20073-13-6

The synthesis of (±)-methyl epijasmonate (1) was carried out by Michael addition of lithium diallylcuprate to enone 3 and diastereoselective enolate protonation with the chelating proton source 2-(methyliminomethyl)phenol (4; 85% ds), followed by ozonolysis, oxidation, esterification, and Lindlar hydrogenation. During the ozonisation, epimerization to the thermodynamically more stable trans-isomer takes place to some extent, so that 1 was isolated with a cis:trans ratio of 72:28. The analogous transformation of enone 7 with lithium diallylcuprate and 2-(methyliminomethyl)phenol (4) furnished ketone 8 with 94% ds; this was then transformed into (±)-methyl dihydroepijasmonate (2) with a cis:trans ratio of 91:9. The olfactory properties of this product are superior to those available from commercial sources.

A novel and efficient synthesis of both (±)-methyl epijasmonate and (±)-cis-3-(2-oxopropyl)-2-(pent-2Z-enyl)-cyclopentan-1-one is described. The key step to establish the cis-stereochemistry on the 5-membered ring is an ionic Diels-Alder reaction, which is high yielding and highly regioselective. Subsequent key steps include oxidative cleavage of the six-membered ring, Wittig coupling and for the synthesis of epijasmonate, the haloform reaction.

1,2-Complexed hexacarbonyl(hepta-1,4-diyne)dicobalt, obtained from hexacarbonyl(propargyl acetate)dicobalt with tri-1-butynylaluminium, has been converted, by selective Khand annulation of the complexed triple bond with vinyl benzoate, to 2-pent-2-yn-1-ylcyclopent-2-en-1-one. By use of standard procedures this alkynyl cyclopentenone has been transformed into methyl jasmonate, allowing replacement of the final hydrogenation step by tritiation to produce the labelled analogue. Two alternative approaches to the intermediate pentynylcyclopentenone were examined and shown to be unsuccessful.

The influence of a protected alcohol group adjacent to the ene or enophile component on diastereoselectivity in both thermal and Lewis acid-catalyzed 5-(3,4) ene reactions of a series of 1,6-dienes 1-7 has been studied. The results indicate that its effect can be considerable, and in one example, with a gem-dimethyl group on the connecting chain and a large silyl protecting group on the hydroxyl, the diastereocontrol was almost perfect, with three stereogenic centers and one double bond geometry set up in one step, e.g., 4 → 10. This new finding was exploited in a synthesis of epijasmonoid natural products, (±)-methyl cucurbate (19) and (±)-methyl epijasmonate (18) starting from aldehyde 24, where the key step was a highly diastereocontrolled 5-(3,4) ene cyclization 23 → 22. 1 Indian Institute of Technology 2 BARC.

The Cbl-catalyzed electroreduction of 3-(2'-bromo-1'-ethoxyethoxy)cyclopenten (1a) in presence of 1-cyanovinyl-acetate (8) gave, in a sequential radical reaction (5-exo-trig-cyclization of 1a following by addition to 8), 1-cyano-2-(2'-ethoxy-hexahydro-2'H-cyclopenta[b]furan-4'-yl)ethyl acetate (10a). This intermediate was transformed to methyl jasmonate (7; four steps) and epituberolide (9; three steps) in 20 and 31% yield, respectively, from cyclopent-2-en-1-ol.

The total synthesis of epijasmonoids, (±)-methyl cucurbate and (±)-methyl epijasmonate is described starting from aldehyde 14, where the key step is a highly stereocontrolled 5-(3,4) ene cyclization 17→18.

The synthesis of 12-Oxophytodienoic acid, and the compounds of its enzymatic degradation sequence, OPC-8:0, -6:0, -4:0 and -2:0, important plant metabolites derived from linolenic acid, is reported.The syntheses use the known cyclopent-3-ene-1,2-diacetic acid as an early intermediate, and this is derived from the Cope rearrangement of 5-vinyltrinorborn-2-ene via bicyclonona-3,7-diene.Iodolactonisation and tributyltin hydride reduction provides the key intermediate (3-oxo-2-oxabicyclooctan-6-yl)acetic acid for the OPC series, whilstphenylselenolactonisation and elimination provides the necessary unsaturated lactone (7-oxo-8-oxabicyclooct-2-en-4-yl)acetic acid for 12-oxoPDA.Members of the OPC-series were made by chain extending the saturated oxabicyclooctane acid: that for the OPC-4:0 involved double Arndt-Eistert reaction, whilst the intermediates for OPC-6:0 and -8:0 were made by Kolbe anodic crossed coupling.The lactones were than converted via their lactols, Wittig reaction, esterfication and oxidation, into the compounds of the OPC ester series, including OPC-2:0 (methyl epi-jasmonate).The unsaturate lactone 8-(7-oxo-8-oxabicyclooct-2-en-4-yl)octanoic acid required for 12-oxoPDA synthesis could also be prepared by anodic synthesis either from (7-oxo-8-oxa-bicyclooct-2-en-4-yl)acetic acid, or from its 2-phenylseleno-2,3-dihydro precursor as elimination occurred concomitantly during the reaction.Since yields were low, the unsaturated acid lactone was converted into its lactol and the (Z)-pent-2-enyl side-chain was inserted first.After TBDMS blocking of the cyclopentene hydroxy group, the side-chain was elaborated to give5-(pent-2-enyl)cyclopent-2-enylacetaldehyde and chain extension carried out by a Grignard-demesylation procedure.Sequential desilylation and depyranylation, followed by oxidation of the diol, gave 12-oxoPDA, isolated as its methyl ester.

