Mukaiyama oxidation mechanism

Although the Mukaiyama oxidation is not in the top list of the most frequently used alcohol oxidants, the authors of this book have decided to pay full attention to this procedure because it succeeds in very sensitive organometallic compounds, where most other oxidants fail. The Mukaiyama oxidation operates via a somehow unique mechanism involving a hydride transfer from a metal alkoxide to a very good hydride acceptor, which resembles the Oppenauer oxidation. In variance with the Oppenauer oxidation, the Mukaiyama protocol involves much milder conditions and it does not promote as easily base-induced side reactions. 

Scheme 5.3 Pedro s proposed Co(lll) Mukaiyama alcohol oxidation mechanism.

The most widely used method for the dehydration of primary nitroalkanes involves their treatment with phenyl isocyanate and triethylamine, introduced in 1960 by Hoshino and Mukaiyama (7). A probable mechanism for the formation of the nitrile oxide is shown in Scheme 6.4. This method is known to be very effective for the preparation of aliphatic or aromatic nitrile oxides. In some cases, the separation of the byproduct A,A -diphenylurea from the reaction mixture may be troublesome. In order to circumvent this problem, 1,4-phenylene diisocyanate was introduced (82,83). The polymeric urea that is formed as a byproduct is largely insoluble in the reaction mixture and can easily be removed. 

Stoichiometric amounts of substituted azo-compounds have been used to oxidize magnesium alkoxides to the corresponding carbonyl compounds Narasaka, K. Morikawa, A. Saigo, K. Mukaiyama, T. Bull. Chem. Soc. Jpn. 1977, 50, 2773 The decomposition mechanism of hydrazines in the presence of copper-complexes has been reported (a) Erlenmeyer, H. Flierl, C. Sigel, H. J. Am. Chem. Soc. 1969, 91, 1065 (b) Zhong, Y. Lim, P. K. J. Am. Chem. Soc 1989, 111, 8398. 

The oxidation-reduction method, developed initially by Mukaiyama et al. [133] and related to the previously described organophosphorus methods, has permitted a variety of important solid-phase applications. The mechanism of the activation is complex and involves the oxidation of the triaryl/ alkyl-phosphine to the oxide as well as reduction of the disulfide to the mercapto derivative. However, different active species, such as 81 (Fig. 11), the 2-pyridyl thioester, or even the symmetrical anhydride, have been postulated to form. For the intermediate 81, the peptide bond formation may proceed through a (cyclic transition state. The method has been used for conventional stepwise synthesis [134], acylation of the first protected amino acid to a hydroxymethyl resin, and to achieve segment condensation on a solid support in the opposite direction (N C) [135,136]. Lastly, it has been used for efficient grafting of a polyethylene glycol (molecular weight 2000) derivative to an aminomethyl resin to prepare PEG-PS resins [137]. 

Early examples of DDQ-mediated oxidative bond-forming reactions were carried out by Mukaiyama and and mechanisms were proposed... 

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