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. 2018 Mar 16;20(6):1580-1583.
doi: 10.1021/acs.orglett.8b00325. Epub 2018 Feb 23.

Palladium-Catalyzed C-O Cross-Coupling of Primary Alcohols

Hong Zhang  1 , Paula Ruiz-Castillo  1 , Stephen L Buchwald  1
Affiliations

Palladium-Catalyzed C-O Cross-Coupling of Primary Alcohols

Hong Zhang et al. Org Lett. .

Abstract

Two catalyst systems are described, which together provide mild and general conditions for the Pd-catalyzed C-O cross-coupling of primary alcohols. For activated substrates, such as electron-deficient aryl halides, the commercially available ligand L2 promotes efficient coupling for a variety of alcohol nucleophiles. In the case of unactivated electrophiles, such as electron-rich aryl halides, the new ligand L8 was developed to improve these challenging C-O bond-forming reactions.

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Conflict of interest statement

The authors declare the following competing financial interest(s): MIT has or has filed patents on ligands/precatalysts that are described in the paper from which S.L.B. and former co-workers receive royalty payments.

Figures

Figure 1
Figure 1
Examples of pharmaceutical molecules containing alkyl aryl ethers.
Figure 2
Figure 2
Biaryl phosphine ligands and their palladacycle precatalysts.
Scheme 1
Scheme 1
General Catalytic Cycle for Pd-Catalyzed C–O Cross-Coupling of Aryl Halides and Primary Alcohols
Scheme 2
Scheme 2
Pd-Catalyzed C–O Cross-Coupling of Activated Aryl Halides with Primary Alcoholsa,b aReaction conditions: ArX (1.0 mmol), n-BuOH (2.0 mmol), NaOt-Bu (1.2 mmol), P2 (1.0–2.0 mol %), 1,4-dioxane (1.0 mL, 1.0 M), rt–60 °C, 6–15 h. bThe reported isolated yields are average results of two runs.
Scheme 3
Scheme 3
Pd-Catalyzed C–O Cross-Coupling of Unactivated Substratesa,b,c,d aReaction conditions: ArX (1.0 mmol), n-BuOH (2.0 mmol), NaOt-Bu (1.2 mmol), P2/P8 (1.0–2.5 mol %), 1,4-dioxane (1.0 mL, 1.0 M), rt–80 °C, 2.5–18 h. bNMRY: yields determined by 1H NMR spectroscopy using an internal standard. cC: conversions determined by GC using an internal standard. dIY: average isolated yields from two runs.
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