Palladium‐Catalyzed Direct CH Arylation of Isoxazoles at the 5‐Position

Shigenobu, Masashi; Takenaka, Kazuhiro; Sasai, Hiroaki

doi:10.1002/anie.201504552

Cited by 48 publications

(22 citation statements)

References 101 publications

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“…S24). Taken together, the descriptors suggest that the propensity of the additive to act as an electrophile influences reaction outcomes (32)(33)(34). We hypothesized that competitive oxidative addition of the isoxazole could be a source of deleterious side reactivity.…”

mentioning

confidence: 99%

Predicting reaction performance in C–N cross-coupling using machine learning

Ahneman

Estrada

Lin

et al. 2018

Science

840

877

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Machine learning methods are becoming integral to scientific inquiry in numerous disciplines. We demonstrated that machine learning can be used to predict the performance of a synthetic reaction in multidimensional chemical space using data obtained via high-throughput experimentation. We created scripts to compute and extract atomic, molecular, and vibrational descriptors for the components of a palladium-catalyzed Buchwald-Hartwig cross-coupling of aryl halides with 4-methylaniline in the presence of various potentially inhibitory additives. Using these descriptors as inputs and reaction yield as output, we showed that a random forest algorithm provides significantly improved predictive performance over linear regression analysis. The random forest model was also successfully applied to sparse training sets and out-of-sample prediction, suggesting its value in facilitating adoption of synthetic methodology.

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mentioning

confidence: 99%

Predicting reaction performance in C–N cross-coupling using machine learning

Ahneman

Estrada

Lin

et al. 2018

Science

840

877

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“…3‐Phenylisoxazole, which was readily prepared from benzaldehyde, was converted into the iodide 5 a (for synthetic details see the Supporting Information), and then Suzuki–Miyaura coupling and Sonogashira coupling were performed with aryl boronic acid and phenylacetylene to afford 6 a (95 %) and 6 b (79 %), respectively. The C−H direct arylation at the 5‐position of 6 a was carried out according to the literature procedure reported by Sasai et al . and gave the triaryl‐substituted isoxazole 7 a in 83 % yield.…”

Section: Methodsmentioning

confidence: 99%

Generation of an 4‐Isoxazolyl Anion Species: Facile Access to Multifunctionalized Isoxazoles

2016

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A direct functionalization of unsubstituted isoxazole (1) was achieved by generation of 4‐isoxazolyl anion species (3). An efficient 4‐iodination of isoxazole and halogen–metal exchange reaction using a turbo Grignard reagent (iPrMgCl⋅ LiCl) were essential for the generation of 3, which reacted with various electrophiles to give 4‐functionalized isoxazoles in good to high yields. Isoxazolyl boronate, boronic acid, and stannane were also synthesized as useful building blocks from 1. The current methods enabled us to synthesize multi‐functionalized isoxazoles by introducing each substituent into the desired positions. Furthermore, total synthesis of triumferol, which was isolated from Triumfetta rhomboidea, was achieved from 1 in only three steps.

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“…Because various functional groups were introduced into the 4-position of 1,n ext we applied the current 4-isoxazolyl anion methods to the synthesis of multifunctionalized isoxazoles,w here each substituent was introduced into the desired positions.S ynthesis of the 3,4,5-trisubstituted isoxazoles 7a and 7b by sequential palladium-catalyzed crosscoupling reactions is shown in Scheme 4. 3-Phenylisoxazole, which was readily prepared from benzaldehyde,w as converted into the iodide 5a (for synthetic details see the Supporting Information), and then Suzuki-Miyaura coupling and Sonogashira coupling were performed with aryl boronic acid and phenylacetylene to afford 6a (95 %) and 6b (79 %), respectively.T he CÀHdirect arylation at the 5-position of 6a was carried out according to the literature procedure reported by Sasai et al [27] and gave the triaryl-substituted isoxazole 7a in 83 %yield. TheC À Hdirect arylation of 6b also proceeded without affecting an alkynyl moiety in the molecule to afford trisubstituted isoxazole 7b in 54 %yield.…”

Section: Angewandte Chemiementioning

confidence: 99%

Generation of an 4‐Isoxazolyl Anion Species: Facile Access to Multifunctionalized Isoxazoles

2016

View full text Add to dashboard Cite

A direct functionalization of unsubstituted isoxazole (1) was achieved by generation of 4-isoxazolyl anion species (3). An efficient 4-iodination of isoxazole and halogen-metal exchange reaction using a turbo Grignard reagent (iPrMgCl⋅ LiCl) were essential for the generation of 3, which reacted with various electrophiles to give 4-functionalized isoxazoles in good to high yields. Isoxazolyl boronate, boronic acid, and stannane were also synthesized as useful building blocks from 1. The current methods enabled us to synthesize multi-functionalized isoxazoles by introducing each substituent into the desired positions. Furthermore, total synthesis of triumferol, which was isolated from Triumfetta rhomboidea, was achieved from 1 in only three steps.

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Palladium‐Catalyzed Direct CH Arylation of Isoxazoles at the 5‐Position

Cited by 48 publications

References 101 publications

Predicting reaction performance in C–N cross-coupling using machine learning

Predicting reaction performance in C–N cross-coupling using machine learning

Generation of an 4‐Isoxazolyl Anion Species: Facile Access to Multifunctionalized Isoxazoles

Generation of an 4‐Isoxazolyl Anion Species: Facile Access to Multifunctionalized Isoxazoles

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