Oxidation with chromium(VI) complexes: Difference between revisions

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==Practical considerations==

Oxidation with chromium(VI) has two primary limitations. Operationally, the tarry byproducts lead to lowered yields. In addition, some such reagents (particularly PCC) 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. The use of adsorbents such as Celite or silica gel facilitates the removal of chromium byproducts and eliminates many of the operational difficulties associated with chromium-mediated oxidations.

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

==Mechanism and stereochemistry==

[[Chromate ester]]s are implicated in these reactions. The chromate ester decomposes to the aldehyde or carbonyl by transfer of a alpha proton. Large kinetic isotope effects are observed.<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 may occur upon treatment with base as shown in equation (3) below.<ref>Corey, E. J.; Boger, D. ''Tetrahedron Lett.'', '''1978''', ''19'', 2461.</ref>

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

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).

<span style="float:right;padding-right:50px;padding-top:30px;">'''''(4)'''''</span><{{center>|[[File:ChroMech2.png]]</center>}}

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. 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.</ref> Subsequent epoxide opening and release of chromium leads to the observed products.

<span style="float:right;padding-right:50px;padding-top:30px;">'''''(5)'''''</span><{{center>|[[File:ChroMech3.png]]</center>}}

==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, J. H.; Coghlan, M. J. ''Synth. Commun.'' '''1976''', ''6'', 469.</ref>

<span style="float:right;padding-right:50px;padding-top:30px;">'''''(6)'''''</span><{{center>|[[File:ChroScope1.png]]</center>}}

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.</ref>

<span style="float:right;padding-right:50px;padding-top:30px;">'''''(7)'''''</span><{{center>|[[File:ChroScope2.png]]</center>}}

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>Majetich, G.; Condon, S.; Hull, K.; Ahmad, S. ''Tetrahedron Lett.'', '''1989''', ''30'', 1033.</ref>

<span style="float:right;padding-right:50px;padding-top:10px;">'''''(8)'''''</span><{{center>|[[File:ChroScope3.png]]</center>}}

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.</ref>

<span style="float:right;padding-right:50px;padding-top:30px;">'''''(9)'''''</span><{{center>|[[File:ChroScope4.png]]</center>}}

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.