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1. Site-selective [2 + 2 + n ] cycloadditions for rapid, scalable access to alkynylated polycyclic aromatic hydrocarbons

   https://doi.org/10.1039/C9SC06102A  

   Kiel, Gavin R.; Bergman, Harrison M.; Tilley, T. Don (March 2020, Chemical Science)

   null (Ed.)

   Polycyclic aromatic hydrocarbons (PAHs) are attractive synthetic building blocks for more complex conjugated nanocarbons, but their use for this purpose requires appreciable quantities of a PAH with reactive functional groups. Despite tremendous recent advances, most synthetic methods cannot satisfy these demands. Here we present a general and scalable [2 + 2 + n ] ( n = 1 or 2) cycloaddition strategy to access PAHs that are decorated with synthetically versatile alkynyl groups and its application to seven structurally diverse PAH ring systems (thirteen new alkynylated PAHs in total). The critical discovery is the site-selectivity of an Ir-catalyzed [2 + 2 + 2] cycloaddition, which preferentially cyclizes tethered diyne units with preservation of other (peripheral) alkynyl groups . The potential for generalization of the site-selectivity to other [2 + 2 + n ] reactions is demonstrated by identification of a Cp 2 Zr-mediated [2 + 2 + 1]/metallacycle transfer sequence for synthesis of an alkynylated, selenophene-annulated PAH. The new PAHs are excellent synthons for macrocyclic conjugated nanocarbons. As a proof of concept, four were subjected to alkyne metathesis catalysis to afford large, PAH-containing arylene ethylene macrocycles, which possess a range of cavity sizes reaching well into the nanometer regime. Notably, these high-yielding macrocyclizations establish that synthetically convenient pentynyl groups can be effective for metathesis since the 4-octyne byproduct is sequestered by 5 Å MS. Most importantly, this work is a demonstration of how site-selective reactions can be harnessed to rapidly build up structural complexity in a practical, scalable fashion. 

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2. Development of an Allenyne‐Alkyne [4+2] Cycloaddition and its Application to Total Synthesis of Selaginpulvilin A

   https://doi.org/10.1002/chem.202202015  

   Le, Anh; Gupta, Saswata; Xu, Man; Xia, Yuanzhi; Lee, Daesung (August 2022, Chemistry – A European Journal)

   Abstract A new [4+2] cycloaddition of allenyne‐alkyne is developed. The reaction is believed to proceed with forming an α,3‐dehydrotoluene intermediate. This species behaves as a σπ‐diradical to react with a hydrogen atom donor, whereas it displays a zwitterionic reactivity toward weak nucleophiles. The efficiency of trapping α,3‐dehydrotoluene depends not only on its substituents but also the trapping agents. Notable features of the reaction are the activating role of the extra alkyne of the 1,3‐diyne that reacts with the allenyne moiety and the opposite mode of trapping with oxygen and nitrogen nucleophiles. Oxygen nucleophiles result in the oxygen‐end incorporation at the benzylic position of the α,3‐dehydrotoluene, whereas with amine nucleophiles the nitrogen‐end is incorporated into the aromatic core. Relying on the allenyne‐alkyne cycloaddition as an enabling strategy, a concise total synthesis of phosphodiesterase‐4 inhibitory selaginpulvilin A is realized. 

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3. Gold‐Catalyzed Diyne‐Ene Annulation for the Synthesis of Polysubstituted Benzenes through Formal [3+3] Approach with Amide as the Critical Co‐Catalyst

   https://doi.org/10.1002/anie.202407360  

   Wei, Jingwen; Pham, Thong; Attah, Emmanuel_Ifeanyi; Liu, Mengjia; Yaroshuk, Timothy; Chen, Hao; Wojtas, Lukasz; Shi, Xiaodong (August 2024, Angewandte Chemie International Edition)

   Abstract The one‐step synthesis of tetra‐substituted benzenes was accomplished via gold‐catalyzed diyne‐ene annulation. Distinguished from prior modification methods, this novel strategy undergoes formal [3+3] cyclization, producing polysubstituted benzenes with exceptional efficiency. The critical factor enabling this transformation was the introduction of amides, which were reported for the first time in gold catalysis as covalent nucleophilic co‐catalysts. This interesting protocol not only offers a new strategy to achieve functional benzenes with high efficiency, but also enlightens potential new reaction pathways within gold‐catalyzed alkyne activation processes. 

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4. Synthesis of oxaboranes via nickel-catalyzed dearylative cyclocondensation

   https://doi.org/10.1039/d2sc01840c  

   Koeritz, Mason T.; Banovetz, Haley K.; Prell, Sean A.; Stanley, Levi M. (July 2022, Chemical Science)

   We report Ni-catalyzed dearylative cyclocondensation of aldehydes, alkynes, and triphenylborane. The reaction is initiated by oxidative cyclization of the aldehyde and alkyne coupling partners to generate an oxanickelacyclopentene which reacts with triphenylborane to form oxaboranes. This formal dearylative cyclocondensation reaction generates oxaboranes in moderate-to-high yields (47–99%) with high regioselectivities under mild reaction conditions. This approach represents a direct and modular synthesis of oxaboranes which are difficult to access using current methods. These oxaboranes are readily transformed into valuable building blocks for organic synthesis and an additional class of boron heterocycles. Selective homocoupling forms oxaboroles, oxidation generates aldol products, and reduction and arylation form substituted allylic alcohols. 

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5. Cycloisomerization of Alkyne‐Tethered N ‐Acyloxycarbamates to 2‐( 3H )Oxazolones through Nitrenoid‐Mediated Carboxyamidation

   https://doi.org/10.1002/chem.202203371  

   Su, Siyuan; Wu, Tongtong; Xia, Yuanzhi; Wink, Donald_J; Lee, Daesung (March 2023, Chemistry – A European Journal)

   Abstract The cycloisomerization of alkyne‐tetheredN‐benzoyloxycarbamates to 2‐(3H)oxazolones is described. Two catalytic systems are tailored for intramolecular 5‐exo‐alkyne carboxyamidation and concomitant alkene isomerization. PtCl₂/CO (5 mol%, toluene, 100 °C) promotes both carboxyamidation and alkene isomerization but has a limited substrate scope. On the other hand, FeCl₃(5 mol%, CH₃CN, 100 °C) promotes carboxyamidation effectively but a cocatalyst is required for the exocyclic alkene isomerization. Thus, a two‐step one‐pot protocol has been developed for a broader reaction scope, which involves FeCl₃‐catalyzed carboxyamidation and base‐induced alkene isomerization. Crossover experiments suggest that these reactions proceed mainly through a mechanism involving acylnitrenoid intermediates rather than carbenoid intermediates. 

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