Highly efficient, catalytic bis addition reactions of allyl phenyl sulfone to vinyl sulfones

Article abstract of DOI:10.1016/j.tetlet.2004.04.162

Highly efficient, electrocatalytic additions of allyl phenyl sulfone to a variety of vinyl sulfones have been accomplished. The additions are catalyzed by electrogenerated bases derived from the reactant itself, and furnish 90-94% yields of highly polar molecules in which 1mol of allyl phenyl sulfone has added consecutively, selectively, and in a linear addition mode to 2mol of the vinyl sulfone. Essentially no products are observed which incorporate other than 2mol of the vinyl sulfone. An addition to a difunctional alkene, divinylsulfone, yields a novel cyclization product, albeit in more moderate yield (41%). The use of tetraalkylammonium salts, as opposed to lithium salts, as electrolytes has been found to provide electrogenerated bases of especially high reactivity.

Full text of DOI:10.1016/j.tetlet.2004.04.162

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4841–4845
Highly efficient, catalytic bis addition reactions of
allyl phenyl sulfone to vinyl sulfonesq
Greg A. N. Felton and Nathan L. Bauld*
Department of Chemistry and Biochemistry, The University of Texas, Austin, TX 78712, USA
Received 18 February 2004; accepted 28 April 2004
Available online
Abstract—Highly efficient, electrocatalytic additions of allyl phenyl sulfone to a variety of vinyl sulfones have been accomplished.
The additions are catalyzed by electrogenerated bases derived from the reactant itself, and furnish 90–94% yields of highly polar
molecules in which 1 mol of allyl phenyl sulfone has added consecutively, selectively, and in a linear addition mode to 2 mol of the
vinyl sulfone. Essentially no products are observed which incorporate other than 2 mol of the vinyl sulfone. An addition to a
difunctional alkene, divinylsulfone, yields a novel cyclization product, albeit in more moderate yield (41%). The use of tetraalkyl-
ammonium salts, as opposed to lithium salts, as electrolytes has been found to provide electrogenerated bases of especially high
reactivity.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
lytic additions of allyl phenyl sulfone (via its conjugate
base) to a variety of vinyl sulfones.
The buildup of basicity around the cathode during an
electrolytic reduction has long been known.1 A promi-
nent example of this phenomenon is the production of
sodium hydroxide by electrolysis of water.2 However,
the application of this concept for the purpose of
organic synthesis did not begin until the late 1960’s.
Since that time, a modest variety of applications of
electrogenerated bases (EGB’s) to organic synthesis
have been reported.1 The typical approach has been to
provide (usually in stoichiometric amount) an additive
(called a pro-base), which serves as a precursor to the
active base. In the context of another investigation, the
present authors have noted that bases generated at
vitreous carbon cathodes in the electrolysis of certain
substrates in acetonitrile solution containing quaternary
ammonium salts (as opposed to lithium salts) as elec-
trolytes possess an especially high level of reactivity. The
present work reports the exploitation of this electro-
chemical system and the corresponding reactive EGB’s
to effect exceptionally efficient and highly electrocata-
A novel aspect of these reactions is that, in contrast to
most of the earlier applications of EGB’s to organic
synthesis, one of the reactants (allyl phenyl sulfone) also
serves as the pro-base in the presently reported chem-
istry, so that no foreign pro-base need be added. An-
other especially novel aspect of these reactions is that
they furnish high (90–94%) yields of highly polar mol-
ecules in which 1 mol of allyl phenyl sulfone has added
consecutively, selectively, and in a linear addition mode
to 2 mol of the vinyl sulfone. Essentially no products are
observed, which incorporate other than 2 mol of the
vinyl sulfone. Finally, an addition to a difunctional
alkene, divinylsulfone, yields a novel cyclization prod-
uct, albeit in more moderate yield (41%).
2. Dimerization of allyl phenyl sulfone
In the initial phase of this research, the reactivity of the
EGB formed under our electrochemical conditions and
the efficiency of base-catalyzed Michael-type additions
under such conditions, was demonstrated in a study of
the self-addition of allyl phenyl sulfone (1a). This reac-
tion was found to afford the dimer 2a in 81% yield,
with a catalytic factor of at least 11.33 (equivalent to a
Keywords: Catalytic; Electrogenerated base; Bis addition; Allyl vinyl
sulfone; Phenyl vinyl sulfone; Cyclization.
q Supplementary data associated with this article can be found, in the
online version, at doi:10.1016/j.tetlet.2004.04.162
* Corresponding author. Tel.: +1-512-471-3017; fax: +1-512-471-8696;
e-mail addresses: greg_felton@hotmail.com; bauld@mail.utexas.edu
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.162

