83-79-4

Basic information

• Product Name: ROTENONE
• Synonyms: (-)-cis-rotenone;(1)Benzopyrano(3,4-b)furo(2,3-h)(1)benzopyran-6(6aalphaH)-one, 1,2,12,12aalpha-tetrahydro-2alpha-isopropenyl-8,9-dimethoxy-;(1)Benzopyrano(3,4-b)furo(2,3-h)(1)benzopyran-6(6aH)-one, 1,2,12,12a-tetrahydro-2-alpha-iospropenyl-8,9-dimethoxy-;(1)Benzopyrano(3,4-b)furo(2,3-h)(1)benzopyran-6(6aH)-one, 1,2,12,12a-tetrahydro-2-alpha-isopropenyl-8,9-dimethoxy-;(1)benzopyrano(3,4-b)furo(2,3-h)(1)benzopyran-6(6alphah)-one,1,2,12,12aalpha-t;(2r-(2alpha,6aalpha,12aalpha))--9-dimethoxy-2-(1-methylethenyl)-;(2R,2alpha,6aalpha,12aalpha)-1,2,12,12a-tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)[1]benzopyrano[3,4-b]furo[2,3-H][1]benzopyran-6(6aH)-one;[1]Benzopyrano[3,4-b]furo[2,3-h][1]benzopyran-6(6aH)-one, 1,2,12,12a-tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-, [2R-(2alpha,6aalpha,12aalpha)]-
• CAS NO: 83-79-4
• Molecular Formula: C₂₃H₂₂O₆
• Molecular Weight: 394.41718
• EINECS: 201-501-9
• Product Categories: Miscellaneous Natural Products;Alpha sort;BotanicalsPesticides&Metabolites;Q-ZAnalytical Standards;BotanicalsAnalytical Standards;Alphabetic;Insecticides;Pesticides;R;Mitochondrial Inhibitors;Cell Stress;Nitric Oxide and Cell Stress;Asymmetric Synthesis;Chiral Building Blocks;Complex Molecules;Inhibitors
• Mol File: 83-79-4.mol
• Article Data: 12

Chemical Properties

• Melting Point: 159-164 °C(lit.)
• Boiling Point: 210-220 °C0.5 mm Hg(lit.)
• Flash Point: 244.6 °C
• Appearance: white or off-white powder
• Density: 1.1917 (rough estimate)
• Vapor Pressure: 1.45E-12mmHg at 25°C
• Refractive Index: 1.4593 (estimate)
• Storage Temp.: Store at RT
• Solubility: insoluble in EtOH; insoluble in H2O; ≥77.6 mg/mL in DMSO
• Water Solubility: 15 mg l-1 (100 °C)
• Stability: Stable, but light and air sensitive. Combustible. Incompatible with oxidizing agents, especially in the presence of alkalies.
• Merck: 14,8271
• BRN: 6773081
• CAS DataBase Reference: ROTENONE(CAS DataBase Reference)
• NIST Chemistry Reference: ROTENONE(83-79-4)
• EPA Substance Registry System: ROTENONE(83-79-4)

Safety Data

• Hazard Codes: T,N
• Statements: 25-36/37/38-50/53
• Safety Statements: 22-24/25-36-45-60-61
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: DJ2800000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 83-79-4(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 83-79-4 differently. You can refer to the following data:
1. The principal source of rotenone is the tuber root of Derris elliptica; however, it is also extracted from the roots of Derris mallaccensis, Lonchocarpus utilis, and Lonchocarpus uruca. Rotenone is both a stomach and contact poison for arthropods. Its fast knockdown action is attributed to decreasing the availability of nicotinamide adenine dinucleotide to serve as a cofactor in various biochemical pathways including the Krebs cycle, thereby inhibiting the mitochondrial respiratory enzymes.
2. Rotenone is a classical inhibitor of complex I of the mitochondrial electron transport chain, inhibiting NADH/DB oxidoreductase and NADH oxidase with IC50 values of 28.8 and 5.1 nM, respectively. In substantia nigra pars compacta neurons, it activates ATP-sensitive potassium channels and increases the production of reactive oxygen species (ROS) in the mitochondria, effects that are decreased by the antioxidant trolox . In rodents, rotenone induces dopaminergic cell death in the substantia nigra, formation of cytoplasmic inclusions similar to Lewy bodies, oxidative damage to proteins, and parkinsonian symptoms of bradykinesia and rigidity. In a rat model of Parkinson’s disease, chronic rotenone administration of 1.5 and 2.5 mg/kg per day for two months reduces tyrosine hydroxylase levels in the posterior striatum and prefrontal cortex, induces catalepsy, and decreases spontaneous locomotion and exploration in the open field test. Formulations containing rotenone have been used as insecticides and piscicides.

Chemical Properties

Rotenone is a colorless to red odorless crystalline solid; a white crystalline solid when pure; oxidation will cause yellowing to bright red coloring. Odorless. Rotenone is related to isoflavonoid compounds derived from the roots of Derris spp., Lonchocarpus spp., and Tephrosia spp., found primarily in Southeast Asia, South America, and East Africa. The isolated compound is an odorless, colorless to red crystalline solid. It is insoluble in water and has a very low vapor pressure (U.S. EPA, 2007; HSDB, 2012a).

Uses

Different sources of media describe the Uses of 83-79-4 differently. You can refer to the following data:
1. Rotenone is used for the control of aphids, thrips, suckers and other insects in fruit and vegetable cultivation. It is also used for control in buildings, for the control of lice, ticks and warble fly on animals and as a piscicide for the management of fish populations.
2. Rotenone is an broad spectrum insecticide that occurs naturally in seeds and stems of several plants. Rotenone was first registered in 1947 and is currently used exclusively to kill fish (U.S. EPA, 2007). In 2006, registrants voluntarily canceled all livestock, residential and home owner uses, domestic pet uses, and all other uses except for piscicide uses. Currently the main uses include fish management strategies to remove nonnative fish species from lakes, ponds, or streams and in catfish aquaculture prior to stocking ponds with with fry to remove undesirable fish species (U.S. EPA, 2006d). Rotenone has been historically used by native people to paralyze fish for capture and consumption. Outside the United States, the compound is still used to control insects in fruit and vegetable cultivation and for control of fire ants and mosquito larvae in pond water (HSDB, 2012a).
3. Insecticide; lotion for chiggers; emulsion for scabies.

