Oxidation with chromium(VI) complexes: Difference between revisions

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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⁺).

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==Mechanism and stereochemistry==

[[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 effectseffect]]s (k_H/k_D) are observed.<ref name=OR/>

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

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 may occur upon treatment with base as shown below.<ref name=OR/>

{{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. Insights into the mechanism is provided by structure-reactivity, implicating 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 limitations==

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;">'''''(6)'''''</span>{{center|[[File:ChroScope1.png]]}}

{{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 name=OR/>

<span style="float:right;padding-right:50px;padding-top:30px;">'''''(7)'''''</span>{{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 name=whatup /><ref name=OR/>

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

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==Comparison with other methods==

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>{{cite journalbook |doi=10.1002/047084289X.rt157m.pub2|titlechapter=1,1,1-Triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one|journaltitle=Encyclopedia of Reagents for Organic Synthesis|year=2009|last1=Boeckman|first1=Robert J.|last2=George|first2=Kelly M.|isbn=978-0471936237 }}</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 name=OR/> However, undesired side reactions mediated by stoichiometric amounts of the terminal oxidant may occur.