2- Methyl-4-heptanol

The fungus responsible for Dutch elm disease is spread by European bark beetles when they burrow into the tree Other beetles congregate at the site attracted by the scent of a mixture of chemicals some emitted by other beetles and some coming from the tree One of the compounds given off by female bark beetles is 4 methyl 3 heptanol Suggest an efficient synthesis of this pheromone from alcohols of five carbon atoms or fewer... 

The absolute configuration of the major aldol product anti-11, obtained from the corresponding (47 ,55)-oxazolidine and propanal, was determined by its conversion to (3A, 4W)-4-methyl-3-heptanol (12)5. 

Sn2 Reactions with epoxides and aziridines are also synthetically useful. An example of epoxide cleavage with an organocopper reagent with sp carbon moieties is the enantioselective synthesis of (3S, 4S)-4-methyl-3-heptanol (53), an elm bark beetle (Scolytus multistriatus) pheromone [42]. The chiral epoxy oxazolidine 51 [43], prepared from (R)-phenylglycinol, reacted with a propylmagnesium bromide-derived cuprate at —70 °C to afford the oxazolidine 52 in 74% yield (Scheme 9.12). Compound 52 was converted into the target molecular 53 by conventional procedures. 

The U.S. Forest Service scientists in New York have isolated and identified chemical sex attractants used by elm bark beetles that are responsible for transmitting the fungus causing Dutch elm disease. Examples of attractants are 2,4-dimethyl-5-ethyl-6,8-dioxabicyclo [3.2.1] octane (called multistriatin) and 4-methyl-3-heptanol. In field trials an artificially produced mixture of the compounds has proved attractive to the elm bark beetle. 

The highest diastereomeric ratios were exhibited by 4-methyl-3-heptanol, after construction of two adjacent stereocenters. Both enantiomers of each boronic ester and all four diastereomers of 4-methyl-3-heptanol were made. One or the other or possibly both diastereomeric ratios in this sequence must exceed 99.9 0.1. However, for (3S,4R)-4-methyl-3-heptanol, the achieved diastereomeric ratio was only >99.4 0.6. An unidentified error in procedure was postulated as the cause. 

Butanediol esters arc mediocre chiral directors and showed no evidence for double diastereoselection in a preliminary exploration of the 4-methyl-3-heptanol synthesis4, but the data in Table 1 does illustrate that starting from 1 or 2 yields the same result21. 

II-NMR analysis of derived pinanediol ester. b By 13C-NMR and GC analyses of derived 4-methyl-3-heptanol see text. c 1H-NMR analysis of derived symmetrical diol. The construction of R3 (Section 1.1.2.1.6.) was not totally stcrcospecific and may have been the source of the 12% diastercomeric contaminant. d From the ee of the homoallylic alcohol derivative formed by reaclion with benzaldchyde, measured by GC on a chiral column. 

After discovery of the higher stereoselectivities made possible by the zinc chloride catalysis, the synthesis was applied to several secondary alcohols having two or more stereocenters15. The first of these (35,4S)-4-methyl-3-heptanol, was first made with (S)-pinanediol as the chiral director, but has since been made more stereoselectively with (R,R)-2,5-dimethyl-3,4-hexanedi-ol (Section 1.1,2.1.2.1.). Another insect pheromone, eldanolide, requires the use of (R)-pinane-diol in order to obtain the natural enantiomer, and introduces the use of an enolate as well as an allylic Grignard reagent for C-C bond formation15. 

Aldol reactions.1 The chiral oxazolidine (1), formed from 3-pentanone and (-)-norephedrine, after conversion to the tin azaenolate reacts with aldehydes to give predominantly anti-aldols (2) in >90% ee. Reduction of the carbonyl group of the anti-aldol 2 provides (3S,4R)-4-methyl-3-heptanol (3) in 95% ee. 

Reaction of the Grignard reagent with the aldehyde yields the desired 4-methyl-3-heptanol. 

Methyl-3-heptanol, stereoselective preparation, 9, 12 Methylidyne cubane, via Ti(IV) complexes, 4, 407 <7-Methyl-(tj5-indenyl)chromium tricarbonyl, rearrangement,... 

Blight M. M., Wadhams L. J. and Wenham M. J. (1978) Volatiles associated with unmated Scolytus scolytus beetles on English elm differential production of a-multistriatin and 4-methyl-3-heptanol, and their activities in a laboratory bioassay. Insect Biochem. 8, 135-142. 

The terpenoid-exocrine theme emphasized by scolytid beetles was again evident when the chemical constitution of the secondary attractant for the smaller European elm bark beetle, Scolytus multistriatus, was elucidated. The aggregation pheromone was identified as a mixture of (-)-4-methyl-3-heptanol, 2,4-dimethyl-5-ethyl-6,8-dioxabicyclo [3.2.1]octane (multistriatin) (XXII), and (-)-a-cubebene (XXIII), a host-derived synergist (70). All three compounds are required for the maximum attraction of beetles. The inactive diastereomers of 4-methyl-3-heptanol and multistriatin did not inhibit the responses of airborne beetles. 

Such a sequence has been successfully used115 for the synthesis of 4-methyl-3-heptanol, the major constituent of the aggregation pheromone of the elm bark beetle (Scolytus multistriatus Marsham)117 and zir-butyM-methyltetrahydro-2-furanone118 known as quercus lactone or oak lactone. ... 

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