Definition

ChEBI: A member of the class of rotenones that consists of 1,2,12,12a-tetrahydrochromeno[3,4-b]furo[2,3-h]chromen-6(6aH)-one substituted at position 2 by a prop-1-en-2-yl group and at positions 8 and 9 by methoxy group (the 2R,6aS,12aS-isomer). A non-systemic insecticide, it is the principal insecticidal constituent of derris (the dried rhizome and root of Derris elliptica).

General Description

Colorless to brownish crystals or a white to brownish-white crystalline powder. Has neither odor nor taste.

Air & Water Reactions

ROTENONE decomposes upon exposure to light or air. Insoluble in water.

Reactivity Profile

ROTENONE is readily oxidized in the presence of alkalis. ROTENONE is incompatible with oxidizers. .

Hazard

Toxic by ingestion, overexposure can be fatal, irritant to skin, eyes and upper respiratory tract. Central nervous system impairment. Ques- tionable carcinogen.

Health Hazard

Rotenone is an irritant and affects the nervous system, causing convulsions.

Fire Hazard

Flash point data for ROTENONE are not available; however, ROTENONE is probably combustible.

Agricultural Uses

Insecticide, Acaracide, Veterinary medicine: The use of rotenone as a pesticide to kill invasive fish species is currently the only allowable use of this pesticide. Rotenone is a selective, nonspecific botanical insecticide with some acaricidal properties, and has been used in agriculture to control insects on vine fruit, flowers and vegetables. Registered for use in the U.S.A U.S. EPA restricted Use Pesticide (RUP) due to acute inhalation, acute oral, and aquatic toxicity. Agricultural and residential uses and all food uses were voluntarily cancelled in 2006[83]. In 2006, registrants requested voluntarily cancellation of all livestock, residential and home owner uses, domestic pet uses, and all other uses except for pesticide uses. In 2011 the use of this pesticide chemical was linked to Parkinson’s disease. Not listed for use in EU countries.

Trade name

ACME? Rotenone; AROL GORDON DUST?; BARBASCO?; BONIDE CUKE AND MELON DUST?; CENOL GARDEN DUST?; CHEM FISH?; CHEM-MITE?; CUBE?; CUBE EXTRACT?; CUBEPULVER?; CUBEROL?; CUBE ROOT?; CUBOR?; CUREX FLEA DUSTER?; DACTINOL?; DERIL?; DERRIN?; DERRIS?; DRI-KIL?; ENT-133?; EXTRAX?; FISH-TOX?; GREEN CROSS WARBLE POWDER?; HAIARI?; LIQUID DERRIS?; MEXIDE?; NICOULINE?; NOXFIRE?; NOXFISH?; PARADERIL?; POWDER AND ROOT?; PRENTOX?; PRO-NOX FISH?; RO-KO?; RONONE?; ROTACIDE?; ROTEFIVE?; ROTEFOUR?; ROTESSENOL?; SINID?; TOX-R?; TUBATOXIN?

Biological Activity

Mitochondrial electron transport chain inhibitor (IC 50 = 1.7 - 2.2 μ M at complex I). Inhibits NADH oxidation by cardiac sarcoplasmic reticulum (IC 50 = 3.4 nM). Commonly used pesticide and induces Parkinsonism in animal models. Cell-permeable and brain penetrant.

Biochem/physiol Actions

Rotenone is an inhibitor of mitochondrial electron transport at nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase. It is readily absorbed through the exoskeletons of arthropods, but poorly absorbed cutaneously or from the gastrointestinal tract of mammals. Rotenone acts as a neurotoxic agent which can produce Parkinson-like condition to serve as an animal model for the study of etiology and interventions.

Potential Exposure

A potential danger to those involved in extraction from derris root, formulation or application of this insecticide. Rotenone is used as a pharmaceutical and veterinary drug.

Carcinogenicity

In human lymphocyte culture assays rotenone did not increase the frequency of chromosomal aberrations or sister chromatid exchanges but did cause an increase in the frequency of binucleated micronuclei and a delay in cell cycle.

Environmental Fate

Rotenone released to the atmosphere will exist as particulates due to the extremely low vapor pressure. Particulate-phase rotenone will be removed from the atmosphere by wet and dry deposition and may be degraded by direct photolysis. It is mobile to moderately mobile in soil and sediment and volatilization from soil surfaces is not expected to occur to any extent. If released to water, rotenone generally degrades quickly through abiotic (hydrolytic and photolytic) mechanisms, with half-lives of a few days to several weeks or longer depending on water temperature (U.S. EPA, 2007; HSDB, 2012a). Rotenone has a relatively low potential for bioconcentration in aquatic organisms (Bioconcentration Factor (BCF) < 30X) (U.S. EPA, 2007).

Metabolic pathway

By hepatic microsomal incubations from rainbow trout with 14C-rotenone, three major and several minor metabolites of rotenone are observed, the major ones being identified as rotenolone and two epimeric forms of 6' ,7' -dihydroxyrotenone.

Shipping

UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required. UN2588 Pesticides, solid, toxic, Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required.

Degradation

Rotenone is racemised in base to less insecticidal compounds and it is decomposed on exposure to light and air (PM). Photochemical degradation in methanol of seven rotenoids isolated from Tephrosa villosa (Krupadanam et al., 1978) resulted generally in much decomposition but rotenone was relatively stable under the conditions used. When the compound was used as an insecticidal spray it was converted by light and air into dehydro-rotenone (2) and rotenonone (3). These structures are shown in Scheme 1.

Toxicity evaluation

Rotenone inhibits the electron transport chain by blocking transport between the flavoprotein and the ubiquinone. The oxidation of pyruvate in rat mitochondria is virtually completely blocked by rotenone in vitro (<1 mmol l-1 concentration). Cell death occurs by apoptosis due to excess generation of free radicals. In addition, rotenone causes a definite anesthetic effect when it comes in contact with nerve axons. Death appears to occur due to depression of the respiratory center. Rotenone is toxic to insects, humans, animals, and fish. Rotenone exerts selective toxicity, as it is highly toxic to fish because of its rapid absorption from the GI tract in comparison to mammalian species in which it is poorly absorbed. The selective toxicity of rotenone in insects and fish versus mammals can also be explained based on the metabolism of this compound. Rotenone converts to highly toxic metabolites in large quantities in insects and fish, while it converts to nontoxic metabolites in mammals.

Incompatibilities

Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explo- sions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides, and alkalies.

