Nitroxide-Catalyzed Alcohol Oxidations in Organic Synthesis - Stable Radicals: Fundamentals and Applied Aspects of Odd-Electron Compounds - page 455

O

(96 %)

TEMPO (cat.), 0.55 V vs. Ag/AgNO 3
MeCN, 5 % H 2 O, 2,6-lutidine

(95 %, GC)

Scheme 12.52

N N

NO 2 NO 2

N N

HO O O O

TEMPO (cat.), NaOCl, KBr,
CH 2 Cl 2 /H 2 O, NaHCO 3 ,

TBDPSO TBDPSO

− 10 ° C

OPiv OPiv

Scheme 12.53

Dess - Martin alcohol oxidations are carried out using periodinane, 195 which may not always be safe. 196
Moffatt - Swern oxidations require carefully dried reagents and solvents, generally low temperatures, and
the byproduct dimethylsulfide has an obnoxious smell, 197 whereas nitroxide-catalyzed oxidations do not
generate unpleasant odors and do not require anhydrous conditions. Isomerizations were observed under
Swern conditions that did not occur using nitroxide-catalyzed sodium hypochlorite oxidation conditions
(Scheme 12.53). 71
Among the metal-based oxidants that are in direct competition to the nitroxide-based systems are the
chromium(VI)-based reagents 198 and manganese dioxide. 199,200 While these oxidants are inexpensive, well
studied, and many quite selective reactions have been developed, they all involve (toxic) metal ions that
must be removed from the reaction mixtures and properly disposed of. Both methods suffer from their
exclusive use in stoichiometric oxidations. Manganese dioxide oxidations also suffer from a restricted
applicability to activated alcohols. 201 Using chromium(VI) reagents, side reactions such as isomerizations
and oxygen migrations and the production of chromic esters have been reported. Also, TEMPO-based
oxidations gave reportedly higher yields compared to pyridinium chlorochromate oxidations. 202

12.13 Nitroxide-catalyzed oxidations and green chemistry

When considering a particular reaction for use, first and foremost its suitability for the desired transfor-
mation has to be considered. If several equivalent reactions are available, increasingly the principles of
Green Chemistry are used to select one reaction over another. How, using the 12 principles of Green
Chemistry, 203 do nitroxide-catalyzed oxidations stack up?

1. Prevent waste: Aqueous nitroxide-mediated oxidations using hypochlorite (bleach), oxygen or chlo-
rine as secondary oxidants generate relatively benign aqueous solutions of (sodium) chloride as waste.
Many nitroxide-catalyzed reactions are also tolerant to very high reactant concentrations, minimizing
the quantities of solvent used.