489-39-4

Usage

Uses

Used in Pharmaceutical Industry:
(+)-Aromadendrene is used as a chiral starting material for the synthesis of other sesquiterpenes such as (-)-apoaromadendrone, (-)-kessane, (+)-spathulenol, (+)-ledene, and (-)-isoledene. These synthesized compounds have potential applications in the development of new drugs and pharmaceuticals due to their diverse chemical structures and biological activities.
Used in Fragrance Industry:
(+)-Aromadendrene, being a major constituent of the essential oil of Eucalypfus globulus, is used as a raw material in the fragrance industry. Its unique scent and properties make it a valuable component in the creation of various perfumes, colognes, and other scented products.
Used in Flavor Industry:
In addition to its use in the fragrance industry, (+)-Aromadendrene can also be utilized in the flavor industry. Its distinct taste and aroma can be incorporated into the development of various food and beverage products, enhancing their overall flavor profile.
Used in Cosmetic Industry:
The potential applications of (+)-Aromadendrene extend to the cosmetic industry as well. Its unique properties can be harnessed to create innovative skincare and beauty products, offering consumers new and improved experiences.

Synthetic route

Methanesulfonic acid (1aR,4S,4aR,7R,7aR,7bS)-1,1,7-trimethyl-decahydro-cyclopropa[e]azulen-4-ylmethyl ester (175985-51-0) → (+)-aromadendrene (489-39-4)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 100℃; for 18h;	89%

(1aR,4aR,7R,7aS,7bS)-1,1,7-Trimethyldecahydro-4H-cyclopropa[e]azulen-4-one (99147-41-8) + Methyltriphenylphosphonium bromide (1779-49-3) → (+)-aromadendrene (489-39-4)

Conditions	Yield
Stage #1: Methyltriphenylphosphonium bromide With n-butyllithium In tetrahydrofuran at -78 - 0℃; for 0.166667h; Inert atmosphere; Stage #2: (1aR,4aR,7R,7aS,7bS)-1,1,7-Trimethyldecahydro-4H-cyclopropa[e]azulen-4-one In tetrahydrofuran at -78 - 20℃; for 24h; Inert atmosphere;	60%

(-)-globulol (489-41-8) → (+)-aromadendrene (489-39-4)

Conditions	Yield
With pyridine; trichlorophosphate

(-)-O-<3,5-dinitro-benzoyl>-globulol → (+)-aromadendrene (489-39-4)

Conditions	Yield
at 140℃; unter vermindertem Druck;

methyl (+)-(1S,7R)-8,8-dimethyl-3-oxobicyclo<5.1.0>octane-4-carboxylate (176199-11-4) → (+)-aromadendrene (489-39-4)

Conditions

Yield

Multi-step reaction with 15 steps 1: 100 percent / LiAlH4 / diethyl ether / 1 h / Ambient temperature 2: imidazole / dimethylformamide / 12 h / Ambient temperature 3: 90 percent / Ley's tetrapropylammonium perruthenate, 4-methylmorpholine N-oxide, molecular sieves / CH2Cl2 / 0.25 h / Ambient temperature 4: 1.) LDA, HMPA / 1.) THF, -78 deg C, 30 min, 2.) THF, from -78 deg C to RT, 4 h 5: 96 percent / PdCl2, CuCl, air / dimethylformamide; H2O / 4.5 h / Ambient temperature 6: 84 percent / NaHMDS, HMPA / tetrahydrofuran / 0.67 h / -78 - -50 °C / a) -78 deg C. 15 min, b) 0 deg C, 15 min, c) 50 deg C, 10 min 7: 1.) lithium hexamethyldisilazane, HMPA / 1.) THF, -78 deg C, 1 h, 2.) THF, from -78 deg C to RT, 2 h 8: 86 percent / lithium tetramethyldisilazane, HMPA / tetrahydrofuran / 2 h / -78 - 20 °C 9: 93 percent / H2 / 5percent Pd/C / methanol / 2 h / 760 Torr / Ambient temperature 10: NaBH4 / methanol / 2 h / Ambient temperature 11: pyridine, DMAP / CH2Cl2 / 6 h / Ambient temperature 12: 68 percent / n-Bu3SnH, AIBN / toluene / 3 h / Heating 13: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 14: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 15: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

(1S,7R)-4-Hydroxymethyl-8,8-dimethyl-bicyclo[5.1.0]octan-3-ol → (+)-aromadendrene (489-39-4)