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G. A. N. Felton, N. L. Bauld / Tetrahedron Letters 45 (2004) 4841–4845
0.087 F molꢀ1 process). This same dimer has been re-
ported in the literature in one other instance, as a
product of a cathodic reduction of the isomeric molecule
phenyl trans-propenyl sulfone, a substrate which would
furnish the same conjugate base as allyl phenyl sulfone.4
In that study, the yield of 2a obtained was only 56%
(catalytic factor of at least 10). Further, an anion radical
mechanism was proposed for the formation of 2a, which
we consider inconsistent with typical anion radical
behavior. Rather, the base-catalyzed Michael-type
addition illustrated in Scheme 1 is presently proposed.
3. Additions of allyl phenyl sulfone to electron
deficient substrates
In view of the observation that the conjugate base of 1a
undergoes efficient conjugate addition to phenyl prop-
enyl sulfone, it appeared likely that cross additions to
vinyl sulfones, might be even more efficient. Such vinyl
sulfones would not be susceptible to deprotonation, so
that they could not fulfill the carbanion role but could
serve as ideal Michael acceptors. However, a plausible
possibility was that additions of the conjugate base of 1a
to these receptors might generate a mixture of dimers,
trimers, oligomers, and even higher polymers. The
addition reactions of 1a with phenyl and tolyl vinyl
sulfone (substrates 1b and 1c) under our conditions
somewhat surprisingly lead to quite high yields of single
compounds, which are not dimers, but trimers, in which
the conjugate base of 1a has added to two and only two
molecules of the receptor. Further, even when a 2.06:1
ratio of receptor to 1a is used, the ‘trimers’ are generated
cleanly and in high yield, unaccompanied by any of the
dimer of 1a. The proposed general mechanism for the
formation of these linear trimers is given in Scheme 2.
Preferential addition of the conjugate base of 1a to the
vinyl sulfone component as opposed to the propenyl
sulfone is expected based not only upon steric effects,
which are minimal in the case of the vinyl sulfone, but
also because of the concentration of 1a0 never rises to a
very high level in these solutions (presumably <2% of
the mixture of 1a and 1a0). The addition of the dimer
carbanion to another mole of the vinyl sulfone then
follows rapidly and equally selectively, leading to a tri-
mer carbanion. Interestingly, these reactions do not
form significant amounts of tetramers, oligomers or
polymers, so that there is no apparent tendency of this
latter carbanion to add to any further molecules of the
vinyl sulfone. It appears reasonable to propose that the
pronounced difference in nucleophilic reactivity between
the trimer carbanion and the dimer carbanion is the
The mechanism of generation of the EGB is by no
means certain, but appears to involve the initial reduc-
tion of 1a to the corresponding anion radical. It is
possible that this anion radical is itself the EGB, which
initiates the deprotonation of 1a. Alternatively, the an-
ion radical may deprotonate adventitious water,5 yield-
ing hydroxide ion as the EGB. Interestingly, the
structure of the dimeric product reveals that the conju-
gate base adds not to the unactivated double bond of 1a,
but to the activated, electron deficient double bond of its
position isomer, phenyl propenyl sulfone (1a0), which
would be produced by a rapid, base-catalyzed equili-
bration of 1a and 1a0 (step 1 of Scheme 1). The latter
isomer has in fact been detected (NMR) in these reacting
solutions. The addition of the conjugate base of 1a/1a0
to the b position of 1a0 yields a dimer carbanion, which
is subsequently protonated either by 1a, to yield more
conjugate base, or by the conjugate acid of the EGB, to
regenerate the EGB. It is noted that the protonation of
the dimer carbanion by 1a should be exergonic, since the
latter carbanion has a greater degree of delocalization.
Finally, the double bond of the initially produced dimer
undergoes base-catalyzed position isomerization (step 3
of Scheme 1). It is of interest that subjection of 1a to
typical base catalysis conditions yields no detectable
amount of dimer 2b, but rather produces various olig-
omers and condensation products.6
Scheme 1. Mechanism of electrogenerated base-catalyzed dimerization of allyl phenyl sulfone.

