than rearrangement and installation of the new functionality
with the incorrect stereochemistry (at least for 2).10,11 During
the course of these studies we became aware of two reports
that suggested a related but alternate strategy. It had been
demonstrated that tetrahydrobenzimidazoles rearrange, on
treatment with base, an alkyl halide and singlet oxygen to
provide a spiro cyclopentyl 4-imidazolone in low yield.12
More recently, the groups of both Foote and Adam have
demonstrated that N-acylindoles would rearrange via the 2,3-
epoxyindole to 2-indolones on treatment with dimethyldiox-
irane (DMDO).13 On the basis of these precedents, it ap-
peared that the rearrangement of tetrahydrobenzimidazoles
to spiroimidazolones with DMDO might be possible (Scheme
1, 10 f 9). Further, if the substrates were functionalized in
the 4-position (E ) Cl or OH), then the net transformation
proposed by Scheuer and Kinnel would have been achieved,
albeit in separate steps.
Scheme 1
attractive strategy to fashion this congested ring system
(Scheme 1, 5 + 6 f 7 f 8). We have recently demonstrated
that 4-vinylimidazoles can participate as dienes in the Diels-
Alder (DA) reaction, both inter- and intramolecularly to
provide the tetrahydrobenzimidazoles (cf. Scheme 2, 11a f
Accordingly, we were delighted to discover that when DA
adduct 13a7b was treated at room temperature with a slight
excess of DMDO, two spiro imidazolones were obtained in
56 and 27% yields.14 The isolation of two products was not
entirely unexpected given that (a) the faces of the imidazole
are diastereotopic and (b), in principle, either 4- or 5-imi-
dazolones could be produced; therefore, there is the potential
for the formation of up to four isomeric rearrangement
products. Fortunately, the major rearrangement product was
amenable to study by X-ray crystallography, the results of
which indicated that it was in fact the exo 5-imidazolone
(Table 1, entry 1, exo-18a).15 The other product was assigned
as the corresponding endo 5-imidazolone (Table 1, entry 1,
endo-18a).16 Enamine 12a7b can be converted into either the
exo alcohol 14a (89%) by oxidation with DMDO or the endo
alcohol 15a (91%, dr ) 5:1) by reaction with NBS/H2O.
The alcohols, after protection as silyl ethers (16a, 17a), were
treated with DMDO and in each case 5-imidazolones, endo-
19a and exo-20a, were obtained (Table 1, entries 2 and 3).
X-ray analysis of each of these products revealed that the
imidazolone carbonyl and the silyl ether were anti to one
another. These results suggested that the stereochemistry of
the rearrangement could be controlled through steric effects
Scheme 2
(9) For related rearrangements, see: (a) Cushing, T. D.; Sanz-Cervera,
J. F.; Williams, R. M. J. Am. Chem. Soc. 1996, 118, 557. (b) Edmondson,
S.; Danishefsky, S. J.; Sepp-Lorenzino, L.; Rosen, N. J. Am. Chem. Soc.
1999, 121, 2147. (c) Ganesan, A.; Wang, H. J. Org. Chem. 2000, 65, 4685.
(10) Dilley and Romo encountered a similar problem in their approach
to the spiro cyclic portion of palau’amine; see ref 8.
(11) Details of these studies will be reported elsewhere.
(12) Bernhart, C. A.; Perreaut, P. M.; Ferrari, B. P.; Muneaux, Y. A.;
Assens, J.-L. A.; Clement, J.; Haudricourt, F.; Muneaux, C. F.; Taillades,
J. E.; Vignal, M.-A.; Gougat, J.; Guiraudou, P. R.; Lacour, C. A.; Roccon,
A.; Cazaubon, C. F.; Breliere, J.-C.; Le Fur, G.; Nisato, D. J. Med. Chem.
1993, 36, 3371.
(13) (a) Adam, W.; Ahrweiler, M.; Sauter, M.; Schmiedeskamp, B.
Tetrahedron Lett. 1993, 34, 5247. (b) Adam, W.; Ahrweiler, M.; Peters,
K.; Schmiedeskamp, B. J. Org. Chem. 1994, 59, 2733. (c) Zhang, X.; Foote,
C. S. J. Am. Chem. Soc. 1993, 115, 8867.
12a or 13a).7 This communication describes our efforts to
convert these DA adducts into spirobicyclic systems related
to those found in 2-4 and the discovery of a novel oxidative
rearrangement reaction.
Our initial investigations centered on electrophile-induced
rearrangement of the DA adduct (Scheme 1, 7 f 8) akin to
that proposed by Kinnel and Scheuer3a as a possible bio-
synthetic route to 2.9 Experiments in this vein were singularly
unsuccessful due to aromatization (Scheme 1, 7 f 10) rather
(14) A third, as yet unidentified product was obtained from this reaction.
(15) Stereochemical descriptors endo/exo are used to indicate the
orientation of the imidazolone carbonyl moiety with respect to the
azabicyclo[3.3.0]octane.
(16) Supportive of this assignment is the 13C NMR chemical shift of the
imidazolone carbonyl carbon (δ ) 180.4), which is consistent with those
obtained for other 5-imidazolones prepared in this study, a number of which
were characterized by X-ray crystallography.
(8) Dilley, A. S.; Romo, D. Org. Lett. 2001, 3, 1535.
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