N-Fluorobenzamide-Directed Formal [4+2] Cycloaddition Reaction with Maleic Anhydride: Access to Fluorescent Aminonaphthalic Anhydrides.

We have developed a formal [4+2] cycloaddition reaction of N-fluorobenzamides and maleic anhydride in the presence of CuI and LiOH, and a series of fluorescent 1-amino-2,3-naphthalic anhydrides were produced in good yields. This reaction proceeded via a multistep process involving nitrogen-centered radical generation, 1,5-hydrogen atom transfer, and benzylic radical addition to the amide carbonyl oxygen to generate an N-(tert-butyl) isobenzofuran-1(3H)-imine intermediate, which isomerized to an N-(tert-butyl) isobenzofuran-1-amine via deprotonation and protonation with the aid of LiOH; finally, the amine underwent a [4+2] cycloaddition reaction with maleic anhydride to give the 1-amino-2,3-naphthalic anhydride product upon dehydrating aromatization. Notably, the corresponding naphthalic anhydride products could be transformed into a diverse array of naphthalimides. Both the naphthalic anhydrides and the naphthalimides exhibited similar fluorescent features.

Divergent Copper-salt-controlled Reactions of Donor-Acceptor Cyclopropanes and N-Fluorobenzene Sulfonimide: Access to the 1,3-Haloamines and Aminoindanes.

We herein report a method for divergent copper salt controlled reactions of donor-acceptor cyclopropanes and N-fluorobenzene sulfonimide (NFSI). Specifically, in the presence of CuX2 (X=Cl, Br), the cyclopropanes underwent formal umpolung 1,3-aminohalogenation bifunctionalization via a free radical mediated ring-opening process to afford 1,3-aminochlorination and 1,3-aminobromination products in moderate to good yields. In addition, by using CuI as a catalyst, we synthesized various aminoindane derivatives via 1,3-aminoarylation cyclization of D-A cyclopropanes, the reactions involved a free radical mediated ring-opening and subsequent ring expansion via C-H bond activation.

Au(I)/(R)-BINOL-Ti(IV) Concerted Catalyzed Asymmetric Cascade Cycloaddition Reaction of Arylalkynols.

An efficient catalytic asymmetric cascade cycloaddition reaction of arylalkynols with dioxopyrrolidines was developed. This reaction was achieved using Au(I) and (R)-BINOL-Ti(IV) bimetallic catalysts and exclusively delivered a series of chiral oxo-bridged bicyclic benzooxacine compounds in up to 86% yield with 96% ee as well as >33:1 dr. Meanwhile, three new σ bonds and three new stereogenic centers were formed in a one-pot process.

Stereospecific Synthesis of cis-2,5-Disubstituted Pyrrolidines via N,O-Acetals Formed by Hydroamination Cyclization-Hydroalkoxylation of Homopropargylic Sulfonamides in HFIP.

We reported a novel two-step stereoselective synthesis of functionalized pyrrolidines from homopropargylic sulfonamides and nucleophiles via an isolable N,O-acetal intermediates. This reaction features mild conditions and good scope of substrates. In addition, the use of hexafluoroisopropanol, acting as a solvent, an additive, a weak nucleophile, and a good leaving group, is pivotal to the success of the method. Moreover, reactions of chiral homopropargylic sulfonamides afford only 2,5-cis-disubstituted pyrrolidines with high diastereoselectivity (up to >99:1 dr) and enantioselectivity (up to >99% ee). The overall reaction constitutes a formal 1,1-bifunctionalization of terminal alkynes, which has hitherto been reported only rarely. Additionally, this method provides efficient access to pharmaceutical intermediate and to carry out postmodification of natural products.

Temperature-Controlled Divergent Hydroamination Cyclization [2+2]-Cycloaddition Cascade Reactions of Homopropargylic Amines with 2-Butynedioates: Direct Access To Pyrrolo- b-cyclobutene and Dihydro-1 H-azepines.

The diversified temperature-controlled hydroamination cyclization cascade reactions of homopropargylic amines and 2-butynedioates were developed for the construction of various pyrrolo- b-cyclobutenes and dihydro-1 H-azepines, respectively. This reaction actually involved an intramolecular hydroamination cyclization of homopropargylic amines to give the active dihydropyrroles intermediates, which subsequently underwent [2+2]-cycloaddition with 2-butynedioates to generate the pyrrolo- b-cyclobutenes at no more than 120 °C. Alternatively, the dihydro-1 H-azepines were directly produced at 150 °C in the reactions of homopropargylic amines and 2-butynedioates. The application of substrate scope was wide, and the corresponding products were obtained in high to excellent yields.

Metal-free multicomponent cascade reactions of homopropargylic amines and acyl chlorides as well as potassium thiocyanate and diiodine: an access to thiazine imides.

A novel metal-free multicomponent cascade reaction was developed for the construction of thiazine imides. This four-component cascade reaction had advantages of mild reaction conditions, wide substrate scope and good atom economy. Four new bonds were formed in one pot via a 6-exo-dig iodothiolation cyclization of homopropargylic amines. The corresponding E-configurational thiazine imide products possess an exocyclic vinyliodide functional group.

The Divergent Cascade Reactions of Arylalkynols with Homopropargylic Amines or Electron-Deficient Olefins: Access to the Spiro-Isobenzofuran- b-pyrroloquinolines or Bridged-Isobenzofuran Polycycles.

