Communications
homologation sequence we had developed to prepare 1
[1] D. Bryce-Smith, A. Gilbert, B. H. Orger, Chem. Commun. 1966,
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[3] J. Cornelisse, Chem. Rev. 1993, 93, 615.
(Scheme 2), the aldehyde 4 was dideuterated by using sodium
deuteromethoxide in deuterated methanol and then con-
verted into 9 as shown in Scheme 4. Photolysis of 9 followed
[4] a) P. A. Wender, L. Siggel, J. M. Nuss in Comprehensive Organic
Synthesis, Vol. 5 (Eds.: B. M. Trost, I. Fleming), Pergamon,
Oxford, 1991, pp. 645 – 673; b) N. Hoffmann, Synthesis 2004, 481.
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Scheme 4. Structural assignment of 6. Reagents and conditions:
a) sodium [D3]methoxide, [D4]MeOH; b) H3CPPh3Br, MeLi, THF, 08C,
77%; c) TBAF, THF, 508C, 96%; d) hn (l=253.7 nm), cyclohexane,
73% (then separate); e) PCC, CH2Cl2, 73%; f) LDA, THF, PhSeCl,
À788C, 61%; g) H2O2 (27.5%), THF, 08C, 94%. PCC=pyridinium
chlorochromate, LDA=lithium diisopropylamide.
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[14] Compound 3 was photolyzed by using 253.7-nm radiation to give
three main cycloadducts, which were derived exclusively from
exo transition states as expected. For studies of compounds
related to 3, see; a) H. M. Barentsen, E. G. Talman, D. P. Piet, J.
Cornelisse, Tetrahedron 1995, 51, 7469; b) H. M. Barentsen,
A. B. Sieval, J. Cornelisse, Tetrahedron 1995, 51, 7495.
[15] A falling-film reactor (Photochemical Reactors Ltd.) equipped
with a 15-W low-pressure mercury lamp was used for irradi-
ations.
[16] CCDC-246803 (8) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
[17] E. J. Corey, J. W. Suggs, Tetrahedron Lett. 1975, 16, 2647.
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by oxidation of the product with pyridinium chlorochro-
mate[17] afforded ketone 10, which on desaturation to 11 by
the Sharpless–Reich protocol[18] allowed the relative stereo-
chemistry at C-10 to be established by NOE measurements
with irradiation of H-2 and H-8(axial) that showed a
significant enhancement at H-10 (Scheme 4). Thus, 1 exhib-
ited a rare high regioselectivity of cyclopropane formation[3,19]
to give 6 starting from a conformation that is analogous to the
exo arrangement shown in Figure 1 and proceeding by an exo
exciplex to give a relative stereochemistry that is appropriate
for the stemodinone ring system (Scheme 3).
In summary, an intramolecular alkene–arene meta photo-
cycloaddition has been carried out on 1 in a high yielding
reaction despite the presence of a four-carbon-atom tether.
Furthermore, this is a unique example of such a reaction
proceeding with a preference for an endo exciplex in an
intramolecular case. Taken with De Keukeleireꢀs and Wen-
derꢀs examples, these results show that with careful design of
the tether, the restriction of three-linking-unit tethers in this
type of reaction is no longer valid. The products of these
reactions hold promise of a rapid entry into the aphidicolin/
stemodinone ring systems and to yield biologically active
analogues.
Received: August 15, 2004
Revised: October 2, 2004
Published online: January 5, 2005
Keywords: cycloaddition · fused-ring systems ·
.
natural products · photochemistry · polycycles
946
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2005, 44, 944 –946