Palladium-Catalyzed Asymmetric Arylation of C(sp<sup>3</sup>)–H Bonds of Aliphatic Amides: Controlling Enantioselectivity Using Chiral Phosphoric Amides/Acids

Yan, Shao-Bai; Zhang, Song; Weng, Duan

doi:10.1021/acs.orglett.5b00968

Cited by 170 publications

(104 citation statements)

References 82 publications

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“…108 Chiral monodentate phosphoramides were used to control the stereoselectivity in the C(sp 3 )–H cleavage step. Although the hydrocinnamic acid-derived amides could furnish the desired products in 47–82% ee, the use of aliphatic acid derivatives led to very poor enantioselectivity.…”

Section: C(sp3)–h Activation Directed By Strongly Coordinating Auxmentioning

confidence: 99%

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

et al. 2016

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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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Section: C(sp3)–h Activation Directed By Strongly Coordinating Auxmentioning

confidence: 99%

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

et al. 2016

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“…However, Pd-catalyzed asymmetric insertion into prochiral C–H bonds using chiral phosphoric acids as anionic ligands has been met with limited success. In particular, prochiral sp 2 C–H bonds (60:40 er) or benzylic C–H bonds (83:17 er) were effectively arylated when pyridine or a bidentate amide-quinoline are employed as directing groups 25,26 . In light of the significance of developing a catalytic, enantioselective method for functionalizing saturated aza-heterocycles, we set out to test whether chiral phosphoric acid ligands can influence the stereoselectivity of metal insertion into prochiral methylene C–H bonds in a cross-coupling reaction via Pd(II)/Pd(0) catalytic cycle.…”

mentioning

confidence: 99%

Enantioselective amine α-functionalization via palladium-catalysed C–H arylation of thioamides

et al. 2016

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Saturated aza-heterocycles are highly privileged building blocks that are commonly encountered in bioactive compounds and approved therapeutic agents. These N-heterocycles are also incorporated as chiral auxiliaries and ligands in asymmetric synthesis. As such, development of methods to functionalize the α-methylene C–H bonds of these systems enantioselectively is of great importance, especially in drug discovery. Currently, enantioselective lithiation with (–)-sparteine followed by Pd(0) catalyzed cross coupling to prepare α-arylated amines is largely limited to pyrrolidines. Here we report a Pd(II)-catalyzed enantioselective α-C–H coupling of a wide range of amines, including ethyl amines, azetidines, pyrrolidines, piperidines, azepanes, indolines, and tetrahydroisoquinolines. Chiral phosphoric acids are demonstrated as effective anionic ligands for the enantioselective coupling of methylene C–H bonds with aryl boronic acids. This catalytic reaction not only affords high enantioselectivities, but also provides exclusive regioselectivity in the presence of two methylene groups in different steric environments.

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“…However, an efficient chiral metal catalyst capable of enantioselective insertion into ubiquitous methylene C–H bonds residing on the same carbon center has not been developed thus far. An effort to achieve such a process using a bidentate 8-aminoquinoline directing group and chiral phosphoric amide has afforded varied enantiomeric ratios (er) (ranging from 74:26 to 91:9) with benzyl C–H bonds and poor er (63:37) with alkyl C–H bonds (15). Recently, a transient chiral directing group has also been shown to perform enantioselective C–H arylation of benzylic C–H bonds (16).…”

Section: Main Textmentioning

confidence: 99%

Ligand-accelerated enantioselective methylene C(sp ³ )–H bond activation

Chen

Gong

Zhuang

et al. 2016

Science

306

140

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The development of catalytic enantioselective C(sp3)–H metal insertion reactions has been a significant challenge. Moderate success has recently been achieved via Pd-catalyzed desymmetrization of prochiral C–H bonds located on two different carbon centers. Herein, we report the discovery of chiral acetyl-protected aminoethyl quinoline (APAQ) ligands that enables Pd(II)-catalyzed enantioselective arylation of prochiral methylene C–H bonds on the same carbon center. The feasibility of performing asymmetric Pd insertion into ubiquitous β-methylene C–H bonds of aliphatic amides offers an alternative disconnection for constructing β-chiral centers. Systematic tuning of the ligand structure reveals that a six-membered instead of a five-membered chelation of these types of ligands with the Pd(II) is essential for accelerating the C(sp3)–H activation thereby achieving enantioselectivity.

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Palladium-Catalyzed Asymmetric Arylation of C(sp³)–H Bonds of Aliphatic Amides: Controlling Enantioselectivity Using Chiral Phosphoric Amides/Acids

Abstract: Enantioselective arylation of secondary β-C(sp(3))-H bonds of 8-aminoquinoline amides was realized with a palladium catalyst. Chiral phosphoric amides and acids were used for the first time to control the stereoselectivity at the C-H bond cleavage step in the C-H activation reactions.

Cited by 170 publications

References 82 publications

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

Enantioselective amine α-functionalization via palladium-catalysed C–H arylation of thioamides

Ligand-accelerated enantioselective methylene C(sp ³ )–H bond activation

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Palladium-Catalyzed Asymmetric Arylation of C(sp3)–H Bonds of Aliphatic Amides: Controlling Enantioselectivity Using Chiral Phosphoric Amides/Acids

Abstract: Enantioselective arylation of secondary β-C(sp(3))-H bonds of 8-aminoquinoline amides was realized with a palladium catalyst. Chiral phosphoric amides and acids were used for the first time to control the stereoselectivity at the C-H bond cleavage step in the C-H activation reactions.

Cited by 170 publications

References 82 publications

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

Enantioselective amine α-functionalization via palladium-catalysed C–H arylation of thioamides

Ligand-accelerated enantioselective methylene C(sp 3 )–H bond activation

Contact Info

Product

Resources

About

Palladium-Catalyzed Asymmetric Arylation of C(sp³)–H Bonds of Aliphatic Amides: Controlling Enantioselectivity Using Chiral Phosphoric Amides/Acids

Ligand-accelerated enantioselective methylene C(sp ³ )–H bond activation