Synthesis of [n]Cyclo‐5,15‐porphyrinylene‐4,4′‐biphenylenes Displaying Size‐Dependent Excitation‐Energy Hopping

A set of 5,15‐biphenylene‐bridged porphyrin wheels, namely, [n]cyclo‐5,15‐porphyrinylene‐4,4′‐biphenylenes [n]CPB , have been synthesized through the platination of 5,15‐bis(4‐(pinacolboranyl)phenyl) nickel(II) porphyrin and subsequent reductive elimination of Pt^II(cod)‐bridged cyclic porphyrin intermediates. The calculated strain energies for [3]CPB , [4]CPB , [5]CPB , and [6]CPB are 49.3, 32.9, 23.5, and 16.0 kcal mol^?1, respectively. UV/Vis absorption spectra and cyclic voltammetry indicated characteristic ring‐size‐dependent absorption‐peak shifts and redox‐potential shifts, which presumably reflect the degree of strain in the π‐systems. Excitation‐energy hopping (EEH) times were determined to be 5.1, 8.0, 8.0, and 9.6 ps for [3]CPB , [4]CPB , [5]CPB , and [6]CPB , respectively, in a pump‐power‐dependent TA experiment.     

Formation of Azulene‐Embedded Nanographene: Naphthalene to Azulene Rearrangement During the Scholl Reaction

Incorporation of a non‐hexagonal ring into a nanographene framework can lead to new electronic properties. During the attempted synthesis of naphthalene‐bridged double [6]helicene and heptagon‐containing nanographene by the Scholl reaction, an unexpected azulene‐embedded nanographene and its triflyloxylated product were obtained, as confirmed by X‐ray crystallographic analysis and 2D NMR spectroscopy. A 5/7/7/5 ring‐fused substructure containing two formal azulene units is formed, but only one of them shows an azulene‐like electronic structure. The formation of this unique structure is explained by arenium ion mediated 1,2‐phenyl migration and a naphthalene to azulene rearrangement reaction according to an in‐silico study. This report represents the first experimental example of the thermodynamically unfavorable naphthalene to azulene rearrangement and may lead to new azulene‐based molecular materials.     

An Unusual Ring‐Contraction/Rearrangement Sequence for Making Functionalized Di‐ and Triquinanes

A novel ring contraction/rearrangement sequence leading to functionalized 2,8‐oxymethano‐bridged di‐ and triquinane compounds is observed in the reaction of various substituted 1‐methyl‐4‐isopropenyl‐6‐oxabicylo[3.2.1]octan‐8‐ones with Lewis acids. The reaction is novel and is unprecedented for the synthesis of di‐ and triquinane frameworks.     

Synergistic Catalysis: Metal/Proton‐Catalyzed Cyclization of Alkynones Toward Bicyclo[3.n.1]alkanones

A highly efficient and practical synergistically metal/proton‐catalyzed Conia–ene reaction for the synthesis of bicyclo[3.n.1]alkanones has been developed. This synergistic catalysis was successfully utilized in modifying natural compounds such as methyl dihydrojasmonate, α,β‐thujone, and 5α‐cholestan‐3‐one. Furthermore, the bridged carbonyl group of bicyclo[3.2.1]alkanones could be easily attacked by nucleophiles to give the ring‐opened cycloheptenone products or bicyclo[4.2.1]amide in excellent yields. These reactions provide rapid access to a diverse range of cyclic structures from simple starting materials or naturally occurring compounds.     

Asperflavipine A: A Cytochalasan Heterotetramer Uniquely Defined by a Highly Complex Tetradecacyclic Ring System from Aspergillus flavipes QCS12

Asperflavipines A ( 1 ) and B ( 2 ), two structurally complex merocytochalasans, were isolated from Aspergillus flavipes . Asperflavipine A ( 1 ), which contains two cytochalasan moieties and two epicoccine moieties, is the first cytochalasan heterotetramer to be discovered. It is uniquely defined by 5/6/11/5/6/5/6/5/6/5/5/11/6/5 fused tetradecacyclic rings with three continuous bridged ring systems. Asperflavipine B ( 2 ) is a cytochalasan heterotrimer containing a cytochalasan and two epicoccine moieties with a 5/6/11/5/5/6/5/6/5 nonacyclic ring system. The hypothetical biosynthesis of 1 and 2 is proposed to involve Diels–Alder and [3+2] cycloaddition reactions as key steps and reveals unparalleled plasticity in the biosynthesis of merocytochalasans. The existence of 1 adds a new dimension to the diversity of the cytochalasan family. Compound 1 showed moderate cytotoxicity and induced apoptosis in Jurkat, NB4, and HL60 cells through the activation of caspase‐3 and degradation of poly(ADP‐ribose) polymerase (PARP).     

