Enantioselective Synthesis of 1-Dihydrobenzazepines through Rh(II)-Catalyzed Cycloisomerization of 1,6-Enyne.

The 1-dihydrobenzazepine skeleton has emerged as a privileged structural motif in bioactive molecules. However, due to a lack of asymmetric methodology, access to chiral 1-dihydrobenzazepines has remained limited. Herein, we report the first intermolecular asymmetric cycloisomerization of benzo-fused enynes for the synthesis of chiral 1-dihydrobenzazepines via dirhodium catalysis.

Gold-Catalyzed 1,2-Rearrangement on Benzene Triggered by a Transient Dearomative Claisen Rearrangement.

1,2-Migration on arenes represents a powerful transformation, because of its chemical skeleton and exit vector editing ability. However, the corresponding dearomative mediated 1,2-migration on arene was ignored for decades, despite tremendous effort being devoted to develop the dearomative reaction, which mainly capitalized on breaking the planarity for three-dimensional diversification. Here, we report on the gold-catalyzed 1,2-rearrangement on benzene by the transient dearomatization of high-resonance energy benzene.

Homologation of Alkenes Using Acetylene as a C2 Feedstock.

Preparation of diverse homologs from lead compounds has been a common and important practice in medicinal, mechano, polymeric and many other branches of chemistry. The homologation of alkenes, though important, remains challenging due to the difficulty of (CH2)n insertion into the main carbon chain of alkenes compared to chains containing other polar functional groups. Here we report the homologation of both terminal and internal alkenes by using acetylene as a cheap and abundant C2 feedstock.

Difluorocarbene-Mediated Trimethylsilylation of Nucleophiles with HCFN(TMS) as a Silylation Reagent.

Described herein is the trimethylsilylation of various nucleophiles using a combination of HCF and NaHMDS. This facile protocol enables the rapid construction of alkynylsilanes, silyl enol ethers, etc., under mild conditions.

Dirhodium-Catalyzed Asymmetric Transformations of Alkynes via Carbene Intermediates.

ConspectusFunctionalization of alkynes is an established cornerstone of organic synthesis. While numerous transition metals exhibit promising activities in the transformations of alkynes via π-insertion or oxidative cyclometalation, Lewis π-acids offer a different approach. By coordinating with alkynes through π-bonding, Lewis π-acids facilitate nucleophilic addition, leading to the formation of alkenyl metal species.

Tandem Rh(ii)-catalyzed 1,3-acyloxy migration/intermolecular [2 + 2] cycloaddition of electron-deficient propargylic esters with alkenes and alkynes.

Transition metal-catalyzed 1,3-acyloxy migration of propargylic esters represents one of the most straightforward routes to access allene intermediates, which could engage in various fascinating subsequent transformations. However, this process is often limited to propargylic esters with electron-donating groups due to intrinsic electronic bias, and the subsequent intermolecular reactions are quite limited. Herein, we disclosed an unprecedented Rh(ii)-catalyzed 1,3-acyloxy migration of electron-deficient propargylic esters, followed by intermolecular [2 + 2] cycloaddition with readily available alkenes and alkynes, and a large array of valuable alkylidenecyclobutane/ene scaffolds could be obtained facilely in one pot.

Dirhodium-Catalyzed [2 + 2 + 2] Cycloaddition of 1,6-Diynes and Alkynes.

A facile method for the construction of fused arenes has been developed through dirhodium-catalyzed [2 + 2 + 2] cycloaddition, which represents a new application of dirhodium complexes. This protocol is convenient to handle without the addition of extra ligands and reductants and tolerates a broad range of functional groups. Mechanistic studies revealed that the two-electron oxidation process, carboxylate ligand departure, and heteroatom coordination-promoted [2 + 2 + 2] cycloaddition were possibly involved.

Leveraging Nonstrained C-C Bonds for Selective Carboacylation of an Unactivated Alkyne via Transient Dearomatization.

Carboacylation of an unsaturated bond represents a powerful transformation. However, only a few examples of carboacylation of alkyne have been reported through C-C bond scission and reconnection. Here, we report a method of carboacylation of an unactivated alkyne by utilizing nonstrained C-C bonds under gold(I) catalysis.

Dirhodium-Catalyzed Enantioselective Synthesis of Difluoromethylated Cyclopropanes via Enyne Cycloisomerization.

(Difluoromethylated cyclopropane represents an important motif, which is widely found in bioactive and functional molecules. Despite significant progress in modern chemistry, the atom-economic and enantioselective synthesis of difluoromethylated cyclopropanes is still challenging. Herein, an Rh (II)-catalyzed asymmetric enyne cycloisomerization is described to construct chiral difluoromethylated cyclopropane derivatives with up to 99% yield and 99% ee in low catalyst loading (0.

Synthesis of -Dienyl Esters Using Acetylene as C2 Synthon.

The stereoselective synthesis of dienyl esters with high atom- and step-economy has been largely unexplored. Herein, we report an efficient approach for the synthesis of -dienyl esters via rhodium catalysis using carboxylic acid and acetylene as C2 synthon through the cascade of cyclometalation and C-O coupling. This protocol features mild conditions, excellent functional group tolerance, and exclusive -stereoselectivity and utility in the late-stage modification of pharmaceuticals and natural products.

1,2-Difunctionalization of Acetylene Enabled by Light.

