Wacker process

The Wacker process was one of the first homogeneous catalysis with organopalladium chemistry applied on an industrial scale.Elschenbroich, C. "Organometallics" (2006) Wiley-VCH: Weinheim. {{ISBN|978-3-527-29390-2}}

In an 1893 doctoral dissertation on Pennsylvanian natural gas, Francis Clifford Phillips had reported that palladium(II) chloride oxidized ethylene to acetaldehyde, but the reaction required stoichiometric quantities of palladium.{{Cite journal|last=Phillips |first=Francis C. |date=March–June 1894 |title=Researches upon the phenomena of oxidation and chemical properties of gases |url={{GBUrl|id=IDogE3L1RLkC|p=163}} |journal=American Chemical Journal |volume=16 |issue=3–6 |pages=163-187, 255-277, 340-365, 406-429 |quote=The reaction between ethylene and palladium chloride in solution is of the second class and complete, the gas being rapidly absorbed. Palladium is deposited as a black powder, but no trace of oxidation to carbon dioxide occurs. The reaction is almost the same in the cold and at 100°. The gas escaping from the palladium-chloride solution (after complete reduction to metallic palladium) produces no precipitate in lime-water. The reaction between palladium chloride and ethylene leads to the production of aldehyde. |via=Google Books}} It remained a niche curiosity until Wacker Chemie began developing its eponymous process in 1956.Acetaldehyde from Ethylene — A Retrospective on the Discovery of the Wacker Process Reinhard Jira Angew. Chem. Int. Ed. 2009, 48, 9034–9037 {{doi|10.1002/anie.200903992}}

At the time, many industrial compounds were produced via acetaldehyde from acetylene, itself from calcium carbide. The overall route exhibited poor thermodynamic efficiency and required great expense. Esso sought to market waste olefins from a new, under-construction oil refinery in Cologne close to a Wacker site. Wacker realized that ethylene would be a cheaper feedstock than acetylene, and began to investigate catalytic oxidation to ethylene oxide.

To Wacker's surprise, they smelled{{#tag:ref|Wacker lacked a gas chromatograph at the time.|group="Note"}} not ethylene oxide but acetaldehyde in the product stream. From Phillips' dissertation, known properties of Zeise's salt, and transformation of the catalyst over the course of a batch reaction, Wacker realized that they needed to reoxidize the palladium to close the catalytic cycle. They began publishing the process outline in 1957.J. Smidt, W. Hafner, R. Jira, J. Sedlmeier, R. Sieber, R. Rüttinger, and H. Kojer, Angew. Chem., 1959, 71, 176–182. {{doi|10.1002/ange.19590710503}}J. Smidt, W. Hafner, J. Sedlmeier, R. Jira, R. Rottinger (Cons. f.elektrochem.Ind.), DE 1 049 845, 1959, Anm. 04.01.1957. However, poor patenting strategy allowed parent corporation Hoechst AG to outrace Wacker to the optimal catalysis conditions.W. Hafner, R. Jira, J. Sedlmeier, and J. Smidt, Chem. Ber., 1962, 95, 1575–1581. {{Doi|10.1002/cber.19620950702}}J. Smidt, W. Hafner, R. Jira, R. Sieber, J. Sedlmeier, and A. Sabel, Angew. Chem. Int. Ed. Engl., 1962, 1, 80–88.

Wacker-Hoechst began jointly constructing pilot plants in 1958, but the relatively aggressive reaction conditions required the first large-scale use of titanium metal in the European chemical industry to protect against corrosion. Production plants started operation in 1960.

The process also sparked a boom in organopalladium chemistry. Studies from the 1960s elucidated several key points about the reaction mechanism through kinetic isotope effects (or lack thereof) and stereochemistry.Henry, Patrick M. In Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley & Sons: New York, 2002; p 2119. {{ISBN|0-471-31506-0}}{{cite journal |author=J. A. Keith |author2=P. M. Henry |year=2009 |title=The Mechanism of the Wacker Reaction: A Tale of Two Hydroxypalladations |journal=Angew. Chem. Int. Ed. |volume=48 |issue=48 |pages=9038–9049 |doi=10.1002/anie.200902194 |pmid=19834921}} Many focused on the hydroxypalladation step, which forms the C–O bond. Early reactions used conditions much milder than the industrial plants and obtained contradictory results; the modern consensus is that the step's stereochemistry is quite sensitive to chloride concentrations.

