{ "id": "ep7eym5kf2", "slug": "dihydroxylation", "title": "Dihydroxylation", "updated": "2026-09-30", "topic_path": [ { "id": "physical", "label": "Physical world and mathematics", "api_url": "https://www.edgepedia.org/api/v1/topics/physical" }, { "id": "physical.chemistry", "label": "Chemistry", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry" }, { "id": "physical.chemistry.methods", "label": "Chemical principles and methods", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.methods" }, { "id": "physical.chemistry.methods.chemical-synthesis", "label": "Chemical synthesis", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.methods.chemical-synthesis" }, { "id": "physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "label": "Named synthetic methods", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.methods.chemical-synthesis.named-preparative-methods" }, { "id": "physical.chemistry.methods.chemical-synthesis.named-preparative-methods.alpha-2-to-he", "label": "Titles 2 to He", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.methods.chemical-synthesis.named-preparative-methods.alpha-2-to-he" } ], "geo": [ { "id": "geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "label": "Non-geographic · 1800 to 1945: Named synthetic methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "path": [ { "id": "geo.nongeo", "label": "Non-geographic", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo" }, { "id": "geo.nongeo.t1800", "label": "Non-geographic · 1800 to 1945", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800" }, { "id": "geo.nongeo.t1800.physical", "label": "Physical world and mathematics", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical" }, { "id": "geo.nongeo.t1800.physical.chemistry", "label": "Chemistry", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry" }, { "id": "geo.nongeo.t1800.physical.chemistry.methods", "label": "Chemical principles and methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry.methods" }, { "id": "geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis", "label": "Chemical synthesis", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis" }, { "id": "geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "label": "Named synthetic methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis.named-preparative-methods" } ] }, { "id": "geo.nongeo.t1946.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "label": "Non-geographic · 1946 to 2000: Named synthetic methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "path": [ { "id": "geo.nongeo", "label": "Non-geographic", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo" }, { "id": "geo.nongeo.t1946", "label": "Non-geographic · 1946 to 2000", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946" }, { "id": "geo.nongeo.t1946.physical", "label": "Physical world and mathematics", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.physical" }, { "id": "geo.nongeo.t1946.physical.chemistry", "label": "Chemistry", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.physical.chemistry" }, { "id": "geo.nongeo.t1946.physical.chemistry.methods", "label": "Chemical principles and methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.physical.chemistry.methods" }, { "id": "geo.nongeo.t1946.physical.chemistry.methods.chemical-synthesis", "label": "Chemical synthesis", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.physical.chemistry.methods.chemical-synthesis" }, { "id": "geo.nongeo.t1946.