Methyl dihydrojasmonate, synthesis

A Me-DuPhos-ruthenium catalyst has found application in the industrial synthesis of the fragrance (+)-d.v-methyl dihydrojasmonate 60 (Scheme 13.18).64 The catalyst gave excellent m-selectivity, and although the enantiomeric excess was modest (76%), it was acceptable for use of the product in perfumery. 

Scheme 7.14 Plaquevent s asymmetric synthesis of methyl dihydrojasmonate [18].

Corey s methodology was also successfully applied by Plaquevent and coworkers to the synthesis of chiral methyl dihydrojasmonate (31), which has a jasmine-like odor. The reaction of a-pentyl cyclopentanone (29) and dimethyl malonate under PTC conditions (11 mol% of 28, K2C03 (0.16 equiv.) at —20 °C) gave the key intermediate 30 for the synthesis of methyl dihydrojasmonate 31 in 91% yield and with 90% ee (Scheme 9.11) [11]. 

By using lV-anthracen-9-ylmethyl-O-benzyldihydrocinchoninium bromide as catalyst, the conjugate addition of nitromethane to l-phenyl-3-p-chlorophenyl-2-propen-l-one yields a mixture of (R/S) adducts in a 85 15 ratio. " After recrystallization, the product is suitable for conversion into (/ )-baclofen hydrochloride, which is an important drug for treatment of spasms caused by spinal cord injury. Also worthy of mention is the application of a similar catalyst for the synthesis of methyl dihydrojasmonate under conditions of solid-liquid... 

Scheme 5.9 Enantioselective synthesis (+ )-methyl dihydrojasmonate using enantio-selective phase-transfer catalysis.

An interesting synthesis of almost pure methyl cis-dihydrojasmonate is provided by Ebert and Krause. [93] The key step is a diastereoselective protonation of an enolate, generated from 2-pentylcyclopent-2-enone and hthium diallylcu-prate. Ozonolysis, oxidation and esterification give methyl dihydrojasmonate, which is 91 % ds configured. 

The industrial synthesis of Hedione starts from cyclopentanone this is reacted with pentanal in an aldol condensation. A Michael reaction with dimethyl malonate, followed by hydrolysis and decarboxylation, generates at the thermodynamic equilibrium a cis/trans-isomeric mixture of methyl dihydrojasmonates in a ratio of 9 1.4. [101]... 

Closely related to methyl dihydrojasmonate, both in terms of structure and olfactory effect, is Magnolion, which carries an acetyl residue instead of an ester function. Its scent is reminiscent of magnolia its synthesis is analogous to that of ifedione , with the difference that methyl acetoacetate is used in place of dimethyl malonate. [108]... 

Moreover, reaction (36) has been applied to the synthesis of a vinylcyclopentanonecarboxylate which has been converted by Tsuyi to methyl dihydrojasmonate XLVII [90] and 18-hydroxyestrone XLVIII[91](39). 

Scheme 16.14 Enantioselective synthesis of both enantiomers of methyl dihydrojasmonate 46.

Another synthesis of methyl dihydrojasmonate (compare Section 1.1), an important fragrance compound, was developed by Tsuji et ai, again using the acetoacetate telomer [20]. 

The addition of diester 178 to cyclic enone was apphed by Plaquevent et al. in the synthesis of methyl dihydrojasmonate, a natural ketone with olfactory properties isolated from Jasminum grandiforum L (Scheme 11.43). Despite the relatively moderate 80% ee and large excess of dimethyl malonate required (30 equiv), the rapidity of the synthesis (two steps to the natural product) and the simple reaction conditions remained attractive for scaleup. 

The cycloaddition between 25 and 26 is a crucial step for the synthesis of methyl cA-dihydrojasmonate, a key constituent of the commercial jasmine fragrance Hedione 27. 

Ethyl ethylthiomethyl sulphoxide anion 325 has been found to give better yield of 1,4-adducts compared with its methyl analogue . This anion has been used by Schlessinger and coworkers as a key reagent in the synthesis of 1,4-dicarbonyl precursors of naturally occurring cyclopentenones, e.g. dihydrojasmone 379 (equation 219). Michael addition of the anion of optically active (-l-)-(S)-p-tolyl p-tolylthiomethyl sulphoxide 380 to the properly substituted cyclopentenone constitutes an important step in the asymmetric synthesis of optically active cyclopentenone 381, which is a precursor of 11-deoxy-ent-prostanoids (equation 220). The reaction proceeds with a high and y-asymmetric induction (92%), but with a poor a-stereoselection (52 48). 

The method has been extended to a synthesis of the 1,4-diketone (2) from the ethylene ketal of methyl levulinate (1). The diketone was cyclized by base to dihydrojasmone (3). The overall yield of (3) from (1) was 49.5%. The process is shown in scheme II. ... 

A synthesis of dihydrojasmone (493) and cis-jasmone (486) has been reported which centres on the formation of 1,4-diketones.Compound (492) was derived from acyloin condensation of methyl levulinate ethylene acetal in the presence of tri-methylchlorosilane the subsequent sequence is outlined in Scheme 27. By means of... 

The terminal methyl group of unsymmetrical ketone dimethylhydrazone is reactive, and is easily metalated with organolithium compounds. Subsequently, the substituted products are produced by reaction with halides as shown in eq. (3.25). These reactions are applied for the synthesis of dihydrojasmone [73]. 

---