Enantioselective Assembly of Ferrocenes with Axial and Planar Chiralities via Palladium/Chiral Norbornene Cooperative Catalysis

Ye, Jinxiang; Li, Lisha; You, Yong; Jiao, Chengkang; Cui, Zhaolei; Zhang, Yabin; Jia, Shihu; Cong, Hengjiang; Liu, Shanshan; Cheng, Hong‐Gang; Zhou, Qianghui

doi:10.1021/jacsau.2c00630

Cited by 25 publications

(10 citation statements)

References 60 publications

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“…It was found that the two ortho substituents of 2 had a significant influence on the reaction regarding both reactivity and stereoselectivity. Generally, one ortho electron-withdrawing group was required to secure both good reactivity and excellent enantioselectivity, such as ester ( 22 and 32 ), amide ( 33 , 34, and 41 ), nitro ( 36 ), phosphoryl ,, ( 42 ), and free carboxylic acid ( 35 ), while the other ortho -substituent of 2 could be extended to alkyl ( 22 and 26 ), hydroxymethyl ( 31 ), TBS-protected hydroxymethyl ( 30 ), chloro ( 27 ), and naphthyl ( 40–42 ) groups, providing the corresponding products with excellent enantioselectivities (95–99% e.e). No enantioselectivity was observed when the sterically less hindered ortho fluoro group was introduced, which is mainly due to the low configurational stability of the product ( 28 ), as supported by the DFT-calculated rotational barrier (Δ G rot ‡ = 27.7 kcal/mol, Figure , vide infra).…”

Section: Resultsmentioning

confidence: 99%

“…Meanwhile, Dong independently developed a Pd 0 /NBE*-promoted resolution of racemic epoxides through annulation with aryl iodides (Figure E, ii) . As a step toward our goal of developing versatile Pd 0 /NBE* cooperative catalysis, we have also realized the construction of axial chiral biaryls, C–N axial chirality, 1,2-diaxial o -terphenyls, and kinetic resolution of tertiary benzyl alcohols successively since 2020 . This full account comprehensively delineates our efforts in developing the atroposelective ortho -C–H arylation of aryl iodides through Pd 0 /NBE* cooperative catalysis that ultimately leads to a general and modular platform for the construction of C–C axial chirality, C–N axial chirality, and chiral fluorenols, including the reaction design, detailed reaction condition optimization, more extensive substrate scope explorations, and axially configurational stability studies.…”

Section: Introductionmentioning

confidence: 89%

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Construction of Axially Chiral Biaryls via Atroposelective ortho-C–H Arylation of Aryl Iodides

et al. 2023

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Due to the dichotomy between reactivity and stereoselectivity, the synthesis of axially chiral biaryls via enantioselective C−H arylation remains a daunting challenge. This full account describes the development of a general and modular platform for the construction of axial chirality through atroposelective ortho-C−H arylation of aryl iodides based on palladium/chiral norbornene cooperative catalysis. It is a three-component cascade process that involves readily available aryl iodides, 2,6-substituted aryl bromides, and various terminating reagents (e.g., olefins, alkynes, boronic acids, etc.) as building blocks. Key features of this method include broad functional group tolerance, high enantioselectivities, a distinct stereoinduction model, and good step economy and scalability. Notably, this method is also amenable for the synthesis of phenanthridinones with C−N axial chirality and chiral fluorenols through axial-to-axial and axial-to-central chirality transfer, respectively. Lastly, the origin of enantioselectivity in this method and the ortho-substituent effect of 2,6-substituted aryl bromides on stereoinduction are elucidated by density functional theory calculations.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 89%

Construction of Axially Chiral Biaryls via Atroposelective ortho-C–H Arylation of Aryl Iodides

et al. 2023

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“…Interestingly, without an external terminating reagent, this chemistry can be extended to the synthesis of dihydrobenzofurans (DHBFs) under slightly modified conditions from Scheme (Scheme A) . Notably, N 1 is still the optimal cocatalyst for this reaction, and only 10 mol % is required, which, to the best of our knowledge, represents the lowest NBE cocatalyst loading in Catellani-type reactions. , It is worth mentioning that this method can be applied in the two-step synthesis of a 5-HT 2C receptor agonist family with 8-aryl-substituted DHBF as the common core structure (>200 members) (Scheme B) . Subjecting 2-aryl-substituted phenyl iodides 1e – g and commercially available chiral epoxide 2e to the standard reaction conditions, the desired chiral 2,3-dihydrobenzofuran products 13e – g were obtained in moderate to good yields.…”

Section: Development Of New Annulations Based On Pd/nbe Cooperative C...mentioning

confidence: 99%

Benzo-Fused-Ring Toolbox Based on Palladium/Norbornene Cooperative Catalysis: Methodology Development and Applications in Natural Product Synthesis

