Pyrone Isomerization Enabled Divergent Access to Multisubstituted Biaryl Phenol via Relay Claisen Rearrangement.

Arene isomerization can simultaneously edit the arene backbone and its periphery, thereby bridging the independent chemistry of two distinct arenes. Herein, a facile pyrone isomerization approach for the divergent synthesis of five- and sixfold-substituted biaryl phenols is achieved by using a relay Claisen rearrangement as a crucial step. This catalyst-free isomerization reaction features high step, atom, and redox economy by transferring the innate oxidation state of pyrone into the biaryl phenols.

Claisen rearrangement enabled efficient access to biaryl phenols.

A rapid method for C2-arylation of hydroxypyranone systems a reductive iodonio-Claisen rearrangement (RICR) of λ-iodanes is reported. By integrating the rearrangement products with a tandem Claisen reaction, a series of otherwise inaccessible biaryl phenols were efficiently synthesized.

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.

Chemoselective Thioacylation of Amines Enabled by Synergistic Defluorinative Coupling.

A mild and chemoselective method for the thioacylation of amines, including amino acids and peptides, using -difluoroalkenes and sulfide, is reported. The distinguishing of the different nucleophilic sites (-site and diverse -sites) by the chemoselective C-F bond functionalization of -difluoroalkenes enables the unique synergistic defluorinative coupling reaction. This reaction features mild conditions, is operationally simple, efficient, and gram-scalable, tolerates various functional groups, and is activator-free and without racemization.

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.

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.

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.

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.

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.

Migratory insertion of copper-allenylidene from propargyl ester.

The highly efficient copper-catalyzed homo-dimerization and cross-coupling of propargyl esters have been developed. Various 1-en-3,5-diynes, [5]cumulenes and 1,3-diynes were successfully furnished the copper-allenylidene intermediates with moderate to excellent yields. Migratory insertion is proposed as the key step to achieve the selectivity at the carbene carbon of the copper-allenylidene.

Rh(ii)-catalyzed enantioselective intramolecular Büchner reaction and aromatic substitution of donor-donor carbenes.

The chiral dirhodium(ii) tetracarboxylate-catalyzed enantioselective intramolecular Büchner reaction of donor/donor-carbenes was reported and a series of valuable chiral polycyclic products were synthesized. Both aryloxy enynones and diazo compounds were efficient carbene precursors for this reaction. Excellent yields (up to 99%) and outstanding enantioselectivities (up to >99% ee) were achieved under standard conditions.

Bottom-up modular synthesis of well-defined oligo(arylfuran)s.

Oligofurans have attracted great attention in the field of materials over the last decades because of their several advantages, such as strong fluorescence, charge delocalization, and increased solubility. Although unsubstituted or alkyl-substituted oligofurans have been well-established, there is an increasing demand for the development of the aryl decorated oligofuran with structural diversity and unrevealed properties. Here, we report the bottom-up modular construction of chemically and structurally well-defined oligo(arylfuran)s by de novo synthesis of α,β'-bifuran monomers and late-stage bromination, stannylation and subsequent coupling reaction.

Enantioselective Rh(II)-Catalyzed Desymmetric Cycloisomerization of Diynes: Constructing Furan-Fused Dihydropiperidines with an Alkyne-Substituted Aza-Quaternary Stereocenter.

Described herein is an enantioselective dirhodium(II)-catalyzed cycloisomerization of diynes achieved by the strategy of desymmetrization, which not only represents a new cycloisomerization reaction of diynes but also constitutes the first Rh(II)-catalyzed asymmetric intramolecular cycloisomerization of 1,6-diynes. This protocol provides a range of valuable furan-fused dihydropiperidine derivatives with an enantiomerically enriched alkynyl-substituted aza-quaternary stereocenter in high efficiency, complete atom economy, and excellent enantioselectivity (up to 98% ee). Besides, the highly functionalized products could be easily transformed into various synthetically useful building blocks and conjugated with a series of pharmaceutical molecules.