Other studies investigated reaction's application to more complex terminal olefins. High-order olefins are insoluble in water, but Clement and Selwitz{{Cite journal |last1=Clement |first1=William H. |last2=Selwitz |first2=Charles M. |date=January 1964 |title=Improved Procedures for Converting Higher α-Olefins to Methyl Ketones with Palladium Chloride |journal=The Journal of Organic Chemistry |volume=29 |issue=1 |pages=241–243 |doi=10.1021/jo01024a517 |issn=0022-3263}} found that aqueous DMF as solvent allowed for the oxidation of 1-dodecene to 2-dodecanone. Fahey{{Cite journal |last1=Fahey |first1=Darryl R. |last2=Zeuch |first2=Ernest A. |date=November 1974 |title=Aqueous sulfolane as solvent for rapid oxidation of higher .alpha.-olefins to ketones using palladium chloride |journal=The Journal of Organic Chemistry |volume=39 |issue=22 |pages=3276–3277 |doi=10.1021/jo00936a023 |issn=0022-3263}} noted the use of 3-methylsulfolane in place of DMF as solvent increased the yield of oxidation of 3,3-Dimethylbut-1-ene. Two years after, Tsuji{{Cite journal |last1=Tsuji |first1=Jiro |last2=Shimizu |first2=Isao |last3=Yamamoto |first3=Keiji |date=August 1976 |title=Convenient general synthetic method for 1,4- and 1,5-diketones by palladium catalyzed oxidation of α-allyl and α-3-butenyl ketones |journal=Tetrahedron Letters |volume=17 |issue=34 |pages=2975–2976 |doi=10.1016/s0040-4039(01)85504-0 |issn=0040-4039}} applied the Clement-Selwitz conditions for selective oxidations of terminal olefins with multiple functional groups, and demonstrated its utility in synthesis of complex substrates.{{Cite journal |last=Tsuji |first=Jiro |date=1984 |title=Synthetic Applications of the Palladium-Catalyzed Oxidation of Olefins to Ketones |journal=Synthesis |volume=1984 |issue=5 |pages=369–384 |doi=10.1055/s-1984-30848 |issn=0039-7881 |s2cid=95604861}}

Carbonylation has mainly superseded the Wacker process for modern bulk chemical synthesis, but small-scale Tsuji-Wacker reactions remain important for fine chemical and laboratory-scale syntheses.

The reaction mechanism for the industrial Wacker process (olefin oxidation via palladium(II) chloride) has received significant attention for several decades. Aspects of the mechanism are still debated. A modern formulation is described below:{{Cite book |last1=Kurti |first1=Laszlo |title=Strategic Applications of named Reactions in Organic Synthesis |last2=Czako |first2=Barbara |publisher=Elsevier Academic Press |year=2005 |isbn=978-0-12-429785-2 |location=525 B Street, Suite 1900, San Diego, California 92101-4495, USA |page=474}}

File:wackonwackoff_updated.tif

This reaction can also be described as follows:

:[PdCl₄]^{2 −} + C₂H₄ + H₂O → CH₃CHO + Pd + 2 HCl + 2 Cl⁻,

followed by reactions that regenerate the Pd(II) catalyst:

: Pd + 2 CuCl₂ + 2 Cl ⁻ → [PdCl₄]²⁻ + 2 CuCl

: 2 CuCl + {{sfrac|1|2}} O₂ + 2 HCl → 2 CuCl₂ + H₂O

Only the alkene and oxygen are consumed. Without copper(II) chloride as an oxidizing agent, Pd(0) metal (resulting from beta-hydride elimination of Pd(II) in the final step) would precipitate, stopping Philips' reaction after one cycle. Air, pure oxygen, or a number of other reagents can then oxidise the resultant CuCl-chloride mixture back to CuCl₂, allowing the cycle to continue.

