Computational design of S‐nitrosothiol “click” reactions

To address a long‐standing problem of finding efficient reactions for chemical labeling of protein‐based S‐nitrosothiols (RSNOs), we computationally explored hitherto unknown (3+2) cycloaddition RSNO reactions with alkynes and alkenes. Nonactivated RSNO cycloaddition reactions have high activation enthalpy (>20 kcal/mol at the CBS‐QB3 level) and compete with alternative S—N bond insertion pathway. However, the (3+2) cycloaddition reaction barriers can be dramatically lowered by coordination of a Lewis acid to the N atom of the —SNO group. To exploit this effect, we propose to use reagents with Lewis acid and a strain‐activated carbon–carbon multiple bond linked by a rigid scaffold, which can react with RSNOs with small activation enthalpies (～5 kcal/mol) and high reaction exothermicities (～40 kcal/mol). The proposed efficient RSNO cycloaddition reactions can be used for future development of practical RSNO labeling reactions. © 2013 Wiley Periodicals, Inc.     

Gold(I)‐Catalyzed 1,2‐Acyloxy Migration/[3+2] Cycloaddition of 1,6‐Diynes with an Ynamide Propargyl Ester Moiety: Highly Efficient Synthesis of Functionalized Cyclopenta[b]indoles

A gold‐catalyzed cycloisomerization of 1,6‐diynes containing an ynamide propargyl ester or carbonate moiety has been developed that provides an attractive route to a diverse‐substituted 3‐acyloxy‐1,4‐dihydrocyclopenta[b]indoles. Mechanistic studies indicate that the reaction likely proceeds through a competitive 1,2‐OAc migration followed by [3+2] cycloaddition of the vinyl gold–carbenoid intermediate with the pendant triple bond. The synthetic utility of the obtained cyclopenta[b]indole products was demonstrated by their efficient transformations by deprotection or double‐bond isomerization reactions.     

Polymer‐Fullerene Network Formation via Light‐Induced Crosslinking

A facile and efficient methodology for the formation of polymer‐fullerene networks via a light‐induced reaction is reported. The photochemical crosslinking is based on a nitrile imine‐mediated tetrazole‐ene cycloaddition reaction, which proceeds catalyst‐free under UV‐light irradiation (λ_max = 320 nm) at ambient temperature. A tetrazole‐functionalized polymer (M_n = 6500 g mol⁻¹, Ð = 1.3) and fullerene C₆₀ are employed for the formation of the hybrid networks. The tetrazole‐functionalized polymer as well as the fullerene‐containing networks are carefully characterized by NMR spectrometry, size exclusion chromatography, infrared spectroscopy, and elemental analysis. Furthermore, thermal analysis of the fullerene networks and their precursors is carried out. The current contribution thus induces an efficient platform technology for fullerene‐based network formation.

     

Ruthenium‐Catalyzed C−C Bond Cleavage of 2H‐Azirines: A Formal [3+2+2] Cycloaddition to Fused Azepine Skeletons

2H‐azirines can serve as three‐atom synthons by C?C bond cleavage, however, it involves a high energy barrier under thermal conditions (>50.0 kcal mol^?1). Reported is a ruthenium‐catalyzed [3+2+2] cycloaddition reaction of 2H‐azirines with diynes, thus leading to the formation of fused azepine skeletons. This approach features an unprecedented metal‐catalyzed C?C bond cleavage of 2H‐azirines at room temperature, and the challenging construction of aza‐seven‐membered rings from diynes. The results of this study provide a new reaction pattern for constructing nitrogen‐containing seven‐membered rings and may find applications in the synthesis of other complex heterocycles.     

Visible‐Light‐Driven Aza‐ortho‐quinone Methide Generation for the Synthesis of Indoles in a Multicomponent Reaction

A visible‐light‐driven radical‐mediated strategy for the in situ generation of aza‐ortho ‐quinone methides from 2‐vinyl‐substituted anilines and alkyl radical precursors is described. This process enables an efficient multicomponent reaction of 2‐vinylanilines, halides, and sulfur ylides, and has a wide substrate scope and good functional group tolerance. Treatment of the cycloaddition products with a base leads to densely functionalized indoles in a single‐flask operation.     