Catalyst-free synthesis of isoxazolidine from nitrosoarene and haloalkyne via a 1,2-halo-migration/[3 + 2] cycloaddition cascade.

An unprecedented catalyst-free three-component reaction to synthesize isoxazolidine from easily accessible haloalkyne, nitrosoarene and maleimide was developed. This reaction was proposed to proceed via a 1,2-halo migration and [3 + 2] cycloaddition cascade, providing a new reaction pattern of alkyne and nitroso containing species wherein a new type of nitrone was generated. Besides, the reaction conditions were efficient and environmentally benign, enabling the formation of various bioactivity-related isoxazolidines.

Copper-Catalyzed Asymmetric Synthesis of Bicyclo[3..1]alkenones.

A series of highly strained bicyclo[3..1]alkenones have been successfully constructed in good-to-excellent enantioselectivities and moderate-to-good yields via copper-catalyzed formal [3+3] cycloaddition.

Benzene-Free Synthesis of Multisubstituted Catechol via Oxidative Dearomatic Reorganization.

A benzene-free synthesis of multisubstituted catechol via an oxidative dearomatic reorganization is reported. This reaction tolerated a wide spectrum of functionalities, which could be applied in the synthesis of an electron-deficient arene-conjugated catechol that is difficult to access via biomimetic oxidative coupling. In addition, a diversification-oriented transformation that leveraged the versatile catechol afforded a series of functionality-rich products.

Catalytic regio- and stereoselective intermolecular [5+2] cycloaddition via conjugative activation of oxidopyrylium.

A catalytic stereodivergent intermolecular [5+2] cycloaddition of maltol-type oxidopyrylium through conjugative activation was reported, which featured high stereoselectivity, good compatibility and mild conditions, providing a convenient access route to various seven-membered heterocycles in moderate to excellent yields. In addition, a discrete mechanism was proposed to illustrate the stereoselectivity.

Deconstructive Reorganization: De Novo Synthesis of Hydroxylated Benzofuran.

An unprecedented deconstructive reorganization strategy for the de novo synthesis of hydroxylated benzofurans from kojic acid- or maltol-derived alkynes is reported. In this reaction, both the benzene and furan rings were simultaneously constructed, whereas the pyrone moiety of the kojic acid or maltol was deconstructed and then reorganized into the benzene ring as a six-carbon component. Through this strategy, at least one free hydroxyl group was introduced into the benzene ring in a substitution-pattern tunable fashion without protection-deprotection and redox adjustment.

Mechanism-Guided Scaffold Diversification: Perturbing and Trapping the Intermediates of Maltol-Type Cascade Claisen Rearrangement.

A mechanism-guided study to harness different kinds of active species in the cascade Claisen rearrangement for scaffold diversification has been developed. These robust and practical processes furnished a series of architectures with a large chemical space, varying from planar to three-dimensional. In addition, several interesting reactions were observed, such as [3 + 3] dimerization, quinone-based vinylogous Nazarov-type cyclization, and a rare 12e [σ2a + π2s + π2a + π2s + (π2a + π2s)] Mobius aromatic transition state mediated rearrangement.

Cascade Claisen Rearrangement: Rapid Synthesis of Polysubstituted Salicylaldehydes and Total Syntheses of Hemigossypol and Gossypol.

A cascade Claisen rearrangement of a well-organized maltol propargyl ether for the construction of polysubstituted salicylaldehydes is reported. This reaction features high atom economy (100 %), as well as catalyst-free and gram-scale conditions. Based on this novel methodology, the total synthesis of hemigossypol, gossypol, and their analogues has been realized.

Gold-Catalyzed Ring Expansion of Enyne-Lactone: Generation and Transformation of 2-Oxoninonium.

An efficient gold-catalyzed ring-expansion reaction of enyne-lactones to form 2-oxoninonium intermediates is reported. The 2-oxoninonium generated in this work could undergo further 6π electrocyclization and aromatization reaction to produce different aromatic compounds.