64726-91-6

Usage

Synthesis Reference(s)

Tetrahedron Letters, 28, p. 4977, 1987 DOI: 10.1016/S0040-4039(00)96674-7

InChI:InChI=1/C14H24O2/c1-2-3-4-5-6-7-8-9-10-13-11-12-14(15)16-13/h9-10,13H,2-8,11-12H2,1H3/b10-9-/t13-/m0/s1

Synthetic route

(R)-(-)-5-(dec-1-ynyl)-tetrahydrofuran-2-one (72151-69-0) → japonilure (64726-91-6)

Conditions	Yield
With quinoline; hydrogen; Lindlar's catalyst In pentane at 0℃; for 4h;	94%
With quinoline; hydrogen; Lindlar's catalyst In pentane at 0℃; for 5h;	91%
With quinoline; hydrogen; palladium on activated charcoal In pentane at 0℃; for 5h;	91%

(R,Z)-methyl 4-hydroxytetradec-5-enoate → japonilure (64726-91-6)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane at 0 - 25℃; Inert atmosphere;	80%

(R)-((Z)-5-Dec-1-enyl)-tetrahydro-furan-2-ol → japonilure (64726-91-6)

Conditions	Yield
With pyridine; chromium(VI) oxide In dichloromethane for 2h; Ambient temperature;	30%

(R)-tetrahydro-5-oxo-2-furancarbaldehyde (70606-00-7) + nonyl(triphenyl)phosphonium bromide → japonilure (64726-91-6)

Conditions	Yield
With sodium methylsulfinylmethanide 1.) THF, 0 deg C, 1 h, 2a.) DMF, -40 deg C, 2 h, 2b.) RT, overnight; Yield given. Multistep reaction;

(S)-5-<(Z)-dec-1-enyl>dihydrofuran-2(3H)-one (64726-93-8) → japonilure (64726-91-6)

Conditions	Yield
With potassium hydroxide; triphenylphosphine; diethylazodicarboxylate 1.) MeOH, 60 deg C, 3 h, 2.) THF, 20 deg C, 13 h; Yield given. Multistep reaction;
With potassium hydroxide; triphenylphosphine; diethylazodicarboxylate 1.) MeOH, 60 deg C, 3h, 2.) benzene, RT, 13h; Yield given. Multistep reaction;

(5S)-1-pentadecen-6-yn-5-ol (397300-95-7) → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: ozone / CH2Cl2 / 0.42 h / -78 °C 1.2: PPh3 / CH2Cl2 / 2 h / -78 °C 1.3: 86 percent / N-iodosuccinimide; N-tetrabutylammonium iodide / CH2Cl2 / 0.25 h / 20 °C 2.1: 94 percent / H2; quinoine / Lindlar catalyst / pentane / 4 h / 0 °C View Scheme

(1R)-1-(3-butenyl)-2-undecynyl 2,2,4,4-tetramethyl-1,3-oxazolidine-3-carboxylate (397300-89-9) → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: MeSO3H / methanol / 8 h / Heating 1.2: 89 percent / Ba(OH)2*8H2O / methanol / 2 h / Heating 2.1: ozone / CH2Cl2 / 0.42 h / -78 °C 2.2: PPh3 / CH2Cl2 / 2 h / -78 °C 2.3: 86 percent / N-iodosuccinimide; N-tetrabutylammonium iodide / CH2Cl2 / 0.25 h / 20 °C 3.1: 94 percent / H2; quinoine / Lindlar catalyst / pentane / 4 h / 0 °C View Scheme

