Exploiting Ancillary Ligation To Enable Nickel-Catalyzed C–O Cross-Couplings of Aryl Electrophiles with Aliphatic Alcohols

Abstract

The use of (L)Ni( o-tolyl)Cl precatalysts (L = PAd-DalPhos or CyPAd-DalPhos) enables the C( sp)-O cross-coupling of primary, secondary, or tertiary aliphatic alcohols with (hetero)aryl electrophiles, including unprecedented examples of such nickel-catalyzed transformations employing (hetero)aryl chlorides, sulfonates, and pivalates. In addition to offering a competitive alternative to palladium catalysis, this work establishes the feasibility of utilizing ancillary ligation as a complementary means of promoting challenging nickel-catalyzed C( sp)-O cross-couplings, without recourse to precious-metal photoredox catalytic methods.

Bulky 1,1′‐Ferrocenyl Ligands Featuring Diazaphospholene or Dioxaphosphepine Donor Fragments: Catalytic Screening in Nickel‐Catalyzed C‐N Cross‐Coupling

“…These observations are in keeping with our prior findings that the meso and rac isomers of PAd2‐DalPhos, featuring two chiral (racemic) phosphaadamantane (CgP) donor fragments, exhibit different catalytic competencies in nickel‐catalyzed C–N cross‐coupling. [15c] While the results featured in Figure establish the basic competence of L1 in such transformations, the poor (< 10 %) conversion achieved by use of Ni(COD) 2 / L1 in reactions of more challenging electron‐rich electrophiles such as 4‐chloroanisole or 2‐chloro‐1,4‐dimethylbenzene with furfurylamine or indole highlights the inferiority of L1 vs. DPPF itself and variants featuring substitution on the P‐aryl rings …”

“…Given the established propensity of L n Ni 0 species to engage in (hetero)aryl chloride oxidative addition, we envisioned that bulky and only modestly electron‐donating ligands featuring the CgP group would work particularly well in promoting rate‐limiting C–N reductive elimination within a presumptive Ni(0/II) (“palladium‐like”) catalytic cycle, while also discouraging unwanted comproportionation to form potentially less active Ni I species . Indeed, PAd‐DalPhos and related variants, are amongst the most effective ligands known for nickel‐catalyzed C–N cross‐coupling, enabling a range of challenging NH substrate/(hetero)aryl (pseudo)halide pairings, in a manner that is commonly competitive with, or superior to, the best palladium catalysts known.…”

PhPAd‐DalPhos: Ligand‐Enabled, Nickel‐Catalyzed Cross‐Coupling of (Hetero)aryl Electrophiles with Bulky Primary Alkylamines

“…Although these transformations involving 2,6-dimethyl substituted anilines (7a-d)proceeded efficiently at room temperature,t he more hindered 2,6-diisopropylaniline was not as uitable nucleophile,e ven at 110 8 8C. Challenging Nicatalyzed CÀOc ross-couplings involving the sterically hindered primary alcohols 3,3-dimethyl-2-butanol and tert-butanol (affording 8a and 8b)p roceeded efficiently under mild conditions (60 8 8C) when using C6.The only previous report of such transformations involving (hetero)aryl chlorides was recently published by our group, [29] whereby C4 was used as ap re-catalyst at 110 8 8C. Thes uperiority of C6 (> 95 %) over C4 (15 %) in CÀOc ross-couplings at 60 8 8C( Scheme 2C) leading to 8bsuggests that C6 might hold promise in effecting other demanding catalytic transformations under mild conditions.…”

“…Challenging Nicatalyzed CÀOc ross-couplings involving the sterically hindered primary alcohols 3,3-dimethyl-2-butanol and tert-butanol (affording 8a and 8b)p roceeded efficiently under mild conditions (60 8 8C) when using C6.The only previous report of such transformations involving (hetero)aryl chlorides was recently published by our group, [29] whereby C4 was used as ap re-catalyst at 110 8 8C. In such test transformations,e lectron-rich, electron-poor, ortho-substituted, and heteroaryl electrophiles were CÀNc ross-coupled successfully,i ncluding variants featuring benzothiophene (7c)o rq uinoline (7d)m otifs.…”

PhPAd‐DalPhos: Ligand‐Enabled, Nickel‐Catalyzed Cross‐Coupling of (Hetero)aryl Electrophiles with Bulky Primary Alkylamines

“…Challenging Ni‐catalyzed C−O cross‐couplings involving the sterically hindered primary alcohols 3,3‐dimethyl‐2‐butanol and tert ‐butanol (affording 8 a and 8 b ) proceeded efficiently under mild conditions (60 °C) when using C6 . The only previous report of such transformations involving (hetero)aryl chlorides was recently published by our group, whereby C4 was used as a pre‐catalyst at 110 °C. The superiority of C6 (>95 %) over C4 (15 %) in C−O cross‐couplings at 60 °C (Scheme C) leading to 8 b suggests that C6 might hold promise in effecting other demanding catalytic transformations under mild conditions.…”