Waste Disposal

Rotenone is decomposed by light and alkali to less insecticidal products. It is readily detoxified by the action of light and air. It is also detoxified by heating; 2 hours @ 100 ? C results in 76% decomposition. Oxidation products are probably nontoxic. Incineration has been recommended as a disposal procedure. Burial with lime would also present minimal danger to the environ- ment . In accordance with 40CFR165, follow recommen- dations for the disposal of pesticides and pesticide containers. Must be disposed properly by following pack- age label directions or by contacting your local or federal environmental control agency, or by contacting your regional EPA office.

references

[1]. chen y, mcmillan-ward e, kong j, et al. mitochondrial electron-transport-chain inhibitors of complexes i and ii induce autophagic cell death mediated by reactive oxygen species. j cell sci, 2007, 120(pt 23): 4155-4166.[2]. newhouse k, hsuan sl, chang sh, et al. rotenone-induced apoptosis is mediated by p38 and jnk map kinases in human dopaminergic sh-sy5y cells. toxicol sci, 2004, 79(1): 137-146.[3]. borland mk, trimmer pa, rubinstein jd, et al. chronic, low-dose rotenone reproduces lewy neurites found in early stages of parkinson's disease, reduces mitochondrial movement and slowly kills differentiated sh-sy5y neural cells. mol neurodegener, 2008, 3: 21.

InChI:InChI=1/C23H22O6/c1-11(2)16-8-14-15(28-16)6-5-12-22(24)21-13-7-18(25-3)19(26-4)9-17(13)27-10-20(21)29-23(12)14/h5-7,9,16,20-21H,1,8,10H2,2-4H3/t16-,20+,21+/m1/s1

Synthetic route

(6aS,12aS,5'R)-rotenone enol acetate (23355-70-6) → rotenone (83-79-4)

Conditions	Yield
With hydrogenchloride In methanol for 2h; Heating;	83%

diazomethane (186581-53-3, 908094-01-9) + (2R,6aS,12aS)-8-hydroxy-9-methoxy-2-(prop-1-en-2-yl)-1,2,12,12a- tetrahydrochromeno[3,4-b]furo[2,3-h]chromen-6(6aH)-one (34487-52-0) → rotenone (83-79-4)

Conditions	Yield
In diethyl ether	59%

2-((2R,6aS,12aS)-8,9-dimethoxy-1,2,6,6a,12,12a-hexahydrochromeno[3,4-b]furo[2,3-h]chromen-2-yl)propan-2-ol (30462-22-7) → rotenone (83-79-4) + Isorotenone (549-22-4)

Conditions	Yield
With Burgess Reagent In toluene for 0.5h; Reflux;	A 50% B 13%
With Burgess Reagent In toluene for 0.5h; Inert atmosphere; Reflux;	A 50% B 13%

2-((2R,6aS,12aS)-8,9-dimethoxy-1,2,6,6a,12,12a-hexahydrochromeno[3,4-b]furo[2,3-h]chromen-2-yl)propan-2-ol (30462-22-7) → rotenone (83-79-4)

Conditions	Yield
With pyridine; thionyl chloride at 0℃; for 0.5h;	40%

(6aS,12aR,5'R)-(trans)-(+)-rotenone (123000-20-4) → rotenone (83-79-4)

Conditions	Yield
With hydrogenchloride In methanol; chloroform for 2h;

(6aR,12aS,5'R)-rotenone (123000-19-1) → rotenone (83-79-4)

Conditions	Yield
With hydrogenchloride In methanol; chloroform
With hydrogenchloride In methanol; chloroform epimerisation;

12a-hydroxyrotenone (509-96-6) → rotenone (83-79-4)

Conditions	Yield
With acetic acid; zinc(II) chloride; zinc In water at 100℃; for 2.5h;	20 mg

6a,12a-dehydrorotenone (3466-09-9) → rotenone (83-79-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 31 mg / diisobutyaluminium hydride / toluene; tetrahydrofuran / 1 h / -78 °C 2: aq. HCl / methanol; CHCl3 / 2 h View Scheme
Multi-step reaction with 2 steps 1: di-isobutylaluminium hydride 2: hydrogen chloride / methanol; CHCl3 / epimerisation View Scheme

(6aS,12aS,5′R)-rotenone-6′-norketone (15130-81-1) → rotenone (83-79-4) + aqueous-alcoholic KOH-solution

Conditions	Yield
Multi-step reaction with 3 steps 1: 50 percent / conc. H2SO4 / 3 h / Heating 2: 1.) n-BuLi / 1.) THF, 35 deg C, 5 min, 2.) THF, 1 h 3: 83 percent / conc. HCl / methanol / 2 h / Heating View Scheme

rotenone 6'-norketone enol acetate (23295-59-2, 23295-65-0) → rotenone (83-79-4) + aqueous-alcoholic KOH-solution

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) n-BuLi / 1.) THF, 35 deg C, 5 min, 2.) THF, 1 h 2: 83 percent / conc. HCl / methanol / 2 h / Heating View Scheme

C11H14F2O2 → rotenone (83-79-4)

Conditions

Yield

Multi-step reaction with 13 steps 1.1: sodium hydride / hexane; mineral oil; N,N-dimethyl-formamide / 0 - 20 °C 2.1: N-ethyl-N,N-diisopropylamine; tetra-(n-butyl)ammonium iodide / dichloromethane / 24 h / 20 °C 3.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / hexane; toluene; diethyl ether; cyclohexane / 1 h / -78 °C 3.2: 1.5 h / -78 - -30 °C 4.1: boron trifluoride diethyl etherate / dichloromethane / 0.25 h / 0 °C 5.1: sodium tetrahydroborate / ethanol / 0.5 h / 20 °C 6.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 8.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 9.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 10.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 11.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 12.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 12.2: 1.5 h / 50 °C 13.1: pyridine; thionyl chloride / 0.5 h / 0 °C View Scheme

C11H14F2O2 → rotenone (83-79-4) + Isorotenone (549-22-4)

Conditions

Yield

Multi-step reaction with 13 steps 1.1: sodium hydride / hexane; mineral oil; N,N-dimethyl-formamide / 0 - 20 °C 2.1: N-ethyl-N,N-diisopropylamine; tetra-(n-butyl)ammonium iodide / dichloromethane / 24 h / 20 °C 3.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / hexane; toluene; diethyl ether; cyclohexane / 1 h / -78 °C 3.2: 1.5 h / -78 - -30 °C 4.1: boron trifluoride diethyl etherate / dichloromethane / 0.25 h / 0 °C 5.1: sodium tetrahydroborate / ethanol / 0.5 h / 20 °C 6.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 8.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 9.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 10.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 11.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 12.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 12.2: 1.5 h / 50 °C 13.1: Burgess Reagent / toluene / 0.5 h / Reflux View Scheme

