Nucleophile Coordination Enabled Regioselectivity in Palladium‐Catalyzed Asymmetric Allylic C−H Alkylation

Fan, Lian‐Feng; Luo, Sanzhong; Chen, Shusen; Wang, Tian‐Ci; Wang, Pu‐Sheng; Gong, Liu‐Zhu

doi:10.1002/anie.201908960

Cited by 52 publications

(17 citation statements)

References 57 publications

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“…In a recent work, Gong and co-workers refined the regioselectivity in asymmetric allylic C–H alkylations by nucleophile coordination. 700 Thus, as observed for azlactones ( Figure 32 b), DFT calculations suggest that coordination of 2-acylimidazoles-enabled inner-sphere attack mode for the enantioselective C–C bond-forming step, which is responsible for the high E/Z - and regioselectivities of the reaction. The authors took advantage of this feature to achieve high yields of 268 in excellent stereoselectivities in the allylic alkylation of 1,4-dienes with 2-acylimidazoles using the Pd/( R )- L158 catalytic system ( Scheme 283 b).…”

Section: Asymmetric Oxidative Allylic Substitutionmentioning

confidence: 61%

“…In a recent work, Gong and co-workers refined the regioselectivity in asymmetric allylic C–H alkylations by nucleophile coordination . Thus, as observed for azlactones (Figure b), DFT calculations suggest that coordination of 2-acylimidazoles-enabled inner-sphere attack mode for the enantioselective C–C bond-forming step, which is responsible for the high E/Z - and regioselectivities of the reaction.…”

Section: Asymmetric Oxidative Allylic Substitutionmentioning

confidence: 99%

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Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

Pàmies

Margalef

Cañellas³

et al. 2021

Chem. Rev.

407

202

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This Review compiles the evolution, mechanistic understanding, and more recent advances in enantioselective Pd-catalyzed allylic substitution and decarboxylative and oxidative allylic substitutions. For each reaction, the catalytic data, as well as examples of their application to the synthesis of more complex molecules, are collected. Sections in which we discuss key mechanistic aspects for high selectivity and a comparison with other metals (with advantages and disadvantages) are also included. For Pd-catalyzed asymmetric allylic substitution, the catalytic data are grouped according to the type of nucleophile employed. Because of the prominent position of the use of stabilized carbon nucleophiles and heteronucleophiles, many chiral ligands have been developed. To better compare the results, they are presented grouped by ligand types. Pd-catalyzed asymmetric decarboxylative reactions are mainly promoted by PHOX or Trost ligands, which justifies organizing this section in chronological order. For asymmetric oxidative allylic substitution the results are grouped according to the type of nucleophile used.

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Section: Asymmetric Oxidative Allylic Substitutionmentioning

confidence: 61%

Section: Asymmetric Oxidative Allylic Substitutionmentioning

confidence: 99%

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

Pàmies

Margalef

Cañellas³

et al. 2021

Chem. Rev.

407

202

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“…Even more surprisingly, with the use of 2-acylimidazoles as nucleophiles, a C3-branched selectivity was observed in the asymmetric allylic C−H alkylation of 1,4-dienes under the catalysis of a chiral palladium−phosphoramidite L24 complex (Scheme 22). 45 A variety of functionalized 2-acylimidazoles and 1,4-dienes performed well to generate chiral 2-acylimidazoles in moderate to high yields and with high levels of regio-and enantioselectivities. Notably, the use of allylarenes also afforded the corresponding allylation products with a branched selectivity.…”

Section: Pd-catalyzed Asymmetric Intermolecular Allylic C−h Alkylationmentioning

confidence: 99%

“…Mechanistic studies performed by DFT calculations suggest that the bond-forming transition state for the C3-branched selectivity prefers an inner-sphere nucleophilic attack mechanism (Scheme 23). 45 Due to the existence of two coordination sites in 2-acylimidazole, eight transition states that determine the stereoselectivity have been analogized by the coordination pattern of either carbonyl oxygen or imidazole nitrogen to palladium. With regard to oxygen coordination (TS-13), the [3,3′]-reductive elimination pathway 46 was found to be disfavored, with a high free energy.…”

