C O M M U N I C A T I O N S
Scheme 2. Reductive Cleavage Experiments with Sulfonamides
charged and, as seen from their redox potentials, relatively
aggressive species. In our case, reagent 3 is neutral and operates at
much milder potentials (E1/2 ) -1.20 V). Moreover, as 3 has
already been prepared from electrochemical reduction of its dication
4,11 the whole process could be driven electrochemically at very
mild potentials, if desired.
Reagent 3 has several advantages: (i) it is neutral; (ii) it can be
conveniently prepared from imidazole and diiodopropane, followed
by treatment with base; (iii) although it could be used as a reagent
coupled to an electrochemical reduction, it can, as here, be
completely decoupled from electrochemistry; this avoids possible
complications with fouling of electrodes; (iv) 3 is used here in
conventional glassware and in organic solvents without added
electrolytes; (v) higher temperatures can be used than are routinely
possible in electrochemical operation; (vi) since electron-donor 3
is available as a pure organic solid, the starting concentration of
the reducing agent can be controlled; this contrasts with indirect
electrochemistry, where the active reducing agent must be produced
in situ.
In summary, donor 3 is the first neutral organic reagent to reduce
arenesulfonyl groups in sulfones and sulfonamides. Unlike the alkali
metals, the reagent shows pronounced selectivity for substrates that
are slightly activated. The ease of preparation of these SED reagents,
their mildness as neutral reagents, and the clear possibilities to
modulate their structures and hence their reactivity (cf. 1 and 3)
suggest wide applications in reductive transformations.
has not previously been undertaken. To understand the basis of
the selectivity seen above, computational investigations were carried
out that examined the nature of the electron-transfer reactions and
the fragmentation of the radical anions. These studies show that
the activation energy required for the electron transfer to 7 is much
larger than in the case of 5, 6, or 10 and that this is the crucial
factor associated with nonreaction of 7 (see Supporting Informa-
tion). For 5, 6, and 10, low activation energy is associated with the
electron transfer and simultaneous dissociation into a sulfinate anion
occurs spontaneously. This dissociation can be explained from an
orbital perspective, where the LUMOs of 5 and 6 have a much
greater overlap than 7, with the σ*-orbital of their respective scissile
C-S bonds (see Supporting Information). Thus, this larger overlap
explains the spontaneous dissociation of the radical anions derived
from 5 and 6 and the lack of cleavage for the radical anion derived
from 7.
Acknowledgment. We thank EPSRC National Mass Spectrom-
etry Service Centre, Swansea, for high-resolution mass spectra and
EPSRC and the University of Strathclyde for funding.
Reductions of sulfonamides with reagent 3 were then addressed,
testing three substrates 24-26 that featured different degrees of
stabilization in their nitrogen leaving groups. The indolesulfonamide
24 underwent cleavage to 27 in 91% yield over 4 h. The
anilinesulfonamide 25 was likewise reacted and over 18 h gave a
very satisfactory 74% yield of 28. However, the piperidine
derivative 26 did not react. Computational studies show that in
analogy to 7, the inactivity of 26 is a result of the large activation
energy associated with the electron transfer, due to the instability
of the radical anion (see Supporting Information for details). It has
been proposed that cleavage of sulfonamide radical anions should
result in aminyl radicals and sulfinate anions,8b but the issue has
never been explored in detail. Analysis of the radical anions derived
from 24 and 25, reveals a spontaneous reaction, akin to a
fragmentation followed by a loose association of the two fragments;
in each case, the associated complex might best be described as a
three-electron N-S bonded intermediate.13 For indole substrate 24,
the charge distribution shows that the negative charge is principally
associated with the indole, possibly reflecting the aromatic stabiliza-
tion of the developing anion. In the case of aniline derivative 25,
the intermediate shows the negative charge principally associated
with the arenesulfonyl unit (see Supporting Information).
As mentioned above, typical sulfones and sulfonamides have very
negative reduction potentials, typically -2.3 V vs SCE.8b As with
halides, their reduction can be achieved by electron-transfer from
molecules with less negative redox potentials, provided that the
radical-anion from the sulfone or sulfonamide can undergo relatively
rapid fragmentation.8b Whereas direct electrochemical reduction of
these groups requires operation at potentials close to the standard
reduction potentials, indirect electrochemical reduction can be
achieved8b,14 by using an electrode to reduce a mediator such as
pyrene (E° ) -2.018 V) or anthracene (E° ) -1.8908 V) to the
corresponding radical-anion. However, these radical ions are
Supporting Information Available: Typical experimental proce-
dures for the preparations and reductions of substrates, spectroscopic
data for the products and details of computational studies. This material
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