C11H13FO2 → rotenone (83-79-4)

Conditions

Yield

Multi-step reaction with 12 steps 1.1: N-ethyl-N,N-diisopropylamine; tetra-(n-butyl)ammonium iodide / dichloromethane / 24 h / 20 °C 2.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / hexane; toluene; diethyl ether; cyclohexane / 1 h / -78 °C 2.2: 1.5 h / -78 - -30 °C 3.1: boron trifluoride diethyl etherate / dichloromethane / 0.25 h / 0 °C 4.1: sodium tetrahydroborate / ethanol / 0.5 h / 20 °C 5.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 7.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 8.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 9.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 10.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 11.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 11.2: 1.5 h / 50 °C 12.1: pyridine; thionyl chloride / 0.5 h / 0 °C View Scheme

C11H13FO2 → rotenone (83-79-4) + Isorotenone (549-22-4)

Conditions

Yield

Multi-step reaction with 12 steps 1.1: N-ethyl-N,N-diisopropylamine; tetra-(n-butyl)ammonium iodide / dichloromethane / 24 h / 20 °C 2.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / hexane; toluene; diethyl ether; cyclohexane / 1 h / -78 °C 2.2: 1.5 h / -78 - -30 °C 3.1: boron trifluoride diethyl etherate / dichloromethane / 0.25 h / 0 °C 4.1: sodium tetrahydroborate / ethanol / 0.5 h / 20 °C 5.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 7.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 8.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 9.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 10.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 11.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 11.2: 1.5 h / 50 °C 12.1: Burgess Reagent / toluene / 0.5 h / Reflux View Scheme

C13H17FO3 → rotenone (83-79-4)

Conditions

Yield

Multi-step reaction with 11 steps 1.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / hexane; toluene; diethyl ether; cyclohexane / 1 h / -78 °C 1.2: 1.5 h / -78 - -30 °C 2.1: boron trifluoride diethyl etherate / dichloromethane / 0.25 h / 0 °C 3.1: sodium tetrahydroborate / ethanol / 0.5 h / 20 °C 4.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 6.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 7.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 8.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 9.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 10.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 10.2: 1.5 h / 50 °C 11.1: pyridine; thionyl chloride / 0.5 h / 0 °C View Scheme

C13H17FO3 → rotenone (83-79-4) + Isorotenone (549-22-4)

Conditions

Yield

Multi-step reaction with 11 steps 1.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / hexane; toluene; diethyl ether; cyclohexane / 1 h / -78 °C 1.2: 1.5 h / -78 - -30 °C 2.1: boron trifluoride diethyl etherate / dichloromethane / 0.25 h / 0 °C 3.1: sodium tetrahydroborate / ethanol / 0.5 h / 20 °C 4.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 6.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 7.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 8.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 9.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 10.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 10.2: 1.5 h / 50 °C 11.1: Burgess Reagent / toluene / 0.5 h / Reflux View Scheme

1,3-Difluorobenzene (372-18-9) → rotenone (83-79-4)

Conditions

Yield

Multi-step reaction with 15 steps 1.1: N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium / tetrahydrofuran; hexane / 1.42 h / -78 °C 1.2: 2 h / 20 °C 2.1: potassium osmate; potassium hexacyanoferrate(III); potassium carbonate; methanesulfonamide; (9S,9"S)-9,9"-[phthalazine-1,4-diylbis-(oxy)]bis[10,11-dihydro-6'-methoxycinchonane] / tert-butyl alcohol; water / 120 h / 0 - 20 °C 3.1: sodium hydride / hexane; mineral oil; N,N-dimethyl-formamide / 0 - 20 °C 4.1: N-ethyl-N,N-diisopropylamine; tetra-(n-butyl)ammonium iodide / dichloromethane / 24 h / 20 °C 5.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / hexane; toluene; diethyl ether; cyclohexane / 1 h / -78 °C 5.2: 1.5 h / -78 - -30 °C 6.1: boron trifluoride diethyl etherate / dichloromethane / 0.25 h / 0 °C 7.1: sodium tetrahydroborate / ethanol / 0.5 h / 20 °C 8.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 9.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 10.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 11.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 12.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 13.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 14.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 14.2: 1.5 h / 50 °C 15.1: pyridine; thionyl chloride / 0.5 h / 0 °C View Scheme

1,3-Difluorobenzene (372-18-9) → rotenone (83-79-4) + Isorotenone (549-22-4)

Conditions

Yield

Multi-step reaction with 15 steps 1.1: N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium / tetrahydrofuran; hexane / 1.42 h / -78 °C 1.2: 2 h / 20 °C 2.1: potassium osmate; potassium hexacyanoferrate(III); potassium carbonate; methanesulfonamide; (9S,9"S)-9,9"-[phthalazine-1,4-diylbis-(oxy)]bis[10,11-dihydro-6'-methoxycinchonane] / tert-butyl alcohol; water / 120 h / 0 - 20 °C 3.1: sodium hydride / hexane; mineral oil; N,N-dimethyl-formamide / 0 - 20 °C 4.1: N-ethyl-N,N-diisopropylamine; tetra-(n-butyl)ammonium iodide / dichloromethane / 24 h / 20 °C 5.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / hexane; toluene; diethyl ether; cyclohexane / 1 h / -78 °C 5.2: 1.5 h / -78 - -30 °C 6.1: boron trifluoride diethyl etherate / dichloromethane / 0.25 h / 0 °C 7.1: sodium tetrahydroborate / ethanol / 0.5 h / 20 °C 8.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 9.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 10.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 11.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 12.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 13.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 14.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 14.2: 1.5 h / 50 °C 15.1: Burgess Reagent / toluene / 0.5 h / Reflux View Scheme

C31H44F2O8Si → rotenone (83-79-4)

Conditions

Yield

Multi-step reaction with 10 steps 1.1: boron trifluoride diethyl etherate / dichloromethane / 0.25 h / 0 °C 2.1: sodium tetrahydroborate / ethanol / 0.5 h / 20 °C 3.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 5.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 6.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 7.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 8.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 9.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 9.2: 1.5 h / 50 °C 10.1: pyridine; thionyl chloride / 0.5 h / 0 °C View Scheme

C31H44F2O8Si → rotenone (83-79-4) + Isorotenone (549-22-4)

