Indirect Electroreductive Cyclization
SCHEME 3. Mediated Electron Transfer
would serve as an electron-transfer agent toward the
substrate. The alternative ligand-centered electron trans-
fer that is also illustrated in Scheme 4 seemed to us to
be less likely.18
Detailed electrochemical, ESR, and UV-vis studies
have been conducted in an effort to differentiate between
inner- and outer-sphere electron-transfer options,19 focus-
ing particularly upon reactions involving alkyl halides.20
In the literature, one finds that nickel(I) salen complexes
16 react by a metal-centered inner-sphere pathway, while
the nickel(II) anion radical 17 functions as an outer-
sphere electron donor.19 This description nicely describes
the chemistry of hard electrophiles. We suggest that it
should be modified, however, to accommodate the chem-
istry of the soft electrophiles whose chemistry is described
herein (vide infra).
substance that serves a role similar to that of a sensitizer
in photochemical transformations.14 In such an experi-
ment, the potential is set at a value where only the
mediator, M, is reduced or oxidized, as the case may be
(Scheme 3). If the overall process to be achieved is a
reduction, then the reduced form of the mediator, M-•,
serves as an electron-transfer agent toward the substrate,
S, thereby converting the latter to a radical anion, S-•,
and simultaneously regenerating the mediator.
One of the salient features of electromediated processes
is that they can occur despite the existence of a thermo-
dynamic hurdle that would seemingly preclude electron
transfer between the mediator and substrate. As Fry has
written:15 “At first sight, mediated electron transfer
appears to present a thermodynamic paradox, in that the
substrate undergoes a redox conversion at a potential
lower than that required to effect its direct electrolysis.”
The key to success is that there be one or more fast
follow-up reactions that can drain the equilibrium toward
the product.15b Of many illustrative examples, we cite two
interesting cases, one from Utley’s laboratory and the
other from Simonet’s research group.16 Utley and co-
workers reported a Diels-Alder reaction between elec-
trochemically generated o-quinodimethane and maleic
anhydride. Maleic anhydride, which is easier to reduce
than the quinodimethane precursor, served both as a
mediator and a dienophile. The Simonet chemistry
featured the use of acenaphthene as a mediator, the
reduced form of which served as an electron-transfer
mediator to several methylenecyclopropanes. The poten-
tial was set at that of the mediator, some 0.2-0.3 V more
positive than the peak potential for the reduction of the
substrate. Several reviews of the field have been written,
and the interested reader is referred to them for ad-
ditional detail.14-16
Results
Voltammetry. Cyclic voltammograms were recorded
to establish the redox behavior of nickel salen, of the ERC
substrate 11, and of the EHC substrate 14. As illustrated
in Figure 1, nickel(II) salen displays a reversible curve
with a cathodic peak potential of -2.1 V versus Ag/
AgNO3. The ERC substrate 11, on the other hand,
displays an irreversible curve with a cathodic peak at
-2.6 V. Thus, the potential required for the direct
reduction of the substrate 11 is 0.5 V more negative than
the potential that is to be used to reduce the mediator.
Success, therefore, will require that there exist one or
more chemical transformations (e.g., protonation, addi-
tion of a second electron, cyclization; see Scheme 1 and
step iii of Scheme 3) that can shift the equilibrium to
the right.8,11,14-16
To determine whether redox catalysis was possible, we
recorded the cyclic voltammogram of nickel salen in the
presence of substrate 11. As illustrated in Figure 2, there
is an increase in current flow, thereby indicating the
existence of a so-called “catalytic current”, namely, the
increase in current that is due to the return of the
mediator to the original redox equilibrium in the manner
illustrated in Scheme 3.14
In accord with the work of Baizer and co-workers,21
the voltammogram for the EHC substrate 14 displays two
poorly resolved peaks, the first at ca. -2.9 V and the
other closer to -3.0 V. When the voltammogram for the
We selected nickel(II) salen (15) since its redox behav-
ior is well defined, and its utility in organic synthesis is
well established.17 We initially imagined a pathway
wherein Ni(II) would be reduced to Ni(I) and the latter
(14) (a) Steckhan, E. Angew. Chem. 1986, 98 (8), 681-99. (b)
Simonet, J.; Pilard, J.-F. Electrogenerated reagents. In Organic
Electrochemistry, 4th ed.; Lund, H., Hammerich, O., Eds.; Dekker:
New York, 2001; pp 1163-1225.