G. A. N. Felton, N. L. Bauld / Tetrahedron Letters 45 (2004) 4841–4845
4843
Scheme 2. Proposed mechanism of the linear cross addition of allyl phenyl sulfone with 2 mol of a vinyl sulfone.
Table 1. Yields and catalytic factors for the dimerization of allyl
reaction.9 No such product is observed in the case of the
cross addition of 1a to phenyl vinyl sulfone.10 Finally,
the absence of anion radical pathways is further indi-
cated by the observation that when the electrolyte is
changed to lithium perchlorate, the dimerization of 1a
does not proceed. No reaction is observed, even after the
passage of several F molꢀ1, yet this electrolyte is known
to favor anion radical promoted cyclizations,7 whilst
allowing at best limited base reactivity.11
phenyl sulfone, and the cross addition of this sulfone, to several elec-
tron deficient alkenes
Substrate
Product
Yield (%) Catalytic
factora
No additional
substrate
2b: Dimer
81.3
11.3
1a0: Propenyl vinyl 2.1
sulfone
1b: Phenyl vinyl
sulfone
2bb: Trimer
90.8
12.7
1c: Tolyl vinyl sulfone 2cc: Trimer
1d: Divinyl sulfone 2d: Cyclic dimer
94.5
41.0b
7.4
6.3b
5. A novel cyclization
a Catalytic factor based upon total charge used and moles of limiting
reagent 1a.
b Corrected for 21.1% of 1a that was recovered.
The reaction of 1a with 1d gives a rather unexpected and
novel product, the eight-membered ring product 2d (Fig.
1). The yield of this product (41%) is more modest than
those observed in the previously described linear di-
merizations and trimerizations, but the coupling of the
conjugate base of allyl phenyl sulfone once at the posi-
tion a to the phenylsulfonyl group and then again c to it,
to yield an eight-membered ring is rather novel. As in
the previously described reactions, coupling undoubt-
edly occurs first at the a position, followed rapidly by
intramolecular addition from the c position (Scheme 3).
Presumably, the preference for reaction at the c position
to give a cyclooctene derivative over addition from the a
position, to give an eight-membered ring product derives
from the circumstance that the a carbon is now tertiary,
and much more highly hindered than the c carbon,
which is primary.
result of increased steric hindrance at the carbanion site
of the trimer (Table 1).
4. Carbanion-mediated versus anion radical
mediated reaction mechanisms
The isomerization of allyl phenyl sulfone to phenyl
propenyl sulfone is required by the structure of the di-
meric product obtained from the former sulfone. It
appears logical, and even essential, to propose a base-
catalyzed mechanism for this isomerization, which
would require the intermediacy of the common conju-
gate base of both sulfones. Since this conjugate base is
obviously present in the reaction medium, and since the
Michael addition of this base/nucleophile to electron
deficient double bonds is highly precedented, it appears
likely that 2a is formed via an exclusively carbanion-
mediated process. Incidentally, the final double bond
isomerization also would appear to require a base-cat-
alyzed process. The formation of the specific trimers
observed in the cross additions’ also appears to be rather
uniquely consistent with a carbanion mechanism. Fur-
ther, the highly catalytic nature of these reactions is
consistent with electrogenerated base-catalyzed chemis-
try. Such high catalytic factors have not been observed
in the case of anion radical chemistry.7;8 Still another
relevant observation is that the anion radical of phenyl
vinyl sulfone undergoes a rapid cyclobutadimerization
Figure 1. View of 2d showing the atom labeling scheme. Displacement
ellipsoids are scaled to the 50% probability level.