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "label": "Named synthetic methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.physical.chemistry.methods.chemical-synthesis.named-preparative-methods" } ] } ], "excerpt": "Dihydroxylation is the addition of two hydroxyl groups across an alkene's double bond to give a vicinal diol, done syn with osmium tetroxide or anti via epoxidation and hydrolysis.", "snippet": "Dihydroxylation is the addition of two hydroxyl groups across an alkene's double bond to give a vicinal diol, done syn with osmium tetroxide or anti via epoxidation and hydrolysis.", "node": "physical.chemistry.methods.chemical-synthesis.named-preparative-methods.alpha-2-to-he", "markdown": "# Dihydroxylation\n\nDihydroxylation is the addition of two hydroxyl groups across the double bond of an alkene to give a vicinal diol, a 1,2-glycol in which the two oxygen atoms are delivered to the same face (syn) or opposite faces (anti) of the original π-bond.[1](https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_%28Organic_Chemistry%29/Alkenes/Reactivity_of_Alkenes/Vicinal_Syn_Dihydroxylation) [Osmium tetroxide](https://www.edgepedia.org/osmium-tetroxide) (OsO4) is the reagent of choice for the syn variant because it stereospecifically produces cis-1,2-glycols, tolerates a wide array of functional groups, and gives few over-oxidation products.[2](https://www.organicreactions.org/pubchapter/asymmetric-dihydroxylation-of-alkenes/) • [1](https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_%28Organic_Chemistry%29/Alkenes/Reactivity_of_Alkenes/Vicinal_Syn_Dihydroxylation) • [3](https://www.organicreactions.org/pubchapter/hydrogen-bonding-mediated-directed-osmium-dihydroxylation/) Osmium-catalyzed dihydroxylation converts mono-, di-, and trisubstituted alkenes to vicinal diols, and tetrasubstituted alkenes also react in several cases.[4](https://science-of-synthesis.thieme.com/app/text/?id=SD-201-00003) With a chiral cinchona-alkaloid ligand, the reaction becomes the [Sharpless asymmetric dihydroxylation](https://www.edgepedia.org/sharpless-asymmetric-dihydroxylation) (AD), one of the standard ways to make enantioenriched diols.\n\n| Key fact | Detail |\n|---|---|\n| Product | Stereospecific cis-1,2-glycol; syn addition, tolerant of many functional groups[2](https://www.organicreactions.org/pubchapter/asymmetric-dihydroxylation-of-alkenes/) |\n| Mechanism | Concerted \\( [3+2] \\) cycloaddition of OsO4 to the alkene through a cyclic osmate ester[1](https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_%28Organic_Chemistry%29/Alkenes/Reactivity_of_Alkenes/Vicinal_Syn_Dihydroxylation) |\n| AD-mix recipe | 1.4 g per mmol olefin: K3Fe(CN)6 (3 mmol), K2CO3 (3 mmol), (DHQD)2- or (DHQ)2-PHAL (0.01 mmol), K2OsO2(OH)4 (0.004 mmol)[5](https://www.york.ac.uk/res/pac/teaching/cr00032a009.pdf) • [6](https://myers.faculty.chemistry.harvard.edu/sites/g/files/omnuum7271/files/myers/files/23-sharpless_asymmetric_dihydroxylation_reaction.pdf) |\n| Enantiomer prediction | DHQD ligands deliver hydroxyls from the re face to give R or R,R diols; DHQ ligands deliver from the si face to give S or S,S diols[7](https://patents.google.com/patent/US5516929A/en) |\n| Standard AD loading | 0.4 mol % Os, 1 mol % PHAL ligand, 3 equiv K3Fe(CN)6/K2CO3, 1:1 t-BuOH/H2O, 0 °C[5](https://www.york.ac.uk/res/pac/teaching/cr00032a009.pdf) |\n| Main waste stream | Stoichiometric ferricyanide generates about 8.1 kg of iron salts per kg of diol product[8](https://pubs.chemsoc.org.cn/doi/full/10.31635/ccschem.022.202201780) |\n| Os-free option | Chiral cinchoninium-catalyzed permanganate dihydroxylation of enoates gives diols in up to 98% ee[9](https://pubs.rsc.org/en/content/articlelanding/2024/qo/d3qo01729j) |\n\n## How it works\n\nOsO4 adds to the alkene in a single concerted step to form a cyclic osmate ester, with no rearrangements; hydrolysis of this ester releases the syn-diol and an osmium(VI) species.