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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/anie.202201213  

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

   Abstract 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. Selective skeletal editing of polycyclic arenes using organophotoredox dearomative functionalization

   https://doi.org/10.1038/s41467-022-32201-7  

   Ji, Peng; Davies, Cassondra C.; Gao, Feng; Chen, Jing; Meng, Xiang; Houk, Kendall N.; Chen, Shuming; Wang, Wei (August 2022, Nature Communications)

   Abstract Reactions that lead to destruction of aromatic ring systems often require harsh conditions and, thus, take place with poor selectivities. Selective partial dearomatization of fused arenes is even more challenging but can be a strategic approach to creating versatile, complex polycyclic frameworks. Herein we describe a general organophotoredox approach for the chemo- and regioselective dearomatization of structurally diverse polycyclic aromatics, including quinolines, isoquinolines, quinoxalines, naphthalenes, anthracenes and phenanthrenes. The success of the method for chemoselective oxidative rupture of aromatic moieties relies on precise manipulation of the electronic nature of the fused polycyclic arenes. Mechanistic studies show that the addition of a hydrogen atom transfer (HAT) agent helps favor the dearomatization pathway over the more thermodynamically downhill aromatization pathway. We show that this strategy can be applied to rapid synthesis of biologically valued targets and late-stage skeletal remodeling en route to complex structures. 

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5. Flow Chemistry‐Enabled Divergent and Enantioselective Total Syntheses of Massarinolin A, Purpurolides B, D, E, 2,3‐Deoxypurpurolide C, and Structural Revision of Massarinolin A

   https://doi.org/10.1002/anie.202109625  

   Wang, Ye‐Cheng; Cui, Chengsen; Dai, Mingji (September 2021, Angewandte Chemie International Edition)

   Abstract Massarinolin A and purpurolides are bioactive bergamotane sesquiterpenes condensed with a variety of synthetically challenging ring systems: a bicyclo[3.1.1]heptane, an oxaspiro[3.4]octane, and a dioxaspiro[4.4]nonane (oxaspirolactone). Herein, we report the first enantioselective total syntheses of massarinolin A, purpurolides B, D, E, and 2,3‐deoxypurpurolide C. Our synthesis and computational analysis also led to a structural revision of massarinolin A. The divergent approach features an enantioselective organocatalyzed Diels–Alder reaction to install the first stereogenic center in highee, a scalable flow photochemical Wolff rearrangement to build the key bicyclo[3.1.1]heptane, a furan oxidative cyclization to form the oxaspirolactone, a late‐stage allylic C−H oxidation, and a Myers’ NBSH‐promoted sigmatropic elimination to install theexomethylene group of massarinolin A. 

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