Conditions	Yield
Multi-step reaction with 10 steps 1.1: boron trifluoride diethyl etherate / dichloromethane / 0.25 h / 0 °C 2.1: sodium tetrahydroborate / ethanol / 0.5 h / 20 °C 3.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 5.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 6.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 7.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 8.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 9.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 9.2: 1.5 h / 50 °C 10.1: Burgess Reagent / toluene / 0.5 h / Reflux View Scheme
Multi-step reaction with 10 steps 1.1: boron trifluoride diethyl etherate / dichloromethane / 0.25 h / 0 °C / Inert atmosphere 1.2: 0.5 h / 20 °C / Inert atmosphere 2.1: pyridinium p-toluenesulfonate / dichloromethane / 3 h / 20 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C / Inert atmosphere 4.1: potassium tert-butylate; bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine / toluene / 2 h / Inert atmosphere; Reflux 5.1: aluminum (III) chloride; lithium aluminium tetrahydride / diethyl ether; dichloromethane / 0.33 h / 0 °C / Inert atmosphere 6.1: sodium hydride; 15-crown-5; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone / toluene / 2 h / 80 °C / Inert atmosphere 7.1: 10 wt% Pd(OH)2 on carbon; hydrogen / tetrahydrofuran; tert-butyl alcohol; water / 3 h / 20 °C 8.1: 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione / dimethyl sulfoxide / 20 °C / Inert atmosphere 9.1: hydrogenchloride / methanol / 1.5 h / 50 °C / Inert atmosphere 10.1: Burgess Reagent / toluene / 0.5 h / Inert atmosphere; Reflux View Scheme

C31H46F2O8Si → rotenone (83-79-4)

Conditions

Yield

Multi-step reaction with 8 steps 1.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 3.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 4.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 5.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 6.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 7.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 7.2: 1.5 h / 50 °C 8.1: pyridine; thionyl chloride / 0.5 h / 0 °C View Scheme

C31H46F2O8Si → rotenone (83-79-4) + Isorotenone (549-22-4)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 3.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 4.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 5.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 6.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 7.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 7.2: 1.5 h / 50 °C 8.1: Burgess Reagent / toluene / 0.5 h / Reflux View Scheme
Multi-step reaction with 9 steps 1: pyridinium p-toluenesulfonate / dichloromethane / 3 h / 20 °C / Inert atmosphere 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C / Inert atmosphere 3: potassium tert-butylate; bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine / toluene / 2 h / Inert atmosphere; Reflux 4: aluminum (III) chloride; lithium aluminium tetrahydride / diethyl ether; dichloromethane / 0.33 h / 0 °C / Inert atmosphere 5: sodium hydride; 15-crown-5; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone / toluene / 2 h / 80 °C / Inert atmosphere 6: 10 wt% Pd(OH)2 on carbon; hydrogen / tetrahydrofuran; tert-butyl alcohol; water / 3 h / 20 °C 7: 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione / dimethyl sulfoxide / 20 °C / Inert atmosphere 8: hydrogenchloride / methanol / 1.5 h / 50 °C / Inert atmosphere 9: Burgess Reagent / toluene / 0.5 h / Inert atmosphere; Reflux View Scheme

C31H44F2O8Si → rotenone (83-79-4)

Conditions

Yield

Multi-step reaction with 9 steps 1.1: sodium tetrahydroborate / ethanol / 0.5 h / 20 °C 2.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 4.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 5.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 6.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 7.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 8.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 8.2: 1.5 h / 50 °C 9.1: pyridine; thionyl chloride / 0.5 h / 0 °C View Scheme

C31H44F2O8Si → rotenone (83-79-4) + Isorotenone (549-22-4)

Conditions

Yield

Multi-step reaction with 9 steps 1.1: sodium tetrahydroborate / ethanol / 0.5 h / 20 °C 2.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 4.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 5.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 6.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 7.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 8.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 8.2: 1.5 h / 50 °C 9.1: Burgess Reagent / toluene / 0.5 h / Reflux View Scheme

C39H52F2O9Si → rotenone (83-79-4)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 2.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 3.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 4.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 5.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 6.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 6.2: 1.5 h / 50 °C 7.1: pyridine; thionyl chloride / 0.5 h / 0 °C View Scheme

C39H52F2O9Si → rotenone (83-79-4) + Isorotenone (549-22-4)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 2.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 3.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 4.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 5.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 6.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 6.2: 1.5 h / 50 °C 7.1: Burgess Reagent / toluene / 0.5 h / Reflux View Scheme
Multi-step reaction with 8 steps 1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C / Inert atmosphere 2: potassium tert-butylate; bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine / toluene / 2 h / Inert atmosphere; Reflux 3: aluminum (III) chloride; lithium aluminium tetrahydride / diethyl ether; dichloromethane / 0.33 h / 0 °C / Inert atmosphere 4: sodium hydride; 15-crown-5; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone / toluene / 2 h / 80 °C / Inert atmosphere 5: 10 wt% Pd(OH)2 on carbon; hydrogen / tetrahydrofuran; tert-butyl alcohol; water / 3 h / 20 °C 6: 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione / dimethyl sulfoxide / 20 °C / Inert atmosphere 7: hydrogenchloride / methanol / 1.5 h / 50 °C / Inert atmosphere 8: Burgess Reagent / toluene / 0.5 h / Inert atmosphere; Reflux View Scheme

C33H38F2O9 → rotenone (83-79-4)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 2.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 3.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 4.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 5.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 5.2: 1.5 h / 50 °C 6.1: pyridine; thionyl chloride / 0.5 h / 0 °C View Scheme

C33H38F2O9 → rotenone (83-79-4) + Isorotenone (549-22-4)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 2.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 3.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 4.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 5.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 5.2: 1.5 h / 50 °C 6.1: Burgess Reagent / toluene / 0.5 h / Reflux View Scheme
Multi-step reaction with 7 steps 1: potassium tert-butylate; bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine / toluene / 2 h / Inert atmosphere; Reflux 2: aluminum (III) chloride; lithium aluminium tetrahydride / diethyl ether; dichloromethane / 0.33 h / 0 °C / Inert atmosphere 3: sodium hydride; 15-crown-5; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone / toluene / 2 h / 80 °C / Inert atmosphere 4: 10 wt% Pd(OH)2 on carbon; hydrogen / tetrahydrofuran; tert-butyl alcohol; water / 3 h / 20 °C 5: 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione / dimethyl sulfoxide / 20 °C / Inert atmosphere 6: hydrogenchloride / methanol / 1.5 h / 50 °C / Inert atmosphere 7: Burgess Reagent / toluene / 0.5 h / Inert atmosphere; Reflux View Scheme

prenyl bromide (870-63-3) → rotenone (83-79-4)

