Oxymercuration Reaction - Wikipedia

Chemical reaction of an alkene with mercuric acetate to form an alcohol

In organic chemistry, the oxymercuration reaction is a chemical reaction that uses mercury salts transforms an alkene (R2C=CR2) into an alcohol. The alkene reacts with mercuric acetate (AcO−Hg−OAc), an electrophile, to yield an organomercury compound, which is subsequently transformed. The intermediate features an acetoxymercury (−HgOAc) group and a hydroxy (−OH) group attached to adjacent carbon atoms. Carbocations are not formed in this process, and thus rearrangements are not observed. The reaction follows Markovnikov's rule (the hydroxy group always add to the more substituted carbon). The oxymercuration part of the reaction involves anti addition of OH group. On the other hand, the demercuration part of the reaction involves free radical mechanism and is not stereospecific, i.e. H and OH may be syn or anti to each other.[2][3][4]

Oxymercuration followed by reductive demercuration is called an oxymercuration–reduction reaction or oxymercuration–demercuration reaction. This reaction, which is almost always done in practice instead of oxymercuration, is treated at the conclusion of the article.

Mechanism

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Oxymercuration can be fully described in three steps (the whole process is sometimes called deoxymercuration), which is illustrated in stepwise fashion to the right. In the first step, the nucleophilic double bond attacks the mercury ion, ejecting an acetoxy group. The electron pair on the mercury ion in turn attacks a carbon on the double bond, forming a mercurinium ion in which the mercury atom bears a positive charge. The electrons in the highest occupied molecular orbital of the double bond are donated to mercury's empty 6s orbital and the electrons in mercury's dxz (or dyz) orbital are donated in the lowest unoccupied molecular orbital of the double bond.

In the second step, the nucleophilic water molecule attacks the more substituted carbon, liberating the electrons participating in its bond with mercury. The electrons collapse to the mercury ion and neutralize it. The oxygen in the water molecule now bears a positive charge.

In the third step, a negatively charged acetate ion deprotonates the alkyloxonium ion, forming the waste product HOAc. The two electrons participating in the bond between oxygen and the attacked hydrogen collapse into the oxygen, neutralizing its charge and creating the final alcohol product.

Regioselectivity and stereochemistry

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Oxymercuration is very regioselective and is a textbook Markovnikov reaction; ruling out extreme cases, the water nucleophile will always preferentially attack the more substituted carbon, depositing the resultant hydroxy group there. This phenomenon is explained by examining the three resonance structures of the mercuronium ion formed at the end of the step one.

By inspection of these structures, it is seen that the positive charge of the mercury atom will sometimes reside on the more substituted carbon (approximately 4% of the time). This forms a temporary tertiary carbocation, which is a very reactive electrophile. The nucleophile will attack the mercuronium ion at this time. Therefore, the nucleophile attacks the more substituted carbon because it retains a more positive character than the lesser substituted carbon.

Stereochemically, oxymercuration is an anti addition. As illustrated by the second step, the nucleophile cannot attack the carbon from the same face as the mercury ion because of steric hindrance. There is simply insufficient room on that face of the molecule to accommodate both a mercury ion and the attacking nucleophile. Therefore, when free rotation is impossible, the hydroxy and acetoxymercuri groups will always be trans to each other.

Shown below is an example of regioselectivity and stereospecificity of the oxymercuration reaction with substituted cyclohexenes. A bulky group like t-butyl locks the ring in a chair conformation and prevents ring flips. With 4-t-butylcyclohexene, oxymercuration yields two products – where addition across the double bond is always anti – with slight preference towards acetoxymercury group trans to the t-butyl group, resulting in slightly more cis product. With 1-methyl-4-t-butylcyclohexene, oxymercuration yields only one product – still anti addition across the double bond – where water only attacks the more substituted carbon. The reason for anti addition across the double bond is to maximize orbital overlap of the lone pair of water and the empty orbital of the mercuronium ion on the opposite side of the acetoxymercury group. Regioselectivity is observed to favor water attacking the more substituted carbon, but water does not add syn across the double bond which implies that the transition state favors water attacking from the opposite side of the acetomercury group.[5]

