A One-Pot Photochemical Method for the Generation of Functionalized Aminocyclopentanes

Collins, James L.; Staveness, Daryl; Sowden, Madison J.; Stephenson, Corey R. J.

doi:10.1021/acs.orglett.2c01483

Cited by 21 publications

(12 citation statements)

References 17 publications

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“…In 2020 the Stephenson group also utilized the masked N-centered radical approach for the synthesis of aminocyclopentanes through an intermolecular (3+2) annulation between cyclopropylimines and alkenes. 51 In 2021, the Aggarwal group reported a highly diastereoselective photoredox-catalyzed (3+2) cycloaddition of N-sulfonyl aminocyclopropane 1g with electron-deficient olefins (Scheme 12). 52 Inorganic bases such as K 3 PO 4 were key for success in this reaction.…”

Section: (3+2) Annulations With Alkenesmentioning

confidence: 99%

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Activation of aminocyclopropanes via radical intermediates

2022

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Section: (3+2) Annulations With Alkenesmentioning

confidence: 99%

Section: Formal (3+2) Cycloadditionsmentioning

confidence: 99%

Activation of aminocyclopropanes via radical intermediates

2022

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“…). [35] While FCA gave good yields, particularly when followed by a one-pot solvolysis and acylation sequence, low d.r. was observed in all cases.…”

Section: Methodsmentioning

confidence: 99%

“…In the intermolecular variant of the reaction, activated alkenes such as styrenes and acrylonitriles were required to compete with background 1‐pyrolline formation (Figure 10C) [35] . While FCA gave good yields, particularly when followed by a one‐pot solvolysis and acylation sequence, low d.r.…”

Section: The β‐Scission Approachmentioning

confidence: 99%

Formal Cycloadditions Driven by the Homolytic Opening of Strained, Saturated Ring Systems

2022

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The field of strain-driven, radical formal cycloadditions is experiencing a surge in activity motivated by a renaissance in free radical chemistry and growing demand for sp 3 -rich ring systems. The former has been driven in large part by the rise of photoredox catalysis, and the latter by adoption of the "Escape from Flatland" concept in medicinal chemistry. In the years since these broader trends emerged, dozens of formal cycloadditions, including catalytic, asymmetric variants, have been developed that operate via radical mechanisms. While cyclopropanes have been studied most extensively, a variety of strained ring systems are amenable to the design of analogous reactions. Many of these processes generate lucrative, functionally decorated sp 3 -rich ring systems that are difficult to access by other means. Herein, we summarize recent efforts in this area and analyze the state of the field.

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“…This methodology exemplified a single-atom extrusion under mild conditions, which rapidly afforded novel vectors for additional bond formations and biological interactions. Specifically for derivatives of piperidine, the third most frequently encountered ring system in small-molecule FDA-approved drugs as of 2020, the ring contraction yielded derivatized aminocyclopentanes that themselves are valuable biorelevant targets. ,, …”

Section: Introductionmentioning

confidence: 99%

Mechanistic Investigation, Wavelength-Dependent Reactivity, and Expanded Reactivity of N–Aryl Azacycle Photomediated Ring Contractions

Kim,

Schwarz,

Jurczyk

et al. 2024

J. Am. Chem. Soc.

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Under mild blue-light irradiation, α-acylated saturated heterocycles undergo a photomediated one-atom ring contraction that extrudes a heteroatom from the cyclic core. However, for nitrogenous heterocycles, this powerful skeletal edit has been limited to substrates bearing electron-withdrawing substituents on nitrogen. Moreover, the mechanism and wavelength-dependent efficiency of this transformation have remained unclear. In this work, we increased the electron richness of nitrogen in saturated azacycles to improve light absorption and strengthen critical intramolecular hydrogen bonding while enabling the direct installation of the photoreactive handle. As a result, a broadly expanded substrate scope, including underexplored electron-rich substrates and previously unsuccessful heterocycles, has now been achieved. The significantly improved yields and diastereoselectivities have facilitated reaction rate, kinetic isotope effect (KIE), and quenching studies, in addition to the determination of quantum yields. Guided by these studies, we propose a revised ET/PT mechanism for the ring contraction, which is additionally corroborated by computational characterization of the lowest-energy excited states of α-acylated substrates through time-dependent DFT. The efficiency of the ring contraction at wavelengths longer than those strongly absorbed by the substrates was investigated through wavelength-dependent rate measurements, which revealed a red shift of the photochemical action plot relative to substrate absorbance. The elucidated mechanistic and photophysical details effectively rationalize empirical observations, including additive effects, that were previously poorly understood. Our findings not only demonstrate enhanced synthetic utility of the photomediated ring contraction and shed light on mechanistic details but may also offer valuable guidance for understanding wavelength-dependent reactivity for related photochemical systems.

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A One-Pot Photochemical Method for the Generation of Functionalized Aminocyclopentanes

Cited by 21 publications

References 17 publications

Activation of aminocyclopropanes via radical intermediates

Activation of aminocyclopropanes via radical intermediates

Formal Cycloadditions Driven by the Homolytic Opening of Strained, Saturated Ring Systems

Mechanistic Investigation, Wavelength-Dependent Reactivity, and Expanded Reactivity of N–Aryl Azacycle Photomediated Ring Contractions

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