Conditions

Yield

Multi-step reaction with 15 steps 1.1: N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium / tetrahydrofuran; hexane / 1.42 h / -78 °C 1.2: 2 h / 20 °C 2.1: potassium osmate; potassium hexacyanoferrate(III); potassium carbonate; methanesulfonamide; (9S,9"S)-9,9"-[phthalazine-1,4-diylbis-(oxy)]bis[10,11-dihydro-6'-methoxycinchonane] / tert-butyl alcohol; water / 120 h / 0 - 20 °C 3.1: sodium hydride / hexane; mineral oil; N,N-dimethyl-formamide / 0 - 20 °C 4.1: N-ethyl-N,N-diisopropylamine; tetra-(n-butyl)ammonium iodide / dichloromethane / 24 h / 20 °C 5.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / hexane; toluene; diethyl ether; cyclohexane / 1 h / -78 °C 5.2: 1.5 h / -78 - -30 °C 6.1: boron trifluoride diethyl etherate / dichloromethane / 0.25 h / 0 °C 7.1: sodium tetrahydroborate / ethanol / 0.5 h / 20 °C 8.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C 9.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 10.1: bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine; potassium tert-butylate / toluene / 2 h / Reflux 11.1: aluminum (III) chloride; lithium aluminium tetrahydride / dichloromethane; toluene; diethyl ether / 0.33 h / 0 °C 12.1: sodium hydride; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; 15-crown-5 / toluene / 2 h / 80 °C 13.1: palladium 10% on activated carbon; hydrogen / tert-butyl alcohol; water / 15 h / 20 °C 14.1: Dess-Martin periodane / dichloromethane / 0.25 h / 20 °C 14.2: 1.5 h / 50 °C 15.1: pyridine; thionyl chloride / 0.5 h / 0 °C View Scheme

rotenone (83-79-4) → 2R,6aS,12aS-2-isopropyl-8,9-dimethoxy-1,2,12,12a-tetrahydrochromeno[3,4-b]furo[2,3-h]chromen-6(6aH)-one (6659-45-6)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In dichloromethane at 20℃;	98%
With hydrogen; palladium on activated charcoal In ethyl acetate Ambient temperature;	94%
With hydrogen; palladium on activated charcoal In acetone	90%

rotenone (83-79-4) → (2R,6aR,12aS)-8,9-dimethoxy-2(prop-1-en-2-yl)-1,2,6,6a,12,12a- hexahydrochromeno[3,4-b]furo[2,3-h]chromen-6-ol

Conditions	Yield
With sodium tetrahydroborate In methanol at 50℃; for 2h;	98%
With sodium tetrahydroborate In methanol at 0℃; for 3h;	95%
Multi-step reaction with 2 steps 1: two-dimensional iron(II) coordination polymer based on a divergent 4'-(4-diphenylamino)phenyl-4,2';6',4''-terpyridine ligand; potassium tert-butylate / tetrahydrofuran / 4 h / 20 °C / Green chemistry 2: silica gel / ethyl acetate; hexane / 20 °C View Scheme
With sodium tetrahydroborate In methanol at 0 - 20℃; for 2h;

S-(trifluoromethyl)thianthrenium triflate + rotenone (83-79-4) → C24H23F3O6

Conditions	Yield
With caesium carbonate; Benzene-1,2-dithiol In 1,4-dioxane at 10℃; for 7h; Inert atmosphere; Glovebox;	96%

rotenone (83-79-4) → (6aS,12S,12aR,5′R)-12-deoxo-12-hydroxyrotenone (88390-15-2)

Conditions	Yield
With sodium tetrahydroborate In methanol at 20℃; for 2h; Inert atmosphere;	92%
With sodium tetrahydroborate In methanol	85%
With lithium aluminium tetrahydride Reduction;
With lithium aluminium tetrahydride In tetrahydrofuran for 3h; Reduction; Heating;

trifluoromethane sulfonyl chloride (421-83-0) + rotenone (83-79-4) → (2R,6aS,12aS)-2-(2-chloro-4,4,4-trifluorobutan-2-yl)-8,9-dimethoxy-1,2,12,12a-tetrahydrochromeno[3,4-b]furo[2,3-h]chromen-6(6aH)-one

Conditions	Yield
With dipotassium hydrogenphosphate; tris(1,10-phenanthroline)ruthenium(II) dichloride In dichloromethane at 25℃; for 15h; Inert atmosphere; Irradiation; regioselective reaction;	92%
With dipotassium hydrogenphosphate; tris(1,10-phenanthroline)ruthenium(II) dichloride In dichloromethane at 25℃; for 15h; Photolysis; regioselective reaction;	92%
With 2,4,6-trimethyl-pyridine; [Hf6(μ3-O)4(mu3-OH)4(formato)5.9(eosinato Y)0.1(4'-(4-carboxylatophenyl)[2,2':6',2''-terpyridine]-5,5''-dicarboxylato-Fe(OTf)2)2] In acetonitrile at 20℃; for 2h; Catalytic behavior; Inert atmosphere; Schlenk technique; Irradiation;	70%

rotenone (83-79-4) → (2R,6aR,12aS)-8,9-dimethoxy-2-(prop-1-en-2-yl)-1,2,12,12a-tetrahydrochromeno[3,4-b]furo[2,3-h]chromen-6(6aH)-one oxime (3276-14-0, 112838-10-5, 112838-11-6, 112838-12-7)

Conditions	Yield
With hydroxylamine hydrochloride; sodium acetate In ethanol for 10h; Reflux;	91%
With hydroxylamine hydrochloride; sodium acetate In ethanol for 18h; Reflux;	74%
With pyridine; hydroxylamine hydrochloride	70%
With hydroxylamine

rotenone (83-79-4) → ((2R,6aR,12aS)-8,9-dimethoxy-2-(prop-1-en-2-yl)-1,2,12,12a-tetrahydrochromeno[3,4-b]furo[2,3-h]chromen-6(6aH)-ylidene)hydrazine

Conditions	Yield
With sodium acetate; hydrazine hydrate In ethanol at 80℃; for 5h;	91%

6-(trimethylsilyl)hex-5-yn-1-yl 2-cyano-2-diazoacetate (1361382-43-5) + rotenone (83-79-4) → C35H39NO8Si

