The Mukaiyama hydration is an
organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, Mechanistic Organ ...
involving formal addition of an equivalent of water across an
olefin
In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond.
Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
by the action of catalytic
bis(acetylacetonato)cobalt(II) complex,
phenylsilane
Phenylsilane, also known as silylbenzene, a colorless liquid, is one of the simplest organosilanes with the formula C6 H5 SiH3. It is structurally related to toluene, with a silyl group replacing the methyl group. Both of these compounds have ...
and atmospheric oxygen to produce an alcohol with Markovnikov selectivity.
The reaction was developed by
Teruaki Mukaiyama at Mitsui Petrochemical Industries, Ltd. Its discovery was based on previous work on the selective hydrations of olefins catalyzed by cobalt complexes with
Schiff base
In organic chemistry, a Schiff base (named after Hugo Schiff) is a compound with the general structure ( = alkyl or aryl, but not hydrogen). They can be considered a sub-class of imines, being either secondary ketimines or secondary aldimine ...
ligands and porphyrin ligands. Due to its
chemoselectivity
Chemoselectivity is the preferential outcome of a chemical reaction over a set of possible alternative reactions.
In another definition, chemoselectivity refers to the selective reactivity of one functional group in the presence of others; often ...
(tolerant of other functional groups) and mild reactions conditions (run under air at room temperature), the Mukaiyama hydration has become a valuable tool in
chemical synthesis
As a topic of chemistry, chemical synthesis (or combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In moder ...
.
Mechanism
In his original publication, Mukaiyama proposed that the reaction proceeded through the intermediacy of a cobalt peroxide adduct. A metal exchange reaction between a hydrosilane and the cobalt peroxide adduct leads to a silyl peroxide, which is converted to the alcohol upon reduction, presumably via action of the cobalt catalyst.
Studies investigating the mechanism of cobalt-catalyzed peroxidation of alkenes by Nojima and coworkers, support the intermediacy of a metal hydride that reacts with the alkene directly to form a transient cobalt-alkyl bond. Homolysis generates a carbon centered radical that reacts directly with oxygen and is subsequently trapped by a cobalt(II) species to form the same cobalt-peroxide adduct as suggested by Mukaiyama. Metal exchange with the hydrosilane produces a silyl peroxide product and further reduction (via homolysis of the oxygen-oxygen bond) leads to the product alcohol. The use of a silane reductant allows for this reaction to be carried out without heat. The authors also note, in accordance with previous studies,
that the addition of ''t''-butylhydroperoxide can increase the rate of slower-reacting substrates. This rate increase is likely due to oxidation of cobalt(II) to alkylperoxo-cobalt(III) complex, which subsequently participates in a rapid metal exchange with the hydrosilane to generate the active cobalt(III)-hydride.
It is important to note that the mechanism laid out above is in marked contrast to previous mechanistic proposals, which suggest that a cobalt-peroxy complex inserts directly into alkenes. The aforementioned study by Nojima and coworkers disagrees with this proposal due to three observations: 1) the intermediacy of a cobalt-hydride observed via
1H NMR 2) the propensity of alkenes to undergo autooxidation to the α, β-unsaturated ketones or allylic alcohols when the same reaction is run in the absence of a hydrosilane 3) the predominant mode of decomposition of alkylperoxo-cobalt(III) species to an alkoxy or alkylperoxy radical via the
Haber–Weiss mechanism.
A recent review by Shenvi and coworkers, proposed that the Mukaiyama hydration operates via the same principles as metal hydride hydrogen atom transfer (MH HAT), elucidated by
Jack Halpern and
Jack R. Norton in their studies on hydrogenation of anthracenes by syngas and
Co2(CO)8 and the chemistry of
vitamin B12 mimics, respectively.
Variations
Carbon-oxygen bond formation
Yamada explored the effect of different solvents and cobalt beta-diketonate ligands on the yield and product distribution of the reaction.
Mukaiyama and Isayama developed conditions to isolate the intermediate silylperoxide.
Treatment of the intermediate silylperoxide with 1 drop of concentrated HCl in methanol leads to the
hydroperoxide
Hydroperoxides or peroxols are Chemical compound, compounds containing the hydroperoxide functional group (ROOH). If the R is organic, the compounds are called organic hydroperoxides. Such compounds are a subset of organic peroxides, which have t ...
product.
Both Mukaiyama and Magnus describe conditions for an α-enone hydroxylation reaction using Mn(dpm)
x in the presence of oxygen and phenylsilane. An asymmetric variant was described by Yamada and coworkers.
Dale Boger and coworkers used a variant of the Mukaiyama hydration, utilizing an
iron oxalate
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in fr ...
catalyst (Fe
2ox
3•6H
2O) in the presence of air, for the total synthesis of
vinblastine
Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small cell lung cancer, bladder ca ...
and related analogs.
Carbon-nitrogen bond formation
Erick Carreira’s group has developed both cobalt and
manganese
Manganese is a chemical element with the symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese is a transition metal with a multifaceted array of industrial alloy use ...
-catalyzed methods for the
hydrohydrazination of olefins.
Both Carreira and Boger have developed
hydroazidation reactions.
Applications
In total synthesis
The Mukaiyama hydration or variants thereof have been featured in the syntheses of (±)-garsubellin A, stigmalone, vinblastine, (±)-cortistatin A, (±)-lahadinine B, ouabagenin,