High-Throughput Discovery and Evaluation of a General Catalytic Method for <i>N</i>-Arylation of Weakly Nucleophilic Sulfonamides

Becica, Joseph; Hruszkewycz, Damian P.; Steves, Janelle E.; Elward, Jennifer M.; Leitch, David C.; Dobereiner, Graham E.

doi:10.1021/acs.orglett.9b03380

Cited by 25 publications

(15 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to C–N couplings with primary and secondary amines, we assessed complex 1 as a precursor for the more challenging arylation of sulfonamides − and imidazoles . For the synthesis of a representative N- arylsulfonamide via Pd-catalyzed coupling, we evaluated several large-cone-angle ligands reported to be effective.…”

Section: Resultsmentioning

confidence: 99%

“…For the synthesis of a representative N- arylsulfonamide via Pd-catalyzed coupling, we evaluated several large-cone-angle ligands reported to be effective. These include biarylphosphines, such as JackiePhos and t BuXPhos, as well as XantPhos and Bippyphos. ,, Under the conditions used (excess K 2 CO 3 and CPME solvent, adapted from previously reported conditions), Pd(OAc) 2 is almost completely ineffective, generating only modest amounts of product and yielding no clear hits. The other three Pd sources fare better, with the combination of 1 and t BuXPhos giving the largest amount of N -arylsulfonamide product.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

^DMPDAB–Pd–MAH: A Versatile Pd(0) Source for Precatalyst Formation, Reaction Screening, and Preparative-Scale Synthesis

et al. 2021

Self Cite

View full text Add to dashboard Cite

We report an easily prepared and bench-stable mononuclear Pd(0) source stabilized by a chelating N,N'-diaryldiazabutadiene ligand and maleic anhydride: DMP DAB-Pd-MAH. Phosphine ligands of all types, including bidentate phosphines and large cone angle biarylphosphines, rapidly and completely displace the diazabutadiene ligand at room temperature to give air-stable Pd(0) phosphine complexes. DMP DAB-Pd-MAH itself is readily soluble and stable in several organic solvents, making it an ideal Pd source for in situ catalyst preparation during reaction screening, as well as solution-dispensing to plate-based reaction arrays for high-throughput experimentation. Evaluation of DMP DAB-Pd-MAH alongside other common Pd(0) and Pd(II) sources in microscale reaction screens reveals that DMP DAB-Pd-MAH is superior at identifying hits across six different C-N, C-C, and C-O coupling reactions. DMP DAB-Pd-MAH, and the phosphine precatalysts derived therefrom, are also effective in preparative-scale cross couplings at low Pd loadings. ASSOCIATED CONTENTDetailed experimental procedures, full tables of screening data, characterization data, and XRD details. This material is available free of charge via the Internet at http://pubs.acs.org. CIFs for complexes 1, 3-5, 8 and 12 are deposited with the CCDC with deposition numbers 2056595-2056600.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

^DMPDAB–Pd–MAH: A Versatile Pd(0) Source for Precatalyst Formation, Reaction Screening, and Preparative-Scale Synthesis

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Leitch and coworkers [38] have shown the power of HTE by identifying a potent Pd catalyst and ligand combination that enables CÀ N coupling to form sterically demanding N,N' diaryl sulfonamides. Initial screens focused on aryl and pyridyl bromides with the same sulfonamide in the presence of multiple palladium sources, phosphine ligands, and carbonate bases.…”

Section: N-arylationmentioning

confidence: 99%

Advancement in Organic Synthesis Through High Throughput Experimentation

2021

View full text Add to dashboard Cite

and cyanoarenes has also been optimized using an HTE approach. [63] Other Photochemical TransformationsNon-activated alkyl bromides were coupled with Michael acceptors in a photoredox Giese-type reaction. [64] Reaction optimization was performed by studying the effect of photocatalyst, solvent, base, and varying amounts of radical initiator (Me 3 Si) 3 SiH on product and by-product profile. Another study of conjugate addition using photocatalytic methodology was shown for the synthesis of unnatural β-alkyl α-amino acid derivatives via decarboxylative photocatalysis. [65] Photocatalysis was performed with oxime and cyanopyridine precursors (Scheme 4g) to form primary amine products. [66] Four different solvents (acetone, DCE, ACN, DMSO), nine different photocatalysts, and two reductants were used to evaluate 45 unique reactions. DMSO with diisopropylamine and Ir[dF(Me) ppy] 2 dtbbpyPF 6 gave the highest yield by UPLC, although many Scheme 4. Photocatalytic transformations in HTE.

show abstract

“…A modest number of publications documenting Cu or Pd‐catalyzed cross‐couplings of sulfonamides with (hetero)aryl bromides or iodides have appeared . By comparison, no such Cu‐catalyzed cross‐couplings of chloride or phenol derivatives have been published, and Pd‐catalyzed cross‐couplings of this type ( that is, (hetero)aryl sulfonate or chloride reaction partners) are limited.…”

Section: Figurementioning

confidence: 99%

Nickel‐Catalyzed Cross‐Coupling of Sulfonamides With (Hetero)aryl Chlorides

et al. 2020

View full text Add to dashboard Cite

The development of Ni-catalyzed C À N crosscouplings of sulfonamides with (hetero)aryl chlorides is reported. These transformations, which were previously achievable only with Pd catalysis, are enabled by use of air-stable (L)NiCl(o-tol) pre-catalysts (L = PhPAd-DalPhos and PAd2-DalPhos), without photocatalysis. The collective scope of (pseudo)halide electrophiles (X = Cl, Br, I, OTs, and OC-(O)NEt 2 ) demonstrated herein is unprecedented for any reported catalyst system for sulfonamide CÀN cross-coupling (Pd, Cu, Ni, or other). Preliminary competition experiments and relevant coordination chemistry studies are also presented.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.202002392. Figure 1. N-Arylation of sulfonamides with (hetero)aryl (pseudo)halides. A) The structure of celecoxib. B) Metal-catalyzed CÀN crosscouplings of sulfonamides. C) DalPhos ligands used in Ni-catalyzed cross-couplings. Angewandte Chemie Communications

show abstract

High-Throughput Discovery and Evaluation of a General Catalytic Method for N-Arylation of Weakly Nucleophilic Sulfonamides

Cited by 25 publications

References 47 publications

^DMPDAB–Pd–MAH: A Versatile Pd(0) Source for Precatalyst Formation, Reaction Screening, and Preparative-Scale Synthesis

^DMPDAB–Pd–MAH: A Versatile Pd(0) Source for Precatalyst Formation, Reaction Screening, and Preparative-Scale Synthesis

Advancement in Organic Synthesis Through High Throughput Experimentation

Nickel‐Catalyzed Cross‐Coupling of Sulfonamides With (Hetero)aryl Chlorides

Contact Info

Product

Resources

About