Conditions	Yield
With Rh2(esp)2 In dichloromethane at 22℃; for 4h; Inert atmosphere; diastereoselective reaction;	88%

rotenone (83-79-4) → (R)-5-(7,8-Dimethoxy-3,3a,4,9b-tetrahydro-chromeno[3,4-c]pyrazol-1-yl)-2-isopropenyl-2,3-dihydro-benzofuran-4-ol

Conditions	Yield
With potassium hydroxide; hydrazine In ethanol Heating;	87%
With hydrazine hydrate In ethanol

rotenone (83-79-4) → (6aS,12aS,5’R)-rotenone hydrobromide (58277-58-0)

Conditions	Yield
With hydrogen bromide; acetic acid at 20℃; for 0.5h;	87%

1,2-propanediene (463-49-0) + rotenone (83-79-4) → C26H28O6

Conditions	Yield
Stage #1: rotenone With copper diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In tetrahydrofuran for 0.0833333h; Inert atmosphere; Stage #2: 1,2-propanediene With (dimethoxy)methylsilane In tetrahydrofuran at 20℃; for 12h; Inert atmosphere; diastereoselective reaction;	86%

phenylhydrazine (100-63-0) + rotenone (83-79-4) → (R)-5-(7,8-Dimethoxy-3-phenyl-3,3a,4,9b-tetrahydro-chromeno[3,4-c]pyrazol-1-yl)-2-isopropenyl-2,3-dihydro-benzofuran-4-ol

Conditions	Yield
With potassium hydroxide In ethanol Heating;	85%

rotenone (83-79-4) → 2-((2R,6aS,12aS)-8,9-dimethoxy-1,2,6,6a,12,12a-hexahydrochromeno[3,4-b]furo[2,3-h]chromen-2-yl)propan-2-ol (30462-22-7)

Conditions	Yield
With iron(III)-acetylacetonate; methyl 4-nitrobenzenesulfonate; phenylsilane; sodium hydrogencarbonate In methanol at 0 - 20℃; for 12h; Schlenk technique; Inert atmosphere; regioselective reaction;	85%
Stage #1: rotenone With mercury(II) diacetate In tetrahydrofuran; water at 20℃; for 18h; Stage #2: With sodium tetrahydroborate; sodium hydrogencarbonate In tetrahydrofuran; water	48%
With sodium tetrahydroborate; mercury(II) diacetate 1) H2O, THF, 20 deg C, 10 h, 2) 30 s; Yield given. Multistep reaction;
Multi-step reaction with 3 steps 1: 1) H2, pyridine / 1) 5percent Pd-BaSO4 2: 0.37 g / m-chloroperbenzoic acid, NaHCO3 / CH2Cl2; H2O / 0.75 h / 19 °C 3: 66 percent / activated Zn-dust / methanol / Ambient temperature View Scheme

rotenone (83-79-4) → 6aS,12aS-8,9-dimethoxy-2-(2-methyloxiran-2-yl)-1,2,12,12a-tetrahydrochromeno[3,4-b]furo[2,3-h]chromen-6(6aH)-one (811451-63-5)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 2h;	85%

methylhydrazine (60-34-4) + rotenone (83-79-4) → (R)-5-(7,8-Dimethoxy-3-methyl-3,3a,4,9b-tetrahydro-chromeno[3,4-c]pyrazol-1-yl)-2-isopropenyl-2,3-dihydro-benzofuran-4-ol

Conditions	Yield
With potassium hydroxide In ethanol Heating;	84%

rotenone (83-79-4) → (6aS,12aS,5′R)-rotenone-6′-norketone (15130-81-1)

Conditions	Yield
With sodium periodate; osmium(VIII) oxide In tetrahydrofuran; water; tert-butyl alcohol	82%
With sodium periodate; osmium(VIII) oxide	46%

rotenone (83-79-4) → 12a-hydroxyrotenone (509-96-6)

Conditions	Yield
With potassium dichromate; acetic acid In water at 20 - 60℃; for 18.5h;	82%
With dichromate anion; acetic acid	51%

rotenone (83-79-4) → (2R,6S,6aS,12aS,2'R,6'S,6'aS,12'aS)-2,2'-Diisopropenyl-8,9,8',9'-tetramethoxy-1,2,12,12a,1',2',12',12'a-octahydro-6aH,6'aH-[6,6']bi[chromeno[3,4-b]furo[2,3-h]chromenyl]-6,6'-diol (82481-44-5)

Conditions	Yield
In acetic acid; acetonitrile electrochemical reduction;	80%
In acetic acid; acetonitrile Product distribution; Mechanism; electrochemical reduction; variation of solvent;	80 % Chromat.

rotenone (83-79-4) → (6aS,12S,12aR,5′R)-6′,7′-dihydro-12-deoxo-12-hydroxyamorphigenin

Conditions	Yield
Stage #1: rotenone With dimethylsulfide borane complex In tetrahydrofuran at 0 - 20℃; for 1.5h; Inert atmosphere; Stage #2: With dihydrogen peroxide; sodium hydroxide In tetrahydrofuran; water at 0 - 20℃; for 18h;	80%
Stage #1: rotenone With borane In tetrahydrofuran Reduction; hydroboration; Stage #2: With sodium hydroxide; dihydrogen peroxide Oxidation;

rotenone (83-79-4) → rotenol (3276-12-8)

Conditions	Yield
In water; acetonitrile electrochemical reduction;	75%
With sodium hydroxide In ethanol Mechanism; Electrochemical reduction; tetrabutylammonium perchlorate, aqueous or aprotic medium;	70%
With sodium hydroxide In ethanol controlled potential electrolysis, tetrabutylammonium perchlorate; other solvent DMF;	70%

ethylamine (75-04-7) + rotenone (83-79-4) → <1-(4-hydroxy-2-methylethenyl-2,3-dihydrobenzofuran-5-yl)-1-(6,7-dimethoxy-2H-chromen-4-yl)methylidene>ethylamine

Conditions	Yield
In ethanol Product distribution; Heating; other amines, also with nitrenonone;	73%
In ethanol Heating;	73%

2-hydroxyethylhydrazine (109-84-2) + rotenone (83-79-4) → (R)-5-[3-(2-Hydroxy-ethyl)-7,8-dimethoxy-3,3a,4,9b-tetrahydro-chromeno[3,4-c]pyrazol-1-yl]-2-isopropenyl-2,3-dihydro-benzofuran-4-ol

