One-Step Synthesis of Racemic 6-Methyloctan-3-One, an Alarm Pheromone Component of Ants of the Genus Crematogaster

Abstract

6-Methyloctan-3-one (1) was identified as a component of the alarm pheromone of ants of the genus Crematogaster [1]. Several syntheses of this compound as the racemate and an enantiomer are known [2–6]. However, many of them involve several steps and most are labor-intensive and require costly starting materials. We developed a convenient and effective synthetic pathway for a racemic analog of 1 that was based on our recently proposed regioselective carbonylation of 1-alkenes using Et2Zn and TaCl5 catalyst [7]. The reaction of but-1-ene with Et2Zn in the presence of TaCl5 (Et2Zn–but-1-ene–TaCl5 = 110:100:5; Et2Zn concentration 1.0 mmol/mL in hexane, 20°C, 5 h) formed organozinc compound 2. For this, hexane (20 mL) was cooled to –15°C and treated with but-1-ene (2.25 ml, 20 mmol) cooled to –30°C. Then, the solution was cooled to –15–20°C, treated with Et2Zn (2.25 mL, 22 mmol) and TaCl5 (0.4 g, 1 mmol), heated gradually to room temperature, stirred for 5 h, cooled to –5°C, and treated dropwise with propionylchloride (3, 1.74 mL, 20 mmol) in hexane. All these operations were performed under a dry Ar atmosphere. The resulting reaction mixture was stirred for 2 h and treated with aqueous HCl solution (10%). The resulting 1 was extracted by Et2O (3 50 mL). The extracts were dried over anhydrous MgSO4. The solvent was distilled off. The residue was chromatographed (SiO2, hexane) to afford 1 (2.69 g, 99% pure) in 95% yield based on 3 (Scheme 1). The structure of 1 was proven using IR, PMR, and 13C NMR spectral methods and GC-MS in addition to comparison with an authentic sample [6].