Conditions

Yield

Multi-step reaction with 14 steps 1: imidazole / dimethylformamide / 12 h / Ambient temperature 2: 90 percent / Ley's tetrapropylammonium perruthenate, 4-methylmorpholine N-oxide, molecular sieves / CH2Cl2 / 0.25 h / Ambient temperature 3: 1.) LDA, HMPA / 1.) THF, -78 deg C, 30 min, 2.) THF, from -78 deg C to RT, 4 h 4: 96 percent / PdCl2, CuCl, air / dimethylformamide; H2O / 4.5 h / Ambient temperature 5: 84 percent / NaHMDS, HMPA / tetrahydrofuran / 0.67 h / -78 - -50 °C / a) -78 deg C. 15 min, b) 0 deg C, 15 min, c) 50 deg C, 10 min 6: 1.) lithium hexamethyldisilazane, HMPA / 1.) THF, -78 deg C, 1 h, 2.) THF, from -78 deg C to RT, 2 h 7: 86 percent / lithium tetramethyldisilazane, HMPA / tetrahydrofuran / 2 h / -78 - 20 °C 8: 93 percent / H2 / 5percent Pd/C / methanol / 2 h / 760 Torr / Ambient temperature 9: NaBH4 / methanol / 2 h / Ambient temperature 10: pyridine, DMAP / CH2Cl2 / 6 h / Ambient temperature 11: 68 percent / n-Bu3SnH, AIBN / toluene / 3 h / Heating 12: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 13: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 14: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

(1aR,4S,4aR,7S,7aR,7bS)-4-(tert-Butyl-dimethyl-silanyloxymethyl)-1,1,7-trimethyl-decahydro-cyclopropa[e]azulen-6-ol → (+)-aromadendrene (489-39-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: pyridine, DMAP / CH2Cl2 / 6 h / Ambient temperature 2: 68 percent / n-Bu3SnH, AIBN / toluene / 3 h / Heating 3: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 4: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 5: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

(+)-(1S,2S,4R,7R)-4-tert-butyldimethylsiloxymethyl-8,8-dimethyl-2-(2-propenyl)bicyclo<5.1.0>octan-3-one (175985-40-7) → (+)-aromadendrene (489-39-4)

Conditions

Yield

Multi-step reaction with 11 steps 1: 96 percent / PdCl2, CuCl, air / dimethylformamide; H2O / 4.5 h / Ambient temperature 2: 84 percent / NaHMDS, HMPA / tetrahydrofuran / 0.67 h / -78 - -50 °C / a) -78 deg C. 15 min, b) 0 deg C, 15 min, c) 50 deg C, 10 min 3: 1.) lithium hexamethyldisilazane, HMPA / 1.) THF, -78 deg C, 1 h, 2.) THF, from -78 deg C to RT, 2 h 4: 86 percent / lithium tetramethyldisilazane, HMPA / tetrahydrofuran / 2 h / -78 - 20 °C 5: 93 percent / H2 / 5percent Pd/C / methanol / 2 h / 760 Torr / Ambient temperature 6: NaBH4 / methanol / 2 h / Ambient temperature 7: pyridine, DMAP / CH2Cl2 / 6 h / Ambient temperature 8: 68 percent / n-Bu3SnH, AIBN / toluene / 3 h / Heating 9: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 10: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 11: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

(+)-(1R,2S,4R,7S,8R,11S)-7-tert-butyldimethylsiloxymethyl-3,3,11-trimethyltricyclo<6.3.0.02,4>undecan-10-one (175985-45-2) → (+)-aromadendrene (489-39-4)

Conditions	Yield
Multi-step reaction with 6 steps 1: NaBH4 / methanol / 2 h / Ambient temperature 2: pyridine, DMAP / CH2Cl2 / 6 h / Ambient temperature 3: 68 percent / n-Bu3SnH, AIBN / toluene / 3 h / Heating 4: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 5: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 6: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

(+)-(1R,2R,4R,7S)-7-tert-butyldimethylsiloxymethyl-3,3-dimethyltricyclo<6.3.0.02,4>undec-8-en-10-one (175985-44-1) → (+)-aromadendrene (489-39-4)