Gold‐Catalyzed [3+2]/Retro‐[3+2]/[3+2] Cycloaddition Cascade Reaction of N‐Alkoxyazomethine Ylides

A novel cascade reaction has been developed for the synthesis of 2,6‐methanopyrrolo[1,2‐b]isoxazoles based on the gold‐catalyzed generation of an N‐allyloxyazomethine ylide. This reaction involves sequential [3+2]/retro‐[3+2]/[3+2] cycloaddition reactions, thus providing facile access to fused and bridged heterocycles which would be otherwise difficult to prepare using existing synthetic methods. Notably, this reaction allows the efficient construction of three C−C bonds, one C−O bond, one C−N bond and one C−H bond, as well as the cleavage of one C−C bond, one C−O bond and one C−H bond in a single operation. The intermolecular cycloaddition of an N‐allyloxyazomethine ylide and the subsequent application of the product to the synthesis of tropenol is also described.     

Lewis Acid or Brønsted Acid Catalyzed Reactions of Vinylidene Cyclopropanes with Activated Carbon–Nitrogen,Nitrogen–Nitrogen,and Iodine–Nitrogen Double‐Bond‐Containing Compounds

Lewis acid or Brønsted acid catalyzed reactions of vinylidene cyclopropanes (VDCPs), 1 , with activated carbon–nitrogen, nitrogen–nitrogen, and iodine–nitrogen double‐bond‐containing compounds have been thoroughly investigated. We found that pyrrolidine and 1,2,3,4‐tetrahydroquinoline derivatives can be formed in good yields in the reactions of VDCPs 1 with ethyl (arylimino)acetates 2 by a [3+2] cycloaddition or intramolecular Friedel–Crafts reaction pathway. Based on these results, we found that activated carbon–nitrogen and nitrogen–nitrogen double‐bond‐containing compounds, such as N‐toluene‐4‐sulfonyl (N‐Ts) imines 5 and diisopropylazodicarboxylate ( 7 ), can also react with VDCPs 1 to give [3+2] cycloaddition products in moderate to good yields in the presence of a Lewis acid. When N‐tert‐butoxycarbonyl aldimine 9 was used as the substrate, six‐membered cycloaddition products 10 and 11 were formed in moderate yields in the presence of a Brønsted acid, trifluoromethanesulfonic acid (TfOH). The reactions of VDCPs 1 with N‐Ts‐iminophenyliodinane ( 12 ) were also carried out in the presence of (CuOTf)₂ ? C₆H₆ and it was found that nitrogen‐containing indene derivatives 13 were obtained, rather than the aziridination products. Plausible mechanisms for all of these transformations are discussed, based on the obtained results.     

Synthesis,photophysics, structure‐tunable photoluminescence,and electrochemical properties of soluble poly(p‐phenylenevinylene)‐based polymers with adjacent 1,3,4‐oxadiazoles in the backbone

Three new poly(p‐phenylenevinylene)‐based polymers containing two 1,3,4‐oxadiazole moieties in the main chain per repeat unit were synthesized by Heck coupling. A single, double, or triple bond was introduced between the oxadiazoles to provide a means for modifying the polymer properties. The polymers were readily soluble in common organic solvents and showed T_g values lower than 50 °C. The color of the emissive light in both the solid state and the solution could be tuned by a change in the nature of the bond between the oxadiazole rings. The polymers emitted ultraviolet‐green light in solution with a photoluminescence (PL) emission maximum at 345–483 nm and blue‐green light at 458–542 nm in thin films. The PL quantum yields in solution were 0.36–0.43. The electrochemical properties are affected by the nature of the bond between the oxadiazoles as well. In polymers with a single bond between the oxadiazoles, a lower ionization potential was observed than in polymers with a double or triple bond. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3079–3090, 2005     

Novel thermotropic liquid crystalline‐cum‐photocrosslinkable polyvanillylidene alkyl/arylphosphate esters