Oxymercuration–reduction

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In practice, the mercury adduct product created by the oxymercuration reaction is almost always treated with sodium borohydride (NaBH4) in aqueous base in a reaction called demercuration. In demercuration, the acetoxymercury group is replaced with a hydrogen in a stereochemically insensitive reaction[6] known as reductive elimination. The combination of oxymercuration followed immediately by demercuration is called an oxymercuration–reduction reaction.[7]

Therefore, the oxymercuration-reduction reaction is the net addition of water across the double bond. Any stereochemistry set up by the oxymercuration step is scrambled by the demercuration step, so that the hydrogen and hydroxy group may be cis or trans from each other. Oxymercuration reduction is a popular laboratory technique to achieve alkene hydration with Markovnikov selectivity while avoiding carbocation intermediates and thus the rearrangement which can lead to complex product mixtures.

Other applications

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Oxymercuration is not limited to an alkene reacting with water to add hydroxyl and mercury groups. The carbon–mercury structure can undergo spontaneous replacement of the mercury by hydrogen, rather than persisting until a separate reduction step. In this manner, the effect is for mercury to be a Lewis acid catalyst. For example, using an alkyne instead of an alkene yields an enol, which tautomerizes into a ketone. Using an alcohol instead of water yields an ether (see also Hofmann-Sand reaction). In both cases, Markovnikov's rule is observed.

Using a vinyl ether in the presence of an alcohol allows the replacement of one alkoxy group (RO–) for another by way of an acetal intermediate. An allyl alcohol and a vinyl ether under the conditions of oxymercuration–reaction can give R–CH=CH–CH2–O–CH=CH2, which is suitable for a Claisen rearrangement.[8]

See also

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• Hydroboration–oxidation reaction
• Mukaiyama hydration

References

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1. ^ Organic Syntheses OS 6:766 Link
2. ^ Loudon, Marc G. (2002). "Addition Reactions of Alkenes". Organic Chemistry (fourth ed.). Oxford University Press. pp. 165–168.
3. ^ McGraw-Hill Higher Education (2000). Oxymercuration–Demercuration of Alkenes.
4. ^ Andreas Schleifenbaum (2001). "Oxymercuration". Reaktionen, Reagenzien und Prinzipien. Archived from the original on 29 August 2004.
5. ^ Pasto, D. J.; Gontarz, J. A. "Studies on the Mechanism of the Oxymercuration of Substituted Cyclohexenes". Journal of the American Chemical Society (1971), 93, pp 6902–6908.
6. ^ Whitesides, George M.; San Filippo, Joseph Jr. (1970). "Mechanism of reduction of alkylmercuric halides by metal hydrides". J. Am. Chem. Soc. 92 (22): 6611–6624. Bibcode:1970JAChS..92.6611W. doi:10.1021/ja00725a039.
7. ^ Bordwell, Frederick G.; Douglass, Miriam L. "Reduction of Alkylmercuric Hydroxides by Sodium Borohydride". Journal of the American Chemical Society (1966), 88, pp 993–99.
8. ^ McMurry, J. E.; Andrus A.; Ksander G. M.; Muesser, J. H.; Johnson, M. A. "Stereospecific Total Synthesis of Aphidicolin.". Journal of the American Chemical Society (1979), 101, pp 1330–32.

[1]

v t e Alkenes
Alkenes	Ethene (C2H4) Propene (C3H6) Butene (C4H8) Pentene (C5H10) Hexene (C6H12) Heptene (C7H14) Octene (C8H16) Nonene (C9H18) Decene (C10H20) Polyenes
Preparations	Dehydrohalogenation from haloalkane Dehydration reaction from alcohol Semihydrogenation from alkyne Bamford–Stevens reaction Barton–Kellogg reaction Boord olefin synthesis Chugaev elimination Cope reaction Corey–Winter olefin synthesis Grieco elimination Hofmann elimination Horner–Wadsworth–Emmons reaction Hydrazone iodination Julia olefination Kauffmann olefination McMurry reaction Peterson olefination Ramberg–Bäcklund reaction Shapiro reaction Takai olefination Wittig reaction Olefin metathesis Ene reaction Cope rearrangement
Reactions	Hydrogenation Halogenation Hydration Electrophilic addition Oxymercuration reaction Hydroboration Cyclopropanation Epoxidation Dihydroxylation Ozonolysis Hydrohalogenation Polymerization Diels–Alder reaction Wacker process Dehydrogenation Ene reaction Friedel-Crafts Alkylation