1-decyne (764-93-2) → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: lithium diisopropylamide / tetrahydrofuran / 0.25 h / -78 °C 1.2: 97 percent / tetrahydrofuran / 18 h / 20 - 25 °C 2.1: 89 percent / hydrogen peroxide; aq. sodium hydroxide / diethyl ether / 2 h / 25 °C 3.1: 69 percent / p-toluenesulfonic acid / CH2Cl2 / 2 h / 100 °C 4.1: 65 percent / hydrogen / palladium on calcium carbonate / pentane / 1 h / 0 °C / 760 Torr View Scheme
Multi-step reaction with 4 steps 1: 86.2 percent / n-butyllithium / tetrahydrofuran / 15 h / 1.) 3 deg C, 1 h, 2.) -50 deg C to r.t., 15 h 2: 70.1 percent / AlCl3 / CH2Cl2 / 1.) -65 deg C, 2.5 h, then -40 deg C, 1 h, 2.) -30 deg C, 2 h, then -30 deg C to 0 deg C, 15 h 3: Chirald, LiAlH4 / diethyl ether / 1.) -100 deg C, 2 h, 2.) -70 to -65 deg C, 2 h 4: 71.7 percent / H2, quinoline / 5percent Pd/CaCO3 / pentane / 1 h / 0 °C View Scheme
Multi-step reaction with 8 steps 1: 1.) ethylmagnesium bromide / 1.) THF, r.t., 1 h, 2.) THF, 5 deg C, 2 h 2: 88 percent / aq. NaIO4 / diethyl ether / 2 h / Ambient temperature 3: 94 percent / silver carbonate on celite (Fetizon's reagent) / benzene / 8.5 h / Heating 4: 89 percent / 90percent trifluoroacetic acid / 0.25 h / Ambient temperature 5: 74.6 percent / H2 / Pb poisoned 5percent Pd/CaCO3 (Lindlar catalyst) / ethanol 6: 770 mg / conc. H2SO4 / 0.25 h / Ambient temperature 7: 1.21 g / acetic anhydride, acetic acid / Heating 8: 1.) CuI, LiI, TMSCl, 2.) n-Bu3SnH / 1.) THF, -60 deg C, 10 min, 2.) up to 0 deg C, 30 min View Scheme
Multi-step reaction with 3 steps 1: Mg / tetrahydrofuran / 1 h / Heating 2: 68 percent / tetrahydrofuran / -65 deg C, 3 h -> room temperature, 20 h 3: 1.) 9-BBN, (+)-α-pinene, 2.) 2-hydroxyethylamine, 3.) NaH, 4.) H2 / 4.) Pd on CaCO3 View Scheme
Multi-step reaction with 3 steps 1: 85 percent / CuBr-(CH3)2S 2: 1.) Alpine-borane, 2.) NaOH/MeOH / 1.) room temp., 7 d, 2.) reflux, 15 min 3: H2 / Pd/CaCO3 poisoned with lead/quinoline View Scheme

(R)-[1,1-dimethylethyl-4-hydroxy-5-tetradecynoate] (325141-84-2) → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 69 percent / p-toluenesulfonic acid / CH2Cl2 / 2 h / 100 °C 2: 65 percent / hydrogen / palladium on calcium carbonate / pentane / 1 h / 0 °C / 760 Torr View Scheme

[2(1'R),4R,5R]-2-[2-[[(1,1-dimethylethyl)oxy]carbonyl]-1-(1-decynyl)propyl]-4,5-dicyclohexyl-1,3,2-dioxaborolane (325141-83-1) → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 89 percent / hydrogen peroxide; aq. sodium hydroxide / diethyl ether / 2 h / 25 °C 2: 69 percent / p-toluenesulfonic acid / CH2Cl2 / 2 h / 100 °C 3: 65 percent / hydrogen / palladium on calcium carbonate / pentane / 1 h / 0 °C / 760 Torr View Scheme

(2R,5R)-2-((Z)-Dec-1-enyl)-5-methoxy-tetrahydro-furan (173464-16-9) → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 76 percent / aq. HCl / tetrahydrofuran / 3 h / 55 - 60 °C 2: 30 percent / CrO3, pyridine / CH2Cl2 / 2 h / Ambient temperature View Scheme

Methyl 3,5,6-trideoxy-2-O-methanesulfonyl-α-L-threo-tetradec-5-(Z)-eno-furanoside (173464-14-7) → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 43 percent / NaBH4 / hexamethylphosphoric acid triamide / 24 h / 100 °C 2: 76 percent / aq. HCl / tetrahydrofuran / 3 h / 55 - 60 °C 3: 30 percent / CrO3, pyridine / CH2Cl2 / 2 h / Ambient temperature View Scheme

Methyl 3,5,6-trideoxy-L-threo-tetradec-5-(Z)-eno-furanoside → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 51 percent / Et3N / CH2Cl2 / 2 h / Ambient temperature 2: 43 percent / NaBH4 / hexamethylphosphoric acid triamide / 24 h / 100 °C 3: 76 percent / aq. HCl / tetrahydrofuran / 3 h / 55 - 60 °C 4: 30 percent / CrO3, pyridine / CH2Cl2 / 2 h / Ambient temperature View Scheme