A new class of linear unsaturated polyphosphate esters based on divanillylidene cyclohexanone possessing liquid crystalline‐cum‐photocrosslinkable properties have been synthesized from 2,6‐bis[n‐hydroxyalkyloxy(vanillylidene)]cyclohexanone [n = 6,8,10] with various alkyl/aryl phosphorodichloridates in chloroform at ambient temperature. The resultant polymers were characterized by intrinsic viscosity, FT‐IR, ¹H, ¹³C, and ³¹P‐NMR spectroscopy. All the polymers showed anisotropic behavior under hot stage optical polarized microscope (HOPM). The liquid crystalline textures of the polymers became more transparent with increasing spacer length. The thermal behavior of the polymers was studied by thermogravimetric analysis and differential scanning calorimetry. The T_g, T_m, and T_i of the polymers decreased with increasing flexible methylene chain. The photocrosslinking property of the polymer was investigated by UV light/UV spectroscopy; the crosslinking proceeds via 2π‐2π cycloaddition reactions of the divanillylidene exocyclic double bond of the polymer backbone. The pendant alkyloxy containing polymers show faster crosslinking than the pendant phenyloxy containing polymers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5215–5226, 2004     

Regioselective Insertion of o‐Carborynes into the α‐CH Bond of Tertiary Amines: Synthesis of α‐Carboranylated Amines

o‐Carboryne can undergo α‐C? H bond insertion with tertiary amines, thus affording α‐carboranylated amines in very good regioselectivity and isolated yields. In this process, the nucleophilic addition of tertiary amines to the multiple bond of o‐carboryne generates a zwitterionic intermediate. An intramolecular proton transfer, followed by a nucleophilic attack leads to the formation of the final product. Thus, regioselectivity is highly dependent upon the acidity of α‐C? H proton of tertiary amines. This approach serves as an efficient methodology for the preparation of a series of 1‐aminoalkyl‐o‐carboranes.     

Dual C(sp3)−H Bond Functionalization of N‐Heterocycles through Sequential Visible‐Light Photocatalyzed Dehydrogenation/[2+2] Cycloaddition Reactions

Herein we describe a mild method for the dual C(sp³)?H bond functionalization of saturated nitrogen‐containing heterocycles through a sequential visible‐light photocatalyzed dehydrogenation/[2+2] cycloaddition procedure. As a complementary approach to the well‐established use of iminium ion and α‐amino radical intermediates, the elusive cyclic enamine intermediates were effectively generated by photoredox catalysis under mild conditions and efficiently captured by acetylene esters to form a wide array of bicyclic amino acid derivatives, thus enabling the simultaneous functionalization of two vicinal C(sp³)?H bonds.     

Visible‐Light‐Induced Formal [3+2] Cycloaddition for Pyrrole Synthesis under Metal‐Free Conditions

A photocatalytic formal [3+2] cycloaddition of 2H‐azirines with alkynes has been achieved under irradiation by visible light in the presence of organic dye photocatalysts. This transformation provides efficient access to highly functionalized pyrroles in good yields and has been applied to the synthesis of drug analogues. A primary trial of photocascade catalysis merging energy transfer and redox neutral reactions was shown to be successful.     

Regioselective Insertion of o‐Carborynes into the α‐C?H Bond of Tertiary Amines: Synthesis of α‐Carboranylated Amines

o‐Carboryne can undergo α‐C H bond insertion with tertiary amines, thus affording α‐carboranylated amines in very good regioselectivity and isolated yields. In this process, the nucleophilic addition of tertiary amines to the multiple bond of o‐carboryne generates a zwitterionic intermediate. An intramolecular proton transfer, followed by a nucleophilic attack leads to the formation of the final product. Thus, regioselectivity is highly dependent upon the acidity of α‐C H proton of tertiary amines. This approach serves as an efficient methodology for the preparation of a series of 1‐aminoalkyl‐o‐carboranes.     

Ortho‐Quinone Methides as Reactive Intermediates in Asymmetric Brønsted Acid Catalyzed Cycloadditions with Unactivated Alkenes by Exclusive Activation of the Electrophile

An efficient method for the highly enantioselective synthesis of chiral chromanes bearing multiple stereogenic centers was developed. A chiral BINOL‐based N‐triflylphosphoramide proved to be an effective catalyst for the in situ generation of ortho‐quinone methides (o‐QMs) and their subsequent cycloaddition reaction with unactivated alkenes provided chromanes with excellent diastereo‐ and enantioselectivity.     

