Chrysanthemic acid, allyl esters

An example of the formation of an ester of an -4,5-alkenoic acid 164 comes in a synthesis of chrysanthemic acid by Ficini and her group.31 Reduction gives the allylic alcohol 163 and [3,3] Claisen rearrangement with triethyl ortho-acetate gives the product 164 in one step. 

Esters of chrysanthemic acid are rapidly acting insecticides with a comparatively low toxicity for human and mammalian organisms. Retrosynthetic disconnection of the cyclopropane ring following the path of a 1,3-elimination leads to a carbanion with the leaving group X in an allyl position. Provided that X stabilizes the carbanion by electron-withdrawing [(-)-M-effect], the intermediate on its part arises from a MICHAEL addition of the dimethylallyl-X-compound to the methyl ester of senecionic acid (3-methyl-2-butenoic acid). 

Hanzawa Y, Ishizawa S, Kobayashi Y. Palladium(O)-catalyzed reactions of trifluoromethylated allylic ester derivatives synthesis of trifluoromethylated chrysanthemic acid ester. Chem. Pharm. Bull. 1988 36 4209-4211. 

AUethrin [584-79-2] (d 1.005—1.015, vp 16 mPa at 30°C) is the aUyl homologue of pyrethrin I, ie, R = allyl, —CH2CH=CH2. The synthetic product contains 75—95% of eight enantiomers, 70% (d=)-trans and 30% (d=)-cis acids esterified with (A)-cyclopentenolone alcohol. The relative insecticidal activities of the enantiomers are shown in Table 2. The rat LD5Qs of aUethrin are 920 (oral) and 11,000 (dermal) mg/kg. BioaUethrin [584-79-2] is the (+)-/rchrysanthemate ester of the (zt)-alcohol (RS) (R) which has enhanced knockdown activity (vp 2 mPa at 25°C, water solubility 4.6 mg/L). AUethrin is as effective as the natural pyrethrins against flies and mosquitoes but has a narrow spectmm of activity against other insect pests. 

It soon became evident that the ester structure is necessary for their activity and both the acidic and the alcoholic hydrolysis products are inactive. Also the geminal methyl groups on the cyclopropane ring and the unsaturated side chains proved to favour insecticidal action. Based on these considerations Schechter et al. (1949) synthesised the ( )-3-allyl-2-methyl-4-oxo-cyclopent-2-en-l-yl ester of ( )-( ,. chrysanthemic iund (27) which became known under the name allethrin. 

---