Nitroxide-Catalyzed Alcohol Oxidations in Organic Synthesis - Stable Radicals: Fundamentals and Applied Aspects of Odd-Electron Compounds - page 451

TEMPO (cat.), 0.35 V vs. Ag/AgNO 3 ,
Pt electrodes, CH 3 CN,
LiClO 4 , 2,6-lutidine, 23 ° C, 2 h

OH

CHO

(59 %)

Scheme 12.40

poor atom economy and the need to remove the organic side products of the oxidants from the reaction
mixtures.

12.9.7 Anodic, electrochemical oxidation

Nitroxide-catalyzed electrochemical oxidations combine the chemical specificity of oxoammonium ion
oxidations with the benefits of electrochemical syntheses: the option to vary the oxidation potential (i.e.,
to adjust to the oxidation potential of the specific nitroxide used) and the lack of byproducts resulting from
a secondary chemical oxidant (Scheme 12.40). 175 Among the disadvantages of electrochemical oxidations
are that they suffer from difficulties involving the choice of the cell architecture, the electrode material and
its surface modification, including the use of electrode-bound nitroxides, 176 and that they require the use of
a polar solvent containing high concentration of an electrolyte to carry the current, potentially complicating
the isolation of the product. Only a few reactions have been carried out using relatively simple substrates.
Thus, the full potential of the electrosynthetic method for organic synthesis has yet to be realized.

12.10 Use of nitroxide-catalyzed oxidations in tandem reactions

A tandem reaction is loosely defined here as one in which the nitroxide-catalyzed reaction is coupled with
a second reaction that takes place in the same flask. In the simplest case, the alcohol oxidation elicits
spontaneously a sequential reaction, such as shown in the lactone cyclization reactions (Section 12.7.2).
An interesting tandem reaction of an ynamide alcohol to generate a pyrrolizidinone and that was initiated
by a nitroxide-catalyzed oxidation is shown in Scheme 12.41. 177 Mechanistically, this reaction proceeds
through the ring opening of an amide-substituted oxetene intermediate that is formed through a [2 2]

cycloaddition pathway between the alkyne and the aldehyde generated in situ during the initial oxidation.
Another one-pot method can be used to convert 2,3-epoxy alcohols into isoxazole derivatives. 178
The reactions that take place in tandem may also take place in two distinct steps. For instance, interme-
diate aldehydes have been trapped by a Wittig reaction (Schemes 12.42 179 and 12.43 180 ).
The nitroxide/hypochlorite- and chlorite-mediated alcohol-to-carboxyl oxidations that have been car-
ried out in a two-step, one-pot fashion may also be considered tandem reactions (Section 12.7.1). 79

+

H

HO

O O

N N

TEMPO (cat.), PhI(OAc) 2 ,
CH 2 Cl 2 , rt

O

Bn

N
CO 2 Me

N

CO 2 Me

Bn

(50 %)

Scheme 12.41