Fleming–Tamao oxidation

In 1983, Tamao and co-workers were the first to report the successful transformation of an allyl alkoxy silyl to an allyl alcohol without an allylic shift. In their report, the chemists observed that the hydroxyl group was introduced exclusively onto the carbon atom to which the silicon atom was attached. In the same year, Tamao and group published another paper that showed that the carbon–silicon bond in alkoxy organosilicon compounds can be cleaved using H2O2 or m-CPBA under acidic, basic (chemistry), or neutral conditions, to afford the corresponding alcohols. A year later, Ian Fleming and group reported that the dimethylphenylsilyl (Me2PhSi) group can be converted to an hydroxyl group in a two-pot sequence. Later, in 1987, Fleming reported a one-pot variant to the two-pot sequence in which either bromine or mercuric ion acts as the electrophile. These early findings paved the way for the development of a large number of silicon-based 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 for the Tamao oxidation is similar under each condition. The mechanism below contains at least one fluorine atom as the substituent, which is the prototype structure that Tamao studied. Fluoride, provided by a fluoride source or a donor solvent, attacks the fluorosilane in a fast and reversible step to give a pentacoordinated species. This species is more electrophilic than the fluorosilane, thereby promoting attack by the nucleophilic oxidant to yield the negatively charged hexacoordinated transition state. This step was determined to be the rate determining step based on kinetic studies done by Tamao. Further studies by Tamao on the steric and electronic effects of different groups attached to the silicon led him to suggest that attack by the oxidant trans to the electronegative fluoride group is energetically favored. The group cis to the peroxide oxygen in the transition state structure then migrates preferentially, thus explaining the retention of configuration at the carbon center. Finally, the new silicon–oxygen bond of the hexaco-ordinated species is hydrolyzed by water in the reaction medium. Subsequent workup produced the expected alcohol. 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 aryl silane is then converted to the more reactive halo- or heterosilane to initiate the oxidation. == Scope ==

The Tamao–Kumada oxidation, or the Tamao oxidation, uses a silyl group with a hydrogen atom, a heteroatom or an electron-donating group attached to the silicon atom to make it more reactive. Tamao used either fluorine or chlorine atom, or an alkoxy (OR) or amine group (NR2) as the substituent on the substrates. , a substituted alkenylsilyl group is transformed to a carbonyl under the same Tamao oxidation conditions employed for alkylsilane. 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. Steric effects One of the major pitfalls of either the Fleming or Tamao oxidations is steric hindrance. Increasing the steric bulk at the silicon center generally slows down reaction, potentially even suppressing reaction entirely when certain substituents are employed. In general, less bulky groups such as methyl or ethyl favor oxidation, while bulkier groups such as 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, 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. == Applications ==

Natural product synthesis The natural product, (+)− pramanicin, became an interesting target for synthesis because it was observed to be active against a fungal pathogen that resulted in meningitis in AIDS patients. Therefore, its synthesis which utilized the Fleming–Tamao oxidation as a crucial step has been relevant to chemists as well as to patients afflicted by AIDS. The antifungal agent has also been shown previously to induce cell death and increase calcium levels in vascular endothelial cells. Furthermore, (+)– pramanicin has a wide range of potential applications against human diseases. -1,3 diols from functionalized silyl anion. Alternatively, Hara, K.; Moralee, and Ojima achieved syn-1,3 diols using Tamao oxidation. ==See also==