Oxidation with chromium(VI) complexes: Difference between revisions

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'''Oxidation with chromium(VI)-amine complexes''' involves the conversion of alcohols to carbonyl compounds or more highly oxidized products through the action of molecular chromium(VI) oxide-amine adductsoxides and salts.<ref Representativename=OR>{{cite membersjournal|author=Luzzio, ofF. thisA.|journal=[[Org. familyReact.]]|title=The Oxidation of Alcohols by Modified Oxochromium(VI)–Amine Reagents|year=1998|volume=53|page=1|doi=10.1002/0471264180.or053.01|isbn=0471264180 }}</ref> The principal reagents includeare [[Collins reagent]], [[pyridiniumPDC, chlorochromate]]and (PCC),. andThese [[pyridiniumreagents dichromate]]represent improvements over inorganic chromium(PDCVI).<ref>Luzzio, F.A.reagents ''Org.such React.''as '''1998''',[[Jones ''53'', 1reagent]].</ref>

==Inventory of Cr(VI)-pyridine and pyridinium reagents==

==Introduction==

Cr(VI)-pyridine and pyridinium reagents have the advantage that they are soluble in organic solvents as are the alcohol substrates.

Sarrett identified the adduct of pyridine and chromium(VI) oxide ([[Collins reagent]]) as a selective compound for the oxidation of primary and secondary alcohols to carbonyl compounds.<ref>Poos, G. I.; Arth, G. E.; Beyler, R. E.; Sarrett, L. H. ''J. Am. Chem. Soc.'', '''1953''', ''75'', 422.</ref> Despite its selectivity, Collins reagent suffers from difficulties associated with its preparation, stability, and efficiency. The less reactive adducts pyridinium chlorochromate (PCC) and pyridinium dichromate (PDC) are more easily handled and more selective than Collins reagent in oxidations of alcohols. These reagents, as well as other, more exotic adducts of nitrogen heterocycles with chromium(VI), facilitate a number of oxidative transformations of organic compounds, including cyclization to form [[tetrahydrofuran]] derivatives and allylic transposition to afford enones from [[allyl]]ic alcohols.

One family of reagents employs the complex CrO₃(pyridine)₂.<ref>{{cite book |doi=10.1007/0-387-25725-X_1|chapter=Chromium-based Reagents|title=Oxidation of Alcohols to Aldehydes and Ketones|series=Basic Reactions in Organic Synthesis|year=2006|pages=1–95|isbn=0-387-23607-4}}</ref>

*[[Sarett oxidation|Sarett's reagent]]: a solution of CrO₃(pyridine)₂ in pyridine. It was popularized for selective oxidation of primary and secondary alcohols to carbonyl compounds.

*[[Collins reagent]] is a solution of the same CrO₃(pyridine)₂ but in dichloromethane. The Ratcliffe variant of Collins reagent relates to details of the preparation of this solution, i.e., the addition of chromium trioxide to a solution of pyridine in methylene chloride.<ref name=JCC>{{cite journal | author = J. C. Collins, W.W. Hess | title = Aldehydes from Primary Alcohols by Oxidation with Chromium Trioxide: Heptanal | journal = Organic Syntheses | volume = 52 | pages = 5 | doi = 10.15227/orgsyn.052.0005 | year = 1972| doi-access = free }}</ref>

The second family of reagents are ''salts'', featuring the pyridinium cation (C₅H₅NH⁺).

Oxidation with chromium(VI) amines has two primary limitations. Operationally, the tarry byproducts of chromium oxidations cause reduced yields and product sequestration.<ref>Ratcliffe, R.; Rodehorst, R. ''J. Org. Chem.'', '''1970''', ''35'', 4000.</ref> In addition, Cr(VI)-amines (particularly PCC) may react with [[acid]]-labile functionality. Thus, these agents have been employed in oxidations of relatively simple substrates, often in excess to account for reagent trapping and decomposition.

*[[pyridinium dichromate]] (PDC) is the pyridium salt of dichromate, [Cr₂O₇]^2-.

<span style="float:right;padding-right:50px;padding-top:30px;">'''''(1)'''''</span><center>[[File:ChroGen.png]]</center>

*[[pyridinium chlorochromate]] (PCC) is the pyridinium salt of [CrO₃Cl]⁻.