[1](https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_%28Organic_Chemistry%29/Alkenes/Reactivity_of_Alkenes/Vicinal_Syn_Dihydroxylation) Because addition is concerted and suprafacial, a cis alkene gives a meso diol when the product has the required symmetry, and a trans alkene gives a racemic mixture when achiral OsO4 is used alone.[1](https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_%28Organic_Chemistry%29/Alkenes/Reactivity_of_Alkenes/Vicinal_Syn_Dihydroxylation) • [30](https://cuny.manifoldapp.org/read/organic-chemistry-i/section/cff6c80f-cf95-4f90-a22b-195972675b59) Coordinating amine ligands such as triethylamine, quinuclidine, or diazabicyclooctane accelerate the osmylation by several orders of magnitude.[2](https://www.organicreactions.org/pubchapter/asymmetric-dihydroxylation-of-alkenes/)\n\nTwo mechanistic pictures were debated: direct \\( [3+2] \\) cycloaddition versus a \\( [2+2] \\) addition followed by rearrangement. Quantum chemical calculations found the \\( [3+2] \\) addition energetically more favorable,[10](https://www.organic-chemistry.org/namedreactions/upjohn-dihydroxylation.shtm) and experimental and theoretical [kinetic isotope effects](https://www.edgepedia.org/kinetic-isotope-effect) support a rate-limiting \\( [3+2] \\) cycloaddition.[11](https://doi.org/10.1021/ja971650e) In the catalytic asymmetric process, a ligand-free \"second cycle\" competes when reoxidation outpaces hydrolysis of the osmium(VI) glycolate, lowering enantioselectivity; it is suppressed by slow olefin addition or higher ligand concentration.[6](https://myers.faculty.chemistry.harvard.edu/sites/g/files/omnuum7271/files/myers/files/23-sharpless_asymmetric_dihydroxylation_reaction.pdf)\n\n## How it is done\n\n**Upjohn dihydroxylation** uses catalytic OsO4 with a stoichiometric amount of N-methylmorpholine N-oxide (NMO), which reoxidizes Os(VI) back to Os(VIII) and thereby makes the osmium catalytic; no chiral ligand is used, and the purpose is racemic syn-diol synthesis.[10](https://www.organic-chemistry.org/namedreactions/upjohn-dihydroxylation.shtm)\n\n**Sharpless AD** adds a cinchona ligand and uses ferricyanide as the co-oxidant. Because OsO4 is volatile and toxic, osmium is usually charged as K2OsO2(OH)4, which forms OsO4 in situ; K2CO3 and methanesulfonamide are rate-enhancing additives, and K3Fe(CN)6 reoxidizes Os(VI) after each catalytic cycle.[12](https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Catalytic_Asymmetric_Synthesis_%28Punniyamurthy%29/05%3A_Oxidation_Reactions/5.06%3A_Dihydroxylation_Aminohydroxylation_and_Aziridination_Reactions) The standard procedure runs 1.4 g of AD-mix per mmol of olefin in 1:1 t-BuOH/H2O at 0 °C for 6–24 h, followed by a Na2SO3 work-up and extraction.[5](https://www.york.ac.uk/res/pac/teaching/cr00032a009.pdf) • [6](https://myers.faculty.chemistry.harvard.edu/sites/g/files/omnuum7271/files/myers/files/23-sharpless_asymmetric_dihydroxylation_reaction.pdf) AD-mix-α contains (DHQ)2-PHAL and AD-mix-β contains (DHQD)2-PHAL; the two give pseudo-enantiomeric diols.