Rhodium‐Catalyzed [(3+2)+2] Carbocyclization of Alkynylidenecyclopropanes with Substituted Allenes: Stereoselective Construction of Tri‐ and Tetrasubstituted Exocyclic Olefins

The development of the stereoselective rhodium‐catalyzed [(3+2)+2] carbocyclization of alkynylidenecyclopropanes (ACPs) with substituted allenes is described. This work demonstrates that activated and unactivated allenes preferentially undergo carbometalation at the distal terminus to generate tri‐ and tetrasubstituted exocyclic olefins with a neutral rhodium catalyst. In addition, this method provides a strategy for the total synthesis of the guaiane family of sesquiterpenes, which are not directly accessible using alkynes as exogenous π‐components. Finally, the preparation of the bicyclo[5.4.0]undecane ring system using a homologated ACP tether serves to further illustrate the versatility of this approach.     

Pd‐Catalyzed Difluoromethylation of Vinyl Bromides,Triflates, Tosylates,and Nonaflates

Pd‐catalyzed difluoromethylation of di‐, tri‐ or tetra‐substituted vinyl bromides, triflates, tosylates and nonaflates under mild conditions is described. The reaction tolerates a wide range of functional groups, such as bromide, chloride, fluoride, ester, amine, nitrile, and protected carbonyl, thus providing a general route for the preparation of difluoromethylated alkenes.     

Direct α‐Vinylidenation of Aldehydes and Subsequent Cascade: Gold and Amine Catalysts Work Synergistically

Carbonyl‐substituted allenes are highly important synthetic intermediates for a number of heterocycles and strained‐ring systems. However, chemistry of allenyl aldehydes has not been explored as extensively as their ketone, ester, or amide analogues because of a lack of general synthetic methods. Described herein is the first direct α‐vinylidenation of aldehydes and an α‐vinylidenation/γ‐functionalization cascade to access tri‐ and tetrasubstituted allenyl aldehydes using a combination of a gold catalyst and an secondary amine. The reactive enamine intermediate of an aldehyde reacts with the gold‐activated hypervalent silylethynyl benziodoxolone to selectively generate the corresponding trisubstituted allenyl aldehyde. The allenyl aldehyde can further react with another equivalent of the alkynylation reagent or other electrophiles to afford tetrasubstituted allenes bearing an aldehyde group, an acetylene, and a halogen functionality. This method enables rapid access to polysubstituted furans from aldehydes.     

Alkenyl Isocyanide Conjugate Additions: A Rapid Route to γ‐Carbolines

Isocyanides are exceptional building blocks, the wide deployment of which in multicomponent and metal‐insertion reactions belies their limited availability. The first conjugate addition/alkylation to alkenyl isocyanides is described, which addresses this deficiency. An array of organolithiums, magnesiates, enolates, and metalated nitriles add conjugately to β‐ and β,β‐disubstituted arylsulfonyl alkenyl isocyanides to rapidly assemble diverse isocyanide scaffolds. The intermediate metalated isocyanides are efficiently trapped with electrophiles to generate substituted isocyanides incorporating contiguous tri‐ and tetra‐substituted centers. The substituted isocyanides are ideally functionalized for elaboration into synthetic targets as illustrated by the three‐step synthesis of γ‐carboline N ‐methyl ingenine B.     

Olefin‐Directed Palladium‐Catalyzed Regio‐ and Stereoselective Hydroboration of Allenes

An olefin‐directed palladium‐catalyzed regio‐ and stereoselective hydroboration of allenes has been developed to afford fully substituted alkenylboron compounds. The reaction showed a broad substrate scope: a number of functionalized allenes, including 2,3‐dienoate, 3,4‐dienoate, 3,4‐dienol, 1,2‐allenylphosphonate, and alkyl‐substituted allenes, could be used in this olefin‐directed allene hydroboration. The olefin unit was proven to be an indispensable element for this transformation.     

Alkene Hydrogenations by Soluble Iron Nanocluster Catalysts

The replacement of noble metal technologies and the realization of new reactivities with earth‐abundant metals is at the heart of sustainable synthesis. Alkene hydrogenations have so far been most effectively performed by noble metal catalysts. This study reports an iron‐catalyzed hydrogenation protocol for tri‐ and tetra‐substituted alkenes of unprecedented activity and scope under mild conditions (1–4 bar H₂, 20 °C). Instructive snapshots at the interface of homogeneous and heterogeneous iron catalysis were recorded by the isolation of novel Fe nanocluster architectures that act as catalyst reservoirs and soluble seeds of particle growth.     

Enantiodivergent Synthesis of Allenes by Point‐to‐Axial Chirality Transfer

An enantiodivergent method for the synthesis of multiply substituted allenes is described. Highly enantioenriched, point‐chiral boronic esters were synthesized by homologation of α‐seleno alkenyl boronic esters with lithiated carbamates and eliminated to form axially chiral allene products. By employing either oxidative or alkylative conditions, both syn and anti elimination could be achieved with complete stereospecificity. The process enables the synthesis of either M or P allenes from a single isomer of a point‐chiral precursor and can be employed for the enantioselective assembly of di‐, tri‐, and tetrasubstituted allenes.     