SarrettThese identifiedsalts the adduct of pyridine and chromium(VI) oxide ([[Collins reagent]]) as a selective compound for the oxidation of primary and secondary alcohols to carbonyl compounds.<ref>Poos, G. I.; Arth, G. E.; Beyler, R. E.; Sarrett, L. H. ''J. Am. Chem. Soc.'', '''1953''', ''75'', 422.</ref> Despite its selectivity, Collins reagent suffers from difficulties associated with its preparation, stability, and efficiency. Theare less reactive adducts pyridinium chlorochromate (PCC) and pyridinium dichromate (PDC) are, more easily handled, and more selective than Collins reagent in oxidations of alcohols. These reagents, as well as other, more exotic adducts of nitrogen heterocycles with chromium(VI), facilitate a number of oxidative transformations of organic compounds, including cyclization to form [[tetrahydrofuran]] derivatives and [[Babler oxidation|allylic transposition]] to afford enones from [[allyl]]ic alcohols.

The above reagents represent improvements over the [[Jones reagent]], a solution of [[chromium trioxide]] in aqueous [[sulfuric acid]].

==Mechanism and Stereochemistry==

===Prevailing Mechanisms===

Chromate esters have been implicated in most oxidations of alcohols by chromium(VI)-amines. After formation of the chromate ester, either deprotonation or hydride transfer leads to the product carbonyl compound. Kinetic isotope effect studies have shown that C-H bond cleavage is involved in the rate-determining step.<ref>Banerji, K. K. ''J. Org. Chem.'', '''1988''', ''53'', 2154.</ref>

<span style="float:right;padding-right:50px;padding-top:30px;">'''''(2)'''''</span><center>[[File:ChroMech1.png]]</center>

Oxidative annulation of alkenols to form six-membered rings may be accomplished with PCC. This process is postulated to occur via initial oxidation of the alcohol, attack of the alkene on the new carbonyl, then re-oxidation to a ketone. Double-bond isomerization is likely under the acidic conditions of the reaction.<ref>Corey, E. J.; Boger, D. Tetrahedron Lett., '''1978''', ''28'', 2461.</ref>

==Mechanism and Stereochemistrystereochemistry==

An important process mediated by chromium(VI)-amines is the oxidative transposition of tertiary allylic alcohols to give enones.<ref>Luzzio, F. A.; Moore, W. J. ''J. Org. Chem.'', '''1993''', ''58'', 2966.</ref> The mechanism of this process likely depends on the acidity of the chromium reagent. Acidic reagents such as PCC may cause ionization and recombination of the chromate ester (path A), while the basic reagents (Collins) likely undergo direct allylic transposition via sigmatropic rearrangement (path B).

[[Chromate ester]]s are implicated in these reactions. The chromate ester decomposes to the aldehyde or carbonyl by transfer of an alpha proton. Large [[kinetic isotope effect]]s (k_H/k_D) are observed.<ref name=OR/>

<span style="float:right;padding-right:50px;padding-top:30px;">'''''(3)'''''</span><center>[[File:ChroMech2.png]]</center>

{{center|[[File:ChroMech1.png]]}}

Oxidative cyclizations of olefinic alcohols to cyclic ethers may occur via [3+2], [2+2],<ref>Piccialli, V. ''Synthesis'' '''2007''', 2585.</ref> or [[epoxidation]] mechanisms. The exact mechanism has been debated, although a recent structure-reactivity study provided evidence for direct epoxidation by the chromate ester.<ref>Beihoffer, L.A; Craven, R.A.; Knight, K.S; Cisson, C.R.; Waddell, T.G. ''Trans. Met. Chem.'' '''2005''', ''30'', 582. </ref> Subsequent epoxide opening and release of chromium leads to the observed products.

Oxidative annulation of alkenols to form six-membered rings may be accomplished with PCC. This process is postulated to occur via initial oxidation of the alcohol, attack of the alkene on the new carbonyl, then re-oxidation to a ketone. Double-bond isomerization ismay likelyoccur underupon thetreatment acidicwith conditionsbase ofas theshown reactionbelow.<ref>Corey, E. J.; Boger, D. Tetrahedron Lett., '''1978''', ''28'', 2461.<name=OR/ref>

<span style="float:right;padding-right:50px;padding-top:30px;">'''''(4)'''''</span><center>[[File:ChroMech3.png]]</center>

{{center|[[File:ChromeScopeCyc.png]]}}

An important process mediated by chromium(VI)-amines is the oxidative transposition of tertiary allylic alcohols to give enones.<ref>Luzzio, F. A.; Moore, W. J. ''J. Org. Chem.'', '''1993''', ''58'', 2966.<name=OR/ref> The mechanism of this process likely depends on the acidity of the chromium reagent. Acidic reagents such as PCC may cause ionization and recombination of the chromate ester (path A), while the basic reagents (Collins) likely undergo direct allylic transposition via sigmatropic rearrangement (path B).