[13](https://www.mdpi.com/1420-3049/28/6/2722) The Sharpless mnemonic predicts which enantiomer forms for six olefin substitution classes (tetra-, tri-, trans-di-, gem-di-, mono-, and cis-disubstituted), with trans-disubstituted olefins reaching more than 99.5% ee; cis-disubstituted olefins are generally poor substrates, though DHQD-IND or (DHQD)2AQN ligands give fair-to-good results.[6](https://myers.faculty.chemistry.harvard.edu/sites/g/files/omnuum7271/files/myers/files/23-sharpless_asymmetric_dihydroxylation_reaction.pdf) MeSO2NH2 accelerates hydrolysis of the osmium(VI) glycolate so reaction times can be up to 50 times shorter, extending the reaction to tetrasubstituted olefins.[5](https://www.york.ac.uk/res/pac/teaching/cr00032a009.pdf) The two-phase ferricyanide conditions virtually eliminate the non-enantioselective second cycle seen under homogeneous NMO conditions.[5](https://www.york.ac.uk/res/pac/teaching/cr00032a009.pdf)\n\n## Origin\n\nThe first application of OsO4 to alkene dihydroxylation is reported in O. Makowka's \"Zur Kenntnis des Osmiums\" (Berichte der deutschen chemischen Gesellschaft, 1908).[14](https://doi.org/10.1002/cber.190804101182) [Asymmetric induction](https://www.edgepedia.org/asymmetric-induction) entered the field with Steven G. Hentges and [K. Barry Sharpless](https://www.edgepedia.org/k-barry-sharpless)'s 1980 [Journal of the American Chemical Society](https://www.edgepedia.org/journal-of-the-american-chemical-society) paper on the reaction of osmium tetroxide with olefins, which used stoichiometric osmium and dihydroquinine/dihydroquinidine acetate ligands to give 25–90% ee.[15](https://doi.org/10.1021/ja00532a050) • [16](https://www.sciencedirect.com/science/article/abs/pii/S0022328X05009307) Published accounts place the advent of catalytic asymmetric turnover with NMO as co-oxidant in 1987 or 1988, a discrepancy the published literature does not settle.[5](https://www.york.ac.uk/res/pac/teaching/cr00032a009.pdf) • [16](https://www.sciencedirect.com/science/article/abs/pii/S0022328X05009307) Hoi-Lun Kwong and colleagues reported in Tetrahedron Letters (1990) that precluding the second cycle with ferricyanide leads to a superior process.[17](https://doi.org/10.1016/s0040-4039%2800%2989008-5) The PHAL ligand class and process improvement were reported by K. Barry Sharpless and colleagues in The Journal of Organic Chemistry (1992),[18](https://doi.org/10.1021/jo00036a003) and the method was consolidated in Hartmuth C. Kolb, Michael S. VanNieuwenhze, and K. Barry Sharpless's 1994 Chemical Reviews review \"Catalytic Asymmetric Dihydroxylation\".[19](https://doi.org/10.1021/cr00032a009) Albert J. DelMonte and colleagues provided the kinetic isotope effect evidence for the rate-limiting \\( [3+2] \\) cycloaddition in 1997.[11](https://doi.org/10.1021/ja971650e) The mnemonic device was updated using Q2MM modeling and competition kinetics, which also rationalized ligand-accelerated catalysis through substrate stabilization by the ligand's aromatic linker.[20](https://onlinelibrary.wiley.com/doi/10.1002/chir.10214)\n\n## Variants\n\n**Anti-diols.** The epoxidation–hydrolysis sequence constitutes an anti dihydroxylation of an alkene and complements syn methods.[1](https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_%28Organic_Chemistry%29/Alkenes/Reactivity_of_Alkenes/Vicinal_Syn_Dihydroxylation) A chiral molybdenum-bishydroxamic acid complex catalyzes anti-dihydroxylation of allylic alcohols with H2O2, giving 1,2,3-triols with dr greater than 95:5; mechanistic studies show an initial enantioselective epoxidation followed by in situ regioselective ring opening, both promoted by the molybdenum catalyst.