High concentrations of chloride and copper(II) chloride favor formation of a new product, ethylene chlorohydrin.H. Stangl and R. Jira, Tetrahedron Lett., 1970, 11, 3589–3592

Evidence for the overall mechanism includes:

• No H/D exchange effects. Experiments with C₂D₄ in water generate CD₃CDO, and runs with C₂H₄ in D₂O generate CH₃CHO. Thus, keto-enol tautomerization is not a possible mechanistic step.
• Negligible kinetic isotope effect with fully deuterated reactants ({{sfrac|k _H|k _D}}=1.07). Hence hydride transfer is not rate-determining.
• Significant competitive isotope effect with C₂H₂D₂, ({{sfrac|k _H|k _D}}= ~1.9), suggests that the rate determining step precedes acetaldehyde formation.

Evidence against the mechanism is a copper-chloride containing byproduct crystallized by Hosokawa et al.T. Hosokawa, T. Nomura, S.-I. Murahashi, J. Organomet. Chem., 1998, 551, 387–389 Questions remain about whether the cocatalyst also helps hydroxylate the ethylene ligand.

The ethylene ligand's hydroxylation is typically a slow process.Zaw, K., Lautens, M. and Henry P.M. Organometallics, 1985, 4, 1286–1296Wan W.K., Zaw K., and Henry P.M. Organometallics, 1988, 7, 1677–1683 Depending on experimental conditions, it can occur either intramolecularly, from a palladium-bound hydroxido ligand, or intermolecularly. In the former case the hydroxylation is anti; in the latter, syn. Assuming small amounts of copper, experiments have shown that syn addition occurs at low chloride concentrations (< 1 mol/L, industrial process conditions)P. M. Henry, J. Am. Chem. Soc., 1964, 86, 3246–3250. and anti addition occurs at high (> 3mol/L) concentrations.James, D.E., Hines, L.F., Stille, J.K. J. Am. Chem. Soc., 1976, 98, 1806 {{doi|10.1021/ja00423a027}}James, D.E., Stille, J.K. J. Organomet. Chem., 1976, 108, 401. {{doi|10.1021/ja00423a028}}Bäckvall, J.E., Akermark, B., Ljunggren, S.O., J. Am. Chem. Soc., 1979, 101, 2411. {{doi|10.1021/ja00503a029}}Stille, J.K., Divakarumi, R.J., J. Organomet. Chem., 1979, 169, 239;{{Excessive footnotes|date=June 2025}} The pathway change is probably due to chloride ions saturating the catalyst.Francis, J.W., Henry, P.M. Organometallics, 1991, 10, 3498. {{doi|10.1021/om00056a019}}Francis, J.W., Henry, P.M. Organometallics, 1992, 11, 2832.{{doi|10.1021/om00044a024}} However, under strictly copper-free conditions, anti addition always occurs, and the rate no longer depends on the ethylene hydrogen isotopes.Comas-Vives, A., Stirling, A., Ujaque, G., Lledós, A., Chem. Eur. J., 2010, 16, 8738–8747.{{doi|10.1002/chem.200903522}}Anderson, B.J., Keith, J.A., and Sigman, M.S., J. Am. Chem. Soc., 2010, 132, 11872-11874

Another key step in the Wacker process is the migration of the hydrogen from oxygen to chloride, followed by reductive elimination to form the C-O double bond. This step is generally thought to proceed through a so-called β-hydride elimination:

File:Wacker hydride elimination.png

The cyclic four-membered transition state shown above is unlikely. In silico studiesJ. A. Keith, J. Oxgaard, and W. A. Goddard, III J. Am. Chem. Soc., 2006, 128, 3132 – 3133; {{doi|10.1021/ja0533139}}H. E. Hosseini, S. A. Beyramabadi, A. Morsali, and M. R. Housaindokht, J. Mol. Struct. (THEOCHEM), 2010, 941, 138–143P. L. Theofanis, and W. A. Goddard, III Organometallics, 2011, 30, 4941 – 4948; {{doi|10.1021/om200542w}} argue that the transition state for this reaction step likely involves a 7-membered ring with a (solvent) water molecule acting as a catalyst.

