Job/Unit: O43479
/KAP1
Date: 10-02-15 15:35:11
Pages: 6
L. Fang, L. Chen, J. Yu, L. Wang
SHORT COMMUNICATION
aqueous NaOH (2.5 n, 6 mL) at room temperature and stirred for
5 min, and then benzoyl chloride (0.215 mL, 1.84 mmol) was added
in one portion. After 5 h, the reaction was diluted with H2O
(5 mL), and extracted with CHCl3 (3ϫ 10 mL). The combined or-
ganic phases were washed with NaOH (2.5 n, 5 mL). The organic
phase was dried with Na2SO4, filtered, and concentrated under re-
duced pressure affording the N-iminopyridinium ylide.
amino protons in benzoic amide, which was generated after
N–N bond fission. Furthermore, the intermolecular kinetic
isotopic experiment confirmed the kH/kD for the arene C–
H bond was 1.4 and kH/kD for alkane C–H was 7.3, indicat-
ing the cleavage of sp3 C–H bond rather than the former
sp2 C–H bond was involved as the rate-determining step for
this transformation [Equation (4), (5)].
General Procedure for the Coupling: An oven-dried reaction vessel
was charged with N-iminopyridinium ylide (1, 0.2 mmol), alkane
or alcohol (2, 4 mL) and BPO (0.06 mmol, 30 mol-%). Then the
reaction vessel was sealed and the resulting solution was stirred at
130 °C for 10 h. After cooling to room temperature, the volatiles
were removed in vacuo and the residue was purified by column
chromatography to give the pure product as a colorless oil.
On the basis of these experimental results, a proposed
mechanism is illustrated in Scheme 3. First, benzoyl perox-
ide can be homolytically cleaved to form two effective ini-
tiating species, benzoxy radical PhCOO·, which can abstract
a hydrogen atom from the alkane to form benzoic acid and
an alkyl radical R· to initiate chain reactions. The alkyl rad-
ical R· is readily trapped by N-iminopyridinium ylide to
form radical cation A, which releases a hydrogen atom to
give an intermediate B. Subsequently, at elevated tempera-
ture, A is not stable and decomposes to give the desired
product 3 and nitrene specie B,[16] which can abstract two
hydrogen atoms from the alkane to form benzoic amide and
alkyl radical R·.
Acknowledgments
The work was supported by the National Nature Science Founda-
tion of China (NSFC, 21272069, 20672035), the Fundamental Re-
search Funds for the Central Universities and Key Laboratory of
Organofluorine Chemistry, Shanghai Institute of Organic Chemis-
try, Chinese Academy of Sciences.
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Scheme 3. Proposed mechanism.
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Conclusions
In summary we have developed a BPO-initiated cross-
dehydrogenative coupling of N-iminopyridinium ylides and
simple alkanes and alcohols. A catalytic amount of BPO is
consumed in this metal-free and open-air system. Besides,
this direct C–H bond alkylation transformation affords the
corresponding C2-alkylated products with high regioselec-
tivity in moderate to excellent yields without an additional
reduction to remove the activated group. This finding offers
a new, simple and mild method for synthesizing the alkyl-
ated pyridine derivatives.
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Experimental Section
Starting Materials: N-iminopyridinium ylides were synthesized by
a method according to literature procedures as follows.[17] Pyridine
(0.1 mL, 1.24 mmol) and O-(2,4-dinitrophenyl)hydroxylamine
(272 mg, 1.36 mmol) were added to H2O/THF (1:1 mixture,
1.0 mL). The reaction flask was sealed with a septum, and the re-
sulting suspension was stirred at 40 °C for 16 h. During this period,
the reaction mixture turned dark red. The reaction was poured into
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iminopyridinium ylides: a) B. Xiao, Z. Liu, L. Liu, Y. Fu, J.
Am. Chem. Soc. 2013, 135, 616; b) Q. Xiao, L. Ling, F. Ye, R.
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