Lewis Acid-Catalyzed Selective Reductive Decarboxylative Pyridylation of <i>N</i>-Hydroxyphthalimide Esters: Synthesis of Congested Pyridine-Substituted Quaternary Carbons

Gao, Liuzhou; Wang, Guoqiang; Cao, Jun; Chen, Hui; Gu, Yuming; Liu, Xueting; Xu, Chong; Ma, Jing; Li, Shuhua

doi:10.1021/acscatal.9b03798

Cited by 53 publications

(15 citation statements)

References 123 publications

(38 reference statements)

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“…Many of the quaternary centers containing C-4-alkylated pyridines (derived from tertiary carboxylic acids) prepared here are new ( 29 – 33 ) and are likely desirable starting materials for medicinal chemistry programs. Of the known alkylated pyridines in this series, two were prepared as mixtures of regioisomers using radical chemistry ( 26 and 28 ) , or via Minisci addition to 4-cyanopyridine …”

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confidence: 99%

Practical and Regioselective Synthesis of C-4-Alkylated Pyridines

et al. 2021

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The direct position-selective C-4 alkylation of pyridines has been a long-standing challenge in heterocyclic chemistry, particularly from pyridine itself. Historically this has been addressed using prefunctionalized materials to avoid overalkylation and mixtures of regioisomers. This study reports the invention of a simple maleate-derived blocking group for pyridines that enables exquisite control for Minisci-type decarboxylative alkylation at C-4 that allows for inexpensive access to these valuable building blocks. The method is employed on a variety of different pyridines and carboxylic acid alkyl donors, is operationally simple and scalable, and is applied to access known structures in a rapid and inexpensive fashion. Finally, this work points to an interesting strategic departure for the use of Minisci chemistry at the earliest possible stage (native pyridine) rather than current dogma that almost exclusively employs Minisci chemistry as a late-stage functionalization technique.

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confidence: 99%

Practical and Regioselective Synthesis of C-4-Alkylated Pyridines

et al. 2021

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“…Meanwhile, Li and co-workers demonstrated a zinc chloridecatalyzed decarboxylative pyridylation of NHPI esters 1 using 4-cyanopyridines 124 with B 2 Pin 2 (Bpin = pinacol boronate) as a reductant under thermal conditions (Scheme 51). 93 The method enabled the synthesis of a wide variety of sterically congested quaternary 4-substituted pyridines 125 in moderate to good yields with high functional group tolerance. Mechanistically, the reaction is initiated through one-electron reduction of NHPI ester 1 by the pyridine-boryl radical A to generate the alkyl radical.…”

Section: C−c Bond Formationmentioning

confidence: 99%

Single Electron Transfer-Induced Redox Processes Involving N-(Acyloxy)phthalimides

et al. 2021

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The past decade has witnessed the emergence of N-(acyloxy)phthalimides (NHPI esters) and its derivatives at the forefront of synthetic methods facilitating the construction of diverse molecular frameworks from the readily available carboxylic acid feedstock. The NHPI esters are predisposed to undergo reductive fragmentation via a single electron transfer (SET) process under thermal, photochemical, or electrochemical conditions to generate the corresponding carbon-or nitrogencentered radicals that participate in a multitude of synthetic transformations to forge carbon−carbon and carbon−heteroatom bonds. The chemistry involving NHPI esters has received broad applicability not only in well-designed cascade annulations but also in medicinal chemistry and natural product synthesis. This comprehensive Review, broadly categorized according to the nature of the bond formation, details the progress made in this field since the initial discovery by providing representative examples with mechanistic details, with an emphasis on challenges and future directions.

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“…This reaction mode is rather different from the pyridine-promoted homolytic B-B bond cleavage discovered in Li's work. [56][57][58][59][60] The nucleophilic N-boryl pyridyl anion can…”

Section: Derivatization Of Pyridines Through the Formation Of Meisenhmentioning

confidence: 99%

“…In 2019, Li and coworkers developed a Lewis-acid-catalyzed reductive decarboxylative alkylation reaction of 4-cyanopyridine for the synthesis of 4-alkyl-substituted pyridines (Scheme 39). 60 The pyridine-boryl radical 75 reacts with RAE 80 to afford the corresponding alkyl radical with regeneration of 4-cyanopyridine. Subsequent radical-radical coupling between the alkyl radical and the pyridine-boryl radical-zinc complex 81, followed by elimination of NCBpin, gives the 4-al-kylated pyridine 82.…”

Section: Scheme 38 Perfluoroalkylative Pyridylation Of Olefinsmentioning

confidence: 99%

Recent Developments in Transition-Metal-Free Functionalization and Derivatization Reactions of Pyridines

Zhou

Jiao²

2020

Synlett

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Pyridine is an important structural motif that is prevalent in natural products, drugs, and materials. Methods that functionalize and derivatize pyridines have gained significant attention. Recently, a large number of transition-metal-free reactions have been developed. In this review, we provide a brief summary of recent advances in transition-metal-free functionalization and derivatization reactions of pyridines, categorized according to their reaction modes.1 Introduction2 Metalated Pyridines as Nucleophiles2.1 Deprotonation2.2 Halogen–Metal exchange3 Activated Pyridines as Electrophiles3.1 Asymmetric 2-Allylation by Chiral Phosphite Catalysis3.2 Activation of Pyridines by a Bifunctional Activating Group3.3 Alkylation of Pyridines by 1,2-Migration3.4 Alkylation of Pyridines by [3+2] Addition3.5 Pyridine Derivatization by Catalytic In Situ Activation Strategies3.6 Reactions via Heterocyclic Phosphonium Salts4 Radical Reactions for Pyridine Functionalization4.1 Pyridine Functionalization through Radical Addition Reactions4.2 Pyridine Functionalization through Radical–Radical Coupling Reactions5 Derivatization of Pyridines through the Formation of Meisenheimer-Type Pyridyl Anions6 Conclusion

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Lewis Acid-Catalyzed Selective Reductive Decarboxylative Pyridylation of N-Hydroxyphthalimide Esters: Synthesis of Congested Pyridine-Substituted Quaternary Carbons

Cited by 53 publications

References 123 publications

Practical and Regioselective Synthesis of C-4-Alkylated Pyridines

Practical and Regioselective Synthesis of C-4-Alkylated Pyridines

Single Electron Transfer-Induced Redox Processes Involving N-(Acyloxy)phthalimides

Recent Developments in Transition-Metal-Free Functionalization and Derivatization Reactions of Pyridines

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