File:Wacker transition state.png

File:One stage Wacker Process flow diagram.JPG

File:Two stage Wacker Process flow diagram.JPG

Two routes are commercialized for the production of acetaldehyde: one-stage process and two-stage. The acetaldehyde yield is about 95% in either, and byproducts are chlorinated hydrocarbons, chlorinated acetaldehydes, and acetic acid. In general, 100 parts of ethene gives:

{{div col}}

• 95 parts acetaldehyde
• 1.9 parts chlorinated aldehydes
• 1.1 parts unconverted ethene
• 0.8 parts carbon dioxide
• 0.7 parts acetic acid
• 0.1 parts chloromethane
• 0.1 parts ethyl chloride
• 0.3 parts ethane, methane, crotonaldehyde

{{div col end}}

and other minor side products.

The production costs are virtually the same across the two processes; the advantage of using dilute gases in the two-stage method is balanced by higher investment costs. Due to the corrosive nature of the catalyst, either process requires a reactor lined with acid-proof ceramic and titanium tubing, but the two-stage process requires more reactors and piping. Generally, the choice of method is governed by the raw material and energy situations as well as by the availability of oxygen at a reasonable price.

Ethene and oxygen are passed co-currently in a reaction tower at about 130 °C and 400 kPa.{{Ullmann | title = Acetaldehyde | doi = 10.1002/14356007.a01_031.pub2 | author = Marc Eckert | author2 = Gerald Fleischmann | author3 = Reinhard Jira | author4 = Hermann M. Bolt | author5 = Klaus Golka}} The catalyst is an aqueous solution of PdCl₂ and CuCl₂. The acetaldehyde is purified by extractive distillation followed by fractional distillation. Extractive distillation with water removes the lights ends having lower boiling points than acetaldehyde (chloromethane, chloroethane, and carbon dioxide) at the top, while water and higher-boiling byproducts, such as acetic acid, crotonaldehyde or chlorinated acetaldehydes, are withdrawn together with acetaldehyde at the bottom.

In two-stage process, reaction and oxidation are carried out separately in tubular reactors. Unlike one-stage process, air can be used instead of oxygen. Ethylene is passed through the reactor along with catalyst at 105–110 °C and 900–1000 kPa. Catalyst solution containing acetaldehyde is separated by flash distillation. The catalyst is oxidized in the oxidation reactor at 1000 kPa using air as oxidizing medium. Oxidized catalyst solution is separated and sent back to reactor. Oxygen from air is used up completely and the exhaust air is circulated as inert gas. Acetaldehyde – water vapor mixture is preconcentrated to 60–90% acetaldehyde by utilizing the heat of reaction and the discharged water is returned to the flash tower to maintain catalyst concentration. A two-stage distillation of the crude acetaldehyde follows. In the first stage, low-boiling substances, such as chloromethane, chloroethane and carbon dioxide, are separated. In the second stage, water and higher-boiling by-products, such as chlorinated acetaldehydes and acetic acid, are removed and acetaldehyde is obtained in pure form overhead.

Development of the reaction system has led to various catalytic systems to address selectivity of the reaction, as well as introduction of intermolecular and intramolecular oxidations with non-water nucleophiles.