Conditions

Yield

Multi-step reaction with 9 steps 1: 1.) lithium hexamethyldisilazane, HMPA / 1.) THF, -78 deg C, 1 h, 2.) THF, from -78 deg C to RT, 2 h 2: 86 percent / lithium tetramethyldisilazane, HMPA / tetrahydrofuran / 2 h / -78 - 20 °C 3: 93 percent / H2 / 5percent Pd/C / methanol / 2 h / 760 Torr / Ambient temperature 4: NaBH4 / methanol / 2 h / Ambient temperature 5: pyridine, DMAP / CH2Cl2 / 6 h / Ambient temperature 6: 68 percent / n-Bu3SnH, AIBN / toluene / 3 h / Heating 7: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 8: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 9: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

(+)-(1S,2S,4R,7R)-4-tert-butyldimethylsiloxymethyl-8,8-dimethyl-2-(2-oxopropyl)bicyclo<5.1.0>octan-3-one (175985-43-0) → (+)-aromadendrene (489-39-4)

Conditions

Yield

Multi-step reaction with 10 steps 1: 84 percent / NaHMDS, HMPA / tetrahydrofuran / 0.67 h / -78 - -50 °C / a) -78 deg C. 15 min, b) 0 deg C, 15 min, c) 50 deg C, 10 min 2: 1.) lithium hexamethyldisilazane, HMPA / 1.) THF, -78 deg C, 1 h, 2.) THF, from -78 deg C to RT, 2 h 3: 86 percent / lithium tetramethyldisilazane, HMPA / tetrahydrofuran / 2 h / -78 - 20 °C 4: 93 percent / H2 / 5percent Pd/C / methanol / 2 h / 760 Torr / Ambient temperature 5: NaBH4 / methanol / 2 h / Ambient temperature 6: pyridine, DMAP / CH2Cl2 / 6 h / Ambient temperature 7: 68 percent / n-Bu3SnH, AIBN / toluene / 3 h / Heating 8: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 9: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 10: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

(1R,2S,4R,7S,8R,11S)-7-tert-butyldimethylsiloxymethyl-3,3,11-trimethyltricyclo<6.3.0.02,4>undec-10-yl phenyl thionocarbonate → (+)-aromadendrene (489-39-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 68 percent / n-Bu3SnH, AIBN / toluene / 3 h / Heating 2: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 3: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 4: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

((1aR,4S,4aR,7R,7aR,7bS)-1,1,7-trimethyldecahydro-1H-cyclopropa[e]azulen-4-yl)methanol (175985-50-9) → (+)-aromadendrene (489-39-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 2: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

(+)-(1S,4RS,7R)-8,8-dimethyl-4-hydroxymethylbicyclo[5.1.0]octan-3-one → (+)-aromadendrene (489-39-4)

Conditions

Yield

Multi-step reaction with 15 steps 1: LiAlH4 / diethyl ether / 0.25 h / 0 °C 2: imidazole / dimethylformamide / 12 h / Ambient temperature 3: 90 percent / Ley's tetrapropylammonium perruthenate, 4-methylmorpholine N-oxide, molecular sieves / CH2Cl2 / 0.25 h / Ambient temperature 4: 1.) LDA, HMPA / 1.) THF, -78 deg C, 30 min, 2.) THF, from -78 deg C to RT, 4 h 5: 96 percent / PdCl2, CuCl, air / dimethylformamide; H2O / 4.5 h / Ambient temperature 6: 84 percent / NaHMDS, HMPA / tetrahydrofuran / 0.67 h / -78 - -50 °C / a) -78 deg C. 15 min, b) 0 deg C, 15 min, c) 50 deg C, 10 min 7: 1.) lithium hexamethyldisilazane, HMPA / 1.) THF, -78 deg C, 1 h, 2.) THF, from -78 deg C to RT, 2 h 8: 86 percent / lithium tetramethyldisilazane, HMPA / tetrahydrofuran / 2 h / -78 - 20 °C 9: 93 percent / H2 / 5percent Pd/C / methanol / 2 h / 760 Torr / Ambient temperature 10: NaBH4 / methanol / 2 h / Ambient temperature 11: pyridine, DMAP / CH2Cl2 / 6 h / Ambient temperature 12: 68 percent / n-Bu3SnH, AIBN / toluene / 3 h / Heating 13: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 14: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 15: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

(1S,4R,7R)-4-(tert-Butyl-dimethyl-silanyloxymethyl)-8,8-dimethyl-bicyclo[5.1.0]octan-3-ol → (+)-aromadendrene (489-39-4)