[21](https://www.nature.com/articles/s42004-019-0208-2)\n\n**Other syn oxidants.** KMnO4 gives syn diols but suffers overoxidation and poor yields,[1](https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_%28Organic_Chemistry%29/Alkenes/Reactivity_of_Alkenes/Vicinal_Syn_Dihydroxylation) and because of the poor selectivity of permanganate and RuO4–H2O2 systems, OsO4 remains the most prominent route to 1,2-diols.[22](https://science-of-synthesis.thieme.com/app/text/?id=SD-036-00592) [Ruthenium](https://www.edgepedia.org/ruthenium) tetroxide with NaIO4 in acetone/water is a major osmium-free alternative, and mechanistic studies confirmed the ruthenium reaction also proceeds via a \\( [3+2] \\) adduct.[23](https://pubs.rsc.org/en/content/articlehtml/2011/cs/b923880h) Selenoxide co-oxidant (SeOAD) and air/selenide (SeAD, rose bengal sensitized) variants reproduce AD-mix results with far less reagent per mmol of substrate.[24](https://list.iupac.org/publications/pac/2002/pdf/7401x0107.pdf) An asymmetric phase-transfer dihydroxylation was reported by Riaz A. Bhunnoo, Yulai Hu, Dramane I. Lainé, and Richard C. D. Brown in [Angewandte Chemie](https://www.edgepedia.org/angewandte-chemie) (2002).[25](https://doi.org/10.1002/1521-3773%2820020916%2941:18<3479::aid-anie3479>3.0.co;2-o) Enantioselective permanganate oxidation of alkenes catalyzed by chiral dicationic bisguanidinium was reported by Chao Wang, Lili Zong, and Choon-Hong Tan in JACS (2015).[26](https://doi.org/10.1021/jacs.5b05792) Chiral cinchoninium-catalyzed permanganate dihydroxylation of enoates under phase-transfer conditions gives chiral vicinal diols in moderate to good yields with up to 98% ee without osmium reagents; tetrasubstituted enoates were oxidized smoothly to vicinal tertiary diols, a result not achieved by other catalytic AD systems.[9](https://pubs.rsc.org/en/content/articlelanding/2024/qo/d3qo01729j) A nonheme manganese complex with a tetradentate aminopyridine ligand catalyzes asymmetric cis-dihydroxylation of 1,4-quinones with hydrogen peroxide and alkyl hydroperoxides, giving cis-1,2-diols with up to 99% ee and complete diastereoselectivity.[27](https://pubs.acs.org/doi/pdf/10.1021/jacs.5c20048) [Nonheme iron](https://www.edgepedia.org/nonheme-iron) and manganese complexes designed as functional mimics of Rieske dioxygenases, enzymes that incorporate both oxygen atoms of O2 into cis-dihydrodiol products, provide further osmium-free cis-dihydroxylations.[8](https://pubs.chemsoc.org.cn/doi/full/10.31635/ccschem.022.202201780) • [28](https://sioc-journal.cn/Jwk_yjhx/EN/10.6023/cjoc202504015) Reviews of the field note a growing landscape of Os-free asymmetric syn-dihydroxylations, including chiral Mn and Fe complexes, bimetallic nanoclusters, and organic phase-transfer catalysts, driven by osmium's toxicity and cost.[21](https://www.nature.com/articles/s42004-019-0208-2) • [29](https://google.iopscience.iop.org/article/10.1070/RCR4904)\n\n## Applications\n\nAD has been a key enantioselective step since 2020 in total syntheses of alkaloids, lactones, polyketides, macrolides, glycosides, and terpenes, typically delivering vicinal diols in good yield and high enantioselectivity.[13](https://www.mdpi.com/1420-3049/28/6/2722) A lomaiviticin aglycon precursor was made on more than 20 g scale with 0.25 mol % K2OsO4·2H2O and 0.5 mol % (DHQ)2AQN, giving 81% yield and more than 95% ee after recrystallization.