A Single Phosphine Ligand Allows Palladium-Catalyzed Intermolecular C-O Bond Formation with Secondary and Primary Alcohols-

Reaction Scheme


The substrate scope of the copper-free Sonogashira coupling has been successfully extended to cyclopropyl iodides, allowing an efficient access to a wide variety of functionalized alkynyl cyclopropanes.



An oven-dried Schlenk tube (equipped with a magnetic stirring bar) was charged with PdCl2(MeCN)2 (2.0 mg, 7.6 �mol, 3 mol %), X-Phos (10.8 mg, 22.7 �mol, 9 mol %), Cs2CO3 (206 mg, 0.632 mmol, 2.5 equiv) or K3PO4 (134 mg, 0.632 mmol, 2.5 equiv) and a solution of cyclopropyl iodide 1 (50.0 mg, 0.253 mmol) in the appropriate solvent (1 mL). The resulting mixture was degassed under a positive pressure of argon for 10 min and phenylacetylene (42.5 ?L, 0.379 mmol, 1.5 equiv) was added. The Schlenk tube was sealed, immersed in a pre-heated oil-bath at the indicated temperature and the reaction mixture was stirred for 1.5 h. The Schlenk tube was cooled to rt, opened to air, and the resulting suspension was filtered through a pad of Celite (EtOAc). The filtrate was concentrated under reduced pressure and the residue was analyzed by 1H NMR spectroscopy. Purification by flash chromatography on silica gel (CH2Cl2/Et2O: 95/5) afforded the corresponding alkynyl cyclopropane 2. When the procedure was scaled-up for the preparation of 2, the quantities of PdCl2(MeCN)2 and X-Phos could be reduced to 1 mol % and 3 mol %, respectively.



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