Conditions

Yield

Multi-step reaction with 13 steps 1: 90 percent / Ley's tetrapropylammonium perruthenate, 4-methylmorpholine N-oxide, molecular sieves / CH2Cl2 / 0.25 h / Ambient temperature 2: 1.) LDA, HMPA / 1.) THF, -78 deg C, 30 min, 2.) THF, from -78 deg C to RT, 4 h 3: 96 percent / PdCl2, CuCl, air / dimethylformamide; H2O / 4.5 h / Ambient temperature 4: 84 percent / NaHMDS, HMPA / tetrahydrofuran / 0.67 h / -78 - -50 °C / a) -78 deg C. 15 min, b) 0 deg C, 15 min, c) 50 deg C, 10 min 5: 1.) lithium hexamethyldisilazane, HMPA / 1.) THF, -78 deg C, 1 h, 2.) THF, from -78 deg C to RT, 2 h 6: 86 percent / lithium tetramethyldisilazane, HMPA / tetrahydrofuran / 2 h / -78 - 20 °C 7: 93 percent / H2 / 5percent Pd/C / methanol / 2 h / 760 Torr / Ambient temperature 8: NaBH4 / methanol / 2 h / Ambient temperature 9: pyridine, DMAP / CH2Cl2 / 6 h / Ambient temperature 10: 68 percent / n-Bu3SnH, AIBN / toluene / 3 h / Heating 11: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 12: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 13: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

tert-Butyl-dimethyl-((1aR,4S,4aR,7R,7aR,7bS)-1,1,7-trimethyl-decahydro-cyclopropa[e]azulen-4-ylmethoxy)-silane (175985-49-6) → (+)-aromadendrene (489-39-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 2: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 3: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

(1S,4R,7R)-4-(tert-Butyl-dimethyl-silanyloxymethyl)-8,8-dimethyl-bicyclo[5.1.0]octan-3-one (175985-39-4) → (+)-aromadendrene (489-39-4)

Conditions

Yield

Multi-step reaction with 12 steps 1: 1.) LDA, HMPA / 1.) THF, -78 deg C, 30 min, 2.) THF, from -78 deg C to RT, 4 h 2: 96 percent / PdCl2, CuCl, air / dimethylformamide; H2O / 4.5 h / Ambient temperature 3: 84 percent / NaHMDS, HMPA / tetrahydrofuran / 0.67 h / -78 - -50 °C / a) -78 deg C. 15 min, b) 0 deg C, 15 min, c) 50 deg C, 10 min 4: 1.) lithium hexamethyldisilazane, HMPA / 1.) THF, -78 deg C, 1 h, 2.) THF, from -78 deg C to RT, 2 h 5: 86 percent / lithium tetramethyldisilazane, HMPA / tetrahydrofuran / 2 h / -78 - 20 °C 6: 93 percent / H2 / 5percent Pd/C / methanol / 2 h / 760 Torr / Ambient temperature 7: NaBH4 / methanol / 2 h / Ambient temperature 8: pyridine, DMAP / CH2Cl2 / 6 h / Ambient temperature 9: 68 percent / n-Bu3SnH, AIBN / toluene / 3 h / Heating 10: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 11: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 12: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

(1aR,4S,7S,7aR,7bR)-4-(tert-Butyl-dimethyl-silanyloxymethyl)-1,1,7-trimethyl-1a,3,4,7,7a,7b-hexahydro-1H,2H-cyclopropa[e]azulen-6-one (176199-13-6) → (+)-aromadendrene (489-39-4)

Conditions

Yield

Multi-step reaction with 7 steps 1: 93 percent / H2 / 5percent Pd/C / methanol / 2 h / 760 Torr / Ambient temperature 2: NaBH4 / methanol / 2 h / Ambient temperature 3: pyridine, DMAP / CH2Cl2 / 6 h / Ambient temperature 4: 68 percent / n-Bu3SnH, AIBN / toluene / 3 h / Heating 5: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 6: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 7: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

(1aR,4S,7R,7aR,7bR)-4-(tert-Butyl-dimethyl-silanyloxymethyl)-1,1,7-trimethyl-1a,3,4,7,7a,7b-hexahydro-1H,2H-cyclopropa[e]azulen-6-one (175985-37-2) → (+)-aromadendrene (489-39-4)