2023

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Metrics & MoreArticle Recommendations CONSPECTUS: Benzo-fused skeletons are ubiquitous in agrochemicals, medicines, natural products, catalysts, and other organic function materials. The assembly of these skeletons in an efficient manner is an actively explored field in organic synthesis. Palladium/norbornene (Pd/NBE) cooperative catalysis is a powerful tool for the expeditious assembly of polysubstituted arenes through bisfunctionalization of the ortho and ipso positions of aryl iodides in one operation.Owing to the efforts of Lautens, Catellani, and others, an array of Pd/NBEpromoted annulations for the syntheses of diversified benzo-fused rings have been developed. However, these methods have not been broadly applied in total synthesis yet.Our group is interested in efficient and practical total synthesis of biologically active molecules. In the past 7 years, we have been devoted to the development of new annulation strategies for the assembly of common benzo-fused skeletons through Pd/NBE-promoted reactions of aryl iodides with novel bifunctional reagents. In this Account, we summarize our laboratory's systematic efforts in this direction. First, readily available epoxides and aziridines were exploited as versatile bifunctional alkylating reagents, which enables quick assembly of a series of valuable benzo-fused heterocycles, including isochromans, dihydrobenzofurans, 1,3-cis-tetrahydroisoquinolines (THIQs), 1,3-trans-THIQs, etc. Second, a convergent access to 5−7-membered benzo-fused carbocycles (including indanes and tetrahydronaphthalenes) was developed by Pd/NBE-promoted annulation of aryl iodides with simple olefinic alcohol-containing alkylating reagents. Third, a Pd/NBE-promoted annulation between aryl iodides and cyclohexanone-containing amination reagents was developed for the construction of benzo-fused N-containing bridged scaffolds. Thus, we have established a practical and versatile toolbox for the quick assembly of diversified benzo-fused skeletons. These new annulation reactions are of high chemo-, regio-, and stereoselectivities with good step and atom economy. Moreover, they are able to rapidly increase molecular complexity from simple building blocks. Finally, their synthetic value has been demonstrated by immediate adoption in several efficient total syntheses of medicines and complex natural products. Compared to conventional synthetic logics, the Pd/NBE-promoted annulation toolbox allows the development of highly convergent strategies, which significantly improves the overall synthetic efficiency.We believe the results presented in this Account will have significant implications beyond our research. It can be envisaged that new Pd/NBE-promoted annulations as well as new applications in complex total synthesis will be revealed in the near future.

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“…In recent years, Pd/norbornene (NBE)-based cooperatively catalyzed Catellani-type reaction has become a valuable multicomponent strategy for the synthesis of polysubstituted arenes. [102] Using this strategy, Liang's group [103] (Scheme 53a) and Zhou's group [104] (Scheme 53b) independently realized the synthesis of ferrocene derivatives bearing axial and planar chirality. Under Pd/NBE cooperative catalysis, ortho-ferrocene-tethered aryl iodides 228 or 231 and aryl bromides 229 or 232 underwent a Catellani reaction, followed by selective CÀ H functionalization to obtain ferrocenes 230 or 233 bearing axial and planar chirality with excellent enantio-and diastereoselectivities.…”

Section: Atropisomers With Other Chiral Elementsmentioning

confidence: 99%

Catalytic Asymmetric Synthesis of Atropisomers Bearing Multiple Chiral Elements: An Emerging Field

Zhang,

Li,

Liu

et al. 2023

Angew Chem Int Ed

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With the rapid development of asymmetric catalysis, the demand for the enantioselective synthesis of complex and diverse molecules with different chiral elements is increasing. Owing to the unique features of atropisomerism, the catalytic asymmetric synthesis of atropisomers has attracted a considerable interest from the chemical science community. In particular, introducing additional chiral elements, such as carbon center chirality, heteroatomic chirality, planar chirality, and helical chirality, into atropisomers provides an opportunity to incorporate new properties into axially chiral compounds, thus expanding the potential applications of atropisomers. Thus, it is important to perform catalytic asymmetric transformations to synthesize atropisomers bearing multiple chiral elements. In spite of challenges in such transformations, in recent years, chemists have devised powerful strategies under asymmetric organocatalysis or metal catalysis, synthesizing a wide range of enantioenriched atropisomers bearing multiple chiral elements. Therefore, the catalytic asymmetric synthesis of atropisomers bearing multiple chiral elements has become an emerging field. This minireview summarizes the rapid progress in this field and indicates challenges, thereby promoting this field to a new horizon.

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Enantioselective Assembly of Ferrocenes with Axial and Planar Chiralities via Palladium/Chiral Norbornene Cooperative Catalysis

Cited by 25 publications

References 60 publications

Construction of Axially Chiral Biaryls via Atroposelective ortho-C–H Arylation of Aryl Iodides

Construction of Axially Chiral Biaryls via Atroposelective ortho-C–H Arylation of Aryl Iodides

Benzo-Fused-Ring Toolbox Based on Palladium/Norbornene Cooperative Catalysis: Methodology Development and Applications in Natural Product Synthesis

Catalytic Asymmetric Synthesis of Atropisomers Bearing Multiple Chiral Elements: An Emerging Field

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