Lactonic pheromones, synthesis

So when the hydroxyketone 49 was needed for a pheromone synthesis, it was made by nucleophilic displacement on the lactone 50 by an organo-lithium compound. This lactone is of the right kind (cf. 45) to be made by a Baeyer-Villiger rearrangement from the cyclohexanone 51 and this can be made by total reduction of the phenol 52 (chapter 36). 

The Baeyer-Villiger reaction is regioselective — the more substituted group migrates—and stereospecific — it does so with retention. Hydroxy ketone (22) was needed for insect pheromone synthesis and is a 1,6-difunctionalised compound. It could be made by nucleophilic displacement by an organo-metallic reagent (R ) on lactone (23), the Baeyer-Villiger product from (24) which can be made from aromatic (26). 

Strained ring systems (epoxides, lactones, etc.) are cleaved by cuprate reagents these reactions have found application in prostaglandin chemistry and in pheromones synthesis. 

Example (see also [13, 14] for other examples) ring opening reaction of lactones [15] synthesis of a pheromone of Danam chrysippys (an African butterfly). 

Both chiral lactones and ketones have been utilized in asymmetric synthesis of bioactive compounds like lipoic acid [175[ and natural products like various insect pheromones [176[. 

Scheme 41 summarizes Couladouros s synthesis of the oviposition attractant pheromone of the Southern house mosquito (Culexpipiensfatigans)y (5R,6S)-6-acetoxy-5-hexadecanolide (28) [66]. The key-steps are (i) -selective Schlosser olefination (A B), asymmetric dihydroxylation (B C), and lactonization of carbonate C to the desired 6-lactone with inversion at C-5. 

Synthesis of Oxygen Heterocycles (Excluding Epoxides, Hemiacetals, Lactones and Acetals) as Pheromones... 

Acetalization of oxo aldehydes is used to protect sensitive aldehyde products, especially in asymmetric hydroformylation preventing racemization of an a-chiral aldehyde product [18-22,27]. Acetal formation can also be applied to the synthesis of monocyclic or spirocyclic pyranes as potential precursors and building blocks for natural products such as pheromones or antibiotics. A representative example is the synthesis of the pyranone subunit of the Prelog-Djerassi lactone. For this purpose, various 1,2-disubstituted homoal-lylic alcohols were used (Scheme 3) [32],... 

Males from Galerucella calmariensis and Galerucellapusilla (Coleoptera Chrysomelidae) emit an aggregation pheromone while feeding on host foliage. The compound was identified by spectrometric and other microchemical tests as the novel dimethylfuran lactone, 12,13-dimethyl-5,l4-dioxabicyclo[9.2.1]-tetradeca-l(13),ll-dien-4-one. The structure was confirmed by synthesis and the synthetic compound attracted both males and females in field tests. 

A highly selective method for the preparation of optically active 3-substituted or 3, y-disubstituted-S-keto esters and related compounds is based on asymmetric Michael additions of chiral hydrazones (156), derived from (5)-l-amino-2-methoxymethylpyrrolidine (SAMP) or its enantiomer (RAMP), to unsaturated esters (154).167-172 Overall, a carbonyl compound (153) is converted to the Michael adduct (155) as outlined in Scheme 55. The actual asymmetric 1,4-addition of the lithiated hydrazone affords the adduct (157) with virtually complete diastereoselection in a variety of cases (Table 3). Some of the products were used for the synthesis of pheromones,169 others were converted to 8-lactones.170 The Michael acceptor (158) also reacts selectively with SAMP hydrazones.171 Tetrahydroquinolindiones of type (159) are prepared from cyclic 1,3-diketones via SAMP derivatives like (160), as indicated in Scheme 56.172... 

Ring-opening95 of tetrahydrofuran with TBDMS-Mn(CO)5, generated in situ from TBDMSOTf and NaMn(CO)5, proved a key step (equation 22) in the synthesis of spiroke-tal lactones, precursors of certain insect pheromones. 

Lactones and the macrocyclic lactones, like the y- and 5-lactones, are of importance since these ring systems are found widespread in nature. The simpler substituted lactones are important building blocks in the synthesis of many natural products, e.g. in the fields of antibiotics, anticancer pharmaceuticals, pheromones and prostaglandins to name but a few. 

Chiral lactones. The aldol type condensation of this reagent with an aldehyde has been used to synthesize two chiral five- and six-membered lactones in > 80% ee. The synthesis of the six-membered lactone (R)-( + )-d-n-hexadecanolactone (5), a pheromone of the Oriental hornet, from the /-butyl ester (1) of the sulfoxide is formulated in equation (I).1... 

Chiral y-iactones (10, 321). Midland3 has extended his synthesis of chiral y-lactones to an efficient synthesis of the sex pheromone (2) of the Japanese beetle. The overall optical yield of (2) from optically pure a-pinene is 97%. 

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