Conditions

Yield

Multi-step reaction with 8 steps 1: 86 percent / lithium tetramethyldisilazane, HMPA / tetrahydrofuran / 2 h / -78 - 20 °C 2: 93 percent / H2 / 5percent Pd/C / methanol / 2 h / 760 Torr / Ambient temperature 3: NaBH4 / methanol / 2 h / Ambient temperature 4: pyridine, DMAP / CH2Cl2 / 6 h / Ambient temperature 5: 68 percent / n-Bu3SnH, AIBN / toluene / 3 h / Heating 6: 100 percent / tetra-n-butylammonium fluoride / tetrahydrofuran / 6 h / Ambient temperature 7: 100 percent / Et3N, DMAP / CH2Cl2 / 2 h / 0 °C 8: 89 percent / DBU / toluene / 18 h / 100 °C View Scheme

thiocyanic acid (463-56-9) + (+)-aromadendrene (489-39-4) → (-)-10(R)-Isothiocyanoaromadendrane (56012-90-9)

Conditions	Yield
In chloroform for 48h; Ambient temperature;	97%
for 48h; Ambient temperature;	96.6%
In chloroform at 20℃; for 48h;	74%

(+)-aromadendrene (489-39-4) → (1aR,4R,7R,7bS)-1,1,4,7-tetramethyl-1a,2,3,4,5,6,7,7b-octahydro-1H-cyclopropa[e]azulene (29484-27-3, 95910-36-4, 110769-61-4)

Conditions	Yield
With aluminum oxide at 100℃;	96%
With aluminum oxide; potassium In hexane at 0 - 20℃; for 12h;	71%

(+)-aromadendrene (489-39-4) → [1aR-(1aα,7α,7aβ,7bα)]-1a,2,3,5,6,7,7a,7b-octahydro-1,1,4,7-tetramethyl-1H-cycloprop[e]azulene (74409-93-1, 77171-52-9, 128779-67-9, 21747-46-6)

Conditions	Yield
With potassium tert-butylate In dimethyl sulfoxide at 100℃;	80%

(+)-aromadendrene (489-39-4) → (1aR)-4ξ-hydroxymethyl-1,1,7c-trimethyl-(1ar,4ac,7at,7bc)-decahydro-cycloprop[e]azulen-4ξ-ol (95924-99-5, 97950-11-3, 145988-09-6)

Conditions	Yield
With osmium(VIII) oxide; 4-methylmorpholine N-oxide In water; tert-butyl alcohol at 20℃; for 64h;	79%
With potassium permanganate In acetone
(i) OsO4, Et2O, (ii) aq. KOH, benzene, EtOH, mannitol; Multistep reaction;

(+)-aromadendrene (489-39-4) + phenylselenyl triflate (112238-64-9) → C21H30OSe (1114568-42-1) + C21H30OSe (1114568-41-0)

Conditions	Yield
With water In acetonitrile at 0 - 20℃; for 40h; optical yield given as %de;	A 56% B 40%

(+)-aromadendrene (489-39-4) + phenylselenyl triflate (112238-64-9) → (((1aR,4R,4aR,7R,7aS,7bS)-4-azido-1,1,7-trimethyldecahydro-1H-cyclopropa[e]azulen-4-yl)methyl)(phenyl)selane + (((1aR,4S,4aR,7R,7aS,7bS)-4-azido-1,1,7-trimethyldecahydro-1H-cyclopropa[e]azulen-4-yl)methyl)(phenyl)selane

Conditions	Yield
Stage #1: phenylselenyl triflate With sodium azide In chloroform at 0℃; for 0.5h; Stage #2: (+)-aromadendrene In acetonitrile at 20℃; for 30h; Further stages.;	A 54% B 16%

(+)-aromadendrene (489-39-4) → C15H24O3 + C15H24O3

Conditions	Yield
Stage #1: (+)-aromadendrene With ferrous(II) sulfate heptahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; ozone In methanol; water at -78 - 20℃; for 0.0833333h; Stage #2: With magnesium bis(monoperoxyphthalate)hexahydrate In methanol; water at 0℃; for 2h;	A 54% B 37%

(+)-aromadendrene (489-39-4) → (1aR,4aR,7R,7aS,7bS)-1,1,7-Trimethyldecahydro-4H-cyclopropa[e]azulen-4-one (99147-41-8)