Highly Stereoselective [3+2] Cycloadditions of Chiral Palladium‐Containing N1‐1,3‐Dipoles: A Divergent Approach to Enantioenriched Spirooxindoles

A catalytic asymmetric [3+2] cycloaddition reaction of chiral palladium‐containing N¹‐1,3‐dipoles with methyleneindolinones has been successfully developed. The reaction allows an efficient construction of 3,3′‐pyrrolinyl spirooxindoles with high yields and excellent stereoselectivities (up to 93 % yield, 19:1 d.r. and >99 % ee). A synthetic application of this methodology is demonstrated and a stereocontrol mechanism is proposed.     

Catalytic Asymmetric Construction of Quaternary α‐Amino Acid Containing Pyrrolidines through 1,3‐Dipolar Cycloaddition of Azomethine Ylides to α‐Aminoacrylates

The first catalytic enantioselective 1,3‐dipolar cycloaddition of azomethine ylides to α‐aminoacrylate catalyzed by a AgOAc/ferrocenyl oxazolinylphosphine (FOXAP) system was developed, which exhibits excellent exo‐ and enantioselectivity (92–99 % ee). This process provides efficient access to useful 4‐aminopyrrolidine‐2,4‐dicarboxylic acid (APDC)‐like compounds containing a unique quaternary α‐amino acid unit.     

De Novo Synthesis of Imidazoles by Visible‐Light‐Induced Photocatalytic Aerobic Oxidation/[3+2] Cycloaddition/Aromatization Cascade

A visible‐light‐induced photocatalytic aerobic oxidation/[3+2] cycloaddition/aromatization cascade between secondary amines and isocyanides has been successfully developed. The reaction provides a general and efficient access to diversely substituted imidazoles and imidazo[1,5‐a]quinoxalin‐4(5 H)‐ones in good yields under mild conditions.     

Total Synthesis of Murrayanine Involving 4,5‐Dimethyleneoxazolidin‐2‐ones and a Palladium(0)‐Catalyzed Diaryl Insertion

A new total synthesis of the natural carbazole murrayanine ( 1 ) was developed by using the 4,5‐dimethyleneoxazolidin‐2‐one 12 as starting material. The latter underwent a highly regioselective Diels–Alder cycloaddition with acrylaldehyde (=prop‐2‐enal; 13 ) to give adduct 14 (Scheme 3). Conversion of this adduct into diarylamine derivative 9 was carried out via hydrolysis and methylation (Scheme 4). Differing from our previous synthesis, in which such a diarylamine derivative was transformed into 1 by a Pd^II‐stoichiometric cyclization, this new approach comprised an improved cyclization through a more efficient Pd⁰‐catalyzed intramolecular diaryl coupling which was applied to 9 , thus obtaining the natural carbazole 1 in a higher overall yield.     

An Efficient Synthesis of Optically Active trans‐(3R,4R)‐3‐Acetoxy‐4‐aryl‐1‐(chrysen‐6‐yl)azetidin‐2‐ones Using (+)‐Car‐3‐ene as a Chiral Auxiliary

An efficient enantioselective synthesis of 3‐acetoxy trans‐β‐lactams 7a and 7b via [2+2] cycloaddition reactions of imines 4a and 4b , derived from a polycyclic aromatic amine and bicyclic chiral acid obtained from (+)‐car‐3‐ene, is described. The cycloaddition was found to be highly enantioselective, producing only trans‐(3R,4R)‐N‐azetidin‐2‐one in very good yields. This is the first report of the synthesis of enantiomerically pure trans‐β‐lactams 7a and 7b with a polycyclic aromatic substituent at N(1) of the azetidin ring.     

An Efficient Approach for the Synthesis of 1,2,3‐Triazole Moiety to Generate Uracil Molecular Architectures Through Cu‐Catalyzed Azide–Alkyne Cycloaddition

A simple and efficient pathway to tether conjugates of monosaccharides or aromatic moieties to uracil establishing a 1,2,3‐triazole linker via click chemistry was reported. The reaction of arylimines of 5‐amino uracil with propargyl bromide in a basic medium gave a di‐propargylated uracil. The latter compound was converted into molecular architectures containing bis‐1,2,3‐triazole rings through Cu‐catalyzed 1,3‐cycloaddition reaction with different azides. The same arylimine of 5‐amino uracil yielded different products under reflux with propargyl bromide in acetonitril with the majority to 6‐propargylated‐5‐amino uracil.