(15) (a) Fry, A. J. Synthetic Organic Electrochemistry, 2nd ed.; Wiley
& Sons: New York, 1989; Chapter 9. (b) In many respects, the situation
is similar to acid-base chemistry wherein even though an initial acid-
base equilibrium might reside on the left, follow-up reactions can drive
the equilibrium toward the product.
(16) (a) Eru, E.; Hawkes, G. E.; Utley, J. H. P.; Wyatt, P. B.
Tetrahedron 1995, 51, 3033-3044. (b) Boujlel, K.; Simonet, J.; Barnier,
J.-P.; Girard, C.; Conia, J.-M. J. Electroanal. Chem. 1981, 117, 161-
166.
(17) (a) Gosden, C.; Healy, K. P.; Pletcher, D. J. Chem. Soc., Dalton
Trans. 1978, 972-976. (b) Gosden, C.; Kerr, J. B.; Pletcher, D.; Rosas,
R. J. Electrochem. Soc. 1981, 117, 101-107. (c) Dunach, E.; Franco,
D.; Olivero, S. Eur. J. Org. Chem. 2003, 1605-1622. (d) Esteves, A.
P.; Freitas, A. M.; Medeiros, M. J.; Pletcher, D. J. Electroanal. Chem.
2001, 499 (1), 95-102. (e) Peters, D. G. Using transition-metal
complexes as catalysts for organic electrochemistry, 226th American
Chemical Society National Meeting, New York, Sept. 7-11, 2003;
American Chemical Society: Washington, DC, 2003; ORGN-638.
(18) Fielder, S. S.; Osborne, M. C.; Lever, A. B. P.; Pietro, W. J.
Am. Chem. Soc. 1995, 117 (26), 6990-3.
(19) (a) Azevedo, F.; Freire, C.; de Castro, B. Polyhedron 2002, 21
(17), 1695-1705. (b) Isse, A. A.; Gennaro, A.; Vianello, E. Electrochim.
Acta 1992, 37 (1), 113-118.
(20) Most often, metal salen complexes have been used in electro-
chemical processes wherein one of the substrates contains an alkyl,
aryl, vinyl, allyl, or propargyl halide. This makes sense mechanistically,
since the reduced form of nickel can oxidatively insert into the carbon-
halogen bond. See ref 16c as well as (a) Condon, S.; Nedelec, J.-Y.
Synthesis 2004, 18, 3070-3078. (b) Nedelec, J.-Y.; Perichon, J.;
Troupel, M. Organic electroreductive coupling reactions using transi-
tion metal complexes as catalysts. In Electrochemistry VI: Electroor-
ganic Synthesis: Bond Formation at Anode and Cathode; Steckhan,
E., Ed.; Topics in Current Chemistry 185; Springer: Berlin, 1997; pp
141-173. (c) Alleman, K. S.; Samide, M. J.; Peters, D. G.; Mubarak,
M. S. Curr. Top. Electrochem. 1998, 6, 1-31. (d) Cannes, C.; Condon,
S.; Durandetti, M.; Perichon, J.; Nedelec, J.-Y. J. Org. Chem. 2000, 65
(15), 4575-4583. (e) Ozaki, S.; Matsushita, H.; Ohmori, H. J. Chem.
Soc., Perkin Trans. 1 1993, (19), 2339-44.
(21) Petrovich, J. P.; Anderson, J. D.; Baizer, M. M. J. Org. Chem.
1966, 31, 3897-3903.
J. Org. Chem, Vol. 70, No. 20, 2005 8019