Assembly of a Benzo‐Fused Bridged Ketone Scaffold from 1,5,10‐Enediynes through One‐Pot Ruthenium‐Catalyzed Cyclization/Iodine‐Mediated Oxidative Ring Expansion

In the presence of a cationic Ru catalyst, 1,6‐diynes bearing a terminal styryl moiety underwent [2+2+2] cyclization to produce dehydrobiphenylenes fused with a five‐membered ring. Although the cycloadducts were unstable toward purification, their one‐pot iodine‐mediated ring expansion successfully afforded unprecedented bridged ketone products containing a benzo‐fused bicyclo[3.2.1] framework.     

Functionalization of Intramolecular Frustrated Lewis Pairs by 1,1‐Carboboration with Conjugated Enynes

The vicinal P/B frustrated Lewis pair (FLP) Mes₂PCH₂CH₂B(C₆F₅)₂ undergoes 1,1‐carboboration reactions with the Me₃Si‐substituted enynes to give ring‐enlarged functionalized C₃‐bridged P/B FLPs. These serve as active FLPs in the activation of dihydrogen to give the respective zwitterionic [P]H⁺/[B]H^? products. One such product shows activity as a metal‐free catalyst for the hydrogenation of enamines or a bulky imine. The ring‐enlarged FLPs contain dienylborane functionalities that undergo “bora‐Nazarov”‐type ring‐closing rearrangements upon photolysis. A DFT study had shown that the dienylborane cyclization of such systems itself is endothermic, but a subsequent C₆F₅ migration is very favorable. Furthermore, substituted 2,5‐dihydroborole products are derived from cyclization and C₆F₅ migration from the photolysis reaction. In the case of the six‐membered annulation product, a subsequent stereoisomerization reaction takes place and the resultant compound undergoes a P/B FLP 1,2‐addition reaction with a terminal alkyne with rearrangement.     

Gold(I)‐Catalyzed Cycloisomerization of 3‐Alkoxyl‐1,6‐diynes: A Facile Access to Bicyclo[2.2.1]hept‐5‐en‐2‐ones

A novel gold‐catalyzed cycloisomerization of 1,6‐diynes was achieved, providing an atom‐economic approach to a diverse set of bicyclo[2.2.1]hept‐5‐en‐2‐ones in moderate to good yields. With unsymmetrical starting materials with two different internal alkynyl substituents, to some extent, the regioselectivity could be controlled by both electronic and steric factors. This unprecedented reactivity pattern may inspire new and unconventional strategies for the preparation of bridged ring systems.     

Type II Intramolecular [5+2] Cycloaddition: Facile Synthesis of Highly Functionalized Bridged Ring Systems

A type II intramolecular oxidopyrylium‐mediated [5+2] cycloaddition reaction allows the efficient and diastereoselective formation of various highly functionalized and synthetically challenging bridged seven‐membered ring systems (such as bicyclo[4.4.1]undecane, bicyclo[4.3.1]decane, bicyclo[5.4.1]dodecane, and bicyclo[6.4.1]]tridecane). This simple, thermal, direct transformation has a broad substrate scope and is high yielding, with high functional‐group tolerance and unique endo selectivity. The highly strained tricyclic cores of ingenol mebutate (picato) and cyclocitrinol are synthesized efficiently and diastereoselectively using this methodology.     

Total Synthesis of Aplydactone by a Conformationally Controlled C−H Functionalization

A concise, protecting‐group‐free total synthesis of the unusual brominated sesquiterpene aplydactone is described. Our synthesis features a [2+2] photocycloaddition, a Wolff ring contraction, an unusual remote C−H functionalization to establish the highly strained tetracyclic core, and a hydrogen‐atom transfer (HAT) reaction to access the bromine‐containing stereocenter. A finely tuned conformation of the α‐diazoketone precursor is the key for the success of the late‐stage transannular C−H insertion to deliver a bridged six‐membered ring and a quaternary stereocenter (C6) between two quaternary carbon atoms (C1 and C7).     