v t e Topics in organic reactions
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Orton Passive binding Phosphaethynolate Polar effect Polyfluorene Ring strain Σ-aromaticity Spherical aromaticity Spiroaromaticity Steric effects Superaromaticity Swain–Lupton equation Taft equation Thorpe–Ingold effect Vinylogy Walsh diagram Woodward–Hoffmann rules Woodward's rules Y-aromaticity Yukawa–Tsuno equation Zaitsev's rule Σ-bishomoaromaticity List of organic reactions Carbon-carbon bond forming reactions Acetoacetic ester synthesis Acyloin condensation Aldol condensation Aldol reaction Alkane metathesis Alkyne metathesis Alkyne trimerisation Alkynylation Allan–Robinson reaction Arndt–Eistert reaction Auwers synthesis Aza-Baylis–Hillman reaction Barbier reaction Barton–Kellogg reaction Baylis–Hillman reaction Benary reaction Bergman cyclization Biginelli reaction Bingel reaction Blaise ketone synthesis Blaise reaction Blanc chloromethylation Bodroux–Chichibabin aldehyde synthesis Bouveault aldehyde synthesis Bucherer–Bergs reaction Buchner ring expansion Cadiot–Chodkiewicz coupling Carbonyl allylation Carbonyl olefin metathesis Castro–Stephens coupling Chan rearrangement Chan–Lam coupling Claisen condensation Claisen rearrangement Claisen-Schmidt condensation Combes quinoline synthesis Corey–Fuchs reaction Corey–House synthesis Coupling reaction Cross-coupling reaction Cross dehydrogenative coupling Cross-coupling partner Dakin–West reaction Darzens reaction Diels–Alder reaction Doebner reaction Wulff–Dötz reaction Ene reaction Enyne metathesis Ethenolysis Favorskii reaction Ferrier carbocyclization Friedel–Crafts reaction Fujimoto–Belleau reaction Fujiwara–Moritani reaction Fukuyama coupling Gabriel–Colman rearrangement Gattermann reaction Glaser coupling Grignard reaction Grignard reagent Hammick reaction Heck reaction Henry reaction Heterogeneous metal catalyzed cross-coupling High dilution principle Hiyama coupling Homologation reaction Horner–Wadsworth–Emmons reaction Hydrocyanation Hydrovinylation Hydroxymethylation Ivanov reaction Johnson–Corey–Chaykovsky reaction Julia olefination Julia–Kocienski olefination Kauffmann olefination Knoevenagel condensation Knorr pyrrole synthesis Kolbe–Schmitt reaction Kowalski ester homologation Kulinkovich reaction Kumada coupling Liebeskind–Srogl coupling Malonic ester synthesis Mannich reaction McMurry reaction Meerwein arylation Methylenation Michael reaction Minisci reaction Mizoroki-Heck vs. Reductive Heck Nef isocyanide reaction Nef synthesis Negishi coupling Nierenstein reaction Nitro-Mannich reaction Nozaki–Hiyama–Kishi reaction Olefin conversion technology Olefin metathesis Palladium–NHC complex Passerini reaction Peterson olefination Pfitzinger reaction Piancatelli rearrangement Pinacol coupling reaction Prins reaction Quelet reaction Ramberg–Bäcklund reaction Rauhut–Currier reaction Reformatsky reaction Reimer–Tiemann reaction Rieche formylation Ring-closing metathesis Robinson annulation Sakurai reaction Seyferth–Gilbert homologation Shapiro reaction Sonogashira coupling Stetter reaction Stille reaction Stollé synthesis Stork enamine alkylation Suzuki reaction Takai olefination Thermal rearrangement of aromatic hydrocarbons Thorpe reaction Ugi reaction Ullmann reaction Wagner-Jauregg reaction Weinreb ketone synthesis