Conditions	Yield
Stage #1: (+)-aromadendrene With sodium hydrogencarbonate; ozone In methanol; dichloromethane at -78℃; for 0.5h; Stage #2: With triphenylphosphine In methanol; dichloromethane at 20℃; Inert atmosphere;	43%
With ozone
Multi-step reaction with 2 steps 1: O3 / pentane / -45 °C 2: 95 percent / Ph3P / CDCl3 View Scheme
Multi-step reaction with 2 steps 1: aq. KMnO4 / acetone 2: aq. NaIO4 / methanol View Scheme
Multi-step reaction with 2 steps 1: 4-methylmorpholine N-oxide; osmium(VIII) oxide / tert-butyl alcohol; water / 64 h / 20 °C 2: sodium periodate / water; methanol / 2 h / 20 °C / Inert atmosphere View Scheme

(+)-aromadendrene (489-39-4) → (1R,2S,6S,7S,10R)-3-Isopropyl-6,10-dimethyltricyclo[5.3.0.02,7]dec-3-ene

Conditions	Yield
With hexane; fluorosulfonylchloride; silver nitrate at -115 - -110℃;	26%

isocyanate de chlorosulfonyle (1189-71-5) + (+)-aromadendrene (489-39-4) → C16H25NO

Conditions	Yield
Stage #1: isocyanate de chlorosulfonyle; (+)-aromadendrene In dichloromethane at 23℃; for 2h; Stage #2: With triethylamine In dichloromethane at 23℃; for 3h; Stage #3: With water In dichloromethane at 23℃; for 24h; diastereoselective reaction;	25%

(+)-aromadendrene (489-39-4) → (1S,2S,4R,7R,8R,11R)-3,3,11-trimethyl-7-hydroxymethyl-tricyclo<6.3.0.02,4>undecan-7-ol (145988-09-6) + (1S,2S,3S,4R,7R,8R,11R)-3,7-bis(hydroxymethyl)-3,11-dimethyltricyclo<6.3.0.02,4>undecan-7-ol (145988-10-9)

Conditions	Yield
In N,N-dimethyl-formamide for 168h; Bacillus megaterium DSM 32;	A 4 mg B 7 mg

(+)-aromadendrene (489-39-4) → Nitrosochlorid von Aromadendren

Conditions	Yield
With nitrosylchloride

methanol (67-56-1) + (+)-aromadendrene (489-39-4) → (1R,2S,6S,7S,10R)-3-Isopropyl-3-methoxy-6,10-dimethyltricyclo[5.3.0.02,7]decane + (1R,2S,6S,7S,10R)-3-Isopropyl-6,10-dimethyltricyclo[5.3.0.02,7]dec-3-ene

Conditions	Yield
With fluorosulfonylchloride at -115 - -110℃;	A 65 % Chromat. B 18 % Chromat.
With fluorosulfonylchloride; fluorosulphonic acid 2.) (C2H5)2O; Yield given. Multistep reaction. Yields of byproduct given;

(+)-aromadendrene (489-39-4) → (1R,3S,7S,8S)-2,2,4,8-tetramethyltricyclo<5.3.1.03.7>undec-4-ene

Conditions	Yield
With formic acid Heating; Yield given;

(+)-aromadendrene (489-39-4) → (1R,2S,6S,7S,10R)-3-Isopropyl-3-methoxy-6,10-dimethyltricyclo[5.3.0.02,7]decane + (1R,2S,6S,7S,10R)-3-Isopropyl-6,10-dimethyltricyclo[5.3.0.02,7]dec-3-ene

Conditions	Yield
With methanol; fluorosulfonylchloride; fluorosulphonic acid 2.) (C2H5)2O; Yield given. Multistep reaction. Yields of byproduct given;

(+)-aromadendrene (489-39-4) → (1R,3S,7S,8S)-2,2,4,8-tetramethyltricyclo[5.3.1.03,7]undec-4-ene

Conditions	Yield
With formic acid Heating; Yield given;

(+)-aromadendrene (489-39-4) → (+)-aromadendrene ozonide

Conditions	Yield
With ozone In pentane at -45℃;

(+)-aromadendrene (489-39-4) → (1S,2S,4R,7R,8R,11R)-3,3,11-trimethyl-7-hydroxymethyl-tricyclo<6.3.0.02,4>undecan-7-ol (145988-09-6)

