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1. Copper( i )-catalyzed highly enantioselective [3 + 3]-cycloaddition of γ-alkyl enoldiazoacetates with nitrones

   https://doi.org/10.1039/D0QO00539H  

   Dong, Kuiyong; Xu, Xinfang; Doyle, Michael P. (June 2020, Organic Chemistry Frontiers)

   null (Ed.)

   Chiral copper( i ) catalysts are preferred over chiral dirhodium( ii ) catalysts for [3 + 3]-cycloaddition reactions of γ-alkyl-substituted enoldiazoacetates compounds with nitrones. Using the In-SaBox ligand these reactions effectively produce cis -3,6-dihydro-1,2-oxazine derivatives under mild conditions in high yield and with exceptional stereocontrol, and enantioselectivity increases with the size of the γ-substituent. Mechanistic studies show that cycloaddition occurs solely through the formation of ( Z )-γ-substituted metallo-enolcarbene intermediates that are catalytically gennerated from both ( Z )- and ( E )-γ-substituted enoldiazoactates via donor–acceptor cyclopropene intermediates. 

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2. Converting Strain Release into Aromaticity Loss for Activation of Donor–Acceptor Cyclopropanes: Generation of Quinone Methide Traps for C-Nucleophiles

   https://doi.org/10.1021/acs.orglett.4c03106  

   Shorokhov, Vitaly V; Chabuka, Beauty K; Tikhonov, Timur P; Filippova, Anastasia V; Zhokhov, Sergey S; Tafeenko, Victor A; Andreev, Ivan A; Ratmanova, Nina K; Uchuskin, Maxim G; Trushkov, Igor V; et al (September 2024, Organic Letters)

   Here, we present a new approach for the activation of donor–acceptor cyclopropanes in ring-opening reactions, which does not require the use of a Lewis or Brønsted acid as a catalyst. Donor–acceptor cyclopropanes containing a phenolic group as the donor undergo deprotonation and isomerization to form the corresponding quinone methides. This innovative strategy was applied to achieve (4 + 1)-annulation of cyclopropanes with sulfur ylides, affording functionalized dihydrobenzofurans. Additionally, the generated ortho- and para-(aza)quinone methides can be trapped by various CH-acids. 

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3. Photo-cycloaddition reactions of vinyldiazo compounds

   https://doi.org/10.1038/s41467-024-48274-5  

   Bao, Ming; Łuczak, Klaudia; Chaładaj, Wojciech; Baird, Marriah; Gryko, Dorota; Doyle, Michael P (December 2024, Nature Communications)

   Abstract Heterocyclic rings are important structural scaffolds encountered in both natural and synthetic compounds, and their biological activity often depends on these motifs. They are predominantly accessible via cycloaddition reactions, realized by either thermal, photochemical, or catalytic means. Various starting materials are utilized for this purpose, and, among them, diazo compounds are often encountered, especially vinyldiazo compounds that give access to donor-acceptor cyclopropenes which engage in [2+n] cycloaddition reactions. Herein, we describe the development of photochemical processes that produce diverse heterocyclic scaffolds from multisubstituted oximidovinyldiazo compounds. High chemoselectivity, good functional group tolerance, and excellent scalability characterize this methodology, thus predisposing it for broader applications. Experimental and computational studies reveal that under light irradiation these diazo reagents selectively transform into cyclopropenes which engage in cycloaddition reactions with various dipoles, while under thermal conditions the formation of pyrazole from vinyldiazo compounds is favored. 

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4. Catalytic asymmetric cycloaddition reactions of enoldiazo compounds

   https://doi.org/10.1039/C9OB00478E  

   Marichev, Kostiantyn O.; Doyle, Michael P. (April 2019, Organic & Biomolecular Chemistry)

   This review describes catalytic asymmetric cycloaddition reactions of silyl-protected enoldiazo compounds for the construction of highly functionalized carbo- and heterocycles which possess one or more chiral center(s). The enoldiazo compound or its derivative, donor–acceptor cyclopropene, form electrophilic vinylogous metal carbene intermediates that combine stepwise with nucleophilic dipolar reactants to form products from [3 + 1]-, [3 + 2]-, [3 + 3]-, [3 + 4]-, and [3 + 5]-cycloaddition, generally in high yield and with exceptional stereocontrol and regioselectivity. 

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5. Chemodivergent, Regio‐ and Enantioselective Cycloaddition Reactions between 1,3‐Dienes and Alkynes

   https://doi.org/10.1002/anie.202216000  

   Singh, Dipshi; RajanBabu, T. V. (February 2023, Angewandte Chemie International Edition)

   Abstract Alkynes and 1,3‐dienes are among the most readily available precursors for organic synthesis. We report two distinctly different, catalyst‐dependent, modes of regio‐ and enantioselective cycloaddition reactions between these classes of compounds providing rapid access to highly functionalized 1,4‐cyclohexadienesorcyclobutenes from thesameprecursors. Complexes of an earth abundant metal, cobalt, with several commercially available chiral bisphosphine ligands with narrow bite angles catalyze [4+2]‐cycloadditions between a 1,3‐diene and an alkyne giving a cyclohexa‐1,4‐diene in excellent chemo‐, regio‐ and enantioselectivities. In sharp contrast, complex of a finely tuned phosphino‐oxazoline ligand promotes unique [2+2]‐cycloaddition between the alkyne and the terminal double bond of the diene giving a highly functionalized cyclobutene in excellent regio‐ and enantioselectivities. 

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