Ab initio studies of benzocyclopropenone, benzocyclopropenone-containing

Ab initio calculations were carried out on cyclopropenone, 1, benzocyclopropenone, 2, the benzocyclopropenone-containing [2.2]paracyclophane derivative tetracyclo[8.3.2.(4,7)O(11,13)]heptadeca-1(13),4,6,10,14,16-hexaen-12-one, 3, its decarbonylation product tricyclo[8.2.2.2(4,7)]hexadeca-1(12), 4,6,10,13-pentaen-15-yne, 5, a benzyne intermediate, and the bridged benzobarrelene derivative, pentacyclo[5.5.2.2.(1,4)O(4,14)O(10,13)]hexadeca-2,7,9,13,15-pentaene, 6. These calculations suggest that benzocyclopropenone-containing [2.2]paracyclophane, 3, and highly strained bridged benzobarrelene, 6, could exist as stable species. Both aryl rings of the benzocyclopropenone derivative 3 are predicted to be distorted from planarity. This distortion relieves some angle strain present in planar benzocyclopropenone due to the presence of the annulated three-membered ring. Calculations on benzobarrelene, 8, and [2.2]paracyclophane, 4, were performed for comparison to gain a better understanding of the strain borne in bridged benzobarrelene 6. The activation barrier for the intramolecular [4 + 2] cycloaddition of 5 to give 6 was estimated at 18.8 kcal/mol while that for the corresponding [2 + 2] cycloaddition, giving the less stable 9, was 54.5 kcal/mol. The [2 + 2] cycloaddition's transition state was twisted in a manner reminiscent of the conservation of orbital symmetry prediction for an unstrained system.     

Lewis Acid‐Catalyzed Intramolecular [3 + 2] Cross‐Cycloaddition of Donor‐ Acceptor Epoxides with Alkenes for Construction of Oxa‐[n.2.1] Skeletons

The first LA‐catalyzed [3 + 2]IMCC of GDA‐epoxides with carbon‐carbon double bonds has been developed. This provides an efficient and general strategy for construction of bridged oxa‐[n.2.1] skeletons. A novel S_N‐like mechanism through a carbon‐carbon bond cleavage of epoxide ring has been proposed.     

Rhodium(I)‐Catalyzed Bridged [5+2] Cycloaddition of cis‐Allene‐vinylcyclopropanes to Synthesize the Bicyclo[4.3.1]decane Skeleton

Previously reported was that cis‐ene‐vinylcyclopropanes (cis‐ene‐VCPs) underwent Rh‐catalyzed [5+2] reaction to give 5,7‐fused bicyclic products, where vinylcyclopropane (VCP) acts as five‐carbon synthon. Unfortunately, this reaction had very limited scope. Replacing the 2π component of cis‐ene‐VCPs to allene moiety, the corresponding cis‐allene‐VCPs did not undergo the expected normal [5+2] cycloaddition to give 5,7‐fused bicyclic products. Instead, the challenging bicyclo[4.3.1]decane skeleton was obtained via an unprecedented bridged [5+2] cycloaddition. DFT calculations were applied to understand why this bridged [5+2] reaction is favored over the anticipated but not realized normal [5+2] reaction.     

Formation of Metal‐Assisted Stable Double Helices in Dimers of Cyclic Bis‐Tetrapyrroles that Exhibit Spring‐Like Motion

Bidipyrrin‐bridged macrocycles, prepared from Ni^II‐bridged dipyrrin‐based nanorings by intramolecular oxidative biaryl coupling reactions, yielded [2+4]‐type Zn^II‐assisted stable twisted‐ring dimers comprising two double helices. These [2+4]‐type metal complexes can be optically resolved by chiral HPLC and exhibit tunable electronic and optical properties as a result of spring‐like motions. The double helices behave as glue to connect two macrocycles and as the screws of hinges to form thermally responsive synchronized spring systems.     