Although the direct conversion of gaseous acetylene into value-added liquid commodity chemicals is becoming increasingly attractive, the majority of the established methodologies are focused on cross-coupling, hydro-functionalization, and polymerization. Herein, we describe a 1,2-difunctionalization method that inserts acetylene directly into readily available bifunctional reagents. This method provides access to diverse C2-linked 1,2-bis-heteroatom products in high regio- and stereoselectivity along with opening up previously unexplored synthetic directions.

Synthesis of vinyl-substituted alcohols using acetylene as a C2 building block.

Vinyl-substituted alcohols represent a highly useful class of molecular skeletons. The current method typically requires either stoichiometric metallic reagents or preformed precursors. Herein, we report a nickel catalysis-enabled synthesis of vinyl-substituted alcohols a 5-membered oxa-metallacycle.

Correction: Synthesis of vinyl-substituted alcohols using acetylene as a C2 building block.

[This corrects the article DOI: 10.1039/D2SC06400F.].

De Novo Synthesis of α-Oligo(arylfuran)s and Its Application in OLED as Hole-Transporting Material.

Tuning the photophysical properties of π-conjugated oligomers by functionalization of skeleton, to achieve an optically and electronically advantageous building block for organic semiconductor materials is a vital yet challenging task. In this work, a series of structurally well-defined polyaryl-functionalized α-oligofurans, in which aryl groups are introduced precisely into each of the furan units, are rapidly and efficiently synthesized by de novo metal-free synthesis of α-bi(arylfuran) monomers for the first time. This new synthetic strategy nicely circumvents the cumbersome substituent introduction process in the later stage by the preinstallation of the desired aryl groups in the starting material.

Gold-Catalyzed Enynal and Enynol Coupling by Selectively Steering Two Transient Vinyl-Gold Intermediates.

The vinyl-gold bond is easily accessible but less exploited in homogeneous gold catalysis, which possesses weak nucleophilicity and would be likely to undergo protodemetalation. Herein, a gold-catalyzed enynal and enynol coupling by selectively steering two transient vinyl-gold intermediates is realized under mild conditions. It exhibits high atom economy and good tolerance of functional groups with the added benefit of operational simplicity.

Palladium-catalyzed intramolecular enantioselective C(sp)-H insertion of donor/donor carbenes.

Herein, the first palladium-catalyzed intramolecular enantioselective C(sp)-H insertion reaction of donor-donor carbenes has been successfully achieved. This facile protocol enables the rapid construction of a collection of enantioenriched decorated indolines with two contiguous stereocenters in a single step. Both enynones and diazo compounds are efficient donor-donor carbene precursors for this reaction.

Construction of [2,5]-Furanophanes by Carbene-Mediated Alkynyl Migration Cyclization.

Heterophanes are widely found in natural products and drug molecules. Herein, an efficient method for the construction of [2,5]-furanophanes with different ring types and ring sizes was developed. This method is carried out with furan-free precursor through intramolecular carbene-mediated alkynyl migration and tandem cyclization strategy.

Identification of the gossypol derivatives as androgen receptor inhibitor.

Prostate cancer (PCa) is the most frequently diagnosed male malignant tumor and remains the second leading cause of male cancer mortality in western countries. The development of novel antiandrogens to circumvent the drug resistance in anti-PCa treatment is highly demanded. Herein, we identified that gossypol (GOS) specificly inhibited the AR signaling.

Thiol-Yne click chemistry of acetylene-enabled macrocyclization.

Macrocycles have fascinated scientists for over half a century due to their aesthetically appealing structures and broad utilities in chemical, material, and biological research. However, the efficient preparation of macrocycles remains an ongoing research challenge in organic synthesis because of the high entropic penalty involved in the ring-closing process. Herein we report a photocatalyzed thiol-yne click reaction to forge diverse sulfur-containing macrocycles (up to 35-membered ring) and linear C2-linked 1,2-(S-S/S-P/S-N) functionalized molecules, starting from the simplest alkyne, acetylene.

Divergent synthesis of benzazepines and bridged polycycloalkanones via dearomative rearrangement.

The dearomative functionalization of aromatic compounds represents a fascinating but challenging transformation, as it typically needs to overcome a great kinetic barrier. Here, a catalyst-free dearomative rearrangement of o-nitrophenyl alkyne is successfully established by leveraging the remote oxygen transposition and a weak N-O bond acceleration. This reaction features high atom-, step- and redox-economy, which provides a divergent entry to a series of biologically important benzazepines and bridged polycycloalkanones.

Cu-catalyzed carboboration of acetylene with Michael acceptors.

A copper-catalyzed three-component carboboration of acetylene with BPin and Michael acceptors is reported. In this reaction, a cheap and abundant C2 chemical feedstock, acetylene, was used as a starting material to afford -alkenyl boronates bearing a homoallylic carbonyl group. The reaction was robust and could be reliably performed on the molar scale.

Diverse synthesis of C2-linked functionalized molecules via molecular glue strategy with acetylene.

As the simplest alkyne and an abundant chemical feedstock, acetylene is an ideal two-carbon building block. However, in contrast to substituted alkynes, catalytic methods to incorporate acetylene into fine chemicals are quite limited. Herein, we developed a photoredox-catalyzed synthetic protocol for diverse C2-linked molecules via a molecular glue strategy using gaseous acetylene under mild conditions.