Photochemical Flow Synthesis of 3‐Hydroxyazetidines

Ruggeri, Michele; Dombrowski, Amanda W.; Djurić, Stevan W.; Baxendale, Ian R.

doi:10.1002/cptc.201900188

Cited by 19 publications

(14 citation statements)

References 44 publications

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“…Several applications demonstrate that their continuous photochemical synthesis based on an intramolecular [2 + 2] cycloaddition ( Figure 11A) can be scaled to kilogram quantities in order to facilitate further derivatization [31,62,63]. The synthesis of 3-hydroxyazetidines via a continuous Norrish-Young photocyclization reaction ( Figure 11B) represents a further demonstration of effectively creating drug-like structures in a simple and atom-economical fashion, and a recent study reports on the versatility of this transformation [64]. A final example outlines the combination of photochemical with thermal processes in a reaction sequence rendering several isoindolin-1-one derivatives in a continuous manner, in which a photobenzylation of substituted phthalimides features as key step [65] ( Figure 11C).…”

Section: Synthesis Of Bioactives: Drugs and Natural Productsmentioning

confidence: 99%

Continuous Flow Photochemistry for the Preparation of Bioactive Molecules

2020

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The last decade has witnessed a remarkable development towards improved and new photochemical transformations in response to greener and more sustainable chemical synthesis needs. Additionally, the availability of modern continuous flow reactors has enabled widespread applications in view of more streamlined and custom designed flow processes. In this focused review article, we wish to evaluate the standing of the field of continuous flow photochemistry with a specific emphasis on the generation of bioactive entities, including natural products, drugs and their precursors. To this end we highlight key developments in this field that have contributed to the progress achieved to date. Dedicated sections present the variety of suitable reactor designs and set-ups available; a short discussion on the relevance of greener and more sustainable approaches; and selected key applications in the area of bioactive structures. A final section outlines remaining challenges and areas that will benefit from further developments in this fast-moving area. It is hoped that this report provides a valuable update on this important field of synthetic chemistry which may fuel developments in the future.

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Section: Synthesis Of Bioactives: Drugs and Natural Productsmentioning

confidence: 99%

Continuous Flow Photochemistry for the Preparation of Bioactive Molecules

2020

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“…In 2019, the Baxendale group began to contribute to the field of photogenerated azetidinol intermediates by applying photoflow conditions in their synthesis [73] . The group was able to incorporate the photogenerated azetidinols 207 in a Ritter‐type‐reaction with several aliphatic and aromatic nitriles followed by an acid‐catalyzed rearrangement reaction furnishing oxazolines 206 in moderate to excellent yield (Scheme 23).…”

Section: Four‐membered Small‐ring Systemsmentioning

confidence: 99%

Strain Release Chemistry of Photogenerated Small‐Ring Intermediates

Luque

Paternoga

Opatz

2021

Chemistry A European J

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Photochemical processes, such as isomerizations and cycloadditions, have proven to be very useful in the construction of highly strained molecular frameworks. Photoinduced ring strain enables subsequent exergonic reactions which do not require the input of additional chemical energy and provides a variety of attractive synthetic options leading to complex structures. This review covers the progress achieved in the application of sequences combining excitation by ultraviolet light to form strained intermediates, which are further transformed to lower energy products in strain‐release reactions. As ring strain is considerable in small ring systems, photogenerated three‐ and four‐membered rings will be covered, mainly focusing on examples from 2000 to May 2020.

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“…17,18 One way to avoid this has been to protect the amine so that its lone pair engages in conjugation with other groups (e.g. by converting it to amides, carbamates, sulfonamides; Figure 2C), [19][20][21] but this necessitates additional steps (introduction and removal of the electron-withdrawing group) and precludes the use of tertiary amines. Cyclic aminals used by Pedrosa and Andrés 22 also likely avoid charge transfer through the anomeric delocalization of the nitrogen lone pair.…”

Section: General Observationsmentioning

confidence: 99%

Aza-Yang Cyclization—Buchner Aromatic Ring Expansion: Collective Synthesis of Cycloheptatriene-containing Azetidine Lactones

Singh

Gaskins

Johnson

et al. 2021

Preprint

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We prepared a collection of complex cycloheptatriene-containing azetidine lactones by ap- plying two key photochemical reactions: “aza-Yang” cyclization and Buchner carbene insertion into aromatic rings. While photolysis of phenacyl amines leads to a rapid charge transfer and elimination, we found that a simple protonation of the amine enables the formation of azetidinols as single diastereomers. We provide evidence, through ultrafast spectroscopy, for the electron transfer from free amines in the excited state. Further, we characterize aza-Yang re- action by establishing the dependence of initial reaction rates on rates of photon absorption. Unanticipated change in reactivity in morpholine analogs is explained through interactions with the tosylate anion. Buchner reaction proceeds with slight preference for one diastereomer over the other, and successful reaction requires electron-donating carbene-stabilizing substituents. Overall, sixteen compounds were prepared over seven steps. Guided by an increase in structural complexity, efforts such as this one extend reach of chemists into unexplored chemical space and provide useful quantities of new compounds for studies focused on their properties.

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Photochemical Flow Synthesis of 3‐Hydroxyazetidines

Cited by 19 publications

References 44 publications

Continuous Flow Photochemistry for the Preparation of Bioactive Molecules

Continuous Flow Photochemistry for the Preparation of Bioactive Molecules

Strain Release Chemistry of Photogenerated Small‐Ring Intermediates

Aza-Yang Cyclization—Buchner Aromatic Ring Expansion: Collective Synthesis of Cycloheptatriene-containing Azetidine Lactones

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