{{center|[[File:ChroMech2.png]]}}

Oxidative cyclizations of olefinic alcohols to cyclic ethers may occur via [3+2], [2+2],<ref>Piccialli, V. ''Synthesis'' '''2007''', 2585.<name=OR/ref> or [[epoxidation]] mechanisms. TheInsights exactinto the mechanism hasis beenprovided debated, although a recentby structure-reactivity, study provided evidence forimplicating direct epoxidation by the chromate ester.<ref>Beihoffer, L.A; Craven, R.A.; Knight, K.S; Cisson, C.R.; Waddell, T.G. ''Trans. Met. Chem.'' '''2005''', ''30'', 582. <name=OR/ref> Subsequent epoxide opening and release of chromium leads to the observed products.

==Scope and Limitationslimitations==

Buffering agents may be used to prevent acid-labile protecting groups from being removed during chromium(VI)-amine oxidations. However, buffers will also slow down oxidative cyclizations, leading to selective oxidation of alcohols over any other sort of oxidative transformation. Citronellol, for instance, which cyclizes to pugellols in the presence of PCC, does not undergo cyclization when buffers are used.<ref>Fieser, L. F.; Fieser, M. ''Reagents for Organic Synthesis''; Wiley-Interscience, New York, 1979, '''7''', 309.</ref><ref name=whatup>Babler,{{cite J.journal|title=A H.;Facile Coghlan,Method M.for J.the ''Synth.Bishomologation Commun.''of '''1976''',Ketones ''6''to α,β-Unsaturated Aldehydes: Application to the Synthesis of the Cyclohexanoid Components of the Boll Weevil Sex 469.</ref>Attractant

|author=James H. Babler, Michael J. Coghlan|pages= 469–474|year= 2007|doi=10.1080/00397917608082626|journal=Synthetic Communications}}</ref>

<span style="float:right;padding-right:50px;padding-top:30px;">'''''(5)'''''</span><center>[[File:ChroScope1.png]]</center>

{{center|[[File:ChroScope1.png]]}}

Oxidative cyclization can be used to prepare substituted tetrahydrofurans. Cyclization of dienols leads to the formation of two tetrahydrofuran rings in a ''syn'' fashion.<ref>McDonald, F. E.; Towne, T. B. ''J. Am. Chem. Soc.'', '''1994''', ''116'', 7921.<name=OR/ref>

<span style="float:right;padding-right:50px;padding-top:30px;">'''''(6)'''''</span><center>[[File:ChroScope2.png]]</center>

{{center|[[File:ChroScope2.png]]}}

Enones can be synthesized from tertiary allylic alcohols through the action of a variety of chromium(VI)-amine reagents, in a reaction known as the [[Babler oxidation]]. The reaction is driven by the formation of a more substituted double bond. (''E'')-Enones form in greater amounts than (''Z'') isomers because of chromium-mediated geometric isomerization.<ref>Majetich, G.;name=whatup Condon, S.; Hull, K.; Ahmad, S. ''Tetrahedron Lett.'', '''1989''', ''30'', 1033.</ref><ref name=whatup><OR/ref>

<span style="float:right;padding-right:50px;padding-top:10px;">'''''(7)'''''</span><center>[[File:ChroScope3.png]]</center>

{{center|[[File:ChroScope3.png]]}}

Suitably substituted olefinic alcohols undergo oxidative cyclization to give tetrahydrofurans. Further oxidation of these compounds to give tetrahydropyranyl carbonyl compounds then occurs.<ref>Schlecht, M. F.; Kim, H.-J. ''Tetrahedron Lett.'', '''1986''', ''27'', 4889.<name=OR/ref>

<span style="float:right;padding-right:50px;padding-top:30px;">'''''(8)'''''</span><center>[[File:ChroScope4.png]]</center>

{{center|[[File:ChroScope4.png]]}}

In addition to the limitations described above, chromium(VI) reagents are often unsuccessful in the oxidation of substrates containing heteroatoms (particularly nitrogen). Coordination of the heteroatoms to chromium (with displacements of the amine ligand originally attached to the metal) leads to deactivation and eventual decomposition of the oxidizing agent.

