Winter et al.
JOCArticle
However, it is highly unlikely that the rearrangement itself
is radical in nature.28 Its concertedness precludes it, as do
results from the following series of experiments. Entries 1-6
of Table 4 show that when N-chlorolactams 11a,c-e were
submitted to different reaction conditions known to generate
the amidyl radical,29 only the parent lactam 11b or decom-
position products were obtained. Also, when 11a was ther-
molyzed to generate the radical pair 46, only the parent
lactam 11b or decomposition was observed (entries 7-9). In
those cases, the parent lactam 11a was likely formed by
H-abstraction from either the solvent (entries 1-3, 7, and 9)
or from tributyltin hydride (entries 4-6) by the amidyl
radical depending on the reaction conditions.
Importantly, the presence of a double bond does not bring
about cyclization of a purported radical intermediate 47
(Scheme 12). Such intermediates, generated by other meth-
ods, have been shown to cyclize onto double bonds in good
yield, including a terminal double bond.30 The fact that two
prenyl units (58a) led to the formation of 8% of the poly-
cyclic compounds 65a,b but that no trace of the correspond-
ing compound was obtained starting from the diallyl
substrate 57a indicates that a cationic intermediate 48 is
more likely than a radical intermediate 47. Indeed, cycliza-
tion to a tertiary carbocation would be more favorable than
cyclization to a primary carbocation, but the difference
between a tertiary and a primary radical is not so pro-
nounced.31
Ionic species could be generated either from the decay of
the electronic or vibrational excited state 45, via a yet
unknown mechanism, directly to the rearranged N-acylium
ion 48 (Scheme 10) or via a single electron transfer from the
lactamyl radical 46 to the chlorine atom inside the solvent
cage with concomitant rearrangement to the N-acylium ion
48. Whatever the case may be, we believe the transition state
to be highly asynchronous as suggested by the effect of the
substitution on the migrating carbon. A single electron
transfer implying an lactamyl radical has been previously
proposed by Edwards and collaborators,11 and single elec-
tron transfer mechanisms between radical species have also
been previously reported.32 The N-acylium ion 48 is then
trapped by the chloride ion in the solvent cage, and the
resulting carbamoyl chloride 49 is converted to the corre-
sponding methyl carbamate by basic methanol treatment.
It should be noted that the [1,2]-migration of the ring
carbon can be assisted by the lone pairs of the carbonyl
group, which are in the same plane as the migrating bond
FIGURE 1. Postulated or known reactive intermediates.
The rearrangement occurs with equal efficiency at 254 or
300 nm wavelengths, all of which are weakly absorbed by the
N-chlorolactam 44 to give an excited state 45. Little is known
about the photochemical transition of N-chlorolactams that
leads to the homolytic cleavage of the N-Cl bond or
perhaps, in our case, directly to the rearrangement. The
UV spectrum of N-chloroamides and N-chlorolactams (see
Supporting Information) only show an end-absorption in
acetonitrile, decreasing in intensity from 200 nm (ε ≈ 12 000
L mol-1 cm-1 for N-chlorolactam 1a) to 350 nm (ε ≈ 0). At
254 and 300 nm, the absorbance is weak with ε = 464 or 140
L mol-1 cm-1, respectively. This behavior is similar to that of
amides for which the absorption in the 220-230 nm region
has been attributed to a n f π* transition.22 For N-chlor-
olactams, the end-absorption could possibly be due to a n f
σ*N-Cl transition or to both transitions if they are close in
energy. Further studies are required to determine the exact
nature of the electronic transition.
We know that the products of the rearrangement are
photochemically stable because we have resubmitted pro-
ducts 5, 29, and 30 to irradiation under the same conditions
only to recover 80-95% of the starting material intact.
On the basis of early works by Lessard,23 Kuehne24 and
others,25 it is highly probable that 45, after internal conver-
sion or intersystem crossing decays, at least in part, to the
radical pair 46 in a solvent cage. Indeed, Scheme 11 shows
examples from these research groups of proven radical chain
reactions of N-chloroamides or N-chlorolactams. Therefore,
escape of the chlorine radical from the solvent cage and
hydrogen abstraction on the substrate would explain some of
the side products observed such as 6 and 19. It would also
explain the formation of the parent lactams 1b, 2b, 4b, 11b,
12b, 15b, 16b, 20b, 24b, 25b, 28b, and 41b-43b. Indeed,
hydrogen abstraction generates HCl, and the latter, via a
Goldfinger type mechanism,26 yields the parent lactam. A
control experiment in which external HCl was added to
N-chlorolactam 11a confirmed its complete and fast trans-
formation into the corresponding parent lactam. The parent
lactam and the chlorinated products can also be formed by
intermolecular hydrogen abstraction from the amidyl radical
(Bloomfield-type mechanism).27
(28) For selected reviews and examples of radical rearrangements that
€
retain stereochemistry, see: (a) Bossart, M.; Fassler, R. R.; Schoenberger, J.;
Studer, A. Eur. J. Org. Chem. 2002, 2742–2757. (b) Chuiko, V. A.; Vyglazov,
O. G. Russ. Chem. Rev. 2003, 72, 49–67. (c) Hodgson, D. M.; Galano, J. M.
Org. Lett. 2005, 7, 2221–2224.
(29) (a) Callier-Dublanchet, A.-C.; Quiclet-Sire, B.; Zard, S. Z. Tetrahe-
dron Lett. 1995, 36, 8791–8794. (b) Boivin, J.; Callier-Dublanchet, A.-C.;
Quiclet-Sire, B.; Schiano, A.-M.; Zard, S. Z. Tetrahedron 1995, 51, 6517–
6528. (c) Boivin, J.; Nguyen, V. T. Beilstein J. Org. Chem. 2007, 3, 47. (d)
Moutrille, C.; Zard, S. Z. Chem. Commun. 2004, 1848–1849. (e) Mackiewicz,
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(22) Nielsen, E. B.; Schellman, J. A. J. Phys. Chem. 1967, 71, 2297–2304.
and references therein.
(23) (a) Daoust, B.; Lessard, J. Tetrahedron 1999, 55, 3495–3514. and
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2597.
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(30) See for example Grainger, R. S.; Innocenti, P. Angew. Chem., Int. Ed.
2004, 43, 3445–3448.
(31) Kosower, E. M. An Introduction to Physical Organic Chemistry; John
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(24) Kuehne, M. E.; Horne, D. A. J. Org. Chem. 1975, 40, 1287–1292.
(25) Edwards, O. E.; Paton, J. M.; Benn, M. H.; Mitchell, R. E.;
Watanatada, C.; Vohra, K. N. Can. J. Chem. 1971, 49, 1648–1658.
(26) Adam, J.; Gosselin, P. A.; Goldfinger, P. Nature 1953, 171, 704–706.
(27) Bloomfield, G. F. J. Chem. Soc. 1944, 114–120.
(32) For selected articles, see: (a) Pincock, J. Acc. Chem. Res. 1997, 30,
43–49. (b) Kropp, P. J. Acc. Chem. Res. 1984, 17, 131–137. (c) Ho, P.-T. Can.
J. Chem. 1979, 56, 733–741. (d) Zimmerman, H. E. Angew. Chem., Int. Ed.
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