Allylations of aryl/heteroaryl ketones: neat, clean, and sustainable. Applications to targets in the pharma- and nutraceutical industries

Li, Xiaohan; Wood, Alex B.; Lee, Nicholas R.; Gallou, Fabrice; Lipshutz, Bruce H.

doi:10.1039/d2gc00776b

Cited by 6 publications

(2 citation statements)

References 81 publications

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“…Finally, as further evidence indicative of the benefits of conducting chemistry in water, and given the still growing library of known reactions enabled under the same aqueous micellar catalysis conditions, [26] a sequence was performed which included a NP‐mediated cross‐coupling. Thus, as seen in Scheme 7, an initial double allylation of p ‐bromopropiophenone 40 , done under neat conditions in minutes, [43] afforded the expected product 41 . Without isolation, dilution with water containing 2 wt % TPGS‐750‐M was followed by introduction of the Grubbs‐2 catalyst along with KHSO 4 (to reduce the pH of the water, thereby accelerating the RCM due to phosphine protonation) [9a] .…”

Section: Resultsmentioning

confidence: 97%

ppm Pd‐Containing Nanoparticles as Catalysts for Negishi Couplings … in Water

Wong

Lipshutz

2022

Angew Chem Int Ed

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New technology is reported that enables Negishi couplings to be run under sustainable, far greener conditions. Thus, ppm Pd-containing nanoparticles (NPs) have been developed that catalyze couplings in recyclable water under very mild conditions. These heterogeneous reactions involve loadings of Pd of typically only 2500 ppm (0.25 mol %). Highly functionalized aromatic and heteroaromatic bromides readily participate, including examples taken from the Merck Informer Library indicative of the functional group tolerance associated with these couplings. Direct comparisons with existing literature routes are made. Very low residual levels of Pd in newly formed products are to be expected, as determined by ICP-MS. The reagent involved has been extensively characterized via DLS, TEM, cryo-TEM, and EDX measurements.

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Section: Resultsmentioning

confidence: 97%

ppm Pd‐Containing Nanoparticles as Catalysts for Negishi Couplings … in Water

Wong

Lipshutz

2022

Angew Chem Int Ed

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“…Lipshutz and colleagues demonstrated a one pot, four-step reaction sequence starting with solvent-free ketone allylation, followed by ring-closing olefin metathesis, Suzuki-Miyaura coupling, and olefin hydrogenation (reduction). Without isolation of the intermediates between each step, the overall yield was 78% following purification by column chromatography [ 129 ].…”

Section: Multistep One-pot Reactionsmentioning

confidence: 99%

Cascade Processes with Micellar Reaction Media: Recent Advances and Future Directions

Tang

McInnes

2022

Molecules

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Reducing the use of solvents is an important aim of green chemistry. Using micelles self-assembled from amphiphilic molecules dispersed in water (considered a green solvent) has facilitated reactions of organic compounds. When performing reactions in micelles, the hydrophobic effect can considerably accelerate apparent reaction rates, as well as enhance selectivity. Here, we review micellar reaction media and their potential role in sustainable chemical production. The focus of this review is applications of engineered amphiphilic systems for reactions (surface-active ionic liquids, designer surfactants, and block copolymers) as reaction media. Micelles are a versatile platform for performing a large array of organic chemistries using water as the bulk solvent. Building on this foundation, synthetic sequences combining several reaction steps in one pot have been developed. Telescoping multiple reactions can reduce solvent waste by limiting the volume of solvents, as well as eliminating purification processes. Thus, in particular, we review recent advances in “one-pot” multistep reactions achieved using micellar reaction media with potential applications in medicinal chemistry and agrochemistry. Photocatalyzed reactions in micellar reaction media are also discussed. In addition to the use of micelles, we emphasize the process (steps to isolate the product and reuse the catalyst).

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ppm Pd‐Containing Nanoparticles as Catalysts for Negishi Couplings … in Water

Wong

Lipshutz

2022

Angewandte Chemie

Self Cite

View full text Add to dashboard Cite

New technology is reported that enables Negishi couplings to be run under sustainable, far greener conditions. Thus, ppm Pd‐containing nanoparticles (NPs) have been developed that catalyze couplings in recyclable water under very mild conditions. These heterogeneous reactions involve loadings of Pd of typically only 2500 ppm (0.25 mol %). Highly functionalized aromatic and heteroaromatic bromides readily participate, including examples taken from the Merck Informer Library indicative of the functional group tolerance associated with these couplings. Direct comparisons with existing literature routes are made. Very low residual levels of Pd in newly formed products are to be expected, as determined by ICP‐MS. The reagent involved has been extensively characterized via DLS, TEM, cryo‐TEM, and EDX measurements.

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Allylations of aryl/heteroaryl ketones: neat, clean, and sustainable. Applications to targets in the pharma- and nutraceutical industries

Abstract: Aromatic and heteroaromatic ketones bearing an α-methine proton can be deprotonated and mono-allylated in minutes in the complete absence of an organic solvent to arrive at the corresponding products in...

Cited by 6 publications

References 81 publications

ppm Pd‐Containing Nanoparticles as Catalysts for Negishi Couplings … in Water

ppm Pd‐Containing Nanoparticles as Catalysts for Negishi Couplings … in Water

Cascade Processes with Micellar Reaction Media: Recent Advances and Future Directions

ppm Pd‐Containing Nanoparticles as Catalysts for Negishi Couplings … in Water

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