==Comparison with Otherother Methodsmethods==

Methods employing dimethyl sulfoxide (the [[Swern oxidation|Swern]] and [[Moffatt oxidation]]s) are superior to chromium(VI)-amines for oxidations of substrates with heteroatom functionality that may coordinate to chromium.<ref>Tidwell, T. ''Org. React.'' '''1990''', ''39'', 297.</ref> [[Dess-Martin periodinane]] (DMP) offers the advantages of operational simplicity, a lack of heavy metal byproducts, and selective oxidation of complex, late-stage synthetic intermediates.<ref>Dess,{{cite D.book B|doi=10.; Martin1002/047084289X.rt157m.pub2|chapter=1,1,1-Triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one|title=Encyclopedia J.of C.Reagents for Organic Synthesis|year=2009|last1=Boeckman|first1=Robert ''J.|last2=George|first2=Kelly OrgM.|isbn=978-0471936237 Chem.'', '''1983''', ''48'', 4156.}}</ref> Additionally, both DMP and [[manganese dioxide]] (MnO₂) can be used to oxidize allylic alcohols to the corresponding enones without allylic transposition. When allylic transpositions is desired, however, chromium(VI)-amine reagents are unrivaled.

Catalytic methods employing cheap, clean terminal oxidants in conjunction with catalytic amounts of chromium reagents produce only small amounts of metal byproducts.<ref>Muzart, J. ''Tetrahedron Lett.'', '''1987''', ''28'', 2133.<name=OR/ref> However, undesired side reactions mediated by stoichiometric amounts of the terminal oxidant may occur.

==Experimental Conditions and Procedure==

===Typical Conditions===

Reagent-grade pyridine is usually sufficient for the preparation of PDC and PCC. Although these reagents may darken over time, their loss in activity is minimal. Isolated reagents should be stored in a desiccator in the dark. Care should be taken when adding chromium trioxide to pyridine, as ignition of pyridine has been known to occur.

Reduced chromium residues can be removed from glassware with concentrated HCl or 10-15% aqueous HF. Solid chromium waste should never be thrown away, as residual CrO₃ may ignite. Chromium(VI) reagents are toxic and should be handled with care in a well-ventilated fume hood.

===Example Procedure<ref>Guziec, F. S., Jr.; Luzzio, F. A. ''J. Org. Chem.'', '''1982''', ''47'', 1787.</ref>===

<span style="float:right;padding-right:50px;padding-top:10px;">'''''(9)'''''</span><center>[[File:ChroEx.png]]</center>

To a suspension of 4-(dimethylamino)pyridinium chlorochromate (1.24 g, 4.8 mmol) in dry dichloromethane (7.0 mL) was added p-(3-hydroxypropyl)-benzyl alcohol (200 mg, 1.2 mmol). Stirring was continued (2 hours) at room temperature under a [[nitrogen]] atmosphere. The reaction mixture was diluted with [[ethyl acetate]] (10 mL) and the brown granular [[chromium]] reduction products were removed by vacuum filtration through a [[Celite]]® pad. Concentration of the solvent and [[column chromatography]] on [[silica gel]] ([[hexane]]/[[ethyl acetate]], 2:1) furnished 121 mg (62%) of p-(3-hydroxypropyl)benzaldehyde as an oil.

==Historic references==

*Poos, G. I.; Arth, G. E.; Beyler, R. E.; Sarrett, L. H. ''J. Am. Chem. Soc.'', '''1953''', ''75'', 422.

*{{cite journal | title = Improved Procedure for Oxidations with the Chromium Trioxide-Pyridine Complex| author = Ronald Ratcliffe and Ronald Rodehorst | journal = [[J. Org. Chem.]] | year = 1970 | volume = 35 | issue = 11 | pages = 4000–4001 | doi = 10.1021/jo00836a108}}

==References==

{{reflist|230em}}

[[Category:Organic oxidation reactions]]

[[Category:Organic redox reactions]]