Methyl epijasmonate (1) was stereoselectively synthesized from 3-hydroxymethylcyclopentanone (7).The intramolecular alkylation of bromoketone (8) or (9) was the key step to exclusively afford thermodynamically more stable oxahydrindanone (10) or (11).Synthesis was achieved in a 6percent overall yield in 12 steps from (7).

The total synthesis of epijasmonoids, (+/-)-methyl epijasmonate and (+/-)-cucurbic acid, starting from norbornene was described, where a key intermediate, 5β-hydroxy-2β-methoxycarbonylmethylcyclopentane 1β-acetic acid γ-lactone was efficiently prepared via a highly regioselective Baeyer-Villiger oxidation of 7-syn-substituted norbornanone based on remote substituent control.

A new and stereoselective approach to cyclopentanoid synthesis is described.The key step is the thermal intramolecular ene reaction of 4-carboxymethyl-7-benzyloxy-5-heptanal, prepared by the Claisen rearrangement, to afford 2,3-disubstituted cyclopentanol derivative in a highly stereoselective fashion.

Palladium-catalyzed alkylation of cyclopent-2-ene-1,2-diol derivatives like 2 is a useful method for enantiodivergent functionalization, resulting both enantiomeric series of chiral building blocks.The chiral building blocks 3 and 13 can be transformed to methyl-jasmonate (1) and its unnatural enantiomer ent-1, recent statement that 1 has no odour at all and that "methyl-jasmonate's" fragrance is actually due to its cis-isomer ent-11 has been confirmed also for the enantiomeric series.

The β-oxidation compounds of the cis series OPC-8:0, 6:0, 4:0, and 2:0 (epi-jasmonic acid), formed metabolically from dihydro-12-oxophytodienoic acid, are synthesised as their methyl esters; plant regulating functions are associated with the acids of this series.

An efficient synthetic method of methyl (+/-)-jasmonate is described. 2-Pentynyl-2-cyclopentenone, the key intermediate in this route, was synthesized by applying the palladium-catalyzed enone formation from allyl β-keto carboxylate as a key reaction.

A novel synthesis of (+/-)-methyl epijasomonate (2) and the first synthesis of (+/-)-methyl cucurbate (4) were achieved startig from 2-allocyclohexane-1,3-dione (8).The synthetic epimer 2 had a stronger jasmin flavor than the trans-isomer 1 with 95percent purity.

An efficient and practical method for the stereospecific synthesis of olefins from vicinal diols via the corresponding 2-methoxy-1,3-dioxolanes is reported.

A Pd-catalyzed allylation of 3-substituted 1-cyclopentenolates with readily obtainable and storable γ-monosubstituted (Z)-allylic acetates in a 1:1 ratio in the presence of 2 mol percent of Pd(PPh3)4 featuring high yields and high stereo- and regioselectivities has been developed and applied to the synthesis of methyl (Z)-jasmonate.

Exceptional conjugate addition of methyl lithiotrimethylsilylacetate to cyclopentenone has been found and can be applied to a convenient synthesis of methyl jasmonate by sequential vicinal double alkylation via succesful stannyl enolate trapping.

Aprotic 1,4-addition of a lithiated α-(methyldiphenylsilyl)acetate to cyclopentenone and in situ enolate alkylation provides a direct synthesis of (+/-)-methyl jasmonate (Scheme 3).

A simple and an efficient synthesis of methyl jasmonate (1) and methyl dihydrojasmonate (5) is described.Starting from alkyl acetoacetate or acetonedicarboxylate, 1 and 5 were obtained in only a few steps via intramolecular Michael addition.

An efficient synthesis of methyl dl-cis-jasmonate is described, starting from the previously described 2-(methoxycarbonyl)-3-cyclopentanone (3), itself easily prepared from succinyl chloride and methyl potassium malonate.Alkylation of 3 with 1-bromo-2-pentyne followed by selective removal of the 2-carbomethoxy group gave dehydrojasmonic acid.On esterification and reduction (H2/Pd/C/pyridine) of the triple bond to the cis olefin, dehydrojasmonic acid afforded methyl dl-cis-jasmonate in 40percent overall yield from succinyl chloride.

A short synthesis of Methyl dl-Jasmonate from bicyclo nona-3,8-diene is described.

1,4-Dioxygenated compounds 4 are constructed by the addition of a Grignard reagent to γ-(trimethylsiloxy)nitriles 1,2, and 3 and subsequent hydrolysis.Oxidation of 4 with pyridinium chlorochromate or Jones reagent yields compounds 5 which are used to produce cyclopentenones 6.Methyl jasmonate and methyl dihydrojasmonate are made by the conjugate addition of silylated ketene acetal 9 to 6a and 6b, respectively, and subsequent protodesilylation. γ-Jasmolactone is also derived from 4a by oxidation with pyridinium dichromate in DMF followed by reduction with NaBH4 in ethanol.

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