4844
G. A. N. Felton, N. L. Bauld / Tetrahedron Letters 45 (2004) 4841–4845
Scheme 3. Proposed mechanism for the addition/cyclization of allyl phenyl sulfone to divinylsulfone.
4. Delaunay, J.; Orliac-Le Moing, A.; Simonet, J. New J.
Chem. 1993, 17, 393–398.
There is no higher order oligomer (such as trimer) for-
mation, such as would be expected if the ring closure
step were slower than addition to another molecule of
1d. Presumably the intramolecularity of the cyclization
process provides the basis for the kinetic preference for
cyclization over oligomerization. The maximized yield
given above is obtained when the ratio of 1d to 1a is
greater than 3:1. In contrast to the other reactions,
unreacted 1a is generally recovered from this cyclization.
When the ratio of 1d to 1a is less than 3:1, the formation
of some 2b is also observed.
5. While water is excluded by use of freshly distilled solvent,
and electron transfer/reduction under a nitrogen atmo-
sphere, the exclusion is by no means rigorous enough to
preclude the presence of the low concentrations postulated
by this mechanism.
6. Conditions examined included tBuOK in tBuOH, and
tBuOK in DMSO, at varied temperatures, for different
lengths of time.
7. Roh, Y.; Jang, H.-Y.; Lynch, V.; Bauld, N. L.; Krische,
M. J. Org. Lett. 2002, 4, 611–613.
8. Wang, L.-C.; Jang, H.-Y.; Roh, Y.; Lynch, V.; Schultz, A.
J.; Wang, X.; Krische, M. J. J. Am. Chem. Soc. 2002,
124(32), 9448–9453.
6. Summary
9. Delaunay, J.; Mabon, G.; Orliac-Le Moing, A.; Simonet,
J. Tetrahedron Lett. 1990, 31, 667–668.
Highly efficient, electrocatalytic additions of allyl phenyl
sulfone to a variety of vinyl sulfones have been accom-
plished.12 The additions are catalyzed by electrogener-
ated bases derived from the reactant itself, and furnish
90–94% yields of highly polar molecules in which 1 mol
of allyl phenyl sulfone has added consecutively, selec-
tively, and in a linear addition mode to 2 mol of the vinyl
sulfone. Essentially no products are observed which
incorporate other than 2 mol of the vinyl sulfone. An
addition to a difunctional alkene, divinylsulfone, yields
a novel cyclization product, albeit in more moderate
yield (41%). The use of tetraalkylammonium salts, as
opposed to lithium salts, as electrolytes has been found
to provide electrogenerated bases of especially high
reactivity.
10. These results have been repeated in our group, with yields in
excess of 80%, with the exact same cell, solution, electrolyte,
and reduction potentials as the reactions reported here.
11. Unpublished research in this group has established a
complete suppression of competing EGB pathways in
intramolecular anion radical mediated cycloadditions,
when the electrolyte is changed from alkylammonium
salts to lithium perchlorate, to be published.
12. Sample experimental and novel compound characteriza-
tions: Electrolysis of 72 mg (0.018 M) of 1a and 137 mg
(0.037 M) of 1b (2.06:1 relative to 1a) was carried out for
3.0 C, at )2.5 V, in a 0.1 M Et4NBF4 acetonitrile solution,
in a divided cell, with glassy carbon electrodes. Voltage
versus silver wire in porous glass. Upon benzene extraction
and PTLC separation, 186 mg (90.8%) of 2bb was recov-
ered. Formation of the trimer occurred with a charge based
catalytic factor of 12.7. E-3,5,7-Tris(phenylsulfonyl)-2-
pentene (2bb): 1H NMR (300 MHz, CDCl3): 2.24 (4H,
m), 3.05 (2H, m), 3.37 (2H, m), 4.98 (1H, d, 17.4 Hz), 5.37
(1H, d, 11.1 Hz), 5.61 (1H, dd, 11.1, 17.1 Hz), 7.49 (2H, m),
7.65 (9H, m), 7.91 (4H, m); LRMS (CI+): 519, 351. E-3,5,7-
Tris(4-methylphenylsulfonyl)-2-pentene (2cc): 1H NMR
(300 MHz, CDCl3): 2.22 (4H, m), 2.46 (6H, s), 3.01 (2H,
m), 3.31 (2H, m), 4.98 (1H, d, 17.4 Hz), 5.37 (1H, d,
11.1 Hz), 5.61 (1H, dd, 11.1, 17.4 Hz), 7.37 (4H, m), 7.45
(2H, t, 7.2 Hz), 7.64 (3H, m), 7.78 (4H, br d, 8.7 Hz); LRMS
(CI+): 547, 405; HRMS (CI+): Calcd: 547.128279. Found:
547.128911. 1-Phenylsulfonyl-5-thia-5,5-dioxycyclohept-1-
ene (2d): 1H NMR (300 MHz, CDCl3): 2.02 (2H, p, 6.6 Hz),
2.60 (2H, m), 2.70 (2H, t, 6.3 Hz), 3.12 (2H, t, 6.3 Hz), 3.22
(2H, t, 5.4 Hz), 7.18 (1H, t, 9.3 Hz), 7.58 (2H, br t, 7.8 Hz),
7.70 (2H, br t, 7.8 Hz), 7.81 (1H, br d, 7.8 Hz); LRMS
(CI+): 301. Crystallographic data (excluding structure
Acknowledgements
The authors thank the Robert A. Welch Foundation
(F-149) for support of this research.
References and notes
1. Utley, J. H. P.; Nielsen, M. F. In Organic Electrochem-
istry; Lund, H., Hammerich, O., Eds.; 4th ed.; Marcel
Dekker, 2001, Chapter 30.
2. Wagenknecht, J. H.; Baizer, M. M. J. Org. Chem. 1966,
31, 3885–3890.
3. The reactions were monitored for completion in a stepwise
fashion, such that the exact amount of charge used to give
completion is not known.

G. A. N. Felton, N. L. Bauld / Tetrahedron Letters 45 (2004) 4841–4845
4845
factors) for 2bb and 2d, have been deposited with the
Cambridge Crystallographic Data Centre as supplemen-
tary publication numbers CCDC 231694 and CCDC
231693, respectively. Copies of the data can be obtained,
free of charge, via www.ccdc.cam.ac.uk/data_request/cif or
on application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK (Fax: +44-1223-336033 or e-mail: deposit@ccdc.
cam.ac.uk).