Synthesis and Functionalization of Allenes by Direct Pd‐Catalyzed Organolithium Cross‐Coupling

A palladium‐catalyzed cross‐coupling between in situ generated allenyl/propargyl‐lithium species and aryl bromides to yield highly functionalized allenes is reported. The direct and selective formation of allenic products preventing the corresponding isomeric propargylic product is accomplished by the choice of SPhos or XPhos based Pd catalysts. The methodology avoids the prior transmetalation to other transition metals or reverse approaches that required prefunctionalization of substrates with leaving groups, resulting in a fast and efficient approach for the synthesis of tri‐ and tetrasubstituted allenes. Experimental and theoretical studies on the mechanism show catalyst control of selectivity in this allene formation.     

Synthesis of some novel derivatives of 1,10‐phenanthroline

The synthesis is described of a set of new N‐heterocyclic compounds which are derivatives of 1,10‐phenanthroline. The compounds are designed to be general purpose chelating agents which could function as tri‐, tetra‐ or hexadentate ligands with transition metal ions. Fused‐ring molecular components have been included in the design of the compounds so that they may function as binding agents to DNA through intercalation. This includes the synthesis of substituted derivatives of pyrazino[2,3‐f][1,10]phenanthroline and dipyrido[3,2‐a:2′3′‐c]phenazine.     

N‐Trifluoromethyl Hydrazines,Indoles and Their Derivatives

Reported herein is the first efficient strategy to synthesize a broad range of unsymmetrical N‐CF₃ hydrazines, which served as platform to unlock numerous currently inaccessible derivatives, such as tri‐ and tetra‐substituted N‐CF₃ hydrazines, hydrazones, sulfonyl hydrazines, and valuable N‐CF₃ indoles. These compounds proved to be remarkably robust, being compatible with acids, bases, and a wide range of synthetic manipulations. The feasibility of RN(CF₃)‐NH₂ to function as a directing group in C?H functionalization is also showcased.     

Rhodium(III)‐Catalyzed [4+1] Annulation of Aromatic and Vinylic Carboxylic Acids with Allenes: An Efficient Method Towards Vinyl‐Substituted Phthalides and 2‐Furanones

A highly regio‐ and stereoselective synthesis of 3,3‐disubstituted phthalides from aryl carboxylic acids and allenes using a rhodium(III) catalyst has been demonstrated. The reaction features broad functional group tolerance and provides a simple and straightforward route to the synthesis of various 3‐vinyl‐substituted phthalides. Furthermore, the catalytic reaction can also be applied to the synthesis of biologically active 5‐vinyl‐substituted 2‐furanones from α,β‐unsaturated carboxylic acids and allenes. The reactions proceed through a carboxylate‐assisted ortho‐C?H activation and [4+1] annulation. The preliminary mechanistic studies suggest that a C?H cleavage is the rate‐determining step.     

Organocatalyzed Domino [3+2] Cycloaddition/Payne‐Type Rearrangement using Carbon Dioxide and Epoxy Alcohols

An unprecedented organocatalytic approach towards highly substituted cyclic carbonates from tri‐ and tetrasubstituted oxiranes and carbon dioxide has been developed. The protocol involves the use of a simple and cheap superbase under mild, additive‐ and metal‐free conditions towards the initial formation of a less substituted carbonate product that equilibrates to a tri‐ or even tetrasubstituted cyclic carbonate under thermodynamic control. The latter are conveniently trapped in situ, providing overall a new domino process for synthetically elusive heterocyclic scaffolds. Control experiments provide a rationale for the observed cascade reactions, which demonstrate similarity to the well‐known Payne rearrangement of epoxy alcohols.     

Synthesis of Dendrimer‐Like Polyindolyl Compounds

Syntheses of polyindolyl compounds from the Friedel–Crafts reaction of indoles and tri‐ or tetra‐aldehydes catalyzed by silica sulfuric acid are described. These dendrimeric supramolecules were effectively prepared at room temperature in quantitative yield. These novel products have potential in the synthesis of dyes and pigments and also in various pharmaceutical applications.     

Rhodium‐Catalyzed Cross‐Cyclotrimerization and Dimerization of Allenes with Alkynes

It has been established that a cationic rhodium(I)/binap complex catalyzes the cross‐cyclotrimerization of two molecules of a monosubstituted allene with one molecule of a functionalized alkyne to give 3,6‐dialkylidenecyclohex‐1‐enes. In contrast, the reactions involving di‐ or trisubstituted allenes and/or unfunctionalized alkynes afforded cross‐dimerization products, substituted dendralenes, through β‐hydrogen elimination from the corresponding rhodacycles.     