Wittig reaction Wurtz reaction Wurtz–Fittig reaction Zincke–Suhl reaction Homologation reactions Arndt–Eistert reaction Hooker reaction Kiliani–Fischer synthesis Kowalski ester homologation Methoxymethylenetriphenylphosphorane Seyferth–Gilbert homologation Wittig reaction Olefination reactions Bamford–Stevens reaction Barton–Kellogg reaction Boord olefin synthesis Chugaev elimination Cope reaction Corey–Winter olefin synthesis Dehydrohalogenation Elimination reaction Grieco elimination Hofmann elimination Horner–Wadsworth–Emmons reaction Hydrazone iodination Julia olefination Julia–Kocienski olefination Kauffmann olefination McMurry reaction Peterson olefination Ramberg–Bäcklund reaction Shapiro reaction Takai olefination Wittig reaction Carbon-heteroatom bond forming reactions Azo coupling Bartoli indole synthesis Boudouard reaction Cadogan–Sundberg indole synthesis Diazonium compound Esterification Grignard reagent Haloform reaction Hegedus indole synthesis Hurd–Mori 1,2,3-thiadiazole synthesis Kharasch–Sosnovsky reaction Knorr pyrrole synthesis Leimgruber–Batcho indole synthesis Mukaiyama hydration Nenitzescu indole synthesis Oxymercuration reaction Reed reaction Schotten–Baumann reaction Ullmann condensation Williamson ether synthesis Yamaguchi esterification Degradation reactions Barbier–Wieland degradation Bergmann degradation Edman degradation Emde degradation Gallagher–Hollander degradation Hofmann rearrangement Hooker reaction Isosaccharinic acid Marker degradation Ruff degradation Strecker degradation Von Braun amide degradation Weerman degradation Wohl degradation Organic redox reactions Acyloin condensation Adkins–Peterson reaction Akabori amino-acid reaction Alcohol oxidation Algar–Flynn–Oyamada reaction Amide reduction Andrussow process Angeli–Rimini reaction Aromatization Autoxidation Baeyer–Villiger oxidation Barton–McCombie deoxygenation Bechamp reduction Benkeser reaction Bergmann degradation Birch reduction Bohn–Schmidt reaction Bosch reaction Bouveault–Blanc reduction Boyland–Sims oxidation Cannizzaro reaction Carbonyl reduction Clemmensen reduction Collins oxidation Corey–Itsuno reduction Corey–Kim oxidation Corey–Winter olefin synthesis Criegee oxidation Dakin oxidation Davis oxidation Deoxygenation Dess–Martin oxidation DNA oxidation Elbs persulfate oxidation Emde degradation Eschweiler–Clarke reaction Étard reaction Fischer–Tropsch process Fleming–Tamao oxidation Fukuyama reduction Ganem oxidation Glycol cleavage Griesbaum coozonolysis Grundmann aldehyde synthesis Haloform reaction Hydrogenation Hydrogenolysis Hydroxylation Jones oxidation Kiliani–Fischer synthesis Kolbe electrolysis Kornblum oxidation Kornblum–DeLaMare rearrangement Leuckart reaction Ley oxidation Lindgren oxidation Lipid peroxidation Lombardo methylenation Luche reduction Markó–Lam deoxygenation McFadyen–Stevens reaction Meerwein–Ponndorf–Verley reduction Methionine sulfoxide Miyaura borylation Mozingo reduction Noyori asymmetric hydrogenation Omega oxidation Oppenauer oxidation Oxygen rebound mechanism Ozonolysis Parikh–Doering oxidation Pinnick oxidation Prévost reaction Reduction of nitro compounds Reductive amination Riley oxidation Rosenmund reduction Rubottom oxidation Sabatier reaction Sarett oxidation Selenoxide elimination Shapiro reaction Sharpless asymmetric