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1. Alder-ene reactions driven by high steric strain and bond angle distortion to form benzocyclobutenes

   https://doi.org/10.1039/c8sc04277b  

   Gupta, Saswata; Lin, Yongjia; Xia, Yuanzhi; Wink, Donald J.; Lee, Daesung (February 2019, Chemical Science)

   A unique aryne-based Alder-ene reaction to form benzocyclobutene is described. In this process, the thermodynamic barrier to form a four-membered ring is compensated by the relief of the strain energy of an aryne intermediate. On the other hand, the driving force to overcome the high kinetic barrier is provided by the gearing effect of the bulky substituent at the ortho -position of the ene-donor alkene. To maximize the steric strain by the ortho -substituent, a structural element for internal hydrogen bonding is installed, which plays a crucial role for both the hexadehydro Diels–Alder and the Alder-ene reactions. DFT calculations show that the bulky hydrogen bonding element lowers the activation barrier for the Alder-ene reaction by destabilizing the intermediate, which is due to the severe bond angle distortion. The preferred formation of cis -isomers can also be explained by the extent of bond angle distortion. 

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2. Diels−Alder Reactions of 1‐Alkoxy-1-amino-1,3-butadienes: Direct Synthesis of 6‐Substituted and 6,6-Disubstituted 2‐Cyclohexenones and 6‐Substituted 5,6-Dihydropyran-2-ones

   https://doi.org/10.1021/acs.orglett.1c01031  

   Elkin, P. K.; Durfee, N. D. (June 2021, Organic letters)

   Gaich, T. (Ed.)

   We report the cycloaddition reactions of 1-alkoxy-1- amino-1,3-butadienes. These doubly activated dienes are prepared on a multigram scale from crotonic acid chloride and its derivatives. The dienes undergo Diels−Alder (DA) and hetero-Diels−Alder (HDA) reactions under mild reaction conditions with a variety of electron- deficient dienophiles to afford cycloadducts in good yields with excellent regioselectivities. The hydrolysis of the DA cycloadducts provides 6-substituted and 6,6-disubstituted 2-cylohexenones, which are versatile building blocks for complex molecule synthesis. The corresponding HDA cycloadducts afford 6-substituted 5,6-dihydropyr- an-2-ones. 

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3. Cascade Reactions of Alkynyl Ketones and Amides to Generate Unsaturated Oxacycles and Aromatic Carbocycles

   https://doi.org/10.1002/chem.202403270  

   Rajapaksa, Kumudi_J_W; Yan_Wong, Hang; Lee, Daesung (November 2024, Chemistry – A European Journal)

   Abstract We describe novel amine‐mediated transformation of alkynyl ketones and amides to generate 2‐methylene‐2H‐pyrans, substituted 3‐hydroxy‐9H‐fluoren‐9‐ones, and amine‐incorporated arenes. These cascade processes are initiated by conjugate addition of secondary amine followed by hydrolysis of the enamine/vinylogous amide intermediates. The product distribution is highly sensitive to the steric and electronic effects of the substituents on both the alkyne moieties, the tether structure connecting them, and the nature of the amine. Alkynyl amide participates in the Alder‐ene reaction favorably to generate more reactive allene amide that reacts with amine to generate amine‐incorporated arene products. These metal‐free cascade reactions are a useful synthetic method that can be exploited for the construction of various hetero‐ and carbocyclic systems. 

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4. Decomposition of the electronic activity in competing [5,6] and [6,6] cycloaddition reactions between C ₆₀ and cyclopentadiene

   https://doi.org/10.1039/C8CP07626J  

   Villegas-Escobar, Nery; Poater, Albert; Solà, Miquel; Schaefer, Henry F.; Toro-Labbé, Alejandro (February 2019, Physical Chemistry Chemical Physics)

   Fullerenes, in particular C 60 , are important molecular entities in many areas, ranging from material science to medicinal chemistry. However, chemical transformations have to be done in order to transform C 60 in added-value compounds with increased applicability. The most common procedure corresponds to the classical Diels–Alder cycloaddition reaction. In this research, a comprehensive study of the electronic activity that takes place in the cycloaddition between C 60 and cyclopentadiene toward the [5,6] and [6,6] reaction pathways is presented. These are competitive reaction mechanisms dominated by σ and π fluctuating activity. To better understand the electronic activity at each stage of the mechanism, the reaction force (RF) and the symmetry-adapted reaction electronic flux (SA-REF, J Γi ( ξ )) have been used to elucidate whether π or σ bonding changes drive the reaction. Since the studied cycloaddition reaction proceeds through a C s symmetry reaction path, two SA-REF emerge: J A′ ( ξ ) and J A′′ ( ξ ). In particular, J A′ ( ξ ) mainly accounts for bond transformations associated with π bonds, while J A′′ ( ξ ) is sensitive toward σ bonding changes. It was found that the [6,6] path is highly favored over the [5,6] with respect to activation energies. This difference is primarily due to the less intensive electronic reordering of the σ electrons in the [6,6] path, as a result of the pyramidalization of carbon atoms in C 60 (sp 2 → sp 3 transition). Interestingly, no substantial differences in the π electronic activity from the reactant complex to the transition state structure were found when comparing the [5,6] and [6,6] paths. Partition of the kinetic energy into its symmetry contributions indicates that when a bond is being weakened/broken (formed/strengthened) non-spontaneous (spontaneous) changes in the electronic activity occur, thus prompting an increase (decrease) of the kinetic energy. Therefore, contraction (expansion) of the electronic density in the vicinity of the bonding change is expected to take place. 

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5. Isomer-selected ion–molecule reactions of acetylene cations with propyne and allene

   https://doi.org/10.1039/D0CP03953E  

   Schmid, P. C.; Greenberg, J.; Nguyen, T. L.; Thorpe, J. H.; Catani, K. J.; Krohn, O. A.; Miller, M. I.; Stanton, J. F.; Lewandowski, H. J. (September 2020, Physical Chemistry Chemical Physics)

   null (Ed.)

   One of the fundamental goals of chemistry is to determine how molecular structure influences interactions and leads to different reaction products. Studies of isomer-selected and resolved chemical reactions can shed light directly on how form leads to function. In the following, we present the results of gas-phase reactions between acetylene cations (C 2 D 2 + ) with two different isomers of C 3 H 4 : propyne (DC 3 D 3 ) and allene (H 2 C 3 H 2 ). Our highly controlled, trapped-ion environment allows for precise determination of reaction products and kinetics. From these results, we can infer details of the underlying reaction dynamics of C 2 H 2 + + C 3 H 4 . Through the synergy of experimental results and high-level quantum chemical potential energy surface calculations, we are able to identify distinct reaction mechanisms for the two isomers. We find long-range charge exchange with no complex formation is favored for allene, whereas charge exchange leads to an intermediate reaction complex for propyne and thus, different products. Therefore, this reaction displays a pronounced isomer-selective bi-molecular reactive process. 

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