Ligand-Enabled Stereoselective β-C(sp<sup>3</sup>)–H Fluorination: Synthesis of Unnatural Enantiopure <i>anti</i>-β-Fluoro-α-amino Acids

This Review summarizes the advancements in Pd-catalyzed C(sp3)–H activation via various redox manifolds, including Pd(0)/Pd(II), Pd(II)/Pd(IV), and Pd(II)/Pd(0). While few examples have been reported in the activation of alkane C–H bonds, many C(sp3)–H activation/C–C and C–heteroatom bond forming reactions have been developed by the use of directing group strategies to control regioselectivity and build structural patterns for synthetic chemistry. A number of mono- and bidentate ligands have also proven to be effective for accelerating C(sp3)–H activation directed by weakly coordinating auxiliaries, which provides great opportunities to control reactivity and selectivity (including enantioselectivity) in Pd-catalyzed C–H functionalization reactions.

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“…226 Using Selectfluor as the fluorinating reagent and Ag 2 CO 3 as the base, this reaction proceeded in a highly diastereoselective fashion.…”

Section: C(sp3)–h Activation Directed By Weakly Coordinating Auxilmentioning

confidence: 99%

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

et al. 2016

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“…[64] A fluorine atom can be incorporated into the CÀHb ond of amide 127 when the palladium-alkyl intermediate is trapped with Selectfluor (141). [65] Borylation can be realized with B 2 pin 2 to afford amide 143. [66] Theresulting CÀBbond can be converted into an array of functionalities.I na ll these examples with perfluorinated amines as the directing group, the exogenous ligands are essential to achieve the desired reactivity.…”

Section: Carbonyl Groups (Perfluorinated Amides)mentioning

confidence: 99%

Complementary Strategies for Directed C(sp³)−H Functionalization: A Comparison of Transition‐Metal‐Catalyzed Activation, Hydrogen Atom Transfer, and Carbene/Nitrene Transfer

2017

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The functionalization of C(sp3)−H bonds streamlines chemical synthesis by allowing the use of simple molecules and providing novel synthetic disconnections. Intensive recent efforts in the development of new reactions based on C−H functionalization have led to its wider adoption across a range of research areas. This Review discusses the strengths and weaknesses of three main approaches: transition‐metal‐catalyzed C−H activation, 1,n‐hydrogen atom transfer, and transition‐metal‐catalyzed carbene/nitrene transfer, for the directed functionalization of unactivated C(sp3)−H bonds. For each strategy, the scope, the reactivity of different C−H bonds, the position of the reacting C−H bonds relative to the directing group, and stereochemical outcomes are illustrated with examples in the literature. The aim of this Review is to provide guidance for the use of C−H functionalization reactions and inspire future research in this area.

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“…Similarly, a quinoline ligand L6 ‐enabled β‐fluorination of alanine and phenylalanine derivatives 70 was accomplished with selectfluor as fluorine source using Pd(TFA) 2 as catalyst and 2 equivalents of silver carbonate in 1,4‐dioxane (Scheme ) . Besides the benzylic C–H bonds of phenylalanine and primary methyl groups of alanine, the more challenging methylene C–H bonds of lysine and other unnatural α‐amino acids were successfully fluorinated to 71 under these conditions.…”

Section: C–h Bond Functionalization On the Peptide Side‐chainsmentioning

confidence: 99%

Site‐Selective C–H Bond Activation/Functionalization of Alpha‐Amino Acids and Peptide‐Like Derivatives

Brandhofer

Mancheño

2018

Eur J Org Chem

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Amino acids and peptides play an important role in nature, as well as in organic and pharmaceutical chemistry. Therefore, the easy, straightforward and versatile access of biogenic and unnatural derivatives is still highly demanding. This micro‐review intends to provide to the reader the current state of the art on site‐selective C–H bond functionalization technology applied on α‐amino acids and peptides, focusing on the different C–H positions that can successfully be addressed to date. It is structured in two main parts implying i) the α‐C–H functionalization at the peptide backbone and ii) the modification of the side‐chain. Herein, metal‐catalyzed C–H activation, oxidative C–H functionalization, as well as light mediated approaches, are discussed considering the challenges in reactivity and selectivity. The great potential of these transformations is also depicted with the derivatization and macrocyclization of complex peptides leading to products of pharmaceutical importance.

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Ligand-Enabled Stereoselective β-C(sp³)–H Fluorination: Synthesis of Unnatural Enantiopure anti-β-Fluoro-α-amino Acids

Cited by 152 publications

References 39 publications

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

Complementary Strategies for Directed C(sp³)−H Functionalization: A Comparison of Transition‐Metal‐Catalyzed Activation, Hydrogen Atom Transfer, and Carbene/Nitrene Transfer

Site‐Selective C–H Bond Activation/Functionalization of Alpha‐Amino Acids and Peptide‐Like Derivatives

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Ligand-Enabled Stereoselective β-C(sp3)–H Fluorination: Synthesis of Unnatural Enantiopure anti-β-Fluoro-α-amino Acids

Cited by 152 publications

References 39 publications

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

Complementary Strategies for Directed C(sp3)−H Functionalization: A Comparison of Transition‐Metal‐Catalyzed Activation, Hydrogen Atom Transfer, and Carbene/Nitrene Transfer

Site‐Selective C–H Bond Activation/Functionalization of Alpha‐Amino Acids and Peptide‐Like Derivatives

Contact Info

Product

Resources

About

Ligand-Enabled Stereoselective β-C(sp³)–H Fluorination: Synthesis of Unnatural Enantiopure anti-β-Fluoro-α-amino Acids

Complementary Strategies for Directed C(sp³)−H Functionalization: A Comparison of Transition‐Metal‐Catalyzed Activation, Hydrogen Atom Transfer, and Carbene/Nitrene Transfer