dihydroxylation Epoxidation of allylic alcohols Sharpless epoxidation Sharpless oxyamination Stahl oxidation Staudinger reaction Stephen aldehyde synthesis Swern oxidation Transfer hydrogenation Wacker process Wharton reaction Whiting reaction Wohl–Aue reaction Wolff–Kishner reduction Wolffenstein–Böters reaction Zinin reaction Rearrangement reactions 1,2-rearrangement 1,2-Wittig rearrangement 2,3-sigmatropic rearrangement 2,3-Wittig rearrangement Achmatowicz reaction Alkyne zipper reaction Allen–Millar–Trippett rearrangement Allylic rearrangement Alpha-ketol rearrangement Amadori rearrangement Arndt–Eistert reaction Aza-Cope rearrangement Baker–Venkataraman rearrangement Bamberger rearrangement Banert cascade Beckmann rearrangement Benzilic acid rearrangement Bergman cyclization Bergmann degradation Boekelheide reaction Brook rearrangement Buchner ring expansion Carroll rearrangement Chan rearrangement Claisen rearrangement Cope rearrangement Corey–Fuchs reaction Cornforth rearrangement Criegee rearrangement Curtius rearrangement Demjanov rearrangement Di-π-methane rearrangement Dimroth rearrangement Divinylcyclopropane-cycloheptadiene rearrangement Dowd–Beckwith ring-expansion reaction Electrocyclic reaction Ene reaction Enyne metathesis Favorskii reaction Favorskii rearrangement Ferrier carbocyclization Ferrier rearrangement Fischer–Hepp rearrangement Fries rearrangement Fritsch–Buttenberg–Wiechell rearrangement Gabriel–Colman rearrangement Group transfer reaction Halogen dance rearrangement Hayashi rearrangement Hofmann rearrangement Hofmann–Martius rearrangement Ireland–Claisen rearrangement Jacobsen rearrangement Kornblum–DeLaMare rearrangement Kowalski ester homologation Lobry de Bruyn–Van Ekenstein transformation Lossen rearrangement McFadyen–Stevens reaction McLafferty rearrangement Meyer–Schuster rearrangement Mislow–Evans rearrangement Mumm rearrangement Myers allene synthesis Nazarov cyclization reaction Neber rearrangement Newman–Kwart rearrangement Overman rearrangement Oxy-Cope rearrangement Pericyclic reaction Piancatelli rearrangement Pinacol rearrangement Pummerer rearrangement Ramberg–Bäcklund reaction Ring expansion and contraction Ring-closing metathesis Rupe reaction Schmidt reaction Semipinacol rearrangement Seyferth–Gilbert homologation Sigmatropic reaction Skattebøl rearrangement Smiles rearrangement Sommelet–Hauser rearrangement Stevens rearrangement Stieglitz rearrangement Thermal rearrangement of aromatic hydrocarbons Tiffeneau–Demjanov rearrangement Vinylcyclopropane rearrangement Wagner–Meerwein rearrangement Wallach rearrangement Weerman degradation Westphalen–Lettré rearrangement Willgerodt rearrangement Wolff rearrangement Ring forming reactions 1,3-Dipolar cycloaddition Annulation Azide-alkyne Huisgen cycloaddition Baeyer–Emmerling indole synthesis Bartoli indole synthesis Bergman cyclization Biginelli reaction Bischler–Möhlau indole synthesis Bischler–Napieralski reaction Blum–Ittah aziridine synthesis Bobbitt reaction Bohlmann–Rahtz pyridine synthesis Borsche–Drechsel cyclization Bucherer carbazole synthesis Bucherer–Bergs reaction Cadogan–Sundberg indole synthesis Camps quinoline synthesis Chichibabin pyridine synthesis Cook–Heilbron thiazole synthesis Cycloaddition Darzens reaction Davis–Beirut reaction De Kimpe aziridine synthesis