The oxidation of terminal olefins generally provide the Markovnikov ketone product. In rare cases where substrate favors the aldehyde (discussed below), different ligands can be used to enforce Markovnikov regioselectivity. Sparteine (Figure 2, A){{Cite journal|last1=Balija|first1=Amy M.|last2=Stowers|first2=Kara J.|last3=Schultz|first3=Mitchell J.|last4=Sigman|first4=Matthew S.|date=March 2006|title=Pd(II)-Catalyzed Conversion of Styrene Derivatives to Acetals: Impact of (−)-Sparteine on Regioselectivity|journal=Organic Letters|volume=8|issue=6|pages=1121–1124|doi=10.1021/ol053110p|pmid=16524283|issn=1523-7060}} favors nucleopalladation at the terminal carbon to minimize steric interaction between the palladium complex and substrate. Quinox (Figure 2, B) favors ketone formation when the substrate contains a directing group.{{Cite journal|last1=Michel|first1=Brian W.|last2=Camelio|first2=Andrew M.|last3=Cornell|first3=Candace N.|last4=Sigman|first4=Matthew S.|date=2009-05-06|title=A General and Efficient Catalyst System for a Wacker-Type Oxidation Using TBHP as the Terminal Oxidant: Application to Classically Challenging Substrates|journal=Journal of the American Chemical Society|volume=131|issue=17|pages=6076–6077|doi=10.1021/ja901212h|issn=0002-7863|pmc=2763354|pmid=19364100}} When such substrate bind to Pd(Quinox)(OOtBu), this complex is coordinately saturated which prevents the binding of the directing group, and results in formation of the Markovnikov product. The efficiency of this ligand is also attributed to its electronic property, where anionic TBHP prefers to bind trans to the oxazoline and olefin coordinate trans to the quinoline.{{Cite journal|last1=Michel|first1=Brian W.|last2=Steffens|first2=Laura D.|last3=Sigman|first3=Matthew S.|date=June 2011|title=On the Mechanism of the Palladium-Catalyzed tert -Butylhydroperoxide-Mediated Wacker-Type Oxidation of Alkenes Using Quinoline-2-Oxazoline Ligands|journal=Journal of the American Chemical Society|volume=133|issue=21|pages=8317–8325|doi=10.1021/ja2017043|issn=0002-7863|pmc=3113657|pmid=21553838}}

File:TW examples.tif

The anti-Markovnikov addition selectivity to aldehyde can be achieved through exploiting inherent stereoelectronics of the substrate.{{Cite journal|last1=Dong|first1=Jia Jia|last2=Browne|first2=Wesley R.|last3=Feringa|first3=Ben L.|date=2014-11-03|title=Palladium-Catalyzed anti-Markovnikov Oxidation of Terminal Alkenes|journal=Angewandte Chemie International Edition|volume=54|issue=3|pages=734–744|doi=10.1002/anie.201404856|pmid=25367376|issn=1433-7851|url=https://pure.rug.nl/ws/files/240464098/Angew_Chem_Int_Ed_2014_Dong_Palladium_Catalyzed_anti_Markovnikov_Oxidation_of_Terminal_Alkenes.pdf }} Placement of directing group at homo-allylic (i.e. Figure 3, A){{Cite journal|last1=Miller|first1=D. G.|last2=Wayner|first2=Danial D. M.|date=April 1990|title=Improved method for the Wacker oxidation of cyclic and internal olefins|journal=The Journal of Organic Chemistry|volume=55|issue=9|pages=2924–2927|doi=10.1021/jo00296a067|issn=0022-3263}} and allylic position (i.e. Figure 3, B){{Cite journal|last1=Stragies|first1=Roland|last2=Blechert|first2=Siegfried|date=October 2000|title=Enantioselective Synthesis of Tetraponerines by Pd- and Ru-Catalyzed Domino Reactions|journal=Journal of the American Chemical Society|volume=122|issue=40|pages=9584–9591|doi=10.1021/ja001688i|issn=0002-7863}} to the terminal olefin favors the anti-Markovnikov aldehyde product, which suggests that in the catalytic cycle the directing group chelates to the palladium complex such that water attacks at the anti-Markovnikov carbon to generate the more thermodynamically stable palladacycle. Anti-Markovnikov selectivity is also observed in styrenyl substrates (i.e. Figure 3, C),{{Cite journal|last1=Wright|first1=Joseph A.|last2=Gaunt|first2=Matthew J.|last3=Spencer|first3=Jonathan B.|date=2006-01-11|title=Novel Anti-Markovnikov Regioselectivity in the Wacker Reaction of Styrenes|journal=Chemistry - A European Journal|volume=12|issue=3|pages=949–955|doi=10.1002/chem.200400644|pmid=16144020|issn=0947-6539}} presumably via η⁴-palladium-styrene complex after water attacks anti-Markovnikov. More examples of substrate-controlled, anti-Markovnikov Tsuji-Wacker Oxidation of olefins are given in reviews by Namboothiri,{{Cite journal|last1=Baiju|first1=Thekke Veettil|last2=Gravel|first2=Edmond|last3=Doris|first3=Eric|last4=Namboothiri|first4=Irishi N.N.|date=September 2016|title=Recent developments in Tsuji-Wacker oxidation|journal=Tetrahedron Letters|volume=57|issue=36|pages=3993–4000|doi=10.1016/j.tetlet.2016.07.081|issn=0040-4039}} Feringa, and Muzart.{{Cite journal|last=Muzart|first=Jacques|date=August 2007|title=Aldehydes from Pd-catalysed oxidation of terminal olefins|journal=Tetrahedron|volume=63|issue=32|pages=7505–7521|doi=10.1016/j.tet.2007.04.001|issn=0040-4020}}

