TETRAHEDRON
LETTERS
Tetrahedron Letters 42 (2001) 2261–2263 Pergamon
Rearrangement of methylenecamphor during electrophilic
bromination: remarkably clean access to the unnatural fenchyl
(1,3,3-trimethylbicyclo[2.2.1]heptane) system
Allen A. Thomas, Keith A. Monk, Sonia Abraham, Stella Lee and Charles M. Garner*
Department of Chemistry, Baylor University, Waco, TX 76798, USA
Received 21 July 2000; accepted 17 January 2001
Abstract—Treatment of (+)-methylenecamphor (2) with NBS in the presence of pyridine resulted in a rapid and remarkably clean
rearrangement to yield a brominated (+)-methylenefenchone (3) in high yield and purity (>96%). The structure of the product was
established by X-ray crystallography and the stereochemistry confirmed by both polarimetric and chiral GC analyses. Two
transformations of the product were also performed to elucidate the structure. © 2001 Elsevier Science Ltd. All rights reserved.
In the course of preparing terpene-derived asymmetric
catalysts and reagents,
1
we desired to brominate
methylenecamphor
2
(2) in the allylic position as had
been reported
3
for -pinene (1), shown below. The
reaction proceeded cleanly (90%), and was improved
to 98% yield of a single product by use of stoichio-
metric pyridine; the presence of diphenyldiselenide was
found to be of no consequence. N -Chlorosuccinimide
gave the same reaction, but less cleanly (80%). How-
ever, these reactions had clearly followed an unexpected
course, evidenced, for example, by the presence of only
two methyl singlets, rather than the expected three, in
the
1
H NMR spectrum. We were able to prove the
structure to be that of a previously unreported com-
pound (3, see Scheme 1).
The structure proof of compound 3 was done primarily
by X-ray analysis of ammonium carboxylate salt 7 and
9-fluorenyl derivative 8, made via the organolithium 5
as shown in Scheme 2. The organolithium was prepared
by either of two ways, via metal–halogen exchange of
the iodide,
4
or direct reaction of the bromide with the
radical anion of 4,4-di-tert -butylbiphenyl.
5
While both
crystal structures confirmed the basic structure of 3, the
absolute configuration could not be assigned with cer-
tainty because of disorder and/or the lack of heavy
atoms. Many other derivatives failed to provide suit-
able crystals for X-ray analysis.
6
Fortunately, the absolute configuration and enantiopu-
rity of compound 3 could be established by chiral gas
chromatography. Reaction of racemic methylenecam-
phor with NBS/pyridine produced racemic 3, the enan-
tiomers of which were adequately separated
7
on a
Cyclosil-B
8
capillary column (30 m×0.25 mm). Similar
analysis of 3 from (+)-methylenecamphor showed only
one peak. To establish the absolute configuration, we
prepared methylenefenchone (10) by debromination of
3 that had been prepared from both (+)-camphor and
racemic camphor, and (in low yield) by Wittig methylen-
ation of natural (-)-fenchone (9). Again, the enan-
tiomers were adequately separated,
9
and each of the
optically active samples exhibited single peaks at differ-
ent retention times (Scheme 3).
The formation of 3 can be understood in terms of an
initial attack by electrophilic bromine, followed by
rearrangement and elimination of the resulting cation,
as shown in Scheme 4. This rearrangement is remark-
able in that cation I does not rearrange further, possi-
Scheme 1.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII:S0040-4039(01)00089-2