Nitration of Norcorrolatonickel(II): First Observation of a Diatropic Current in a System Comprising a Norcorrole Ring

A one‐pot reaction of 5,14‐bis(mesityl)‐norcorrolatonickel(II) with isoamyl nitrite under mild reaction conditions resulted in the consecutive formation of 3‐nitro‐, 3,12‐dinitro‐ and 3,16‐dinitro‐, 3,7,12‐trinitro‐, and 3,7,12,16‐tetranitro‐norcorrolatonickel(II) in 50–80 % yield. The substituted macrocycles retained their antiaromatic character. The observed regioselectivity of the substitution was analyzed by comparing the relative energies of the DFT energy‐optimized models of the radical or arenium cationic intermediates that can be formed upon reaction with NO₂. The nitrated systems were characterized by high‐resolution mass spectrometry, NMR and UV/Vis spectroscopy, X‐ray diffraction analysis, cyclic voltammetry, and DFT calculations. A significant and systematic cathodic shift of the redox couples was observed to correlate with an increasing number of the NO₂ group. A decrease of the LUMO energies in the tri‐ and tetra‐nitrated products stabilizes mono‐ and bis‐reduced complexes of these ligands. The reduction takes place on the macrocycle rather than on the metal ion leading to the consecutive formation of stable paramagnetic monoanion radicals and water‐soluble diamagnetic dianions with an aromatic character, which were revealed by ESR and ¹H NMR measurements, respectively. The electronic structures of the reduced forms were analyzed by extensive TD‐DFT calculations.     

Manganese‐Catalyzed C−H Functionalizations: Hydroarylations and Alkenylations Involving an Unexpected Heteroaryl Shift

A manganese‐catalyzed regio‐ and stereoselective hydroarylation of allenes is reported. The C−H functionalization method provides access to various alkenylated indoles in excellent yields. Moreover, a hydroarylation/cyclization cascade involving an unexpected C−N bond cleavage and aryl shift has been developed, which provides a new synthetic approach to substituted pyrroloindolones.     

Practical Chemical Synthesis of Atypical Ubiquitin Chains by Using an Isopeptide‐Linked Ub Isomer

Chemical ubiquitination is an effective approach for accessing structurally defined, atypical ubiquitin (Ub) chains that are difficult to prepare by other techniques. Herein, we describe a strategy that uses a readily accessible premade isopeptide‐linked 76‐mer (isoUb), which has an N‐terminal Cys and a C‐terminal hydrazide, as the key building block to assemble atypical Ub chains in a modular fashion. This method avoids the use of auxiliary‐modified Lys and instead employs the canonical and therefore more robust Cys‐based native chemical ligation technique. The efficiency and capacity of this isoUb‐based strategy is exemplified by the cost‐effective synthesis of several linkage‐ and length‐defined atypical Ub chains, including K27‐linked tetra‐Ub and K11/K48‐branched tri‐, tetra‐, penta‐, and hexa‐Ubs.     

Three Short Stories about Hexaarylbenzene–Porphyrin Scaffolds

A feasible two‐step synthesis and characterization of a full series of hexaarylbenzene (HAB) substituted porphyrins and tetrabenzoporphyrins is presented. Key steps represent the microwave‐assisted porphyrin condensation and the statistical Diels–Alder reaction to the desired HAB‐porphyrins. Regarding their applications, they proved to be easily accessible and effective high molecular mass calibrants for (MA)LDI mass spectrometry. The free‐base and zinc(II) porphyrin systems, as well as the respective tetrabenzoporphyrins, demonstrate in solid state experiments strong red‐ and near‐infrared‐light emission and are potentially interesting for the application in “truly organic” light‐emitting devices. Lastly, they represent facile precursors to large polycyclic aromatic hydrocarbon (PAH) substituted porphyrins. We prepared the first tetra‐hexa‐peri‐hexabenzocoronene substituted porphyrin, which represents the largest prepared PAH‐porphyrin conjugate to date.     

Stereoselective Synthesis of α‐Linked 2‐Deoxy Glycosides Enabled by Visible‐Light‐Mediated Reductive Deiodination

2‐Deoxy sugars and their derivatives occur abundantly in many pharmaceutically important natural products. However, the construction of specific 2‐deoxy‐glycosidic bonds remains as a challenge. Herein, we report an efficient way to prepare 2‐deoxy‐α‐glycosides by glycosylation of 2‐iodo‐glycosyl acetate and subsequent visible‐light‐mediated tin‐free reductive deiodination. We have successfully applied the postglycosylational‐deiodination strategy in the synthesis of more than 30 mono‐, di‐, tri‐, tetra‐ and pentadeoxysaccharides with excellent stereoselectivity and efficiency. This method has also been applied to the synthesis of a 2‐deoxy‐tetrasaccharide containing four α‐linkages.     

Enantioselective Alkylation of N‐Arylhydrazones Derived from α‐Keto Esters and Isatin Derivatives through Asymmetric Phase‐Transfer Catalysis

The phase‐transfer‐catalyzed asymmetric alkylation reactions of N‐arylhydrazones derived from α‐keto‐esters and isatin derivatives afford enantioenriched azo compounds that bear a tetra‐substituted carbon stereocenter in good yields with high chemo‐ and enantioselectivity. The alkylation products can be readily converted into chiral amino esters, hydrazine derivatives, and aza‐β‐lactams without loss of enantiopurity.