Conditions	Yield
With osmium(VIII) oxide; potassium carbonate; potassium hexacyanoferrate(III) In water; tert-butyl alcohol for 24h; Ambient temperature;	900 mg

(+)-aromadendrene (489-39-4) → 7-isopropyl-1,4-dimethyl-azulene (489-84-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 96 percent / K/Al2O3 / 100 °C 2.1: BF3*Et2O / CH2Cl2 / 3 h / 20 °C 2.2: 42 mg / sulfur / 1,3,5-trimethyl-benzene / 160 °C View Scheme

(+)-aromadendrene (489-39-4) → (1aR,4S,7R,7aS,7bR)-1,1,4,7-tetramethyl-1a,2,3,4,6,7,7a,7b-octahydro-1H-cyclopropa[e]azulen-4-ol (63181-42-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 80 percent / KOtBu / dimethylsulfoxide / 100 °C 2: 96 percent / oxone; NaHCO3; 18-crown-6 / CH2Cl2; H2O; acetone / 2 h / 0 °C 3: 57 percent / diethylamine; n-butyllithium / diethyl ether; hexane / 0 - 20 °C View Scheme

(+)-aromadendrene (489-39-4) → (1aR,4S,4aR,7R,7aS,7bR)-1,1,4,7-tetramethyldecahydro-4aH-cyclopropa[e]azulene-4,4a-diol (6894-71-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / KOtBu / dimethylsulfoxide / 100 °C 2: 54 percent / KMnO4 / ethanol; H2O / 2 h / 0 °C View Scheme

(+)-aromadendrene (489-39-4) → (2aR,8R,8aR,8bR)-2,2,5,8-tetramethyl-2a,3,4,6,7,8,8a,8b-octahydro-2H-naphtho[1,8-bc]furan

Conditions	Yield
Multi-step reaction with 3 steps 1: 80 percent / KOtBu / dimethylsulfoxide / 100 °C 2: 54 percent / KMnO4 / ethanol; H2O / 2 h / 0 °C 3: acetic acid; iodine / tetrahydrofuran; H2O / 96 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: 80 percent / KOtBu / dimethylsulfoxide / 100 °C 2: 96 percent / oxone; NaHCO3; 18-crown-6 / CH2Cl2; H2O; acetone / 2 h / 0 °C 3: 45 percent / sulfuric acid / tetrahydrofuran; H2O / 2 h / 30 °C View Scheme

(+)-aromadendrene (489-39-4) → (1R,3aR,4aS,6aR,7aR,7bS)-1,4a,7,7-tetramethyldecahydrocyclopropa[7,8]azuleno[3a,4-b]oxirene (178602-94-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / KOtBu / dimethylsulfoxide / 100 °C 2: 96 percent / oxone; NaHCO3; 18-crown-6 / CH2Cl2; H2O; acetone / 2 h / 0 °C View Scheme

Upstream product

• 489-41-8 (-)-globulol 
• 99147-41-8 (1aR,4aR,7R,7aS,7bS)-1,1,7-Trimethyldecahydro-4H-cyclopropa[e]azulen-4-one 
• 1779-49-3 Methyltriphenylphosphonium bromide 
• 6790-66-5 (-)-alloaromadendrone 
• 2344-80-1 Chloromethyltrimethylsilane 
• 6790-66-5 (-)-apoaromadendrone 
• 141564-33-2 Trimethyl-((1aR,7R,7aS,7bR)-1,1,7-trimethyl-1a,2,3,5,6,7,7a,7b-octahydro-1H-cyclopropa[e]azulen-4-yloxy)-silane 
• 27200-84-6 methyl triphenylphosphonium bromide 
• 175985-37-2 (1aR,4S,7R,7aR,7bR)-4-(tert-Butyl-dimethyl-silanyloxymethyl)-1,1,7-trimethyl-1a,3,4,7,7a,7b-hexahydro-1H,2H-cyclopropa[e]azulen-6-one 
• 176199-13-6 (1aR,4S,7S,7aR,7bR)-4-(tert-Butyl-dimethyl-silanyloxymethyl)-1,1,7-trimethyl-1a,3,4,7,7a,7b-hexahydro-1H,2H-cyclopropa[e]azulen-6-one 
• 175985-39-4 (1S,4R,7R)-4-(tert-Butyl-dimethyl-silanyloxymethyl)-8,8-dimethyl-bicyclo[5.1.0]octan-3-one 
• 175985-49-6 tert-Butyl-dimethyl-((1aR,4S,4aR,7R,7aR,7bS)-1,1,7-trimethyl-decahydro-cyclopropa[e]azulen-4-ylmethoxy)-silane 
• 175985-50-9 ((1aR,4S,4aR,7R,7aR,7bS)-1,1,7-trimethyldecahydro-1H-cyclopropa[e]azulen-4-yl)methanol 
• 175985-43-0 (+)-(1S,2S,4R,7R)-4-tert-butyldimethylsiloxymethyl-8,8-dimethyl-2-(2-oxopropyl)bicyclo<5.1.0>octan-3-one 

