Nitroxide Radicals: Properties, Synthesis and Applications - Stable Radicals: Fundamentals and Applied Aspects of Odd-Electron Compounds - page 202

O

O

Ph C N

O

TEMPO TEMPO

h n O

PhCH=C=O

Ph N

Ph C

O

O

N

N 2

Scheme 5.41 Reaction of TEMPO with phenylketene

I

N

1)

OH

(2 mol%)

O

OH

CHO

N N

OH

DBU / THF, RT

+ 2

+ 2

N
O

2) aq. HCl or
MeOH / THF, 80 ° C

N
O

Cl 92 %

Cl

3) O 2

Scheme 5.42 N-Heterocyclic carbene-catalyzed oxidation of aldehydes by TEMPO

10 8 M − 1 s − 1

. ×

Diphenylcarbene reacts with TEMPO with a rate constant of 2 7 at room tem-

perature leading to benzophenone and 2,2,6,6-tetramethylpiperidinyl radical in nearly quantitative

yields. 219
N-Heterocyclic carbene-catalyzed oxidation of aldehydes by using TEMPO as oxidant affords carboxylic
acids in good to very good yields, even with sensitive aldehydes such as 2-thiophenecarboxaldehyde, 2-
pyridinecarboxaldehyde, phenylglyoxal monohydrate or crotonaldehyde (Scheme 5.42). 220 The suggested
mechanism implies the reaction of the N-heterocyclic carbene catalyst with an aldehyde to give the corre-
sponding enamine that is oxidized by SET by two equivalents of TEMPO, followed by further reaction of
the TEMPO hydroxylamine as a nucleophile to yield the corresponding ester, leading finally to the acid
after hydrolysis.
Reactions of chiral nitroxides with prochiral carbon-centered radicals can yield two diastereomeric
alkoxyamines (Scheme 5.43). Rigid C 2 -symmetric nitroxides have shown to be the most efficient stereos-
elective trapping agents; however, low diastereoselectivities were observed. 221
A tandem anionic/oxidative reaction sequence terminated by a TEMPO trapping reaction was developed
and has shown to be an interesting strategy for the efficient preparation of functionalized chiral pyrrolidines
in a one-pot sequence 222 and for the synthesis of 15-F 2t - isoprostane 223

(Scheme 5.44).

Recently, an enantioselective radical-mediated α -oxygenation of aldehydes using organocatalysts has

been successfully developed (Scheme 5.45). 224

The methodology proceeds by oxidation of a chiral enamine

R 4 *

N O

R 2

R 2

R 4 * *R 4

R 1

R 1 R 2

R 5 *

R 1

O

O

+ N

N

R 5 * R 3

R 3 R 3 R 5 *

Scheme 5.43 Trapping of a prochiral radical with a chiral nitroxide