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1. Selective ring-rearrangement or ring-closing metathesis of bicyclo[3.2.1]octenes

   https://doi.org/10.1039/d0cc04624h  

   Semenova, Evgeniya ; Lahtigui, Ouidad ; Scott, Sarah K. ; Albritton, Matthew ; Abboud, Khalil A. ; Ghiviriga, Ion ; Roitberg, Adrian E. ; Grenning, Alexander J. ( October 2020 , Chemical Communications)

   null (Ed.)

   Explored was the competitive ring-closing metathesis vs. ring-rearrangement metathesis of bicyclo[3.2.1]octenes prepared by a simple and convergent synthesis from bicyclic alkylidenemalono-nitriles and allylic electrophiles. It was uncovered that ring-closing metathesis occurs exclusively on the tetraene-variant, yielding unique, stereochemically and functionally rich polycyclic bridged frameworks, whereas the reduced version (a triene) undergoes ring-rearrangement metathesis to 5 – 6 – 5 fused ring systems resembling the isoryanodane core. 

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2. Programmable meroterpene synthesis Nat Commun 11, 508 (2020). https://doi.org/10.1038/s41467-020-14354-5

   https://doi.org/10.1038/s41467-020-14354-5  

   Shen, X. ; Ting, C. P. ; Xu, G. ; Maimone, T. J. ( January 2020 , Nature communications)

   The bicyclo[3.3.1]nonane architecture is a privileged structural motif found in over 1000 natural products with relevance to neurodegenerative disease, bacterial and parasitic infection, and cancer among others. Despite disparate biosynthetic machinery, alkaloid, terpene, and polyketide-producing organisms have all evolved pathways to incorporate this carbocyclic ring system. Natural products of mixed polyketide/terpenoid origins (meroterpenes) are a particularly rich and important source of biologically active bicyclo[3.3.1]nonane-containing molecules. Herein we detail a fully synthetic strategy toward this broad family of targets based on an abiotic annulation/rearrangement strategy resulting in a 10-step total synthesis of garsubellin A, an enhancer of choline acetyltransferase and member of the large family of polycyclic polyprenylated acylphloroglucinols. This work solidifies a strategy for making multiple, diverse meroterpene chemotypes in a programmable assembly process involving a minimal number of chemical transformations. 

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3. Total Synthesis of (+)‐Cochlearol B by an Approach Based on a Catellani Reaction and Visible‐Light‐Enabled [2+2] Cycloaddition**

   https://doi.org/10.1002/ange.202201213  

   Richardson, Alistair D. ; Vogel, Trenton R. ; Traficante, Emily F. ; Glover, Kason J. ; Schindler, Corinna S. ( June 2022 , Angewandte Chemie)

   A 14‐step synthesis of (+)‐cochlearol B is reported. This renoprotective meroterpenoid features a unique core structure containing a densely substituted cyclobutane ring with three stereocenters. Our strategy employed an organocatalytic Kabbe condensation in route to the key chromenyl triflate. A subsequent Catellani reaction incorporated the remaining carbon atoms featured in the skeleton of cochlearol B. An ensuing visible‐light‐mediated [2+2] photocycloaddition closed the cyclobutane and formed the central bicyclo[3.2.0]heptane core. Notably, careful design and tuning of the Catellani and photocycloaddition reactions proved crucial in overcoming undesired reactivity, including cyclopropanation reactions and [4+2] cycloadditions.

    

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4. Total Synthesis of (+)‐Cochlearol B by an Approach Based on a Catellani Reaction and Visible‐Light‐Enabled [2+2] Cycloaddition**

   https://doi.org/10.1002/anie.202201213  

   Richardson, Alistair D. ; Vogel, Trenton R. ; Traficante, Emily F. ; Glover, Kason J. ; Schindler, Corinna S. ( June 2022 , Angewandte Chemie International Edition)

   A 14‐step synthesis of (+)‐cochlearol B is reported. This renoprotective meroterpenoid features a unique core structure containing a densely substituted cyclobutane ring with three stereocenters. Our strategy employed an organocatalytic Kabbe condensation in route to the key chromenyl triflate. A subsequent Catellani reaction incorporated the remaining carbon atoms featured in the skeleton of cochlearol B. An ensuing visible‐light‐mediated [2+2] photocycloaddition closed the cyclobutane and formed the central bicyclo[3.2.0]heptane core. Notably, careful design and tuning of the Catellani and photocycloaddition reactions proved crucial in overcoming undesired reactivity, including cyclopropanation reactions and [4+2] cycloadditions.

    

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5. 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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