Downstream Products

• 56012-90-9 (+)-axisothiocyanate 2 
• 74409-93-1 [1aR-(1aα,7α,7aβ,7bα)]-1a,2,3,5,6,7,7a,7b-octahydro-1,1,4,7-tetramethyl-1H-cycloprop[e]azulene 
• 489-84-9 7-isopropyl-1,4-dimethyl-azulene 
• 1114568-42-1 C₂₁H₃₀OSe 
• 1114568-41-0 C₂₁H₃₀OSe 
• 29484-27-3 (1aR,4R,7R,7bS)-1,1,4,7-tetramethyl-1a,2,3,4,5,6,7,7b-octahydro-1H-cyclopropa[e]azulene 
• 6750-60-3 spathulenol 
• 99147-42-9 (+)-11β-hydroxy-apoaromadendrone 
• 22567-17-5 [1R-(1α,3aβ,4α,7β)]-1,2,3,3a,4,5,6,7-octahydro-1,4-dimethyl-7-(1-methylethenyl)-azulene 
• 186318-55-8 Toluene-4-sulfonic acid (1aR,4R,4aR,7R,7aS,7bS)-4-hydroxy-1,1,7-trimethyl-decahydro-cyclopropa[e]azulen-4-ylmethyl ester 

Relevant academic research and scientific papers

Synthetic studies on aromadendrane-type compounds. III. Stereoselective total syntheses of (+)-aromadendrene and (-)-alloaromadendrene

The stereoselective total syntheses of (+)-aromadendrene (5) and (-)-alloaromadendrene (6) were achieved via (+)-(1S,2R,4R,7S,11R)-7-tert-butyldimethylsiloxymethyl-3,3,11-trimethy ltricyclo[6.3.0.02,4]undec-8-en-10-one (7) as a common intermediate.

Convenient synthesis of deuterium labelled sesquiterpenes

Sesquiterpenes are an important class of molecules, with roles ranging from pollination and signalling to defense mechanisms. Despite their apparent importance, the limited number of commercial standards has hindered their study and precise quantification. Herein, we report the syntheses of fourteen labelled sesquiterpenes with a high level of deuterium incorporation (>95%) for applications in MS-based studies.

The synthesis of mono- and dihydroxy aromadendrane sesquiterpenes, starting from natural (+)-aromadendrene-III

The monoalcohols (-)-globulol (2), (-)-epiglobulol (3), (-)-ledol (4), and (+)-viridiflorol (5) were synthesized from (+)-aromadendrene (1). The cis-fused alloaromandedrone (14), the key intermediate used in the synthesis of 4 and 5, was obtained from the trans-fused apoaromadendrone (13) via a selective protonation of the thermodynamic enol trimethylsilylether 15. After hydroxylation of the tertiary C11 of 13 with RuO4, (+)-spathulenol (6), (-)-allospathulenol (7), and the aromadendrane diols 8-11 could be prepared. Compounds 2-11 were tested for antifungal properties, but their activity was only moderate.

The conversion of natural (+)-aromadendrene into chiral synthons-I

(-)-Apoaromadendrone (3) can be obtained easily in large quantities from (+)-aromadendrene which is the main constituent in a commercially available distillation tail of the oil of Eucalyptus globules. Acid catalyzed selective cleavage of the C3-C4 bond of the cyclopropane ring in 3 gave (-)-isoapoaromadendrone(9) in high yield. The regioselectivity of the cyclopropane ring opening was proved by NMR spectroscopy in combination with chemical transformations. Ozonolysis of 9 afforded the keto alcohol 14 which is a suitable chiral intermediate for the syntheses of guaianes and guaianolides.