Pd-catalyzed methylene γ-C(sp3)—H alkenylation of N-picolinoylcycloalkylamines with alkenyl iodides promoted by 2-tert-butyl-1,4-benzoquinone

Seki, Atsushi; Takahashi, Yoshiaki

doi:10.1016/j.tetlet.2021.153130

Cited by 16 publications

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“…In particular, the regioselective functionalization of C(sp 2 )–H bonds of arenes and heteroarenes has been extensively developed and widely adopted by synthetic organic chemists, whereas the corresponding selective functionalization of C(sp 3 )–H bonds of alkanes has, in comparison, been far less studied. In recent years, the Pd-catalyzed methodologies with the assistance of transition metal coordinating directing groups have shown tremendous progress toward the functionalization of remote (β, γ, or δ) C(sp 3 )–H bonds, including aspects of regio- and stereoselectivity. − Remarkably, among the various organohalide electrophiles used alkenyl halides have rarely been reported as reactants. − Moreover, these remote alkenylations of C(sp 3 )–H bonds all require superstoichiometric halide scavenging of silver reagents. With one exception, using a ( E )-β-bromostyrene, these are all limited to alkenyl iodides, which are more expensive and less available than the corresponding bromides…”

Section: Introductionmentioning

confidence: 99%

“…Remarkably, for the γ-C(sp 3 )–H alkenylation of cycloalkanamines, only two methods have been reported so far (Scheme ). The first method reported by Chen and co-workers is a Pd-catalyzed γ-C(sp 3 )–H alkenylation of methyl 1-picolinoylaminocyclohexane-1-carboxylate, which employs cycloalkenyl iodides as alkenyl coupling partners and silver acetate reagent (Scheme A) . The second method, reported by Seki and Takahashi, discloses a Pd-catalyzed γ-C(sp 3 )–H alkenylation of N -picolinoylcyclohexanamine employing alkenyl iodides as reactant and silver carbonate reagent (Scheme B) .…”

Section: Introductionmentioning

confidence: 99%

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Directed Palladium-Catalyzed γ-C(sp³)–H Alkenylation of (Aza and Oxa) Cyclohexanamines with Bromoalkenes: Bromide Precipitation as an Alternative to Silver Scavenging

Gadde,

Bheemireddy,

Heitkämper

et al. 2024

ACS Catal.

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Directed palladium-catalyzed coupling of remote C(sp3)–H bonds of aliphatic amines with organohalides is a powerful synthetic tool. However, these reactions still possess limitations with respect to cost and resource efficiency, requiring more reactive iodinated reactants and superstoichiometric silver salt reagents. In this work, an efficient regio- and stereospecific silver-free Pd-catalyzed γ-C(sp3)–H alkenylation of cyclohexanamines and heterocyclic analogues with bromoalkenes is reported, which can also be applied on five- and seven-membered rings. DFT methods revealed that the oxidative addition of the organobromide to Pd(II) is not the rate-limiting step but rather γ-C(sp3)–H bond activation in the substrate. The lowest energy complex in the catalytic cycle is a Pd(II)-Br complex coordinated with the reaction product (η2-alkene and a bidentate directing group). The stability of this complex defines the overall energy span of the reaction. Co-catalyst KOPiv plays a pivotal role by exchanging bromide for pivalate in the complex, via precipitation of the KBr coproduct. This removal of bromide from the reaction media decreases the energy span, avoiding the use of superstoichiometric silver salt reagents and allowing decoordination of the reaction product. In addition, pivalate facilitates the C(sp3)–H bond activation in the substrate once another substrate molecule is coordinated. The reaction conditions could be directly applied for (hetero)arylation given the weaker coordination of the reaction product, featuring a (hetero)aryl versus alkenyl and change in resting state. The picolinoyl directing group can be removed via amide esterification.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Directed Palladium-Catalyzed γ-C(sp³)–H Alkenylation of (Aza and Oxa) Cyclohexanamines with Bromoalkenes: Bromide Precipitation as an Alternative to Silver Scavenging

Gadde,

Bheemireddy,

Heitkämper

et al. 2024

ACS Catal.

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Expanding the Utility of Inexpensive Pyridine‐N‐oxide Directing Group for the Site‐selective sp²/sp³γ‐C−H and sp²δ‐C−H Functionalization of Carboxamides

et al. 2022

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We have shown our efforts toward expanding the utility of the relatively inexpensive pyridine-N-oxide directing group in the Pd(II)-catalyzed site-selective γ-C(sp 2 )À H, γ-C(sp 3 )À H and δ-C(sp 2 )À H functionalization. The functionalization βÀ CÀ H bonds using bidentate directing group (DG) pyridine-N-oxide which operates through the N,O-coordination mode has been well documented in the literature. However, there exist rare reports dealing with the functionalization of remote sp 2 /sp 3 γand δ-CÀ H bonds of carboxamides assisted by the bidentate directing groups operating via the N,O-coordination. In this paper, the scope of pyridine-N-oxide DG was examined for accomplishing the siteselective (mono) γ-C(sp 2 )À H arylation in substrates containing competitive C(sp 3 )À H and C(sp 2 )À H bonds. The investigation has enabled to assemble a library of pyridine-N-oxide-based biarylacetamides, heteroaryl-based biaryl carboxamides, tricyclic quinolones, arylheteroarylmethanes, biaryl-based aliphatic carboxamides and mono (ortho) arylated phenylglycine derivatives. In general, biaryl derivatives and in particular, arylacetamide, arylacetic acid derivatives and pyridine-N-oxide (2-aminopyridyl) motifs are medicinally relevant classes of compounds. This work enabled the assembling of a library of the above-mentioned types of compounds through the pyridine-N-oxide directing groupaided site-selective sp 2 /sp 3 γ-CÀ H and sp 2 δ-CÀ H functionalization of carboxamides.

