Chrysanthemic acid, ester intermediate

When phosphane-free nickel complexes, such as bis(cycloocta-l,5-diene)nickel(0) or te-tracarbonylnickel, are employed in the codimerization reaction of acrylic esters, the codimer arising from [2-1-1] addition to the electron-deficient double bond is the main product. The exo-isomer is the only product in these cyclopropanation reactions. This is opposite to the carbene and carbenoid addition reactions to alkenes catalyzed by copper complexes (see previous section) where the thermodynamically less favored e Jo-isomers are formed. This finding indicates that the reaction proceeds via organonickel intermediates rather than carbenoids or carbenes. The introduction of alkyl substituents in the /I-position of the electron-deficient alkenes favors isomerization and/or homo-cyclodimerization of the cyclopropenes. Thus, with methyl crotonate and 3,3-diphenylcyclopropene only 16% of the corresponding ethenylcyc-lopropane was obtained. Methyl 3,3-dimethylacrylate does not react at all with 3,3-dimethyl-cyclopropene, so that the methylester of tra 5-chrysanthemic acid cannot be prepared in this way. This reactivity pattern can be rationalized in terms of a different tendency of the alkenes to coordinate to nickel(O). This tendency decreases in the order un-, mono- < di-< tri- < tet-... 

In a large number of carbene and carbenoid addition reactions to alkenes the thermodynamically less favored jjyn-isomers are formed The finding that in the above cyclopropanation reaction the an/i-isomer is the only product strongly indicates that the intermediates are organonickel species rather than carbenes or carbenoids. Introduction of alkyl groups in the 3-position of the electron-deficient alkene hampers the codimerization and favors isomerization and/or cyclodimerization of the cyclo-propenes. Thus, with methyl crotylate and 3,3-diphenylcyclopropene only 16 % of the corresponding vinylcyclopropane derivative has been obtained. 2,2-Dimethyl acrylate does not react at all with 3,3-dimethylcyclopropene to afford rranj-chrysanthemic acid methyl ester. This is in accordance with chemical expectations since in most cases the tendency of alkenes to coordinate to Ni(0) decreases in the order un-, mono-< di- tri- < tetrasubstituted olefines. 

The first step is conjugate addition of the highly stabilized anion. The intermediate enolate then closes the three-membered ring by favourable nucleophilic attack on the allyUc carbon. The leaving group is the sulfinate anion and the stereochemistry comes from the most favourable arrangement in the transition state for this ring closure. The product is the methyl ester of the important chrysanthemic acid found in the natural pyrethrum insecticides. 

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). 

Formation of the actual alcohol component for insecticidally active esters occurs during the Claisen rearrangement [882] (Reaction scheme 265) of an intermediate generated from chrysanthemic acid anhydride and an allylbenzyl alcohol, which does not give insecticidal esters. 

Isopropylidene-D-glyceraldehyde (readily obtained from D-raannose) has been used to prepare the -unsaturated ester (77) by a Wittig reaction, and hence the cyclopropyl derivatives (1R,3R)-caronaldehyde metnyl ester (78) and (1R,3R)-chrysanthemic acid methyl ester (79) following isopropylidene addition to the double bond (Scheme 15). The same intermediate (77) has been utilized... 

Besides classical monoterpenes that are formed via a head-to-tail addition of IPP to DMAPP (and the analogous addition of IPP to advanced intermediates toward higher terpenes), there are also monoterpenes known where the CIO skeleton cannot be rationalized by this standard coupling of the two activated isoprene units. Two important examples are chrysanthemic acid (60) and pyrethric acid (61), which are the main (ester bound) building blocks for the well-known family of the pyrethrins [1, 13]. In this case, an enzyme-catalyzed... 

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