1-decynyltrimethylsilane (54559-17-0) → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 70.1 percent / AlCl3 / CH2Cl2 / 1.) -65 deg C, 2.5 h, then -40 deg C, 1 h, 2.) -30 deg C, 2 h, then -30 deg C to 0 deg C, 15 h 2: Chirald, LiAlH4 / diethyl ether / 1.) -100 deg C, 2 h, 2.) -70 to -65 deg C, 2 h 3: 71.7 percent / H2, quinoline / 5percent Pd/CaCO3 / pentane / 1 h / 0 °C View Scheme

Methyl 4-Oxo-5-tetradecynoate (77889-02-2) → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: Chirald, LiAlH4 / diethyl ether / 1.) -100 deg C, 2 h, 2.) -70 to -65 deg C, 2 h 2: 71.7 percent / H2, quinoline / 5percent Pd/CaCO3 / pentane / 1 h / 0 °C View Scheme
Multi-step reaction with 2 steps 1: 1.) Alpine-borane, 2.) NaOH/MeOH / 1.) room temp., 7 d, 2.) reflux, 15 min 2: H2 / Pd/CaCO3 poisoned with lead/quinoline View Scheme
Multi-step reaction with 3 steps 1: 1.) lithium aluminum hydride, R-2,2'-dihydroxy-1,1'-binaphthyl, CH3OH / 1.) THF, room temperature, 2.) -100 deg C, 1 h and -78 deg C, 2 h 2: p-toluenesulfonic acid / benzene / 1 h / Heating 3: 90 percent / Lindlar cat. View Scheme

methyl (RS)-4-hydroxy-5-tetradecynoate (78685-94-6) → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaOH / methanol / 0.25 h / Heating 2: 0.5 h / 120 °C / 0.2 Torr 3: 71.7 percent / H2, quinoline / 5percent Pd/CaCO3 / pentane / 1 h / 0 °C View Scheme
Multi-step reaction with 3 steps 1: 83 percent / pyridine 2: 41 percent / 24 h / 25 °C / lipase OF, phosphate buffer, pH 7 3: 91 percent / H2, quinoline / Lindlar catalyst / pentane / 5 h / 0 °C View Scheme
Multi-step reaction with 3 steps 1: 41 percent / diisopropyl ether / 48 h / Ambient temperature; lipase PS 2: 83 percent / 23 h / 25 °C / lipase OF, phosphate buffer, pH 7 3: 91 percent / H2, quinoline / Lindlar catalyst / pentane / 5 h / 0 °C View Scheme
Multi-step reaction with 3 steps 1: 43 percent / diisopropyl ether / 30 h / Ambient temperature; lipase PS 2: 81 percent / 5percent KOH, methanol / 0.25 h / Heating 3: 91 percent / H2, quinoline / Lindlar catalyst / pentane / 5 h / 0 °C View Scheme
Multi-step reaction with 5 steps 1: 88 percent / pyridine 2: 43 percent / H2O / 16 h / 25 °C / palatase A, phosphate buffer, pH 7 3: 80 percent / diisopropyl ether / 10 h / Ambient temperature; lipase PS 4: 81 percent / 5percent KOH, methanol / 0.25 h / Heating 5: 91 percent / H2, quinoline / Lindlar catalyst / pentane / 5 h / 0 °C View Scheme

(4R,5S,6R)-5,6-dihydroxy-tetradecan-4-olide (111192-37-1) → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 90 percent / p-TsOH / CH2Cl2 / 0.5 h / Ambient temperature 2: 2) aq. sodium acetate / 1) acetic anhydride, reflux, 140 deg C, 1.5 h; 2) H2O, 4 h, 10 deg C View Scheme

(R)-4-hydroxy-5-tetradecynoic acid (88939-18-8) → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 0.5 h / 120 °C / 0.2 Torr 2: 71.7 percent / H2, quinoline / 5percent Pd/CaCO3 / pentane / 1 h / 0 °C View Scheme

(4R,5S,6R)-ethyl-4-benzyloxy-5,6-(isopropylidenedioxy)-2,7-tetradecadienate → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1) H2; 2) 90 percent aq. CF3COOH / 1) Pd-black / 1) 5 percent CH3COOH/MeOH, RT, 4-6 h; 2) H2O, RT, 3 h 2: 90 percent / p-TsOH / CH2Cl2 / 0.5 h / Ambient temperature 3: 2) aq. sodium acetate / 1) acetic anhydride, reflux, 140 deg C, 1.5 h; 2) H2O, 4 h, 10 deg C View Scheme

