547.72.74 (S)-6-Methyl-3-octanone, a component of the alarm pheromone of Grematogaster ants, was synthesized through a key step of stereoselective Michael addition reaction using (4S)-4-benzyloxazolidinone as chiral auxiliary. The target product was obtained with an overall yield of 43.0% over six steps in high enantiomeric purity.Several insects show a remarkable ability to distinguish the stereoisomers of their chiral pheromone components [1]. For instance, specificity of response to the enantiomers of their alarm pheromones has been demonstrated for the leaf cutting ants, Atta texana and Atta cephalotes, and the myrmicine ant, Pogonomyrmex barbatus. 6-Methyl-3-octanone was isolated and identified as a component of the alarm pheromone of Grematogaster ants [2], a pest causing serious losses of croppers throughout the world. Since effective and cost-efficient control of Grematogaster ant populations can be foreseen with the aid of the alarm pheromone, several total syntheses of the racemate and the (R) enantiomer or (S) enantiomer have been published [2][3][4][5].Recently, our group has undertaken a research program on preparation of chiral auxiliaries [6-8] and application of them to synthesize the insect pheromones [9,10]. In this paper, we have developed an efficient procedure to stereoselectively synthesize (S)-6-methyl-3-octanone (1) via a key step of asymmetric Michael addition using optically pure (4S)-4-benzyloxazolidinone as chiral auxiliary (Scheme 1).

547.268(R)-4-Methyl-1-nonanol, the sex pheromone of the yellow mealworn (Tenebrio molitor L.), was synthesized with high stereoselectivity using (S)-4-benzyloxazolidinone as chiral auxiliary. The stereoselective synthesis was achieved by asymmetric Michael addition of organocopper reagent to N-crotoyloxazolidinone, and the target product was obtained in an overall yield of 41.8% over 7 steps.The yellow mealworm (Tenebrio molitor L.) is known to cause serious losses in stored cereal grains throughout the world. Effective, cost-efficient grain weevil management can be accomplished by monitoring pest populations with pheromonebaited insect traps and applying control methods only when pest densities reach economic thresholds. Its common sex pheromone was firstly identified by Tanaka et al as 4-methyl-nonan-1-ol (1) in 1984 [1]. Bioassays of the two possible stereoisomers of 1 revealed that the (R) isomer was the active form of the pheromone and the (S) isomer had minimum activity [2]. Since effective and cost-efficient control of the yellow mealworm populations can be foreseen with the aid of the sex pheromone, several total syntheses of the racemate and (R)-1 have been published [3][4][5][6].The Michael addition reaction of organometallics is an important method for carbon-carbon bond formation in organic synthesis [7][8][9]. Organocopper reagents are among the most versatile reagents available for Michael addition reactions [10][11][12][13]. The addition of organocopper reagents to chiral alkenoate derivatives such as Evansc oxazolidinone has provided high diastereoselectivities [14][15][16].Recently, our group has undertaken a research program on the preparation of chiral auxiliaries [17][18][19] and their application to the synthesis of insect pheromones [20,21]. In this paper, we have developed an efficient procedure to prepare the sex pheromone of the yellow mealworm (R)-1 through a key step of stereoselective Michael addition using (S)-4-benzyloxazolidinone as chiral auxiliary (Scheme 1).The synthesis of (R)-4-methyl-1-nonanol ((R)-1) was carried out as shown in Scheme 1, and the stereoselective Michael addition of organocopper reagent to N-crotonyloxazolidinone was the key step. Firstly, crotonoyl chloride reacted with (S)-4-benzyloxazolidinone 2 to give N-crotonyloxazolidinone 3 in 83.8% yield in the presence of NaH. Then the diastereoisomeric mixture of (S)-3-(3-methyloctanoyl)-4-benzyloxazolidinone was obtained via Michael addition of organocopper reagent to N-crotonyloxazolidinone 3 in 98% yield, which was analyzed by HPLC. The diastereoisomeric mixture was separated by silica gel column chromatography, and the (R) isomer 4, (S)-3-((R)-3-methyloctanoyl)-4-benzyloxazolidinone, was obtained in 86.5% yield. Nondestructive removal of the auxiliary group of the (R) isomer 4 gave (R)-3-methyloctan-1-ol 5 in 81.6% yield. The (R)-5 was subjected to further manipulation by four steps of reaction to get the sex pheromone of yellow mealworm (R)-1. In these reactions, the stereocenter of the compounds was not touched...

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