Two divergent cascade reactions of arylalkynols with homopropargylic amines or electron-deficient olefins were developed to synthesize the spiro-isobenzofuran- b-pyrroloquinolines or bridged-isobenzofuran heterocycles in good yields, respectively. One reaction actually involved intramolecular 5- endo-dig hydroamination cyclization-protonation of homopropargylic amines to give cycloiminium ions and intramolecular 5- exo-dig hydroalkoxylation cyclization of arylalkynols to generate isobenzofuran with exocyclic double bond, followed by the nontypical Povarov-type reaction in the presence of PtCl2/FeCl3 cocatalysts. The other underwent intramolecular hydroalkoxylation cycloisomerization of alkynols with the subsequent normal [4 + 2] cycoaddition with dienophiles. Herein, the arylalkynols acted as both "masked" electron-rich olefins and "masked" electron-rich dienes.

Copper Promoted Regio- and Stereoselective Aminochlorination of Alkynes and Alkenes with NFSI.

A simple and rapid copper-promoted aminochlorination of unactivated alkynes and alkenes with N-fluorobenzenesulfonimide (NFSI) was developed. Two series of chloroenamines and chloroamines were obtained in good to high yields. The chlorinated enamines could be obtained in a single E configuration. This reaction involved a radical process and the CuCl2 acted as the Cl source and NFSI as the N source.

Cu(OAc)2 /TEMPO Cooperative Promoted Hydroamination Cyclization and Oxidative Dehydrogenation Cascade Reaction of Homopropargylic Amines.

A novel and efficient Cu(OAc)2 -catalyzed hydroamination cyclization and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidative dehydrogenation cascade reaction of homopropargylic amines has been developed. A library of 1,2-disubstituted pyrrole derivatives were obtained in good-to-high yields in one pot with no step-by-step feeding process. This reaction involved TEMPO playing dual roles as both an oxidative dehydrogenation reagent and a ligand. An insight into the reaction mechanism was obtained by using several analytical determination methods.

Povarov Reaction of Cycloiminium Formed in Situ via Hydroamination Cycloisomerization of Homopropargylic Amines with Electron-Rich Olefins.

A new, one-pot cascade reaction of homopropargylic amines with electron-rich olefins is developed in the presence of Cu(OTf)2 and affords a series of octahydrofuro[3,2-c]pyrrolo[1,2-a]quinoline derivatives in yields of 38-80%. This reaction proceeds through an intramolecular hydroamination cyclization of homopropargylic amine to generate a highly reactive cycloenamine intermediate in situ that subsequently isomerizes to the cycloiminium cation followed by the Povarov-type reaction with dihydrofuran, dihydropyran, or dihydropyrrole. Notably, the Al2O3 additive plays a key role for the effective inhibition of competitive self-dimerization of homoproargylic amines.

Copper-Catalyzed Cascade Reaction via Intramolecular Hydroamination Cyclization of Homopropargylic Amines and Intermolecular Povarov Reaction with Imines.

A new one-pot cascade reaction of homopropargylic amines with simple imines is developed in the presence of Cu(OTf)2 and affords a series of hexahydro-1H-pyrrolo[3,2-c]quinoline derivatives in good to high yields. This reaction proceeds through an intramolecular hydroamination cyclization of homopropargylic amine to generate a highly reactive dihydropyrrole intermediate in situ. It subsequently reacts with imine via an intermolecular inverse-electron-demand aza-Diels-Alder reaction and a 1,3-H shift to give the fused pyrroloquinoline structures, forming two new C-C bonds and one C-N bond and one N-H bond.

Mutual Cooperation in the Formal Allyl Alcohol Nucleophilic Substitution and Hydration of Alkynes for the Construction of γ-Substituted Ketones.

Mutual cooperation in the formal allyl alcohol nucleophilic substitution reaction and hydration of an alkyne has been utilized in the presence of a gold catalyst to give a series of γ-functionalized ketones with high to excellent yields. This reaction actually involved an intramolecular O-H insertion cyclization of an alkyne to form the dihydrofuran intermediate, which was followed by the nucleophilic addition ring-opening of a dihydrofuran to give the target compound.

Controllable and Reversible Dimple-Shaped Aggregates Induced by Macrocyclic Recognition Effect.

A novel dimethyl acrylate 18-membered macrocycle (DMECE), acting as both bifunctional monomer and cross-linker, was designed and synthesized, and thus employed to construct a series of macrocycle-containing amphiphilic hyperbranched polymers (HBPs). The macrocyclic recognition effect between the HBPs and alkali metal ions showed that Na(+) was introduced in 1:1 interactive mode, whereas K(+) and Rb(+) were in 2:1 ratio. Through the formation of the DMECE/K(+) = 2:1 rigid "sandwich" complex of amphiphilic hyperbranched polymers, dimple-shaped aggregates were observed by TEM, SEM and AFM. Moreover, the initial concentration, the nature of solvent, the mode and affinity of the macrocyclic recognition effect as well as the amount of K(+), were essential control factors for the formation of dimple-shaped aggregates. Most importantly, the macrocyclic recognition effect endows the reversibility of the dimple-shaped aggregates and the size controllability of its circular opening, which provides a new strategy for design novel macrocycle-containing HBPs and great potential application in the field of capture and release.

An unexpected double Diels-Alder reaction of (E)-2-bromo-4-aryl-1,3-pentadiene involving [1,5]-hydrogen migration and HBr elimination: synthesis of bicyclo[2.2.2]octene derivatives.

An unexpected double Diels-Alder (DDA) reaction of (E)-2-bromo-4-aryl-1,3-pentadiene was developed and resulted in a series of "butterfly-like" bicyclo[2.2.2]octene derivatives in moderate to good yields without the need for a metal catalyst. The proposed mechanism involves a [1,5]-sigmatropic hydrogen migration and HBr elimination. Through this decisive [1,5]-hydrogen shift step, the electronic properties and steric hindrance of the conjugated diene substrate are completely altered and the DDA reaction of this potential diene synthon is successfully achieved.