Organophosphine as an Alkyl Transfer Shuttle for the Direct ß-Alkylation of Chalcones Using Alkyl Halides.

We report an efficient alkyl transfer strategy for the direct ß-alkylation of chalcones using commercially available alkyl bromides as alkyl reagents. In this transformation, the ortho-phosphanyl substituent in the chalcones is crucial for controlling their reactivity and selectivity. It also serves as a reliable alkyl transfer shuttle to transform electrophilic alkyl bromides into nucleophilic alkyl species in the form of quaternary phosphonium salts and transfer the alkyl group effectively to the ß-position of the chalcones. This alkyl transfer strategy can be further extended to the alkenylation of ortho-phosphanyl benzaldehydes to assemble functionalized polyenes.

Dearomative Periphery Modification of Quinolinium Salts to Assemble Ring-Encumbered Pyrrolidine-Tetrahydroquinoline Polycycles.

We report an unexpected dearomative periphery modification strategy for transforming quinolinium salts into structurally crowded pyrrolidine-tetrahydroquinoline polycyclic systems with complete regio- and diastereoselectivity. Importantly, the reaction pathway was regulated by simply tuning the substituents, achieving substituent-directed divergent synthesis. The notable features of this transformation include readily available starting materials, green conditions, a simple workup procedure, high bond- and ring-forming efficiency, and substituent-directed diverse synthesis.

Delivering 2-Aryl Benzoxazoles through Metal-Free and Redox-Neutral De-CF3 Process.

An unexpected cleavage of the Csp3-CF3 bond of CF3-hydrobenzoxazoles has been disclosed, affording a range of 2-aryl benzoxazoles under metal-free and redox-neutral conditions. This transformation has demonstrated broad substrate scope and good compatibility of functional groups. 2-Aryl benzothiazole and 2-aryl benzoimidazole could be smoothly assembled in the same manner. On the basis of preliminary mechanistic studies, base initiated and aromatization driven ß-carbon elimination was considered to be the key step for the formation of 2. This reaction offers an alternative, facile, and sustainable route to access important 2-aryl benzoxazole motifs.

Regioselective and Diastereoselective Dearomative Multifunctionalization of In-Situ-Activated Azaarenes: An Access to Bridged Azaheterocycles.

Reported herein is an unprecedented multicomponent one-pot dearomative multifunctionalization of commercially available azaarenes through an in situ activation strategy, which not only achieved the first full exploitation of the reactive sites of the azaarenes, but also accomplished the efficient synthesis of bridged hydrogenated pyridines and (iso)quinolines in a highly regioselective and diastereoselective manner. In addition, we could successfully realize the step-controlled dearomative trifunctionalization and bifunctionalization of quinolines.

Chalcone-Based Pyridinium Salts and Their Diastereoselective Dearomatization To Access Bibridged Benzoazepines.

New chalcone-based pyridinium salts have been successfully exploited, which could smoothly participate in the highly diastereoselective dearomatization with binucleophilic enaminones by taking advantage of their multiple reactive sites to construct bibridged benzoazepines in up to 89% yields. The key to the success was the skillful and unprecedented C-3 functionalization of the new pyridinium salts. This work not only provides a kind of novel pyridinium salt synthon but also achieves the first C-3 functionalization of pyridinium salts to construct complex and challenging bibridged benzoazepines with high synthetic efficiency.

Regio- and diastereoselective dearomatizations of N-alkyl activated azaarenes: the maximization of the reactive sites.

An unprecedented base-promoted multi-component one-pot dearomatization of N-alkyl activated azaarenes was developed, which enabled the synthesis of complex and diverse bridged cyclic polycycles with multiple stereocenters in a highly regio- and diastereoselective manner. Besides, we realized the step-controlled dearomative bi- and trifunctionalization of quinolinium salts. These transformations not only achieved the maximization of the reaction sites of pyridinium, quinolinium and isoquinolinium salts to enhance structural complexity and diversity, but also opened up a new reaction mode of these N-activated azaarenes. A unique feature of this strategy is the use of easily accessible and bench-stable N-alkyl activated azaarenes to provide maximum reactive sites for dearomative cascade cyclizations. In addition, the salient characteristics including high synthetic efficiency, short reaction time, mild conditions and simple operation made this strategy particularly attractive.

Diastereoselective construction of 4-indole substituted chromans bearing a ketal motif through a three-component Friedel-Crafts alkylation/ketalization sequence.

The first TfOH-catalyzed three-component Friedel-Crafts alkylation/ketalization sequence of indoles, alcohols and ortho-hydroxychalcones was developed to afford a wide range of 4-indole substituted chromans bearing a ketal motif in 77-99% yields. Notably, only a simple filtration was needed to purify them. By altering methanol to CHCl3, 2,4-bisindole substituted chroman with the same indole substituent at the C2 and C4 positions was afforded. Moreover, 2,4-bisindole substituted chromans with different indole substituents could be obtained by treatment of 4-indole monosubstituted chromans with another indole molecule.

A copper-catalyzed tandem reaction for the construction of coumarin fused 9H-pyrrolo[1,2-a]indoles.

An efficient copper-catalyzed Friedel-Crafts alkylation/cyclization/isomerization sequence of 3-arylcarbonyl coumarins and 3-methyl indole was developed to afford a wide range of functionalized coumarin fused 9H-pyrrolo[1,2-a]indoles, which feature a 6-6-5-5-6 pentacyclic core, in 34-99% yields. Moreover, gram-scale experiment and chemical transformations were conducted to demonstrate the synthetic value of this protocol.

A Copper-Catalyzed Friedel-Crafts Alkylation/Cyclization Sequence: an Approach to Functionalized Pyrrolo[1,2-a]indole Spirooxindoles and 9H-Pyrrolo[1,2-a]indoles.

An efficient Cu(OTf)2-catalyzed Friedel-Crafts alkylation/cyclizaiton sequence of 3-substituted indoles with isatin-derived oxodienes was developed, and a series of structurally complex and diverse pyrrolo[1,2-a]indole spirooxindoles were first obtained in up to 99% yields. This protocol proved to be quite general and was also robust for the synthesis of 9H-pyrrolo[1,2-a]indoles.

A DBU-catalyzed Michael-Pinner-isomerization cascade reaction of 3-hydroxyoxindoles with isatylidene malononitriles: access to highly functionalized bispirooxindoles containing a fully substituted dihydrofuran motif.

The first DBU-catalyzed Michael/Pinner/isomerization cascade reaction of 3-hydrooxindoles with isatylidene malononitriles was developed, and the corresponding highly functionalized bispirooxindoles containing a fully substituted dihydrofuran motif were obtained in up to 92% yields. This protocol also provides an efficient method for the synthesis of an α-cyano-γ-butyrolactone bispirooxindole. In addition, a one-pot three-component cascade reaction was conducted. Also, the asymmetric version of the cascade reaction was achieved.

A FeCl3-catalyzed highly regioselective 1,2-addition/substitution sequence for the construction of coumarin-substituted bis(indolyl)methanes.

A FeCl3-catalyzed highly regioselective 1,2-addition/substitution sequence of 3-acetylcoumarins and indoles has been developed to afford highly hindered tetrasubstituted bis(indolyl)methanes bearing a biologically useful coumarin motif in 56-99% yields.