Recent advances in Garratt-Braverman cyclization: Mechanistic and synthetic explorations

Bhattacharya, Prabuddha; Singha, Monisha; Das, Eshani; Mandal, Arundhoti; Maji, Manasi; Basak, Amit

doi:10.1016/j.tetlet.2018.06.056

Cited by 10 publications

(3 citation statements)

References 95 publications

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“…Allenes are involved in a number of cycloisomerization reactions, such as the Garratt–Braverman, Myers–Saito, and Schmittel cyclizations. These processes, depending on the substituents present, often undergo cyclization to benzenoid products via diradical intermediates .…”

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confidence: 99%

In Situ Allene Formation via Alkyne Tautomerization to Promote [4 + 2]-Cycloadditions with a Pendant Alkyne or Nitrile

2022

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We have explored the net-[4 + 2]-cycloadditions of a variety of aryl (or alkenyl) alkynes. Tautomerization via base-catalyzed alkyne-to-allene isomerization produces a transient allene, which undergoes stepwise cyclization with not only a pendant alkyne but also a nitrile. The operative mechanisms for these reactions were studied by density functional theory and compared with the slower thermal cyclization of the precursor alkyne.Letter pubs.acs.org/OrgLett

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confidence: 99%

In Situ Allene Formation via Alkyne Tautomerization to Promote [4 + 2]-Cycloadditions with a Pendant Alkyne or Nitrile

2022

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“…The resulting products were deuterated only at the newly formed aromatic ring. This result confirms that the reaction occurs via a TDDA mechanism through initial [4 + 2] cycloaddition, resulting in a cyclic allene intermediate, which immediately tautomerizes into a benzene ring (a process facilitated by D 2 O). , An alternative Garratt–Braverman cyclization mechanism, , proceeding via an alkyne–allene isomerization, is ruled out, as it would result in deuteration at the ethereal α-positions.…”

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confidence: 99%

Tetradehydro-Diels–Alder Reactions of Flexible Arylalkynes via Folding Inside a Molecular Cage

et al. 2023

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The tetradehydro-Diels−Alder (TDDA) reaction is a useful transformation for the rapid assembly of polycyclic scaffolds from simple linear precursors in a single synthetic step. However, the reaction requires careful substrate design and harsh reaction conditions to overcome the inherent entropic cost for this transformation. Herein we report an efficient site-selective TDDA transformation within a self-assembled Pd 6 L 4 cage. Despite the large size, the flexibility of the employed substrates allows for efficient encapsulation within the host cavity. The rate of thermal cyclization of the encapsulated guest was found to be greatly enhanced, and high product selectivity for an unsymmetrical substrate was observed. The efficiency of this system relies on the precise conformational control of the substrate within the confined space of the host cage.

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“…DFT calculations only afford the further H-abstraction structure C1* with the absence of any unpaired electron. In fact, the intermediate C1* and its diradical resonance structure similar to the Garratt−Braverman cyclization69 intermediate would undergo intramolecular reaction to form 6* via either diradical self-quenching or formal [2+2] cycloadditions70 with a barrier of 16.2 kcal/mol over TS-C2. Overall, the DFT calculation results suggest that the diradicals formed from MSC could become diamagnetic through various HAT pathways depending on the substrates, eventually yielding the thermodynamically stable products.…”

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Experimental and Computational Study on the Intramolecular Hydrogen Atom Transfer Reactions of Maleimide-Based Enediynes After Cycloaromatization

Zhang

Lü

et al. 2020

J. Org. Chem.

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The follow-up reaction pathways of the diradical species formed from cycloaromatization of enediynes or enyne–allenes determine their ability of H-abstraction from DNA, significantly affecting their biological activity performance. To gain a deeper understanding of subsequent reaction pathways of the diradical intermediates formed from acyclic enediynes based on maleimide-assisted rearrangement and cycloaromatization (MARACA), a maleimide-based enediyne featuring methylene groups adjacent to the propargyl sites of the terminal alkynes was synthesized through the Sonogashira coupling reaction. Three thermal cyclization products after intramolecular hydrogen atom transfer (HAT) were obtained from the thermolysis experiment and their structures were confirmed by 1D and 2D nuclear magnetic resonance spectroscopic analysis. Density functional theory was employed to analyze the important elementary steps including rearrangement, cycloaromatization, and intramolecular HAT processes toward the formation of the cyclized products, where the low-energy barriers of HAT pathways relative to the formation of diradicals from cycloaromatization were successfully identified. Overall, the HAT processes to consume diradicals intramolecularly have become competitive with that of intermolecular H-abstraction, implying that the DNA-cleavage ability of enediynes can be further boosted once the HAT processes are halted. This study offers a promising direction for designing novel and potent acyclic enediynes for antitumor applications.

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Recent advances in Garratt-Braverman cyclization: Mechanistic and synthetic explorations

Cited by 10 publications

References 95 publications

In Situ Allene Formation via Alkyne Tautomerization to Promote [4 + 2]-Cycloadditions with a Pendant Alkyne or Nitrile

In Situ Allene Formation via Alkyne Tautomerization to Promote [4 + 2]-Cycloadditions with a Pendant Alkyne or Nitrile

Tetradehydro-Diels–Alder Reactions of Flexible Arylalkynes via Folding Inside a Molecular Cage

Experimental and Computational Study on the Intramolecular Hydrogen Atom Transfer Reactions of Maleimide-Based Enediynes After Cycloaromatization

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