Conditions	Yield
With potassium hydroxide In ethanol Heating;	71%

dimethylsulfoxonium methylide (70775-39-2, 5367-24-8) + rotenone (83-79-4) → 6a,12a-methanorotenol

Conditions	Yield
In tetrahydrofuran 1.) room temperature, 10 min, 2.) 45-55 deg C, 50 min;	71%

(Difluoromethyl)triphenylphosphonium bromide (58310-28-4) + rotenone (83-79-4) → (2R,6aS,12aS)-2-(2-bromo-4,4-difluorobutan-2-yl)-8,9-dimethoxy-1,2,12,12a-tetrahydrochromeno[3,4-b]furo[2,3-h]chromen-6(6aH)-one

Conditions	Yield
With tris[2-phenylpyridinato-C2,N]iridium(III); copper(ll) bromide In N,N-dimethyl-formamide at 20℃; for 10h; Schlenk technique; Inert atmosphere; Irradiation;	71%

N-4-methylphenylhydrazine (539-44-6) + rotenone (83-79-4) → (R)-5-(7,8-Dimethoxy-3-p-tolyl-3,3a,4,9b-tetrahydro-chromeno[3,4-c]pyrazol-1-yl)-2-isopropenyl-2,3-dihydro-benzofuran-4-ol

Conditions	Yield
With potassium hydroxide In ethanol Heating;	70%

methyl iodide (74-88-4) + rotenone (83-79-4) → (6aS,12aR,5'R)-/(6aR,12aS,5'R)-12a-methylrotenone (59456-14-3, 143838-84-0, 143838-90-8, 149116-35-8)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 6h;	66%

rotenone (83-79-4) → 1-(4-hydroxy-2-methylethenyl-2,3-dihydrobenzofuran-5-yl)-7,8-dimethoxy-1,9b,3a,4-tetrahydro-2H-<1>-benzopyrano<4,3-d>isoxazol-1-ene

Conditions	Yield
With potassium hydroxide; hydroxylamine hydrochloride In ethanol for 3.5h; Heating;	66%

dibromodifluoromethane (75-61-6) + rotenone (83-79-4) → (2R,6aS,12aS)-2-((R)-4-bromo-4,4-difluorobutan-2-yl)-8,9-dimethoxy-1,2,12,12a-tetrahydrochromeno[3,4-b]furo[2,3-h]-chromen-6(6aH)-one

Conditions	Yield
Stage #1: dibromodifluoromethane; rotenone With tetrahydrofuran; eosin at 20℃; for 5h; Irradiation; Inert atmosphere; Schlenk technique; Stage #2: With potassium hydrogencarbonate for 5h; Inert atmosphere; Irradiation; Cooling with ice; Schlenk technique;	65%

dibromodifluoromethane (75-61-6) + rotenone (83-79-4) → C24H23BrF2O6

Conditions	Yield
With eosin y In tetrahydrofuran at 20℃; for 10h; Inert atmosphere;	65%

Upstream product

• 186581-53-3 diazomethane 
• 34487-52-0 (2R,6aS,12aS)-8-hydroxy-9-methoxy-2-(prop-1-en-2-yl)-1,2,12,12a- tetrahydrochromeno[3,4-b]furo[2,3-h]chromen-6(6aH)-one 
• 3466-09-9 6a,12a-dehydrorotenone 
• 372-18-9 1,3-Difluorobenzene 
• 870-63-3 prenyl bromide 
• 30462-22-7 2-((2R,6aS,12aS)-8,9-dimethoxy-1,2,6,6a,12,12a-hexahydrochromeno[3,4-b]furo[2,3-h]chromen-2-yl)propan-2-ol 
• 23295-59-2 rotenone 6'-norketone enol acetate 
• 15130-81-1 (6aS,12aS,5′R)-rotenone-6′-norketone 
• 509-96-6 12a-hydroxyrotenone 
• 23355-70-6 (6aS,12aS,5'R)-rotenone enol acetate 
• 123000-19-1 (6aR,12aS,5'R)-rotenone 

Downstream Products

• 549-22-4 (+/-)-cis-isorotenone 
• 3466-09-9 6a,12a-dehydrorotenone 
• 105257-32-7 rotenone-isophenylhydrazone 
• 30990-44-4 dehydrorotenone 
• 4439-62-7 Rotenonone 
• 3276-13-9 Derritol 
• 13137-60-5 (6,7-dimethoxy-chroman-4-yl)-(4-hydroxy-2-isopropenyl-2,3-dihydro-benzofuran-5-yl)-methanone 
• 526-48-7 (R)-4-hydroxy-2-isopropenyl-2,3-dihydro-benzofuran-5-carboxylic acid , (-)-tubaic acid 
• 6659-45-6 2R,6aS,12aS-2-isopropyl-8,9-dimethoxy-1,2,12,12a-tetrahydrochromeno[3,4-b]furo[2,3-h]chromen-6(6aH)-one 
• 6544-83-8 rotenone-iso oxime 
• 16431-42-8 6aα,12aα-rotenolone 
• 545-76-6 6aβ,12aα-rotenolone 
• 49715-76-6 6aα,12aβ-rotenolone 
• 509-96-6 12a-hydroxyrotenone 

Relevant articles and documents

ROTENOIDS FROM ROOTS OF MILLETTIA PACHYCARPA

Roots of Millettia pachycarpa furnished rotenone, cis-12a-hydroxyrotenone, rot-2'-enonic acid and cis-12a-hydroxyrot-2'-enonic aicd.Key Word Index - Millettia pachycarpa; Leguminosae; Lototoidae; rotenone; cis-12a-hydroxyrotenone; rot-2'-enonic acid; cis-12a-hydroxyrot-2'-enonic acid.

General Synthetic Approach to Rotenoids via Stereospecific, Group-Selective 1,2-Rearrangement and Dual S N Ar Cyclizations of Aryl Fluorides

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The first stereoselective synthesis of the natural product, rotenone

The total syntheses of rotenone and munduserone are reported in this paper. The synthesis of rotenone involves two key transformations, the first of which is a Pd π-allyl mediated cyclisation for the construction of the dihydrobenzofuran skeleton. The second is a 6-endo-hydroarylation which yields the chromene as a precursor to rotenone. The synthesis of rotenone was achieved in 17 steps from resorcinol and constitutes the first stereoselective synthesis of this complex natural product.

Synthesis of trans-B/C-Rotenoids: X-Ray and NMR Data for cis- and trans-Forms of Isorotenone

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