/química , Cetonas/química , Enxofre/química , Ciclização , Reação de Cicloadição , Cinética , Modelos Moleculares , Conformação Molecular , EstereoisomerismoRESUMO
Cationic rearrangement reactions usually follow Markovnikov's rule to give more substituted carbocations as stable intermediates. During our study on sulfur mediated allylic C-H amination of olefins, very rare cases of anti-Markovnikov rearrangement from secondary carbocations toward primary carbocations or primary triflates were observed.
RESUMO
A palladium-catalyzed alkoxylation of N(9)-arylpurines with primary or secondary alcohols has been developed successfully, which is a rare C-H activation reaction of polynitrogenated purines and offers a late-stage strategy to synthesize N(9)-(ortho-alkoxyl)arylpurines. Although there are more than four nitrogen atoms present in the purine moiety, the reaction can be effectively conducted by sterically blocking the N(1) site for catalyst coordination and first employing the purinyl N(3) atom as a directing group.
RESUMO
A novel copper-catalyzed intramolecular dehydrogenative alkoxylation of purine nucleosides has been developed successfully, providing the 5'-O,8-cyclopurine nucleosides in one-step with a yield up to 90%. The method, which utilized an inexpensive CuCl catalyst and a di-tert-butyl peroxide (DTBP) oxidant was suitable in a broad substrate scope and proceeded well even in gram scale.
RESUMO
In this study, we report BF066, a novel adenine derivative, inhibits platelet activation and thrombosis via the adenosine receptor (A(2A)) activation and phosphodiesterase (PDE) inhibition. BF066 inhibits platelet aggregation and ATP releasing induced by multiple platelet agonists in a dose-dependent manner. The inhibition of BF066 on ADP-induced aggregation is potentiated by adenosine and can be dramatically antagonized by the A(2A) antagonist SCH58261. BF066 also inhibits the PDE activity and platelet spreading on fibrinogen. In FeCl(3)-injured mouse mesenteric arterial thrombosis model, BF066 prevents thrombus formation effectively, similar to clopidogrel. Intriguingly, at dose achieving similar antithrombotic effect compared to clopidogrel, BF066 does not increase bleeding significantly. Taken together, these results suggest that BF066 may be an effective and safe antiplatelet agent targeting both PDE and A(2A). Considering the successful use of combined antiplatelet therapy, BF066 may be further developed as a novel dual target antiplatelet agent.