Grubbs and co-workers paved way for anti-Markovnikov oxidation of stereoelectronically unbiased terminal olefins, through the use of palladium-nitrite system (Figure 2, D).{{Cite journal|last1=Wickens|first1=Zachary K.|last2=Morandi|first2=Bill|last3=Grubbs|first3=Robert H.|date=2013-09-13|title=Aldehyde-Selective Wacker-Type Oxidation of Unbiased Alkenes Enabled by a Nitrite Co-Catalyst|journal=Angewandte Chemie International Edition|volume=52|issue=43|pages=11257–11260|doi=10.1002/anie.201306756|pmid=24039135|issn=1433-7851|url=https://authors.library.caltech.edu/42230/7/anie_201306756_sm_miscellaneous_information.pdf}} In his system, the terminal olefin was oxidized to the aldehyde with high selectivity through a catalyst-control pathway. The mechanism is under investigation, however evidence suggests it goes through a nitrite radical adds into the terminal carbon to generate the more thermodynamically stable, secondary radical. Grubbs expanded this methodology to more complex, unbiased olefins.{{Cite journal|last1=Wickens|first1=Zachary K.|last2=Skakuj|first2=Kacper|last3=Morandi|first3=Bill|last4=Grubbs|first4=Robert H.|date=2014-01-13|title=Catalyst-Controlled Wacker-Type Oxidation: Facile Access to Functionalized Aldehydes|journal=Journal of the American Chemical Society|volume=136|issue=3|pages=890–893|doi=10.1021/ja411749k|pmid=24410719|issn=0002-7863|url=https://authors.library.caltech.edu/43469/7/ja411749k_si_001.pdf}}{{Cite journal|last1=Kim|first1=Kelly E.|last2=Li|first2=Jiaming|last3=Grubbs|first3=Robert H.|last4=Stoltz|first4=Brian M.|date=2016-09-30|title=Catalytic Anti-Markovnikov Transformations of Hindered Terminal Alkenes Enabled by Aldehyde-Selective Wacker-Type Oxidation|journal=Journal of the American Chemical Society|volume=138|issue=40|pages=13179–13182|doi=10.1021/jacs.6b08788|pmid=27670712|issn=0002-7863|url=https://authors.library.caltech.edu/70776/2/ja6b08788_si_001.pdf}}

File:TW AM examples.tif

The intermolecular oxidations of olefins with alcohols as nucleophile typically generate ketals, where as the palladium-catalyzed oxidations of olefins with carboxylic acids as nucleophile generates vinylic or allylic carboxylates. In case of diols, their reactions with alkenes typically generate ketals, whereas reactions of olefins bearing electron-withdrawing groups tend to form acetals.{{Cite book|title=Organotransition Metal Chemistry: From Bonding to Catalysis|last=Hartwig|first=John F.|publisher=University Science Books|year=2010|isbn=978-1-891389-53-5|location=USA|pages=717–734}}