Section: Pd-catalyzed Asymmetric Intermolecular Allylic C−h Alkylationmentioning

confidence: 99%

Palladium-Catalyzed Asymmetric Allylic C–H Functionalization: Mechanism, Stereo- and Regioselectivities, and Synthetic Applications

2020

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Metrics & MoreArticle Recommendations CONSPECTUS: Asymmetric functionalization of inert C−H bonds is undoubtedly a synthetically significant yet challenging bond-forming process, allowing for the preparation of densely functionalized molecules from abundantly available feedstocks. In the past decade, our group and others have found that trivalent phosphorus ligands are capable of facilitating Pdcatalyzed allylic C−H functionalization of α-alkenes upon using p-quinone as an oxidant. In these reactions, a 16-electron Pd(0) complex bearing a monodentate phosphorus ligand, a p-quinone, and an α-alkene has been identified as a key intermediate. Through a concerted proton and two-electron transfer process, electrophilic π-allylpalladium is subsequently generated and can be leveraged to forge versatile chemical bonds with a wide range of nucleophiles. This Account focuses on describing the origin, evolution, and synthetic applications of Pdcatalyzed asymmetric allylic C−H functionalization reactions, with an emphasis on the fundamental mechanism of the concerted proton and two-electron transfer process in allylic C−H activation.Enabled by the cooperative catalysis of the palladium complex of triarylphosphine, a primary amine, and a chiral phosphoric acid, an enantioselective α-allylation of aldehydes with α-alkenes is established. The combination of chiral phosphoric acid and a palladium complex of a chiral phosphoramidite ligand allows the allylic C−H alkylation of α-alkenes with pyrazol-5-ones to give excellent enantioselectivities, wherein the chiral ligand and chiral phosphoric acid synergistically control the stereoselectivity. Notably, the palladium−phosphoramidite complexes are also efficient catalysts for allylic C−H alkylation, with a wide scope of nucleophiles. In the case of 1,4-dienes, the geometry and coordination pattern of the nucleophile are able to vary the transition states of bondforming events and thereby determine the Z/E-, regio-, and stereoselectivities. These enantioselective allylic C−H functionalization reactions are tolerant of a wide range of nucleophiles and α-alkenes, providing a large library of optically active building blocks. Based on enantioselective intramolecular allylic C−H oxidation, the formal synthesis of (+)-diversonol is accomplished, and enantioselective intramolecular allylic C−H amination can enable concise access to letermovir. In particular, the asymmetric allylic C−H alkylation of 1,4-dienes with azlactones offers highly enantioenriched α,αdisubstituted α-amino acid derivatives that are capable of serving as key building blocks for the enantioselective synthesis of lepadiformine alkaloids. In addition, a tachykinin receptor antagonist and (−)-tanikolide are also synthesized with chiral molecules generated from the corresponding allylic C−H alkylation reactions.

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“…Skipped dienes (1,4-dienes) are versatile structural motifs in various biologically active molecules such as ripostatin A, jerangolid A, and biselyngbyolide B (Figure ). They also serve as useful building blocks in organic synthesis . For example, Jamison and coworkers − utilized the skipped dienes in the concise synthesis of polyether products.…”

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confidence: 99%

Nickel-Catalyzed Carboalkenylation of 1,3-Dienes with Aldehydes and Alkenylzirconium Reagents: Access to Skipped Dienes

et al. 2021

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A regio- and stereoselective nickel-catalyzed three-component coupling reaction of aldehydes, 1,3-dienes, and alkenylzirconium reagents was realized. The ligand- and additive-free protocol afforded a convenient approach to the synthesis of skipped diene compounds bearing various functionals (e.g., hydroxyl, carbonyl, halide) and heterocyclic groups. The products were readily transformed into structurally diverse polyenes. The utility of this reaction was also demonstrated by the one-pot operation and scale-up preparation.

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Nucleophile Coordination Enabled Regioselectivity in Palladium‐Catalyzed Asymmetric Allylic C−H Alkylation

Cited by 52 publications

References 57 publications

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

Palladium-Catalyzed Asymmetric Allylic C–H Functionalization: Mechanism, Stereo- and Regioselectivities, and Synthetic Applications

Nickel-Catalyzed Carboalkenylation of 1,3-Dienes with Aldehydes and Alkenylzirconium Reagents: Access to Skipped Dienes

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