Preparation,Structural Properties and Thermal Isomerization of Hex‐3‐ene‐1,5‐diyne Bridged [2.2]Paracyclophanes

The [2.2]paracyclophane moiety is used as a spacer to connect the ends of a hex‐3‐ene‐1,5‐diyne unit, a π‐system that on thermolysis usually cycloaromatizes to a benzene ring (Bergman cyclization). For the preparation of the pseudo‐geminally‐bridged system 9 , the diacetylene 3 was chain‐extended to the diol 16 , which after conversion to the pseudo‐geminal dibromide 17 was ring‐closed by treatment with LiHMDS/HMPA to the [2.2]paracyclophane enediyne 9 . Whereas the McMurry coupling of the pseudo‐ortho bisaldehyde 24 resulted in the formation of the hexadienyne‐bridged cyclophane 27 , the pseudo‐ortho‐bridged hydrocarbon 11 was obtained by preparing first the diol 28 from 24 , converting the latter into the dioxolane 29 , which in the last step furnished the olefin 11 by treatment with Tf₂O/EtN(iPr)₂. The authentic Bergman product 10 of the pseudo‐gem‐bridged hexenediyne 9 was synthesized by a conventional sequence starting from the ethynyl formyl substrate 18 . Since the pseudo‐ortho‐enediyne‐bridged hydrocarbon 11 is thermally labile, its benzannelated derivate 34 was prepared. No classical Bergman cyclization reactions could be observed for any of the [2.2]paracyclophane‐bridged hexenediynes prepared here. In the pseudo‐gem‐series the fulvenes 14 and 15 were the only products that could be identified under thermal conditions (McMurry coupling); the benzannelated substrate 34 gave the benzofulvene‐bridged cyclophane 36 on photolysis. Bergman cyclizations yielding fulvene derivatives are extremely rare. The mechanism of the cyclization of 9 and 34 is discussed, using compliance constants. The structure assignments of the hydrocarbons synthesized in this study are based on spectroscopic studies as well as X‐ray structural analyses for 9 , 10 , 11 , 27 , and 34 .     

Studies on intramolecular Diels-Alder reactions of furo[3,4-c]pyridines in the synthesis of conformationally restricted analogues of nicotine and anabasine

En route to conformationally restricted analogues of nicotine and anabasine, a novel synthetic route to bridged anabasines is described that hinges on a domino intramolecular [4 + 2]-cycloaddition/ring opening-elimination sequence of 3-amino-substituted furo[3,4-c]pyridines. Extension of this route to bridged nicotines, however, proved abortive, even when the dienophile tether is activated by a p-tolylsulfonyl group or when the diene moiety is activated by an electron-releasing methoxy substituent. A detailed density functional theoretical study (B3LYP/6-31+G) was undertaken to provide insight into the factors that facilitate an intramolecular Diels-Alder reaction in the former case.     

Enantioselective formal total synthesis of roseophilin

[formula: see text] An enantioselective formal total synthesis of roseophilin 3 is presented. The 13-membered ring of macrotricycle 1 was formed via an efficient ring-closing metathesis reaction of bicycle 4. A palladium-catalyzed methoxycarbonylation reaction of enol triflate 5 was utilized to functionalize the right-hand ring of bicycle 2. The allyl substituent was introduced by a radical allylation of alpha-bromoketone 17.     

Effects of Axle‐Core,Macrocycle, and Side‐Station Structures on the Threading and Hydrolysis Processes of Imine‐Bridged Rotaxanes

Imine‐bridged rotaxanes are a new type of rotaxane in which the axle and macrocyclic ring are connected by imine bonds. We have previously reported that in imine‐bridged rotaxane 5 , the shuttling motion of the macrocycle could be controlled by changing the temperature. In this study, we investigated how the axle and macrocycle structures affect the construction of the imine‐bridged rotaxane as well as the dynamic equilibrium between imine‐bridged rotaxane 5 and [2]rotaxane 7 by using various combinations of axles ( 1 A , B ), macrocycles ( 2 a – e ), and side‐stations (XYL and TEG). In the threading process, the flexibility of the macrocycle and the substituent groups at the para position of the aniline moieties affect the preparation of the threaded imines. The size of the imine‐bridging station and the macrocyclic tether affects the hydrolysis of the imine bonds under acidic conditions.     

An application of the phosphine-catalyzed [4 + 2] annulation in indole alkaloid synthesis: formal syntheses of (+/-)-alstonerine and (+/-)-macroline

[reaction: see text] An application of the phosphine-catalyzed [4 + 2] annulation in the formal synthesis of alstonerine and macroline is reported. A phosphine-catalyzed [4 + 2] reaction between imine 7a and allene 8 formed the D ring of the target indole alkaloids. A subsequent intramolecular Friedel-Crafts acylation provided the C ring of the bridged tetracycle. Deprotection, followed by methylation of the bridged nitrogen, deoxygenation of the C6 ketone, and reduction of the C16 carbethoxy group provided the previously known intermediate 3.