Palladium-catalyzed intermolecular oxidations of dienes with carboxylic acids and alcohols as donors give 1,4-addition products. In the case of cyclohexadiene (Figure 4, A), Backvall found that stereochemical outcome of product was found to depend on concentration of LiCl.{{Cite journal|last1=Baeckvall|first1=Jan E.|last2=Bystroem|first2=Styrbjoern E.|last3=Nordberg|first3=Ruth E.|date=November 1984|title=Stereo- and regioselective palladium-catalyzed 1,4-diacetoxylation of 1,3-dienes|journal=The Journal of Organic Chemistry|volume=49|issue=24|pages=4619–4631|doi=10.1021/jo00198a010|issn=0022-3263}} This reaction proceeds by first generating the Pd(OAc)(benzoquinone)(allyl) complex, through anti-nucleopalladation of diene with acetate as nucleophile. The absence of LiCl induces an inner sphere reductive elimination to afford the trans-acetate stereochemistry to give the trans-1,4-adduct. The presence of LiCl displaces acetate with chloride due to its higher binding affinity, which forces an outer sphere acetate attack anti to the palladium, and affords the cis-acetate stereochemistry to give the cis-1,4-adduct. Intramolecular oxidative cyclization: 2-(2-cyclohexenyl)phenol cyclizes to corresponding dihydro-benzofuran (Figure 4, B);{{Cite journal|last1=Hosokawa|first1=Takahiro|last2=Miyagi|first2=Shyogo|last3=Murahashi|first3=Shunichi|last4=Sonoda|first4=Akio|date=July 1978|title=Oxidative cyclization of 2-allylphenols by palladium(II) acetate. Changes in product distribution|journal=The Journal of Organic Chemistry|volume=43|issue=14|pages=2752–2757|doi=10.1021/jo00408a004|issn=0022-3263}} 1-cyclohexadiene-acetic acid in presence of acetic acid cyclizes to corresponding lactone-acetate 1,4 adduct (Figure 4, C),{{Cite journal|last1=Baeckvall|first1=Jan E.|last2=Granberg|first2=Kenneth L.|last3=Andersson|first3=Pher G.|last4=Gatti|first4=Roberto|last5=Gogoll|first5=Adolf|date=September 1993|title=Stereocontrolled lactonization reactions via palladium-catalyzed 1,4-addition to conjugated dienes|journal=The Journal of Organic Chemistry|volume=58|issue=20|pages=5445–5451|doi=10.1021/jo00072a029|issn=0022-3263}} with cis and trans selectivity controlled by LiCl presence.

File:TW oxygen nucleophiles v1.tif

{{See also|Ammoxidation}}

The oxidative aminations of olefins are generally conducted with amides or imides; amines are thought to be protonated by the acidic medium or to bind the metal center too tightly to allow for the catalytic chemistry to occur. These nitrogen nucleophiles are found to be competent in both intermolecular and intramolecular reactions, some examples are depicted (Figure 5, A,{{Cite journal|last1=Timokhin|first1=Vitaliy I.|last2=Stahl|first2=Shannon S.|date=December 2005|title=Brønsted Base-Modulated Regioselectivity in the Aerobic Oxidative Amination of Styrene Catalyzed by Palladium|journal=Journal of the American Chemical Society|volume=127|issue=50|pages=17888–17893|doi=10.1021/ja0562806|pmid=16351120|issn=0002-7863}} B{{Cite journal|last1=Larock|first1=Richard C.|last2=Hightower|first2=Timothy R.|last3=Hasvold|first3=Lisa A.|last4=Peterson|first4=Karl P.|date=January 1996|title=Palladium(II)-Catalyzed Cyclization of Olefinic Tosylamides|journal=The Journal of Organic Chemistry|volume=61|issue=11|pages=3584–3585|doi=10.1021/jo952088i|pmid=11667199|issn=0022-3263}})

File:TW nitrogen nucleophiles.tif

{{reflist|2}}

{{Alkenes}}

{{Authority control}}

Category:Organic redox reactions

Category:Organometallic chemistry

Category:Homogeneous catalysis

Category:Acetylene

Category:Ethylene

Category:Palladium

Category:Name reactions