[6](https://myers.faculty.chemistry.harvard.edu/sites/g/files/omnuum7271/files/myers/files/23-sharpless_asymmetric_dihydroxylation_reaction.pdf) On industrial scale, a 2.5 kg (13 mol) run with 0.7 mol % K2OsO2(OH)4 and 7.7 mol % (DHQ)2PHAL in aqueous NMO at 20 °C gave 90% ee, and a 15.38 kg (105.2 mol) run with 0.2 mol % osmate, 1 mol % ligand, and 3.5 mol % ferricyanide at 0–5 °C gave 99.4% ee.[6](https://myers.faculty.chemistry.harvard.edu/sites/g/files/omnuum7271/files/myers/files/23-sharpless_asymmetric_dihydroxylation_reaction.pdf) A chiral intermediate for (R)-bicalutamide was obtained efficiently by permanganate dihydroxylation of a methacrylic acid derivative.[9](https://pubs.rsc.org/en/content/articlelanding/2024/qo/d3qo01729j) Asymmetric dihydroxylation of olefinic groups is widely used to obtain optically pure pharmaceuticals and other fine chemicals.[29](https://google.iopscience.iop.org/article/10.1070/RCR4904)\n\n## Limitations and alternatives\n\nOsO4 is expensive, highly toxic, and volatile, which is why catalytic osmium with a stoichiometric co-oxidant is standard.[1](https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_%28Organic_Chemistry%29/Alkenes/Reactivity_of_Alkenes/Vicinal_Syn_Dihydroxylation) • [12](https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Catalytic_Asymmetric_Synthesis_%28Punniyamurthy%29/05%3A_Oxidation_Reactions/5.06%3A_Dihydroxylation_Aminohydroxylation_and_Aziridination_Reactions) The early inorganic co-oxidants, sodium or potassium chlorate and hydrogen peroxide, can diminish yields through overoxidation; alkaline tert-butyl hydroperoxide and NMO give much better results.[5](https://www.york.ac.uk/res/pac/teaching/cr00032a009.pdf) Stoichiometric ferricyanide leaves about 8.1 kg of iron salts per kg of diol product as by-product.[8](https://pubs.chemsoc.org.cn/doi/full/10.31635/ccschem.022.202201780) Substrate scope has limits: cis-disubstituted olefins are generally poor AD substrates,[6](https://myers.faculty.chemistry.harvard.edu/sites/g/files/omnuum7271/files/myers/files/23-sharpless_asymmetric_dihydroxylation_reaction.pdf) and (E)-alkyl crotonates are among the most challenging, giving cis-diols with only 80–92% ee because of low steric recognition.[8](https://pubs.chemsoc.org.cn/doi/full/10.31635/ccschem.022.202201780) Where anti diols are needed, epoxidation–hydrolysis or molybdenum-catalyzed anti-dihydroxylation are the complementary choices.[1](https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_%28Organic_Chemistry%29/Alkenes/Reactivity_of_Alkenes/Vicinal_Syn_Dihydroxylation) • [21](https://www.nature.com/articles/s42004-019-0208-2)\n\n## References\n\n1. [Vicinal Syn Dihydroxylation (chem.libretexts.org)](https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_%28Organic_Chemistry%29/Alkenes/Reactivity_of_Alkenes/Vicinal_Syn_Dihydroxylation)\n2. [Asymmetric Dihydroxylation of Alkenes, Organic Reactions Vol. 66 (Noe, Letavic, Snow, McCombie, 2005)](https://www.organicreactions.org/pubchapter/asymmetric-dihydroxylation-of-alkenes/)\n3. [Hydrogen-bonding-mediated Directed Osmium Dihydroxylation (Organic Reactions, vol. 76, 2012)](https://www.organicreactions.org/pubchapter/hydrogen-bonding-mediated-directed-osmium-dihydroxylation/)\n4. [Science of Synthesis: Stereoselective Synthesis, 1, 5 (Muñiz, 2011), 1,2-Dihydroxylation of Alkenes, DOI 10.1055/sos-SD-201-00002](https://science-of-synthesis.thieme.com/app/text/?id=SD-201-00003)\n5. [Catalytic Asymmetric Dihydroxylation (Kolb, VanNieuwenhze, Sharpless, Chem. Rev. 1994, 94, 2483–2547)](https://www.york.ac.uk/res/pac/teaching/cr00032a009.pdf)\n6. [Myers Chem 115: Sharpless Asymmetric Dihydroxylation Reaction (Harvard lecture