A practical method is introduced for the catalytic conversion of terminal alkynes into α-substituted vinyl boronic esters. The process employs catalytic amounts of nanoparticle-supported gold catalysts and catalytic amounts of copper to effect the overall transformation.
The synthesis of bibenzyl derivatives holds significance in organic chemistry due to their diverse pharmacological and synthetic applications. Herein, we report a novel copper-promoted dimerization reaction for the efficient synthesis of functionalized bibenzyls from benzyl thiocyanates. The coupling reaction proceeds under aerobic and mild conditions through a cascade C–S bond cleavage in one pot. Diverse substituents, including electron-withdrawing groups on the aryl ring, are well tolerated to afford the desired products in moderate to good yields. The developed protocol could be utilized to obtain the cross-coupling product from two different electron-deficient benzyl thiocyanates.
We have developed an efficient method for the synthesis of 2,3-dihydro-1H-1-benzosiloles in 19% to 90% isolated yield from 1-hydrosilyl-2-ethynylbenzenes by using two equivalents of diisobutylaluminum hydride. The reaction mechanism involves regioselective double hydroalumination of the alkyne moiety followed by cyclization to a 2-alanyldihydrobenzosilole. A silacyclopentane (silolane) was also synthesized in 97% isolated yield from the corresponding 4-silylbut-1-yne under the same reaction conditions. Although the substrate-scope study was conducted on a 0.5-mmol scale, a gram-scale reaction of (2-ethynylphenyl)(diphenyl)silane under the optimized reaction conditions successfully afforded the desired product in 94% isolated yield without loss of reactivity.
The NBS-mediated organocatalytic cascade synthesis of 4,5-dihydronaphtho[2,1-b]furan-1-carbaldehydes from α,β-unsaturated aldehydes and 2-tetralones have been developed. In this synthesis strategy, the C1 of in situ generated brominated 2-tetralone was used as identical twin electron donor–acceptor, and the Cβ and Cα of enals were used as the heterogeneous twin electron acceptor–donors. The process has been realized by a synergistic amine/p-TSA catalyzed one-pot cascade Michael addition–cyclopropanation–ring opening–oxa-Michael addition under mild conditions and without the use of transition metals.
Cross-coupling methods for the introduction of various substituents onto the olefin moiety of cyclooctenes were developed. A range of 1-substituted cis-cyclooctenes were synthesized. These protocols unlocked routes to previously inaccessible derivatives, permitting the syntheses of cis-cyclooctenes bearing various functional groups. Moreover, the method was applied to the synthesis of a 1,2-disubstituted trans-cyclooctene for the first time, which proved to be a significantly more active organocatalyst than the previously developed monosubstituted trans-cyclooctene.
The modification of biomolecules, particularly peptides, has garnered considerable attention from researchers, effectively serving as a connection between chemistry and biology. The modification of peptides can facilitate, among others, the generation of peptide drugs, antibody–drug conjugates, and probes for molecular imaging. Herein, we have carefully curated reactions and chemical transformations of bioactive peptide sequences equipped with histidine amino acids that are conducive for biological applications. This Account also highlights strategies for the chemical modification of histidine that might capture the imagination of both peptide researchers and synthetic chemists.1 Introduction2 Histidine Modification in Bioactive Peptides and Proteins3 Remote Bioactive Peptides and Protein Modification Adjacent to Histidine4 Conclusions and Future Directions
An unprecedented post-Ugi Brønsted acid catalyzed fragmentation followed by in situ trapping of the alkylideneindolenine intermediate by indole nucleophiles was developed to furnish novel bis(indolyl)acetamides. The amide fragment formed during this acid-catalyzed fragmentation of the Ugi adduct was also isolated and characterized. The carboxylic acid and amine components of the Ugi reaction were carefully chosen to permit a simple water wash for the removal of the amide fragment to obtain the desired bis(indolyl)acetamides in a pure form.
The practical, rapid development of chemical leads for drug discovery depends strongly on scalable building block synthesis procedures. N-Heterocyclic moieties, especially unsaturated ones, remain essential tools in the hands of screening and medicinal chemists. Here, we report four novel chemical block families and the interconversions between them. The synthesis of 4,4-disubstituted 3-oxopyrrolidones was an essential milestone in the diversity-oriented production of 3-aminopyrrolidones, 3-hydroxypyrrolidones, and 3,3′-difluoropyrrolidines. These compounds can be functionalized with conformationally flexible spirocyclic substituents. We developed a multigram procedure to access 4,4-disubstituted 3-oxopyrrolidones from commercially accessible and cost-saving reagents via a short three-step procedure. Here, we report the robust conversion of 3-oxopyrrolidones into 3-aminopyrrolidones, 3,3′-difluoropyrrolidones, and 3-hydroxypyrrolidones, involving a minimal number of steps. We demonstrate the scope and limitations and further perspectives for such synthetic approaches.
Propylene liquid-phase epoxidation with 50–75% H2O2 is an important process for the industrial production of propylene oxide (PO). To realize a propylene epoxidation process that proceeds with low hydrogen peroxide concentration, we developed an integrated Mn/TS-1/N catalytic system via in-situ reaction of Mn/TS-1 with an N-donor ligand, affording the PO product in excellent yield with only 30 wt% H2O2. Other long-chain aliphatic epoxides were also readily synthesized by this catalytic epoxidation system. Moreover, in addition to the standard micro-pressure reactor, a continuous-flow microreactor was developed that executed the hydrogen peroxide propylene oxide (HPPO) process with excellent efficiency for 1300 hours. This innovative Mn/TS-1/N catalyzed epoxidation represents a promising direction for advancing HPPO industrial processes, offering improved efficiency while minimizing the reliance on high concentrations of H2O2.
A highly enantioselective synthetic method for 3,4-trans-dihydropyrans was developed by the reaction of α-acyl-β-aryl-substituted acrylonitrile and aldehyde catalyzed by diphenylprolinol silyl ether. This is an asymmetric domino reaction via a catalytic Michael reaction/enolization/acetalization.