pubs.acs.org/joc
lactase mediated by TEMPO.4 We are aware of only one
Oxidative Cleavage of Benzylic and Related Ethers,
Using an Oxoammonium Salt
study of the reaction of benzylic ethers with a stoichiometric
quantity of oxoammonium salt: Miyazawa and Endo found
that oxidation of dibenzyl ether with an oxoammonium
bromide in methylene chloride solution afforded benzylde-
hyde and benzyl bromide.5
Priya P. Pradhan, James M. Bobbitt,* and William
F. Bailey*
In light of the disparate results reported for the reaction of
benzylic ethers with the oxoammonium cation, it seemed
worthwhile to investigate the oxidation of a variety of
ArCH2OR substrates with an oxoammonium salt containing
a non-nucleophilic counterion. As detailed below (Scheme
1), benzylic ethers are oxidatively cleaved by readily avail-
able 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoam-
monium tetrafluoroborate6 (1) upon stirring for 8 h in
CH3CN-water (90:10 by vol) at room temperature to afford
the corresponding aromatic aldehyde and alcohol in high
yield. As noted in Scheme 1 and further discussed below,
primary and secondary alcohol products are further oxidized
quite rapidly by 1 under these conditions to give carboxylic
acids and ketones, respectively, as products. Consequently, 1
molar equiv of 1 is needed to cleave ethers derived from
tertiary alcohols, 2 molar equiv of 1 is required for oxidative
cleavage of substrates derived from secondary alcohols, and
3 molar equiv of 1 is necessary when the ether is derived from
a primary alcohol.
Oxidative cleavages were conducted by stirring approxi-
mately 0.7 M solutions of the ArCH2OR ether and a
stoichiometric quantity of 1 appropriate for the substrate
in CH3CN-water (90:10 by vol) at room temperature for 8 h
at which time the oxidant was fully consumed as evidenced
by a negative test with starch-KI paper. The results of these
experiments are summarized in Table 1. It might be noted
that NMR analysis of crude reaction mixtures prior to
workup indicated that the products depicted in Table 1 were
generated in virtually quantitative yield; the lower isolated
yields that are reported are likely the result of the slight water
solubility of low molecular mass products. Nonetheless,
oxidative cleavage of ArCH2OR substrates under these
conditions is a high-yield process.
Department of Chemistry, University of Connecticut, Storrs,
Connecticut 06269-3060
james.bobbitt@uconn.edu; william.bailey@uconn.edu
Received October 13, 2009
Benzylic ethers and related ArCH2OR substrates are
oxidatively cleaved by 4-acetamido-2,2,6,6-tetramethyl-
piperidine-1-oxoammonium tetrafluoroborate (1) in wet
CH3CN at room temperature to give the corresponding
aromatic aldehyde and alcohol in high yield. Primary or
secondary alcohol products are further oxidized by 1 to
give carboxylic acids and ketones, respectively. The oxi-
dation likely involves a formal hydride abstraction from
the benzylic carbon as evidenced by slow reaction of
substrates bearing electron-withdrawing substituents.
Benzylic ethers constitute one of the most widely used
protecting groups for alcohols.1 The benzylic ether bond is
readily cleaved by a variety of either oxidative or reductive
methods1 but little is known concerning the behavior of
benzylic ethers when treated with an oxoammonium salt.2
Some time ago, Cho and Park reported that oxidation of
benzylic ethers in a two-phase medium using a catalytic
quantity of a nitroxide and sodium hypochlorite as co-
oxidant affords the benzoate in moderate yield along with
variable amounts of benzaldehyde and benzoic acid.3 Low
yields of benzoates were also detected in the oxidation of a
limited set of benzylic ethers by oxygen and the enzyme
SCHEME 1
(1) Wuts, P. G. M.; Green, T. W. Protective Groups in Organic Synthesis,
4th ed.; Wiley & Sons: New York, 2007; pp 102-120.
(2) Oxoammonium salts contain the NdO cation and are derived from
stable nitroxides such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) by
one-electron oxidation. It should be noted that terms such as nitrosonium,
immonium oxide, iminoxyl, and oxoamminium have been used in the
(4) (a) Acunzo, F.; Baiocco, P.; Fabbrini, M.; Galli, C.; Gentili, P. Eur. J.
Org. Chem. 2002, 4195. (b) Acunzo, F.; Baiocco, P.; Galli, C. New J. Chem.
2003, 27, 329.
(5) Miyazawa, T.; Endo, T. Tetrahedron Lett. 1986, 27, 3395.
(6) Bobbitt, J. M.; Merbouh, N. Organic Syntheses; Wiley: New York,
2005; Vol. 82, p 80. The 4-acetamido group on 1 raises the melting point of the
salt and results in a much increased stability relative to salts derived from
TEMPO.
€
older literature to describe such species. See: Bobbitt, J. M.; Bruckner, C.;
Merbouh, N. Org. React. (N.Y.) 2009, 74, in press.
(3) (a) Cho, N. S.; Park, C. H. Bull. Korean Chem. Soc. 1994, 15, 924. (b)
Cho, N. S.; Park, C. H. J. Korean Chem. Soc. 1995, 39, 657.
9524 J. Org. Chem. 2009, 74, 9524–9527
Published on Web 10/30/2009
DOI: 10.1021/jo902144b
r
2009 American Chemical Society