and 3 (Scheme 2) were prepared. When the reactions of 2
and 3 with PTAD were carried out in CDCl3, CH2Cl2,
acetone, acetonitrile, and DMSO at ambient temperature, they
exclusively afforded the ene adducts 2e and 3e respectively
(Scheme 2), bearing an intact cyclopropyl group. These
results provide strong evidence that in non-hydroxylic
solvents the ene reaction proceeds via the established, closed
AI intermediate, leading exclusively to the formation of the
ene products 2e and 3e. Had the biradical intermediate, with
a lifetime greater than 10-11 s (rate of phenyl-substituted
cyclopropyl ring opening: 3 × 1011 s-1),14d been formed,
the characteristic ring-opened products would have been
detected.
To shed more light to this mechanistic problem, and be
able to distinguish between biradical and dipolar intermedi-
ate, a second-generation hypersensitive probe, developed by
Newcomb and co-workers,17,18 was used. For example,
cyclopropylcarbinyl probe 4 (Scheme 4), containing both a
Scheme 4. Mechanistic Probe Capable of Distinguishing
between a Radical and a Cation on the Cyclopropylcarbinyl
Carbon
When the reaction was carried out in methanol-d4,
apart from the ene adducts 2e and 3e, which were formed
in a relatively small percentage, rearranged methanol-
trapping derivatives 2t and 3t were mainly isolated (Scheme
2). When ethanol was used as the solvent analogous
ethanol-trapping adducts were isolated. The trans stereo-
chemistry of the newly formed double bonds in 2t and 3t
was assigned by nuclear Overhauser effect difference experi-
ments (DNOE).
phenyl and a methoxy group, not only maintains the
hypersensitive radical reactivity, but also permits high
discrimination between radical and cationic intermediates.
Consequently, in ring openings of this cyclopropyl carbinyl
system, the phenyl group stabilizes an incipient radical more
effectively than the methoxy group and conversely, the
alkoxy group favors an incipient carbocation.
Indeed, cyclopropylcarbinyl radical 4 (Scheme 4) rear-
ranges with high regioselectivity, 170:1 at ambient temper-
ature, to the benzylic radical 5, while, cyclopropylcarbinyl
cation 4 opens with even higher selectivity, >1000:1, to
oxonium ion 6.17,18
The proposed mechanism that could account for the
formation of these ring-opened trapping products is shown
in Scheme 3: The initially formed tertiary carbocation or
Scheme 3. Proposed Mechanism for the Formation of the
Rearranged Trapping Derivatives
The efficiency of this useful mechanistic probe to distin-
guish between radical and dipolar intermediates has already
been demonstrated.17,18 Moreover, thionocarbonate 7 and
mesylate 8 (Figure 2) were tested under radical (Barton-
Figure 2. Substrates utilized to study the cation and radical trapping
ability of the cyclopropylcarbinyl moiety containing both a phenyl
and a methoxy group.
radical undergoes ring opening to the more stable, benzylic
cation or radical intermediate, which is subsequently been
trapped by one molecule of methanol-d4.
Although the cyclopropyl rearranged and methanol-trapped
products unambiguously indicate the formation of an open
intermediate, this probe is unfortunately insufficient to
discriminate between radical or carbocation intermediates.16
It has been previously shown that radicals as well as the
corresponding carbocation intermediates may be trapped
equally effectively.17
McCombie deoxygenation) and cationic reaction conditions,
respectively. The exclusive formation of the benzylic radical
or oxonium cationic intermediate respectively led to two
distinctive products.
To test the biradical/dipolar intermediacy in the present
system, alkenes 9 and 10 (Scheme 5) were prepared and their
reactions with PTAD were performed in methanol and
ethanol. Similarly to the PTAD addition toward 2 and 3 in
methanol-d4, the ene adducts 9e and 10e were formed in a
relatively small percentage, while the only rearranged
(16) (a) Pasto, D. J. Tetrahedron Lett. 1973, 713-716. (b) Sarel, S.;
Felzestein, A.; Yovell, J. Tetrahedron Lett. 1976, 451-452. (c) Shimizu,
N.; Fujioka, T.; Ishizuka, S.; Tsuji, T.; Nishida, S. J. Am. Chem. Soc. 1977,
99, 5972-5977.
(17) Le Tadic-Biadatti, M.-H.; Newcomb, M. J. Chem. Soc., Perkin
Trans. 2 1996, 1467-1473.
(18) (a) Newcomb, M.; Chestney, D. L. J. Am. Chem. Soc. 1994, 116,
9753-9754. (b) Newcomb, M.; Le Tadic-Biadatti, M.-H.; Chestney, D.
L.; Roberts, E. S.; Hollenberg, P. F. J. Am. Chem. Soc. 1995, 117, 12085-
12091.
Org. Lett., Vol. 8, No. 1, 2006
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