charge on the less-substituted position of the olefinic groups.
The incoming nucleophile (C6H6) then reacts at the less-
substituted position, and subsequent protonation gives the
anti-Markovnikov addition products (2a-c). In the addition
reaction between 1b and CF3SO3D with C6D6 (eq 5), there
is incomplete deuterium incorporation onto the pyrazine ring,
suggesting that the addition reaction is occurring at a faster
rate than protonation of the pyrazine ring. This leaves open
the possibility of an alternative mechanism involving proto-
solvation of the olefin group with concominent nucleophilic
attack by the arene nucleophile, an AdE3-type mechanism
(eq 6).10 Deuterium incorporation could then occur in a
secondary reaction at the pyrazine ring. The alcohol sub-
of the highest occupied molecular orbitals (HOMOs) of
benzene and cyclohexane. Free-radical chemistry is well
known to produce anti-Markovnikov addition products, so
to determine if radical cations are involved in the chemistry
of the vinyl pyrazines, CIDNP experiments were done. For
example, 4-(3-phenylpropyl)pyridine (12) was reacted with
vinylpyrazine (1a) in triflic acid (eq 8) as a completely
homogeneous liquid phase.12 When the reaction is followed
1
by H NMR at 25 °C, no CIDNP signal enhancements or
absorptions are observed. The reaction between 12 and 1a,
however, gives the expected addition product (13) in good
yield. While the failure to observe CIDNP effects cannot
rigorously exclude the possiblity of SET mechanisms and
radical intermediates, it should be noted that a SET mech-
anism between a trication (like 9a) and the protonated form
of 12 would produce a pair of radical dications from a SET
pathway. Although dimerizations of radical cations have been
reported previously,13 there are no known examples of
dimerizations involving radical dications. The present results
suggest that long-lived radical intermediates are not present
in the reaction of 1a and 12 and, consequently, SET
mechanisms are not involved in the reactions of the olefinic
pyrazines (1a-c).
On the basis of the preliminary results described above, it
is clear that the doubly charged pyrazine ring plays an
important role in the protonation equilibria and the regio-
chemistry of nucleophilic attack. Moreover, this chemistry
provides further evidence that superelectrophilic activation
can be the basis for Michael addition leading to anti-
Markovnikov-type products. When the earlier studies involv-
ing acrylic acid and 2-nitropropene are also considered, these
strates give two types of products: direct substitution
products (7a-c) and the addition-type products (2a-c;
Scheme 2). These results can be explained by assuming that
the pyrazine rings are doubly protonated and an oxonium
ion is formed by protonation of the hydroxy group (eq 7).
The resulting trications (10a-c) can either undergo direct
nucleophilic attack by benzene or dehydration leading to a
highly unstable carbocation (11a-c). Deprotonation then
gives intermediates 8a-c leading to the anti-Markovnikov
addition products. Despite having the favorable resonance
stabilization, the phenyl-substituted carbocation (11c) rapidly
undergoes deprotonation leading to the olefin (8c) and the
addition product (2c). This suggests that the doubly pro-
tonated pyrazine ring exerts a powerful destabilizing effect
on the adjacent carbocationic center. We believe that this is
the basis for the anti-Markovnikov addition involving the
olefinic pyrazines.
There has been a recent suggestion that some reactions of
superelectrophiles may occur by single electron transfer
(SET) pathways on the basis of the results of quantum
mechanical calculations.11 These computational studies showed
that the lowest unoccupied molecular orbitals (LUMOs) of
several dicationic electrophilies were energetically below that
systems all have a considerable amount of positive charge
generated at the terminal (less-substituted) carbon (eqs 9 and
10).14 This causes nucleophilic attack to occur at the terminal
carbon, leading to formal anti-Markovnikov addition in the
case of acrylic acid.
(7) Assignment of the regiochemistry of deuteration was based on 1H
NMR, 13C NMR, HETCOR, and mass spectral data, see Supporting
Information. Further comparisons were made with published NMR data of
an alkylpyrazine, see: Cox, R. H.; Bothner-By, A. A. J. Phys. Chem. 1968,
72, 1646.
(8) Chia, A. S.-C.; Trimble, Jr., R. F. J. Phys. Chem. 1961, 65, 863.
(9) Olah, G. A.; Prakash, G. K. S.; Sommer, J. In Superacids; Wiley:
New York, 1985.
(10) (a) Fahey, R. C.; Monahan, M. W. J. Am. Chem. Soc. 1970, 92,
2816. (b) See also: Emery, S. L.; Fies, C. H.; Hester, E. J.; McClusky, J.
V. J. Org. Chem. 1999, 64, 3788.
(12) With benzene as a substrate, two phases separate: the acidic-ionic
phase and the nonpolar benzene phase.
(13) (a) Masui, M.; Ueda, C.; Moriguchi, T.; Michida, T.; Kataoka, M.;
Ohmori, H. Chem. Pharm. Bull. 1984, 32, 1392. (b) Park, J. W.; Choi, N.
H.; Kim, J. H. J. Phys. Chem. 1996, 100, 769. (c) Apperloo, J. J.;
Groenendaal, L. B.; Verheyen, H.; Jayakannan, M.; Jayakannan, M.; Janssen,
R. A. J.; Dkhissi, A.; Beljonne, D.; Lazzaroni, R.; Bredas, J.-L. Chem. Eur.
J. 2002, 8, 2384.
(11) Koltunov, K. Y.; Prakash, G. K. S.; Rasul, G.; Olah, G. A. J. Org.
Chem. 2002, 67, 8943.
Org. Lett., Vol. 7, No. 12, 2005
2507