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1. 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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2. Complexity‐Building Exhaustive Dearomatization of Benzenoid Aromatics within an ESIPT‐Initiated Three‐Step Photochemical Cascade.

   https://doi.org/10.1002/anie.202415176  

   Beduru, Srinivas; Huple, Deepak_B; Kutateladze, Andrei_G (November 2024, Angewandte Chemie International Edition)

   Abstract Dearomative cycloadditions offer rapid access to complex 3D molecular architectures, commonly via a sp²‐to‐sp³rehybridization of two atoms of an aromatic ring. Here we report that the 6e π‐system of a benzenoid aromatic pendant could be exhaustively depleted within a single photochemical cascade. An implementation of this approach involves the initial dearomative [4+2] cycloaddition of the Excited State Intramolecular Proton Transfer (ESIPT)‐generated azaxylylene, followed by two consecutive [2+2] cycloadditions of auxiliary π moieties strategically positioned in the photoprecursor. Such photochemical cascade fully dearomatizes the benzenoid aromatic ring, saturating all six sp²atoms to yield a complex sp³‐rich scaffold with high control of its 3D molecular shape, rendering it a robust platform for rapid systematic mapping of underexplored chemical space. Significant growth of molecular complexity—starting with a modular synthesis of photoprecursors from readily available building blocks—is quantified by Böttcher score calculations. 

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3. Bioinspired Synthesis of (−)‐PF‐1018

   https://doi.org/10.1002/anie.201912452  

   Quintela‐Varela, Hugo; Jamieson, Cooper S.; Shao, Qianzhen; Houk, K. N.; Trauner, Dirk (February 2020, Angewandte Chemie International Edition)

   Abstract The combination of electrocyclizations and cycloadditions accounts for the formation of a range of fascinating natural products. Cascades consisting of 8π electrocyclizations followed by a 6π electrocyclization and a cycloaddition are relatively common. We now report the synthesis of the tetramic acid PF‐1018 through an 8π electrocyclization, the product of which is immediately intercepted by a Diels–Alder cycloaddition. The success of this pericyclic cascade was critically dependent on the substitution pattern of the starting polyene and could be rationalized through DFT calculations. The completion of the synthesis required the instalment of a trisubstituted double bond by radical deoxygenation. An unexpected side product formed through 4‐exo‐trig radical cyclization could be recycled through an unprecedented triflation/fragmentation. 

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

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

   Singh, Dipshi; RajanBabu, T. V. (January 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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5. Huisgen's 1,3‐Dipolar Cycloadditions to Fulvenes Proceed via Ambimodal [6+4]/[4+2] Transition States

   https://doi.org/10.1002/anie.202005265  

   Liu, Fang; Chen, Yu; Houk, K. N. (June 2020, Angewandte Chemie International Edition)

   Abstract Huisgen's 1960 announcement of the concept of 1,3‐dipolar cycloadditions was published the year before Alder's study of the reaction of diazomethane and dimethylfulvene. The diazomethane reaction was studied again in 1970 by Houk et al. and shown to give a [6+4] adduct. Padwa's nitrile ylide cycloaddition to dimethylfulvene (1978) gave [6+4] and [4+2] adducts. We performed computational studies of these reactions with density functional theory (DFT) and show that they involve ambimodal [6+4]/[4+2] transition states that can lead to either type of cycloadduct from one transition state. We dedicate this paper to the extraordinary life and humanity of Rolf Huisgen, and to the undying influence of his discoveries on chemistry. 

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