notes)](https://myers.faculty.chemistry.harvard.edu/sites/g/files/omnuum7271/files/myers/files/23-sharpless_asymmetric_dihydroxylation_reaction.pdf)\n7. [US5516929A - Method for catalytic asymmetric dihydroxylation of olefins using heterocyclic chiral ligands](https://patents.google.com/patent/US5516929A/en)\n8. [Nonheme Iron-Catalyzed Enantioselective cis-Dihydroxylation of Aliphatic Acrylates as Mimics of Rieske Dioxygenases (CCS Chemistry)](https://pubs.chemsoc.org.cn/doi/full/10.31635/ccschem.022.202201780)\n9. [Asymmetric permanganate dihydroxylation of enoates: substrate scope, mechanistic insights and application in bicalutamide synthesis (Organic Chemistry Frontiers, 2024, 11, 836)](https://pubs.rsc.org/en/content/articlelanding/2024/qo/d3qo01729j)\n10. [Upjohn Dihydroxylation (named-reaction page)](https://www.organic-chemistry.org/namedreactions/upjohn-dihydroxylation.shtm)\n11. [Albert J. DelMonte and colleagues (1997). Experimental and Theoretical Kinetic Isotope Effects for Asymmetric Dihydroxylation. Evidence Supporting a Rate-Limiting “(3 + 2)” Cycloaddition. Journal of the American Chemical Society.](https://doi.org/10.1021/ja971650e)\n12. [5.06: Dihydroxylation Aminohydroxylation and Aziridination Reactions (chem.libretexts.org)](https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Catalytic_Asymmetric_Synthesis_%28Punniyamurthy%29/05%3A_Oxidation_Reactions/5.06%3A_Dihydroxylation_Aminohydroxylation_and_Aziridination_Reactions)\n13. [Sharpless Asymmetric Dihydroxylation: An Impressive Gadget for the Synthesis of Natural Products: A Review (Molecules 2023, 28, 2722)](https://www.mdpi.com/1420-3049/28/6/2722)\n14. [O. Makowka (1908). Zur Kenntnis des Osmiums. Berichte der deutschen chemischen Gesellschaft.](https://doi.org/10.1002/cber.190804101182)\n15. [Steven G. Hentges, K. Barry Sharpless (1980). 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[cuny.manifoldapp.org](https://cuny.manifoldapp.org/read/organic-chemistry-i/section/cff6c80f-cf95-4f90-a22b-195972675b59)\n\n---\n*Topic: Encyclopedia › Physical world and mathematics › Chemistry › Chemical principles and methods › Chemical synthesis › Named synthetic methods › Titles 2 to He*\n\n*Initially written Sep 29, 2026 · Reviewed: Sep 30, 2026 · Edited: Sep 30, 2026 · Last review: Sep 30, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n", "same_as": [], "url": "https://www.edgepedia.org/dihydroxylation", "markdown_url": "https://www.edgepedia.org/dihydroxylation.md", "license": { "name": "Edgepedia Community License 1.0", "url": "https://www.edgepedia.org/edgepedia/license", "summary": "Free with credit, commercial use included. AI training is open to everyone. For other uses, organizations over USD 100M in revenue or 100M monthly users license separately.", "spdx": "LicenseRef-Edgepedia-Community-1.0" }, "credit": "\"Dihydroxylation\", Edgepedia (EdgeChat), https://www.edgepedia.org/dihydroxylation. Edgepedia Community License 1.0.", "credit_md": "\"[Dihydroxylation](https://www.edgepedia.org/dihydroxylation)\", Edgepedia (EdgeChat), [https://www.edgepedia.org/dihydroxylation](https://www.edgepedia.org/dihydroxylation). [Edgepedia Community License 1.0](https://www.edgepedia.org/edgepedia/license).", "credit_html": "\"Dihydroxylation\", Edgepedia (EdgeChat), https://www.edgepedia.org/dihydroxylation. Edgepedia Community License 1.0.", "speakable": "Dihydroxylation is the addition of two hydroxyl groups across an alkene's double bond to give a vicinal diol, done syn with osmium tetroxide or anti via epoxidation and hydrolysis." }