Integrated Micro‐Flow Synthesis Based on Photochemical Wolff Rearrangement

Fuse, Shinichiro; Otake, Yuma; Nakamura, Hiroyuki

doi:10.1002/ejoc.201700789

Cited by 22 publications

(13 citation statements)

References 49 publications

(76 reference statements)

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“…Flow chemistry offers many advantages over batch chemistry especially when scaleup is considered, [17] but its application in complex natural product total synthesis is still quite rare [18] . We decided to explore the possibility of using flow photochemical Wolff rearrangement [19] to produce key intermediate 17 in large scale. Fortunately, we were able to transfer the batch chemistry result to flow chemistry at a much larger scale to produce 17 in 65 % yield.…”

Section: Figurementioning

confidence: 99%

Flow Chemistry‐Enabled Divergent and Enantioselective Total Syntheses of Massarinolin A, Purpurolides B, D, E, 2,3‐Deoxypurpurolide C, and Structural Revision of Massarinolin A

2021

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Massarinolin A and purpurolides are bioactive bergamotane sesquiterpenes condensed with a variety of synthetically challenging ring systems: a bicyclo[3.1.1]heptane, an oxaspiro[3.4]octane, and a dioxaspiro[4.4]nonane (oxaspirolactone). Herein, we report the first enantioselective total syntheses of massarinolin A, purpurolides B, D, E, and 2,3‐deoxypurpurolide C. Our synthesis and computational analysis also led to a structural revision of massarinolin A. The divergent approach features an enantioselective organocatalyzed Diels–Alder reaction to install the first stereogenic center in high ee, a scalable flow photochemical Wolff rearrangement to build the key bicyclo[3.1.1]heptane, a furan oxidative cyclization to form the oxaspirolactone, a late‐stage allylic C−H oxidation, and a Myers’ NBSH‐promoted sigmatropic elimination to install the exo methylene group of massarinolin A.

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Section: Figurementioning

confidence: 99%

Flow Chemistry‐Enabled Divergent and Enantioselective Total Syntheses of Massarinolin A, Purpurolides B, D, E, 2,3‐Deoxypurpurolide C, and Structural Revision of Massarinolin A

2021

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“…Very recently, a review has been published of photochemical Wolff rearrangements and their application in integrated microflow syntheses. 95 In the photo-Wolff rearrangement, an α-diazocarbonyl compound undergoes rearrangement, obtaining a ketene intermediate that can react with different nucleophiles. In this way, an interesting application based on an Arndt−Eistert homologation sequence was developed by Kappe et al for the synthesis of β-amino acids from the respective protected α-amino acids (Scheme 23).…”

Section: Organic Process Research and Developmentmentioning

confidence: 99%

“…Very recently, a review has been published of photochemical Wolff rearrangements and their application in integrated microflow syntheses . In the photo-Wolff rearrangement, an α-diazocarbonyl compound undergoes rearrangement, obtaining a ketene intermediate that can react with different nucleophiles.…”

Section: Flow Photochemistrymentioning

confidence: 99%

“…With the continuous multi-step, one-flow sequence the thymidine and anti-HIV drug edoxudine were successfully synthesized with 72% and 66% yields respectively. Synthesis of '-deoxy and ',3'-dideoxynucleosides via a sequence of glycosylation, photo-sensitized deoxygenation and deprotection reactions.Very recently, a review has been published of photochemical Wolff rearrangements and their application in integrated microflow syntheses 94. In the photo-Wolff rearrangement, an -diazocarbonyl compound undergoes rearrangement, obtaining a ketene intermediate, which can react with different nucleophiles.…”

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confidence: 99%

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Light on the Horizon: Current Research and Future Perspectives in Flow Photochemistry

Politano

Oksdath‐Mansilla

2018

Org. Process Res. Dev.

146

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The research area of synthetic organic photochemistry is a powerful tool for creating both natural products and molecules with high structural complexity, in a simple way and under mild conditions. However, because of the challenges in scaling-up, it has been difficult to apply a photochemical reaction in an industrial process. Flow chemistry provides an opportunity for better control over the conditions of the reaction and, additionally, improved reaction selectivity and enhanced reproducibility. Taking into account that significant interest has focused on the use of flow photochemistry as a method for the synthesis of heterocycles and its applications in target-oriented synthesis over the last few years, the aim of this review is to highlight the recent efforts to apply flow photochemistry methodology to diverse reactions as a greener and more scalable process for the pharmaceutical and fine chemical industries. Additionally, the review highlights future perspectives in the development of scale-up strategies, combining photochemical reactions in the continuous flow multistep synthesis of organic molecules, being of interest for scientists and engineers alike.

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“…There are some examples revealing the extension of the scope of the VWR as an efficient synthetic route, [6] such as the preparation of angularly functionalized polycyclic systems, [7] synthesis of substituted malonates, [8] affording mono‐, bi‐ and tricyclic piperidone compounds, [9] and preparation of α‐Diazo Sulfoxides [10] besides of α‐diazo carbonyl compounds. [11] The conversion of ketenes into carboxylic acids, esters, or amides is also an important step in synthetic applications of the Wolff rearrangement. [6] …”

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confidence: 99%

Potential Energy Surfaces of Vinylogous Wolff Rearrangement: NBO Analysis and Molecular Dynamic Simulation

Nahzomi

Divsar

2021

ChemistryOpen

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The potential energy surfaces of the Vinylogous Wolff Rearrangement, an alternative process for the Wolff Rearrangement that takes place β,γ‐unsaturated diazoketones have been fully explored employing M062X model chemistry and in a complementary task by means of the CASSCF method. The NBO analysis has been invoked to reveal the alternations of orbital occupancies and their stabilization energies through some of the critical structures located on the pathways. The calculations establish a two steps process for each pathway involving a second higher energy transition state that seems likely to be the rate determining step in agreement with experimental results. Energy analysis indicates more feasibility of the pathway including diradical intermediate. The most striking feature of the study concerns the finding out a transition state providing a channel in between two pathways through interconversion of the two keys bicyclo[2.1.0]pentanone and diradical intermediates.

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Integrated Micro‐Flow Synthesis Based on Photochemical Wolff Rearrangement

Cited by 22 publications

References 49 publications

Flow Chemistry‐Enabled Divergent and Enantioselective Total Syntheses of Massarinolin A, Purpurolides B, D, E, 2,3‐Deoxypurpurolide C, and Structural Revision of Massarinolin A

Flow Chemistry‐Enabled Divergent and Enantioselective Total Syntheses of Massarinolin A, Purpurolides B, D, E, 2,3‐Deoxypurpurolide C, and Structural Revision of Massarinolin A

Light on the Horizon: Current Research and Future Perspectives in Flow Photochemistry

Potential Energy Surfaces of Vinylogous Wolff Rearrangement: NBO Analysis and Molecular Dynamic Simulation

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