Andrea Porcheddu and Lidia De Luca
COMMUNICATIONS
Scheme 4. Trapping the acyl radical.
well giving the corresponding N-mono-substituted duced pressure. The crude product was purified by silica gel
column chromatography to provide the desired amide.
amides (Scheme 2, products 3n and 3o).
With regards to the reaction mechanism we postu-
late the plausible catalytic cycle presented in
Scheme 3. In the first step (Scheme 3, a) the FeACTHNUGTRNEUNG(III)
Acknowledgements
reacts with TBHP forming the tert-butylperoxy radi-
cal, Fe(II) and H+ following the mechanism demon-
strated by Barton and co-workers.[24] The protonated
N-chloroamine is converted to an amino radical by
a redox reaction as was well documented by Minis-
ci.[25] (Scheme 3, c).The tert-butylperoxy radical then
abstracts hydrogen from the aldehyde to generate an
acyl radical as reported in the literature by Wan
(Scheme 3, b).[19] Finally the amino radical B and the
acyl radical A couple to form the desired amide
(Scheme 3, d). To prove our hypothesis we trapped
the acyl radical, which is generated in situ from the al-
dehyde, by 2,2,6,6-tetramethylpiperidine 1-oxyl
(TEMPO), following the reports of Wan[19] and Li,[26]
under our reaction conditions, obtaining the TEMPO
adduct C instead of the amide (Scheme 4).
The authors thank Prof. Maurizio Taddei, Prof. Sergio Stoc-
coro and Prof. Serafino Gladiali for helpful discussions. This
work was financially supported by Regione Autonoma della
Sardegna within the project: “High-throughput screening
(HTS) per l’identificazione di nuove molecule per il tratta-
mento della Sclerosi Laterale Amiotrofica e della Malattia di
Parkinson”.
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Experimental Section
General Procedure for Amides 3a–o
TBHP (1.16 mmol, 0.16 mL of a 70 wt% solution in water)
was added to a mixture of aldehyde (1.6 mmol), N-chloro-
ACHTUNGTRENNUNGamine (0.32 mmol), FeCl3·6H2O (0.15 mol%) in 5 mL of
acetonitrile, under an N2 atmosphere. The reaction mixture
was heated in an oil bath at 828C for 40 min (the reaction
was monitored by TLC until disappearance of N-chloroa-
mine). Then the reaction mixture was quenched with 40 mL
of a saturated solution of Na2SO3 (for removal of excess
TBHP) and extracted three times with 20 mL of diethyl
ether. The combined organic phases were dried over anhy-
drous Na2SO4 and the solvent was evaporated under re-
2952
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 2949 – 2953