Palladium(II)-Catalyzed Highly Enantioselective C–H Arylation of Cyclopropylmethylamines

Chan, Kelvin S. L.; Fu, Haiyan; Yu, Jin‐Quan

doi:10.1021/ja512529e

Cited by 227 publications

(76 citation statements)

References 31 publications

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“…Through a Pd(II)/Pd(IV) catalytic system, we developed highly enantioselective arylation of cyclopropyl C–H bonds with aryl iodides, providing a new route for the preparation of chiral cis -aryl-cyclopropylmethylamines 239 (Scheme 71). 232 …”

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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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 Weakly Coordinating Auxilmentioning

confidence: 99%

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

et al. 2016

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“…While Pd-catalyzed enantioselective functionalizations of C(sp 3 )–H bonds via desymmetrization of two different carbon centers have recently gained momentum 11-16 , enantioselective α -arylation of aza-heterocycles would require the differentiation of methylene C–H bonds on the same carbon center. We began our investigations by extensively screening previously developed chiral mono-protected amino acid (MPAA) ligands 11,12 in presence of Pd(OTFA) 2 as the palladium source, but did not obtain any desired arylation products. This result is consistent with our previous unsuccessful attempts to utilize MPAA ligands to achieve enantioselective activation of methylene C–H bonds despite success of these ligands with desymmetrization of cyclobutyl C–H bonds at two different carbon centers.…”

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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, asymmetric C(sp 3 )–H activation reactions via metal insertion are largely limited to the desymmetrization of C–H bonds located on two different carbon centers. For example, desymmetrizations of cyclopropyl and cyclobutyl C–H bonds have been achieved with Pd(II) catalysts and chiral mono-protected amino acid ligands (7–10). Desymmetrization of prochiral C–H bonds has also been achieved through a Pd(0)-catalyzed intramolecular arylation as demonstrated in a series of pioneering studies (11–14) (Fig.…”

Section: Main Textmentioning

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

Chen

Gong

Zhuang

et al. 2016

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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(II)-Catalyzed Highly Enantioselective C–H Arylation of Cyclopropylmethylamines

Cited by 227 publications

References 31 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(II)-Catalyzed Highly Enantioselective C–H Arylation of Cyclopropylmethylamines

Cited by 227 publications

References 31 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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Ligand-accelerated enantioselective methylene C(sp ³ )–H bond activation