A General Copper Catalytic System for Suzuki–Miyaura Cross-Coupling of Unactivated Secondary and Primary Alkyl Halides with Arylborons

Zhou, Yonglei; Qiu, Liping; Li, Jian; Xie, Weilong

doi:10.1021/jacs.3c10628

“…In addition, X-ray structure analysis of chiral catalysts, the isolation of different intermediates, in situ NMR spectroscopy as well as electron paramagnetic resonance spectroscopy (EPR) analysis also contributed to the discourse of the mechanism. Finally, trace metal impurities 27 c ,35 (Pd, Ag, and other 3d transition metals, etc. ) might be responsible for some catalytic activity in the asymmetric reaction and should be considered and investigated in future research.…”

Section: Discussionmentioning

confidence: 99%

The first-row transition metal-catalysed enantioconvergent radical Suzuki–Miyaura C(sp³)–C coupling of racemic alkyl halides

Liu,

Yang,

Li

et al. 2024

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“…In this vein, cobalt, [12][13][14][15] copper [16][17][18][19][20] and nickel [6,21] catalysts have been explored successfully for C(sp 3 )À C(sp 2 ) couplings. Notable breakthroughs were achieved with nickel for the more challenging alkyl-alkyl coupling of primary (1°) and 2°alkyl halides and 1°alkyl boranes.…”

Section: Introductionmentioning

confidence: 99%

A Rationally Designed Iron(II) Catalyst for C(sp³)−C(sp²) and C(sp³)−C(sp³) Suzuki–Miyaura Cross‐Coupling

Chen,

Lepori,

Guillot

et al. 2024

Angewandte Chemie

0

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Despite the paramount importance of the Suzuki‐Miyaura coupling (SMC) in academia and industry, and the great promise of iron to offer sustainable catalysis, iron‐catalyzed SMC involving sp3‐hybridized partners is still in its infancy. We herein report the development of a versatile, well‐defined electron‐deficient anilido‐aldimine iron(II) catalyst. This catalyst effectively performed C(sp3)‐C(sp2) and C(sp3)‐C(sp3) SMC of alkyl halide electrophiles and (hetero)aryl boronic ester and alkyl borane nucleophiles respectively, in the presence of a lithium amide base. These couplings operated under mild reaction conditions and displayed wide functional group compatibility including various medicinally relevant N‐, O‐ and S‐based heterocycles. They also tolerated primary, secondary and tertiary alkyl halides (Br, Cl, I), electron‐neutral, ‐rich and ‐poor boronic esters and primary and secondary alkyl boranes. Our methodology could be directly and efficiently applied to synthesize key intermediates relevant to pharmaceuticals and a potential drug candidate. For C(sp3)‐C(sp2) couplings, radical probe experiments militated in favor of a carbon‐centered radical derived from the electrophile. At the same time, reactions run with a pre‐formed activated boron nucleophile coupled to competition experiments supported the involvement of neutral, rather than an anionic, (hetero)aryl boronic ester in the key transmetalation step.

show abstract

“…In this vein, cobalt, [12][13][14][15] copper [16][17][18][19][20] and nickel [6,21] catalysts have been explored successfully for C(sp 3 )À C(sp 2 ) couplings. Notable breakthroughs were achieved with nickel for the more challenging alkyl-alkyl coupling of primary (1°) and 2°alkyl halides and 1°alkyl boranes.…”

Section: Introductionmentioning

confidence: 99%

A Rationally Designed Iron(II) Catalyst for C(sp³)−C(sp²) and C(sp³)−C(sp³) Suzuki–Miyaura Cross‐Coupling

Chen,

Lepori,

Guillot

et al. 2024

Angew Chem Int Ed

0

View full text Add to dashboard Cite

Despite the paramount importance of the Suzuki‐Miyaura coupling (SMC) in academia and industry, and the great promise of iron to offer sustainable catalysis, iron‐catalyzed SMC involving sp3‐hybridized partners is still in its infancy. We herein report the development of a versatile, well‐defined electron‐deficient anilido‐aldimine iron(II) catalyst. This catalyst effectively performed C(sp3)‐C(sp2) and C(sp3)‐C(sp3) SMC of alkyl halide electrophiles and (hetero)aryl boronic ester and alkyl borane nucleophiles respectively, in the presence of a lithium amide base. These couplings operated under mild reaction conditions and displayed wide functional group compatibility including various medicinally relevant N‐, O‐ and S‐based heterocycles. They also tolerated primary, secondary and tertiary alkyl halides (Br, Cl, I), electron‐neutral, ‐rich and ‐poor boronic esters and primary and secondary alkyl boranes. Our methodology could be directly and efficiently applied to synthesize key intermediates relevant to pharmaceuticals and a potential drug candidate. For C(sp3)‐C(sp2) couplings, radical probe experiments militated in favor of a carbon‐centered radical derived from the electrophile. At the same time, reactions run with a pre‐formed activated boron nucleophile coupled to competition experiments supported the involvement of neutral, rather than an anionic, (hetero)aryl boronic ester in the key transmetalation step.

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A General Copper Catalytic System for Suzuki–Miyaura Cross-Coupling of Unactivated Secondary and Primary Alkyl Halides with Arylborons

Cited by 13 publications

References 65 publications

The first-row transition metal-catalysed enantioconvergent radical Suzuki–Miyaura C(sp³)–C coupling of racemic alkyl halides

The first-row transition metal-catalysed enantioconvergent radical Suzuki–Miyaura C(sp³)–C coupling of racemic alkyl halides

A Rationally Designed Iron(II) Catalyst for C(sp³)−C(sp²) and C(sp³)−C(sp³) Suzuki–Miyaura Cross‐Coupling

A Rationally Designed Iron(II) Catalyst for C(sp³)−C(sp²) and C(sp³)−C(sp³) Suzuki–Miyaura Cross‐Coupling

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A General Copper Catalytic System for Suzuki–Miyaura Cross-Coupling of Unactivated Secondary and Primary Alkyl Halides with Arylborons

Cited by 13 publications

References 65 publications

The first-row transition metal-catalysed enantioconvergent radical Suzuki–Miyaura C(sp3)–C coupling of racemic alkyl halides

The first-row transition metal-catalysed enantioconvergent radical Suzuki–Miyaura C(sp3)–C coupling of racemic alkyl halides

A Rationally Designed Iron(II) Catalyst for C(sp3)−C(sp2) and C(sp3)−C(sp3) Suzuki–Miyaura Cross‐Coupling

A Rationally Designed Iron(II) Catalyst for C(sp3)−C(sp2) and C(sp3)−C(sp3) Suzuki–Miyaura Cross‐Coupling

Contact Info

Product

Resources

About

The first-row transition metal-catalysed enantioconvergent radical Suzuki–Miyaura C(sp³)–C coupling of racemic alkyl halides

The first-row transition metal-catalysed enantioconvergent radical Suzuki–Miyaura C(sp³)–C coupling of racemic alkyl halides

A Rationally Designed Iron(II) Catalyst for C(sp³)−C(sp²) and C(sp³)−C(sp³) Suzuki–Miyaura Cross‐Coupling

A Rationally Designed Iron(II) Catalyst for C(sp³)−C(sp²) and C(sp³)−C(sp³) Suzuki–Miyaura Cross‐Coupling