(2S,3R,4S,5Z)-2,3-dihydroxy-5-tetradecen-4-olide (147618-20-0) → japonilure (64726-91-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 770 mg / conc. H2SO4 / 0.25 h / Ambient temperature 2: 1.21 g / acetic anhydride, acetic acid / Heating 3: 1.) CuI, LiI, TMSCl, 2.) n-Bu3SnH / 1.) THF, -60 deg C, 10 min, 2.) up to 0 deg C, 30 min View Scheme

japonilure (64726-91-6) → (4R,5Z)-5-tetradecene-1,4-diol (105676-77-5)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 1h; Ambient temperature;

japonilure (64726-91-6) → (Z)-(R)-1-(tert-Butyl-dimethyl-silanyloxy)-tetradec-5-en-4-ol

Conditions	Yield
Multi-step reaction with 2 steps 1: LiAlH4 / tetrahydrofuran / 1 h / Ambient temperature 2: 4-dimethylaminopyridine, triethylamine / CH2Cl2 / 2 h View Scheme

japonilure (64726-91-6) → (4R,5Z)-1-t-butyldimethylsilyloxy-5-tetradecene-1-yl benzoate

Conditions	Yield
Multi-step reaction with 3 steps 1: LiAlH4 / tetrahydrofuran / 1 h / Ambient temperature 2: 4-dimethylaminopyridine, triethylamine / CH2Cl2 / 2 h 3: pyridine / 1 h / Ambient temperature View Scheme

japonilure (64726-91-6) → (4R,5Z)-5-tetradecene-1,4-diyl dibenzoate

Conditions	Yield
Multi-step reaction with 2 steps 1: LiAlH4 / tetrahydrofuran / 1 h / Ambient temperature 2: pyridine / 1 h / Ambient temperature View Scheme

Upstream product

• 70606-00-7 (R)-tetrahydro-5-oxo-2-furancarbaldehyde 
• 64726-93-8 (S)-5-<(Z)-dec-1-enyl>dihydrofuran-2(3H)-one 
• 77889-02-2 methyl 4-oxo-5-tetradecyonate 
• 128657-75-0 4-Hydroxy-tetradec-5-ynoic acid 
• 72151-69-0 (R)-(-)-5-(dec-1-ynyl)-tetrahydrofuran-2-one 
• 76695-87-9 (4S,5Z)-tetradeca-2,5-dien-4-olide 
• 397300-89-9 (1R)-1-(3-butenyl)-2-undecynyl 2,2,4,4-tetramethyl-1,3-oxazolidine-3-carboxylate 
• 173464-16-9 (2R,5R)-2-((Z)-Dec-1-enyl)-5-methoxy-tetrahydro-furan 
• 52713-82-3 dec-1-yn-1-ylmagnesium bromide 
• 81793-47-7 1-methoxycarbonyltridec-4-ol-5-ynyl monophthalate 
• 136992-12-6 Methyl (RS)-4-succinoyloxy-5-tetradecynoate 
• 137119-89-2 methyl (R)-4-succinoyloxy-5-tetradecynoate 
• 52813-63-5 (5R)-2,3,4,5-tetrahydro-5-hydroxymethyl-2-furanone 
• 111-83-1 1-bromo-octane 

Relevant academic research and scientific papers

Asymmetric Synthesis of γ-Lactones. A Facile Synthesis of the Sex Pheromone of the Japanese Beetle

The sex pheromone of the Japanese beetle, (R)-(-)-(Z)-5-tetradecen-4-olide, has been prepared in essentially 100percent optical purity by using the asymmetric reducing agent B-3-pinanyl-9-borabicyclononane to introduce chirality.

LIPASE-CATALYZED KINETIC RESOLUTION OF METHYL 4-HYDROXY-5-TETRADECYNOATE AND ITS APPLICATION TO A FACILE SYNTHESIS OF JAPANESE BEETLE PHEROMONE

A kinetic resolution of methyl 4-hydroxy-5-tetradecynoate is accomplished by a lipase-catalyzed enantioselective acylation in organic solvent.Acylation of methyl 4-hydroxy-5-tetradecynoate with succinic anhydride in a organic solvent yields methyl (R)-4-succinoyloxy-5-tetradecynoate with over 90percent e.e..Furthermore, this optically active diester was converted to (R)-5-(1-decynyl)oxacyclopentane-2-one by lipase-catalyzed enantioselective lactonization which enhanced its e.e. over 99percent.The Japanese beetle pheromone (R,Z)-(-)-5-(1-decenyl)oxacyclopentan-2-one is synthesized in one step from this optically active lactone.

