6-Octenal, 7-methylene reaction

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

As an example of this strategy, let s consider the synthesis of 2-methyl-6-methylene-7-octen-4-ol, an insect pheromone. (As described in the Focus On box on pages 1025-1026, pheromones are compounds used by animals, especially insects, for communication.) The synthesis of this alcohol, a component of the sex attractant of the male bark beetle, has been described in the literature. Retrosynthetic analysis, similar to that described earlier, suggested the use of a Grignard reaction to prepare this alcohol ... 

Williams and Reeves138 developed a powerful cascade reaction process for the construction of functionalized cA-bicyclo[3.3.0]octenes. Carbolithiation of 3-methylene-1,4-cyclooctadiene 227 with 1°, 2° or 3° alkyllithium reagents leads to cyclooctadienyl anions,... 

As a result of an extensive study, it has been found that methylene groups are attacked much more readily than a methyl group. For example, 2-methyl-2-butene requires 16 hours for completion of the reaction, whereas, 2-methyl-2-hexene requites 10 minutes. The conversion of cyclohexene to 3-broraocyclohexene is accomplished in 20 minutes in 87% yield. It is noteworthy that the bromination of 1-octene with N-btomo-succinimide yields a mixture of l-bromo-2-octene and 3-bromo-1-octene and that the proportion of these isomers is in close agreement with the equilibrium mixture formed at 100° by analogous bromides. ... 

Alkynes are generally more reactive than alkenes as enophiles in both inter- and intra-molecular ene reactions. - 6-Octen-l-yne (100) cyclizes to l-methylene-2-vinylcyclopentane (101) on brief heating at 400 Dehydrolinalool (102) undergoes an ene reaction at 200 C to give (103) in quantitative... 

Olefins such as 1-octene and cyclohexene demonstrated unusually low turnover rates compared to adamantane and cis-decalin (Table 1, entry 7), although in competitive oxidations 1-octene was twice as reactive as adamantane (Table 1, entry 8). Apparently, the catalyst is inhibited in the presence of olefins. Interestingly, upon a stoichiometric reaction of Ru VtPFPP)(0)2 with cyclohexene in methylene chloride, rapid transformation of the ruthenium porphyrin into Ru (TPFPP)(CO) was observed (Fig. 6). 

Potassium peroxymonosulfate has been used in the Nef reaction to convert 1-nitrohexane to caproic acid in 98% yield.275 Replacement of the potassium ion by tetrabuty-lammonium ion allows the oxidant to be used in acetonitrile and methylene chloride. (Less toxic solvents would be desirable.) When this reagent was used with a manganese catalyst, 1-octene was epoxidized in more than 99% yield.276 It also converted ethylbenzene to acetophenone with more than 99% selectivity. 

Extended reaction times cause colored by-products to form, that are difficult to separate. TLC analysis was performed on E. Merck silica gel 60F-254 glass plates of 0.25-mm thickness purchased from EM Reagents. The eluting solvent was 20% ethyl acetate-hexane in this solvent system, the Rf s of 7-methylene-8-hexadecyn-6-ol and 2-bromo-1-octen-3-ol are 0.68 and 0.55, respectively. 

Considerable evidence exists to support the suggestion that intramolecular peroxides are more important than intermolecular or cross-linked peroxides. In addition to Bailey s work, intramolecular peroxides have been identified during the oxidation of vinyl chloride [180] and of poly-vinylene chloride [181]. In the octene, where such peroxides cannot be formed, hydroperoxides are produced by the more conventional radical reaction involving attack on the a-methylene hydrogen atom... 

Sulfonyl Methyl Lithium Reagent. ter -Butylsulfonylmethyllithium, which was prepared from the reaction of methyllithium and tert-butyl methyl sul-fone, was shown to be a methylene-transfer reagent in the presence of nickel(II) acetylacetonate as a catalyst (Scheme 5) (56). Nonactivated olefins such as 1-octene and 1-decene could be cyclopropanated in good yield. 

Compound (LXVI) is particularly interesting as it undergoes a 1,7 addition with tetracyanoethylene. This transannular addition is possible since the opposite pairs of double bonds in (LXVI) parallel each other at a distance of only about 2.7 A, which must lead to appreciable ir-orbital interaction 105). In the presence of acetylene, with Ni(CO)2 2P(OC6H5)3 as the catalyst, a co-cyclopolymerization of allene to 3,5- and 3,6-dimethylene-cyclohexene (LXVII) and (LXVIII), respectively, is possible (106). With nickel acetylacetonate as catalyst, (LXVII) and 3,5,7-trimethylenecyclo-octene (LXVIII) are produced in 45% and 5% yield respectively. 106). This reaction makes exo-methylene cyclic compounds which are unsaturated easily accessible. The chemistry of (LXVII) has been studied in some detail 107). 

The direct reaction of 2-trimethylsilylmethyl-1,3-butadiene with isovaleraldehyde gives ( )-ipsenol (2-methyl-6-methylene-7-octen-4-ol) in rather low yield (30%) (eq 5). However, ipsenol is obtained in 62% overall yield by the reaction of 2-trimethylsilylmethyl-1,3-butadiene with isovaleryl chloride, followed by reduction with diisobutylaluminum hydride (eq 7). Similarly, ( )-ipsdienol (2-methyl-6-methylene-2,7-octadien-4-ol) is obtained by reduction of myrcenone, prepared by the reaction of 2-trimethylsilylmethyl-1,3-butadiene with 3,3-dimethylacryloyl chloride, in 75% overall yield (eq 8). 

It is the biosynthesis of the oxygenated monoterpenes that influence bark beetle behavior that provides us with an interesting and largely unresolved problem. The main compounds identified in this category are tra 5-verbenol (232) 373), c/s-verbenol (234), 2-methyl-6-methylene-7-octen-4-ol (ipsenol) (240), and 2-methyl-6-methylene-2,7-octadien-4-ol (ipsdienol) (266) (see Chart 1) 136). The reaction for the biosynthesis of all these compounds seems to be the allylic hydroxylation of a-pinene and mycrene, both of which occur in abundant amounts in host pine trees. 

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