We recently reported7 an electron transfer initiated cy-
clization (ETIC) reaction in which homobenzylic ethers
containing pendent nucleophiles are converted to cyclic
acetals (Figure 1). This transformation employs NMQPF6
Figure 2. Aerobic quinolinium catalyst regeneration.
To test this proposal homobenzylic ether 1, a substrate
that cyclized only to partial conversion under the original
reaction conditions,7 was photoirradiated with concurrent
aeration in the presence of substoichiometric amounts of
NMQPF6 (Table 1). These experiments showed that the
Figure 1. Electron transfer initiated cyclization.
Table 1. Examination of Catalyst Loading and Cosensitizera
as a single-electron oxidant in a photoinitiated carbon-
carbon σ-bond activation process. Although this procedure
has been used in efficient syntheses of several cyclic acetals,
we noted that these transformations occasionally do not
progress to completion, especially when the reactions were
conducted on >0.5 mmol scale and when cyclizations
proceed slowly. We concluded that this problem arises from
the formation of covalent adducts between the N-meth-
ylquinoline radical (NMQ•) produced from the initial electron
transfer and the benzyl radical produced in the displacement
reaction.8 These adducts are expected to be oxidized in
preference to the substrate,9 producing a range of aromatic
products while consuming the oxidant. As a consequence
of the need for at least 2 equiv of NMQPF6, large quantities
of aromatic byproducts are generated in these reactions,
necessitating product isolation by laborious chromatographic
separations.
entry NMQPF6 (mol %) cosensitizer time (h) yield (%)b
1
2
3
4
5
200c
50
10
2.5
2.5
TBBd
TBB
TBB
TBB
toluene
4
55e
79
82
86
82
1.5
1.5
2
3
a Reaction conditions: 1 (50 mg), NMQPF6, NaOAc (100 mg), 1,2-
dichloroethane (6 mL), cosensitizer (1 mL), gentle air bubbling, irradiation
with a medium-pressure mercury lamp. b Reported yields are of isolated,
purified products unless noted otherwise. c Air was not used in this example.
d TBB ) tert-butylbenzene. e 74% yield based on 76% conversion.
efficiency of these cyclizations actually increased as the
catalyst loading was lowered. Reactions using as little as
2.5 mol % of the catalyst were shown to proceed to
completion in good yield and in a reasonable amount of time.
The characteristic pink color of the stoichiometric reactions,
resulting from the oxidative decomposition of quinoline-
derived products, was not observed in these cyclizations.
These studies also showed that tert-butylbenzene, used as
the cosensitizer in the initial studies, can be replaced by
toluene, a more volatile and much less expensive solvent.
The ease of solvent removal and the minimization of
aromatic waste production significantly facilitate product
isolation. Since O2 is known to quench triplet excited states,11
these results also provide evidence that the singlet excited
state of NMQPF6 is the relevant oxidant for this process.
Attempts to apply these conditions to larger scale (g1 g)
reactions, however, resulted in very low isolated product
yields despite the complete consumption of starting material.
For example, the cyclization of 1 g of 3a only provided a
15% isolated yield of 4. We ascribed these low yields to
In transient absorption spectroscopy studies of NMQPF6-
mediated arene oxidations, Dinnocenzo and co-workers
observed10 that signals arising from NMQ• could be sup-
pressed by conducting the reactions in the presence of O2.
This result was attributed to an essentially diffusion-
controlled oxidation of NMQ• to NMQ+ through a single-
electron-transfer reaction. We postulated that aerobic NMQ•
oxidation could be used in the design of a catalytic variant
of the ETIC reaction as illustrated in Figure 2. Dioxygen
was also expected to trap the benzyl radicals to form benzyl
peroxy radicals.
(7) Kumar, V. S.; Floreancig, P. E. J. Am. Chem. Soc. 2001, 123, 3842.
(8) Fukuzumi, S.; Ohkubo, K.; Suenobu, T.; Kato, K.; Fujitsuka, M.;
Ito, O. J. Am. Chem. Soc. 2001, 123, 8459 and references therein. Adducts
can also be formed between NMQPF6 and benzyl radicals; see: Minisci,
F.; Vismara, E.; Fontane, F.; Morini, G.; Serravalle, M.; Giordano, C. J.
Org. Chem. 1987, 52, 730.
(9) (a) Aromatic amines are oxidized much more readily than alkylarenes.
For a list of ionization potentials of organic molecules, see: Rosenstock,
H. M.; Draxl, K.; Steiner, B. W.; Herron, J. T. J. Chem. Phys. Ref. Data
1997, 6, Suppl. 1. Ionization potentials can be correlated to oxidation
potentials according to relationships established in ref 9b. (b) Howell, J.
O.; Goncalves, J. M.; Amatore, C.; Klasinc, L.; Wightman, R. M.; Kochi,
J. K. J. Am. Chem. Soc. 1984, 106, 3968.
(10) Dockery, K. P.; Dinnocenzo, J. P.; Farid, S.; Goodman, J. L.; Gould,
I. R. J. Am. Chem. Soc. 1997, 119, 1876.
(11) Kopecky′, J. Organic Photochemistry: A Visual Approach; VCH:
New York, 1991.
4124
Org. Lett., Vol. 3, No. 25, 2001