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BrettPhos Ligand Supported Palladium-Catalyzed C-O Bond Formation through an Electronic Pathway of Reductive Elimination: Fluoroalkoxylation of Activated Aryl Halides

Reaction Scheme

Abstract

A Pd/N-heterocyclic carbene-based catalyst achieves the Sonogashira coupling of an array of functionalized, ?-hydrogen-containing alkyl bromides and iodides under mild conditions. By furnishing the first example of a nonphosphine-based palladium catalyst for cross-coupling unactivated alkyl electrophiles, this study provides an impetus for future efforts at catalyst development that extend beyond phosphine ligands.

Substrates

Procedure

General Procedure. In a glove box, 1,3-bis(1-adamantyl)imidazolium chloride (9.3 mg, 0.050 equiv), CuI (7.2 mg, 0.075 equiv), [(?-allyl)PdCl2 (4.6 mg, 0.025 equiv), and Cs2CO3 (228 mg, 1.4 equiv) were added in turn to a vial equipped with a stir bar. A mixture of Et2O and DMF (2:1, 1.0 mL) was added, followed by the alkyne (0.65 mmol, 1.3 equiv) and the alkyl halide (0.50 mmol). The vial was sealed with a Teflon-lined cap and removed from the glove box. The heterogeneous reaction mixture was stirred vigorously at 45 �C (for alkyl bromides) or 40 �C (for alkyl iodides) for 16 hours. The crude reaction mixture was then purified by flash chromatography. Note: Although all of the Sonogashira reactions that are reported in Table 2, eq 3, and eq 4 were set up on a 0.50-mmol scale in a glove box, the couplings can be performed with nearly comparable efficiency without a glove box and on a larger scale. For example, for Table 2: entries 1 (68% yield), 2 (72% yield), and 8 (67% yield) were performed on a 0.50-mmol scale, and entry 9 was conducted on a 0.50-mmol (66% yield) as well as 5.0-mmol scale (66% yield), using standard Schlenk technique

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