Debus–Radziszewski imidazole synthesis Dieckmann condensation Diels–Alder reaction Feist–Benary synthesis Ferrario–Ackermann reaction Fiesselmann thiophene synthesis Fischer indole synthesis Fischer oxazole synthesis Friedländer synthesis Gewald reaction Graham reaction Hantzsch pyridine synthesis Hegedus indole synthesis Hemetsberger indole synthesis Hofmann–Löffler reaction Hurd–Mori 1,2,3-thiadiazole synthesis Iodolactonization Isay reaction Jacobsen epoxidation Johnson–Corey–Chaykovsky reaction Knorr pyrrole synthesis Knorr quinoline synthesis Kröhnke pyridine synthesis Kulinkovich reaction Larock indole synthesis Madelung synthesis Nazarov cyclization reaction Nenitzescu indole synthesis Niementowski quinazoline synthesis Niementowski quinoline synthesis Paal–Knorr synthesis Paternò–Büchi reaction Pechmann condensation Petrenko-Kritschenko piperidone synthesis Pictet–Spengler reaction Pomeranz–Fritsch reaction Prilezhaev reaction Pschorr cyclization Reissert indole synthesis Ring-closing metathesis Robinson annulation Sharpless epoxidation Simmons–Smith reaction Skraup reaction Urech hydantoin synthesis Van Leusen reaction Wenker synthesis Cycloaddition 1,3-Dipolar cycloaddition 4+4 Photocycloaddition (4+3) cycloaddition 6+4 Cycloaddition Alkyne trimerisation Aza-Diels–Alder reaction Azide-alkyne Huisgen cycloaddition Bradsher cycloaddition Cheletropic reaction Conia-ene reaction Cyclopropanation Diazoalkane 1,3-dipolar cycloaddition Diels–Alder reaction Enone–alkene cycloadditions Hexadehydro Diels–Alder reaction Intramolecular Diels–Alder cycloaddition Inverse electron-demand Diels–Alder reaction Ketene cycloaddition McCormack reaction Metal-centered cycloaddition reactions Nitrone-olefin (3+2) cycloaddition Oxo-Diels–Alder reaction Ozonolysis Pauson–Khand reaction Povarov reaction Prato reaction Retro-Diels–Alder reaction Staudinger synthesis Trimethylenemethane cycloaddition Vinylcyclopropane (5+2) cycloaddition Wagner-Jauregg reaction Heterocycle forming reactions Algar–Flynn–Oyamada reaction Allan–Robinson reaction Auwers synthesis Bamberger triazine synthesis Banert cascade Barton–Zard reaction Bernthsen acridine synthesis Bischler–Napieralski reaction Bobbitt reaction Boger pyridine synthesis Borsche–Drechsel cyclization Bucherer carbazole synthesis Bucherer–Bergs reaction Chichibabin pyridine synthesis Cook–Heilbron thiazole synthesis Diazoalkane 1,3-dipolar cycloaddition Einhorn–Brunner reaction Erlenmeyer–Plöchl azlactone and amino-acid synthesis Feist–Benary synthesis Fischer oxazole synthesis Gabriel–Colman rearrangement Gewald reaction Hantzsch ester Hantzsch pyridine synthesis Herz reaction Knorr pyrrole synthesis Kröhnke pyridine synthesis Lectka enantioselective beta-lactam synthesis Lehmstedt–Tanasescu reaction Niementowski quinazoline synthesis Nitrone-olefin (3+2) cycloaddition Paal–Knorr synthesis Pellizzari reaction Pictet–Spengler reaction Pomeranz–Fritsch reaction Prilezhaev reaction Robinson–Gabriel synthesis Stollé synthesis Urech hydantoin synthesis Wenker synthesis Wohl–Aue reaction

1. ^ Ambidge, I. C.; Dwight, Stephen K.; Rynard, Carolyn M.; Tidwell, Thomas T. (September 1977). "Structural effects on reactivity in the oxymercuration reaction". Canadian Journal of Chemistry. 55 (17): 3086–3095. doi:10.1139/v77-433. ISSN 0008-4042.