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Utility of 4‐Amino‐2,1,3‐benzothiadiazole Directing Group in the Pd(II)‐catalyzed Arylation of γ‐C−H Bonds of Carboxamides and β‐C‐H Bonds of Amino Acid Carboxamides

2022

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Expanding the availability, scope, and limitations of directing groups (DGs) for executing the site-selective CÀ H activation and functionalization and substrate scope development are valuable efforts. This paper reports the scope and extension of the utility of the 4-amino-2,1,3-benzothiadiazole (ABTD) directing group in the Pd(II)-catalyzed arylation of remote sp 2 /sp 3 γ-CÀ H bonds of aromatic carboxamides and sp 3 β-CÀ H bonds of amino acid carboxamides. The performance of the ABTD DG in the arylation of remote γ-CÀ H bonds of carboxamides and sp 3 β-CÀ H bonds of amino acid carboxamides was compared with other known DGs. For example, we have observed that the mono arylation of the methyl sp 3 β-CÀ H bonds of alanine carboxamide possessing the ABTD DG with iodopyridine yielded the pyridylalanine derivative. Conversely, the same reaction using 8-AQ DG did not yield the expected pyridylalanine derivative. Furthermore, 2,1,3-benzothiadiazole moiety-containing compounds are an important class of molecules in materials chemistry and medicinally relevant molecules. While this work reveals the utility of ABTD as the DG in the Pd(II)-catalyzed CÀ H arylation of carboxamides including amino acid derivatives. On the other hand, indirectly the process of ABTD-aided CÀ H arylation reactions has enabled to accomplish the synthesis of a library of 2,1,3-benzothiadiazole moiety containing new carboxamides.

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Pd-catalyzed methylene γ-C(sp3)—H alkenylation of N-picolinoylcycloalkylamines with alkenyl iodides promoted by 2-tert-butyl-1,4-benzoquinone

Cited by 16 publications

References 40 publications

Directed Palladium-Catalyzed γ-C(sp³)–H Alkenylation of (Aza and Oxa) Cyclohexanamines with Bromoalkenes: Bromide Precipitation as an Alternative to Silver Scavenging

Directed Palladium-Catalyzed γ-C(sp³)–H Alkenylation of (Aza and Oxa) Cyclohexanamines with Bromoalkenes: Bromide Precipitation as an Alternative to Silver Scavenging

Expanding the Utility of Inexpensive Pyridine‐N‐oxide Directing Group for the Site‐selective sp²/sp³γ‐C−H and sp²δ‐C−H Functionalization of Carboxamides

Utility of 4‐Amino‐2,1,3‐benzothiadiazole Directing Group in the Pd(II)‐catalyzed Arylation of γ‐C−H Bonds of Carboxamides and β‐C‐H Bonds of Amino Acid Carboxamides

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Pd-catalyzed methylene γ-C(sp3)—H alkenylation of N-picolinoylcycloalkylamines with alkenyl iodides promoted by 2-tert-butyl-1,4-benzoquinone

Cited by 16 publications

References 40 publications

Directed Palladium-Catalyzed γ-C(sp3)–H Alkenylation of (Aza and Oxa) Cyclohexanamines with Bromoalkenes: Bromide Precipitation as an Alternative to Silver Scavenging

Directed Palladium-Catalyzed γ-C(sp3)–H Alkenylation of (Aza and Oxa) Cyclohexanamines with Bromoalkenes: Bromide Precipitation as an Alternative to Silver Scavenging

Expanding the Utility of Inexpensive Pyridine‐N‐oxide Directing Group for the Site‐selective sp2/sp3γ‐C−H and sp2δ‐C−H Functionalization of Carboxamides

Utility of 4‐Amino‐2,1,3‐benzothiadiazole Directing Group in the Pd(II)‐catalyzed Arylation of γ‐C−H Bonds of Carboxamides and β‐C‐H Bonds of Amino Acid Carboxamides

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Directed Palladium-Catalyzed γ-C(sp³)–H Alkenylation of (Aza and Oxa) Cyclohexanamines with Bromoalkenes: Bromide Precipitation as an Alternative to Silver Scavenging

Directed Palladium-Catalyzed γ-C(sp³)–H Alkenylation of (Aza and Oxa) Cyclohexanamines with Bromoalkenes: Bromide Precipitation as an Alternative to Silver Scavenging

Expanding the Utility of Inexpensive Pyridine‐N‐oxide Directing Group for the Site‐selective sp²/sp³γ‐C−H and sp²δ‐C−H Functionalization of Carboxamides