Convergent and enantioselective syntheses of both enantiomers of (5Z)-tetradecen-4-olide, scarab beetle pheromones

Japonilure and its enantiomer, that is, (R)-(-)- and (S)-(+)-(5Z)-tetradecen-4-olide, have been synthesised in satisfactory overall yields using a highly convergent procedure. In situ prepared 1-decynylethylzinc was enantioselectively coupled to isopropyl 4-oxobutanoate in the presence of (S)- or (R)-BINOL. The alkoxy-ester intermediates obtained were cyclised to the corresponding substituted γ-lactones, carrying a triple bond in the side chain. Lindlar-hydrogenation of the latter yielded the target compounds.

Catalytic asymmetric synthesis of Japonilure and its enantiomer

A mild, concise, and highly enantioselective (93% ee) synthesis of Japonilure and its enantiomer, Anomala osakana pheromone, is described. The key steps involve the asymmetric addition of methyl propionate to undec-2-ynal with a Zn-ProPhenol catalyst and the selective and partial reduction of the diynol ester to the cis-enol ester with Brown's P2-Ni catalyst, providing the first synthesis of the enol ester via semi-hydrogenating diynol ester.

Synthesis of (R)-japonilure and (4R,9Z)-9-octadecen-4-olide, pheromones of the Japanese beetle and currant stem girdler

Asymmetric total synthesis of the sex pheromones of Japanese beetle and currant stem girdler, (R)-japonilure (1) and (4R,9Z)-9-octadecen-4-olide (2), has been achieved. Copyright Taylor & Francis Group, LLC.

The preparation of nonracemic secondary α-(carbamoyloxy)alkylzinc and copper reagents. A versatile approach to enantioenriched alcohols

(matrix presented) Chiral α-(carbamoyloxy)alkyllithium reagents, prepared using Hoppe's sBuLi/(-)-sparteine methodology, were transmetalated with ZnCl2. Further transmetalation with CuCN with overall retention of configuration gave chiral species that reacted with various electrophiles to give enantiomerically pure alcohols after deprotection. A short, highly efficient synthesis of an industrially relevant pheromone, japonilure, illustrates the value of the methodology.

Asymmetric synthesis of the Japanese beetle pheromone via boronic esters

The pheromone of the Japanese beetle, [R-(Z)]-5-(1-decenyl)dihydro-2(3H)-furanone (7), has been synthesized efficiently in high enantiomeric purity via 1,2-dicyclohexyl-1,2-ethanediol boronic esters. The synthetic route involves reaction of an α-chloro boronic ester with an alkynyllithium, and provides the first successful example of this substitution process in an asymmetric synthesis.

The synthesis of three important lactones via an enzymatic resolution strategy that improves ee's and yields

Three important lactones have been synthesized in high enantiomeric purity by a complimentary, two-enantioselective-step strategy. In this approach, an enzymatic kinetic resolution is performed on a starting material that has been enriched in the faster-reacting enantiomer by an earlier enantioselective step. The results show that percent conversions, yields and ee's can be dramatically increased by this complimentary approach, and they illustrate how modestly enantioselective techniques can be combined with kinetic resolution procedures to yield optically pure compounds. The utility of many modestly enantioselective (and hence sometimes disregarded) techniques can be enhanced thereby.

Chiral Synthesis of (R)-(-)-(5Z)-4-Hydroxy-5-tetradecenoic Acid-4-lactone

(R)-(-)-(5Z)-4-Hydroxy-5-tetradecenoic acid-4-lactone has been synthesized from D-glucose as the precursor.Regio and stereoselective transformations of hydroxyl groups as well as protection-deprotection protocols provide a novel route to this compound. - Keywords: Chiral Pool, Lactone, Isopropylidene, Olefination, Pheromone

Method for manufacturing 4-substituted-Y-lactone and novel substance

An alkynyl group having a triple bond at the carbon atom at the 1-position is introduced to a carbon atom at the 1-position of 2,3-O-isopropylidene-D-ribofuranose. The diol part is then cleaved to obtain a lactol compound. This lactol compound is oxidized to obtain a lactone compound. The ketal part of the lactone compound is hydrolyzed and the compound is further subjected to a reduction reaction. The hydroxyl groups at the 2- and 3-positions are then eliminated, and the double bond between the 2- and 3-positions of the resultant compound is reduced to obtain a 4-substituted-γ-lactone.