The Fleming–Tamao oxidation, or Tamao–Kumada–Fleming oxidation, converts a carbon–silicon bond to a carbon–oxygen bond with a peroxy acid or hydrogen peroxide. Fleming–Tamao oxidation refers to two slightly different conditions developed concurrently in the early 1980s by the Kohei Tamao and Ian Fleming research groups.[1][2][3]
Summary of the Fleming–Tamao oxidation
The reaction is
immunosuppressant
.
History
In 1983, Tamao and co-workers were the first to report the successful transformation of an
reagents
and the use of various silyl groups as functional equivalents of the hydroxyl group.
Mechanisms
Tamao–Kumada oxidation
Although the mechanism below is for the basic condition, the proposed mechanism
hydrolyzed
by water in the reaction medium. Subsequent workup produced the expected alcohol.
Mechanism of Tamao oxidation
Fleming oxidation
Two-pot sequence
Unlike the Tamao oxidation whose starting material is an activated heteroatom-substituted silyl group, the Fleming oxidation utilizes a more robust silyl group which has only carbon atoms attached to the silicon atom. The prototype silyl structure that Fleming used was dimethylphenylsilyl. This
alkyl group undergoes 1,2 migration from the silicon to the oxygen atom. Aqueous acid mediated hydrolysis
and subsequent workup yield the desired alcohol. It is difficult to prevent small resulting silyl-alcohols from dehydrating to form siloxanes.
Two-pot oxidation mechanism
One-pot sequence
The main difference between the one-pot and two-pot sequences is that the former has bromine or mercuric ion as the electrophile that is attacked by the
AcOH to provide the oxidizing conditions. The mechanism for the one-pot and two-pot sequences is the same since the bromine or mercuric ion are attacked by the phenyl ring instead of the hydrogen ion.[3][9]
Scope
The Tamao–Kumada oxidation, or the Tamao oxidation, uses a silyl group with a
sodium hydrogen carbonate (NaHCO3) to make the reaction conditions slightly acidic, neutral, and alkaline, respectively. The different conditions were used to observe the effect that pH environment had on the oxidative cleavage
of the various alkoxy groups. Below is an example of each reaction condition.
Variations
Recently, the Fleming–Tamao oxidation has been used to generate phenol and substituted phenols in very good yield.[10]
The generation of phenol using Fleming–Tamao oxidation[10]
The Tamao oxidation was used to synthesize
carbonyl under the same Tamao oxidation conditions employed for alkylsilane.[11]
aldehyde, acid and ketone syntheses with the use of the Tamao oxidation[11]
Advantages of a C–Si linkage
The silyl group is a non-polar and relatively unreactive species and is therefore tolerant of many reagents and reaction conditions that might be incompatible with free alcohols. Consequently, the silyl group also eliminates the need for introduction of hydroxyl protecting groups. In short, by deferring introduction of an alcohol to a late synthetic stage, opting instead to carry through a silane, a number of potential problems experienced in total syntheses can be mitigated or avoided entirely.[1]
Steric effects
One of the major pitfalls of either the Fleming or Tamao oxidations is
tert-butyl slow down or stop oxidation. There are special cases in which this pattern in not followed. For example, alkoxy groups tend to enhance oxidation,[6]
while oxidation does not proceed under normal conditions when three alkyl substituents are attached to the silicon atom. The trend below illustrates the order in which oxidation proceeds.
The effect of substituents attached to the silicon atom on the Fleming–Tamao oxidation
Applications
Natural product synthesis
The natural product, (+)− pramanicin, became an interesting target for synthesis because it was observed to be active against a
human diseases
.
The total synthesis of pramanicin usintg Fleming–Tamao oxidation[12]
![{\displaystyle {\begin{matrix}{\text{Reaction conditions of Tamao oxidation}}\\{}\\{\ce {R}}{-}{\color {Blue}{\ce {Si}}}{\ce {R'_{2}X}}{\begin{cases}{\ce {->[30\%\ {\ce {H2O2,\ KHCO3\ or\ NaHCO3}}][{\ce {MeOH/THF,\ 60^{\circ }C}}]R}}{-}{\color {Blue}{\ce {O}}}{\ce {H}}&{\color {Blue}{\text{basic conditions}}}\\\\{\ce {->[30\%\ {\ce {H2O2,\ Ac2O,\ KHF2}}][{\text{DMF, r.t.}}]R}}{-}{\color {Blue}{\ce {O}}}{\ce {H}}&{\color {Blue}{\text{acidic conditions}}}\\\\{\ce {->[30\%\ {\ce {H2O2,\ KHF2}}][{\text{DMF, r.t. to }}60^{\circ }{\text{C}}]R}}{-}{\color {Blue}{\ce {O}}}{\ce {H}}&{\color {Blue}{\text{neutral conditions}}}\end{cases}}\\\\{\ce {X}}={\ce {H,F,Cl,OR,NR2}}\\{\ce {R'}}={\ce {X,Me,Et,iPr,Ph}}\\\end{matrix}}}](https://wikimedia.org/api/rest_v1/media/math/render/svg/50f7b1479d911f1ddf107a7c0a64cefaae55d992)
