S- -4-Methyl-3-heptanone

S)-4-methyl-3-heptanone (146), the alarm pheromone of the leafcutting ant Atta texarta is about 400 times more active than its optical isomer. This acyclic ketone (146) could be prepared by simply starting from diethyl ketone and propyliodide. 

C. (S)-(+)-4-Methyl-3-heptanone f(S>-A]. A 100-mL Schlenk tube, fitted with a gas inlet and Teflon stopcocks, is charged with 4.3 g (18 mmol) of crude (ZSS)-3 dissolved in 50 mL of dichloromethane (Note 11), and cooled to -78°C (acetone/dry ice bath) under nitrogen. Dry ozone (Note 12) is passed through the yellow solution until a green-blue color appears (ca. 4 hr). The... 

S)-(+)-4-Methyl-3-heptanone 3-Heptanone, 4-methyl-, (S)- (9) (51532-30-0) 3-Pentanone SAMP-hydrazone 1-Pyrrolidinamine, N-(1-ethyl propylidene)-2-(methoxymethyl)-, (S)- (9) (59983-36-7)... 

Riley et aK (157) identified S-(+)-4-methyl-3-heptanone as the alarm pheromone of Atta texana and reported that it was 100X more active as an alarm releaser than the unnatural (-)-enantiomer. Similarly, Benthuysen and Blum (158) demonstrated that workers of Pogonomyrmexbadius were more sensitive to the S(+) enantiomer than to the R-(-) enantiomer of this compound, which is the primary alarm pheromone of this species. 

Methylenetiiphenylphosphorane, 307 Methylenomycin A, 183 Methylenomycin B, 184 N-Mcthylephedrine, 308 N-Methyl-i//-ephedrine, 421 Methyl fluorosulfonale, 302, 307 (+)-(S)-4-Methyl-3-heptanone, 17 Methyl 3-hydroxybutyrate, 406 Methyl hydroxymethoxyacetate, 19, 20 Methyl hypobromite, 501 Methyl iodide, 308-309 5-Methylisoxazole, 309 3-Methyl-5(4/0-isoxazolone, 309 Methyl jasmonate, 92, 358 Methylketene methyl trimethylsilyl acetal, 310... 

Asymmetric a-alkylatlon of ketones (7, 10-11 8, 16-17). Enders and Eichenauer have now obtained almost complete asymmetric a-alkylation of acyclic ketones by way of hydrazones formed with 1. An example is the synthesis of (+)-(S)-4-methyl-3-heptanone (4), an ant alarm pheromone, from diethyl ketone. The hydrazone 2 was metalated and alkylated with n-propyl iodide in ether to give 3. 

Hydrazones prepared from (S)- l-amino-2-(methoxymethyl)pyrrolidine (242) and acyclic ketones have been shown to undergo deprotonation and alkylation with almost complete asymmetric induction at the a-center (79AG(e)397). The ant alarm pheromone, (+)-(,S)-4-methyl-3-heptanone (245), was prepared from the metallated hydrazone of diethyl ketone (243) by alkylation with n-propyl iodide and subsequent cleavage of the crude product via its A-methyl iodide with acid (Scheme 52). The optical purity of the product was >99%. 

Reaction of 3-pentanone with the commercially available hydrazine (5)-l-amino-2-methoxymethylpyrrolidine (SAMP) affords the corresponding chiral hydrazone. Deprotonation with LDA followed by alkylation and hydrolysis furnishes (S)-4-methyl-3-heptanone in greater than 99% enantiomeric excess. Using the corresponding (R)-hydrazine (RAMP) provides (R)-4-methyl-3-heptanone. 

Most social insects use alarm and trail pheromones. Their specificity is not so important, but fast release and dispersal are important. They tend to be small volatile substances for instance, (S)-4-methyl-3-heptanone is an alarm pheromone in the leaf-cutting ant, Atta textata. 

This method has two limitations. Yields of ketones are low unless R is a primary alkyl, aryl, or allyl group. The rhodium reagent is expensive, even if prepared rather than purchased. However, it is attractive for synthesis of sensitive ketones, since conditions are mdd. It was used, for example, for synthesis of (S)-(+)-4-methyl-3-heptanone, the alarm pheromone of a fungus-growing ant of the genus A ffa, with complete retention of stereochemistry (equation I). 

Alkylation of lithiated hydrazones forms the basis of an efficient method for the asymmetric alkylation of aldehydes and ketones, using the optically active hydrazines (5)-l-amino-2-(methoxymethyl)pyrroUdine (SAMP) 59 and its enantiomer (RAMP) as chiral auxiliaries. Deprotonation of the optically active hydra-zones, alkylation and removal of the chiral auxiliary under mild conditions (ozonol-ysis or acid hydrolysis of the A-methyl salt) gives the alkylated aldehyde or ketone with, generally, greater than 95% optical purity. This procedure has been exploited in the asymmetric synthesis of several natural products. Thus, (S)-4-methyl-3-heptanone, the principal alarm pheromone of the leaf-cutting ant Am texana, was prepared from 3-pentanone in very high optical purity as shown in Scheme 1.74. 

Figure 4.9 The biosynthesis of 4-methyl-3-heptanone can be supposed to proceed through either of two routes. The imaginary polyketide intermediates are shown, although the former route is more likely because it allows decarboxylation of a p-keto-acid at the final stage The final structure shown in this figure is (S)-(+)-4-methyl-3-heptanone, an ant trail pheromone...

It is often possible to convert an achiral compound to a chiral compound by (1) addition of achiral group (2) running an asymmetric synthesis, and (3) cleavage of the original chiral group. An example is conversion of the achiral 2-pentanone to the chiral 4-methyl-3-heptanone 39.w In this case more than 99% of the product was the (S) enantiomer. 

Blight M. M., Henderson N. C. and Wadhams L. J. (1983) The identification of 4-methyl-3-heptanone from Scolytus scolytus (F.) and Scolytus multistriatus (Marsham). Absolute configuration, laboratory bioassay and electrophysiological studies on S. scolytus. Insect Biochem. 13, 27-38. 

Methyl-3-heptanone SAMP-hydrazone, (S)-(+)- 1-Pyrrol Id Inamine,... 

Figure 3.10 Natural product synthesis imploying SAMP-RAMP hydrazones 5-(+)-4-methyl-3-heptanone, the leaf cutting ant alarm pheromone [105] serricornin, the sex pheromone of the cigarette beetle [120] S,E-4,6-dimethyl-6-octen-3-one, the defense substance of daddy longlegs [120] (+)-eremophilenolide [120] and antibiotic X-14547A [121], Stereocenters formed by asymmetric alkylation are indicated by. ...

Cole, L. K. and Blum, M. S. (1975) Antifungal properties of the insect alarm pheromones, citral, 2-heptanone and 4-methyl-3-heptanone. Mycologia, 67, 701-8. 

Fig. 15.4 Predicted active spaces of 4-methyl-3-heptanone for workers of Atta texana, 20 s after deposition of 10% of mandibular gland contents, at the point arrowed, on a flat surface in still air. The area of attraction is shaded (compare Figs 15.5 and 15.6) (calculated from data in Moser et aL, 1968).

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