Activator-Promoted Aryl Halide-Dependent Chemoselective Buchwald–Hartwig and Suzuki–Miyaura Type Cross-Coupling Reactions

Dhital, Raghu Nath; Sen, Abhijit; Sato, Takuma; Hu, Hao; Ishii, Rikako; Hashizume, Daisuke; Takaya, Hikaru; Uozumi, Yasuhiro; Yamada, Yoichi M. A.

doi:10.1021/acs.orglett.0c01600

Cited by 19 publications

(19 citation statements)

References 44 publications

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“…The reaction system includes two reaction pathways that occur simultaneously: Buchwald–Hartwig-type cross-coupling (BHCC) and Suzuki–Miyaura-type cross-coupling (SMCC) . The SMCC reaction mainly proceeds when substrate 1 is an aryl chloride (X = Cl), whereas the BHCC reaction mainly proceeds when substrate 1 is an aryl iodide (X = I); however, the detailed mechanisms underlying this selectivity are not clear . Therefore, we analyzed an experimental dataset consisting of the yields of the products of the BHCC and SMCC reactions when the functional group X of substrate 1 is changed to Cl, Br, and I, the functional group R of substrate 1 is changed to Me and OMe, and the transition-metal catalyst is changed.…”

Section: Methodsmentioning

confidence: 99%

“…20 The SMCC reaction mainly proceeds when substrate 1 is an aryl chloride (X = Cl), whereas the BHCC reaction mainly proceeds when substrate 1 is an aryl iodide (X = I); however, the detailed mechanisms underlying this selectivity are not clear. 21 Therefore, we analyzed an experimental dataset consisting of the yields of the products of the BHCC and SMCC reactions when the functional group X of substrate 1 is changed to Cl, Br, and I, the functional group R of substrate 1 is changed to Me and OMe, and the transition-metal catalyst is changed. All experimental conditions were the same except for substrate 1 and the transitionmetal catalyst.…”

Section: ■ Methodsmentioning

confidence: 99%

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Design of Experimental Conditions with Machine Learning for Collaborative Organic Synthesis Reactions Using Transition-Metal Catalysts

et al. 2021

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To improve product yields in synthetic reactions, it is important to use appropriate catalysts. In this study, we used machine learning to design catalysts for a reaction system in which both Buchwald−Hartwig-type and Suzuki−Miyaura-type cross-coupling reactions proceed simultaneously. First, using an existing dataset, yield prediction models were constructed with machine learning between experimental conditions, including the substrate and catalyst and the yields of the two products. Seven methods for calculating both the substrate and catalyst descriptors were proposed, and the predictive ability of the yield prediction models was discussed in terms of the descriptors and machine learning methods. Then, the constructed models were used to predict the compound yields for new combinations of substrates and catalysts, and the predictions were experimentally validated with high reproducibility, confirming that machine learning can predict yields from experimental conditions with high accuracy. In addition, to design catalysts that will improve the yields in our dataset, we added datasets collected from scientific papers and designed catalyst ligands. The proposed catalyst candidates were tested in actual synthetic experiments, and the experimental results exceeded the existing yields.

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Section: Methodsmentioning

confidence: 99%

Section: ■ Methodsmentioning

confidence: 99%

Design of Experimental Conditions with Machine Learning for Collaborative Organic Synthesis Reactions Using Transition-Metal Catalysts

et al. 2021

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“…Recently, we reported phenylboronic acid/ ester-assisted Buchwald−Hartwig type amination, wherein the phenylboronic acid/ester acts as an activator for the formation of an ate complex with the amines. 14 In the absence of phenylboronic acid, the amination did not occur. On the basis of this observation, we hypothesized that phenylboronic acid might activate amide substrates via boron−amide complex formation (Scheme 1), and this complex might enable the Narylation of the amides.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Unfortunately, there are few reports on nickel-catalyzed amidation of aryl/alkyl amide and aryl halides, probably because of the poor nucleophilicity of the amide nitrogen. Recently, we reported phenylboronic acid/ester-assisted Buchwald–Hartwig type amination, wherein the phenylboronic acid/ester acts as an activator for the formation of an ate complex with the amines . In the absence of phenylboronic acid, the amination did not occur.…”

Section: Introductionmentioning

confidence: 99%

Switching from Biaryl Formation to Amidation with Convoluted Polymeric Nickel Catalysis

et al. 2020

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A stable, reusable, and insoluble poly(4-vinylpyridine) nickel catalyst (P4VP-NiCl2) was prepared through the molecular convolution of poly(4-vinylpyridine) (P4VP) and nickel chloride. We proposed a coordination structure of the Ni center in the precatalyst based on elemental analysis and Ni K-edge XANES, and we confirmed that it is consistent with Ni K-edge EXAFS. The Suzuki–Miyaura-type coupling of aryl halides and arylboronic esters proceeded using P4VP-NiCl2 (0.1 mol % Ni) to give the corresponding biaryl compounds in up to 94% yield. Surprisingly, when the same reaction of aryl halides and arylboronic acid/ester was carried out in the presence of amides, the amidation proceeded predominantly to give the corresponding arylamides in up to 99% yield. In contrast, the reaction of aryl halides and amides in the absence of arylboronic acid/ester did not proceed. P4VP-NiCl2 successfully catalyzed the lactamization for preparing phenanthridinone. P4VP-NiCl2 was reused five times without significant loss of catalytic activity. Pharmaceuticals, natural products, and biologically active compounds were synthesized efficiently using P4VP-NiCl2 catalysis. Nickel contamination in the prepared pharmaceutical compounds was not detected by ICP-MS analysis. The reaction was scaled to multigrams without any loss of chemical yield. Mechanistic studies for both Suzuki–Miyaura and amidation were performed.

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“…These methods have been constantly improved by the development of new ligands, precatalysts, and extensive investigations of the reaction mechanisms . In addition, with the development of C–H activation, the use of metal-catalyzed C–N bond formation to prepare diphenylamines has been extensively explored; however, most of these methods require the use of toxic and expensive metal catalysts, which makes it necessary to remove metal residues in many applications, such as in the pharmaceutical industry. Hence, increasing attention has been devoted to the development of metal-free synthetic strategies .…”

Section: Introductionmentioning

confidence: 99%

Direct para-Selective C–H Amination of Iodobenzenes: Highly Efficient Approach for the Synthesis of Diarylamines

et al. 2021

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Iodine(III)-mediated synthesis of 4-iodo-N-phenylaniline from iodobenzene has been achieved, and the reaction can proceed under mild conditions. A variety of functional groups were well tolerated, providing the corresponding products in moderate to good yields. The remaining iodine group provides an effective platform for converting the products into several valuable asymmetric diphenylamines. Most importantly, this reaction can be easily scaled up to the ten-gram scale, highlighting its synthetic utility. The mechanistic study revealed that the in situ generated aryl hypervalent iodine intermediate is the key factor to realize this para-selective C–H amination reaction.

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Activator-Promoted Aryl Halide-Dependent Chemoselective Buchwald–Hartwig and Suzuki–Miyaura Type Cross-Coupling Reactions

Cited by 19 publications

References 44 publications

Design of Experimental Conditions with Machine Learning for Collaborative Organic Synthesis Reactions Using Transition-Metal Catalysts

Design of Experimental Conditions with Machine Learning for Collaborative Organic Synthesis Reactions Using Transition-Metal Catalysts

Switching from Biaryl Formation to Amidation with Convoluted Polymeric Nickel Catalysis

Direct para-Selective C–H Amination of Iodobenzenes: Highly Efficient Approach for the Synthesis of Diarylamines

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