ORGANIC
LETTERS
2012
Vol. 14, No. 1
378–381
Intermolecular Oxonium Ylide Mediated
Synthesis of Medium-Sized Oxacycles
Daniel J. Mack,† Lindsay A. Batory,† and Jon T. Njardarson*,†,‡
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University,
Ithaca, New York 14853, United States, and Department of Chemistry and
Biochemistry, The University of Arizona, 1306 East University Boulevard, Tucson,
Arizona 85721, United States
Received November 22, 2011
ABSTRACT
Detailed in this account are our efforts toward efficient oxacycle syntheses. Two complementary approaches are discussed, with both employing
chemoselective allyl ether activation and rearrangement as the key step. Vinyl substituted oxiranes and oxetanes provide a single step access to
dihydropyrans and tetrahydrooxepines. Oxiranes proved to be poor substrates, while oxetanes were slightly better. An alternative approach using
substituted allyl ethers proved successful and addressed the limitations encountered in the ring expansions.
The formation and rearrangement of allyl ether oxo-
nium ylides has been investigated over the past four
decades by several research groups.1 These types of oxo-
nium ylides are usually generated by decomposing a diazo
precursor toa reactivemetallocarbenoid, which thenreacts
with the lone pairs of the allylic ether to form the requisite
oxonium ylide. Depending on the substrate, this intermediate
then undergoes either a [2,3]-rearrangement or a [1,2]-alkyl
shift. The majority of these studies are intramolecular.2 The
more challenging intermolecular variant has received far less
attention.3 In these handful of studies, diastereoselectivity is
moderate at best and competing cyclopropanation and car-
benoid dimerizations pathways commonly interfere. Only a
few intermolecular asymmetric allyl ether activation studies
have been reported. These used rhodium catalysts and were
limited by either low yield or poor enantioselectivity.4
It was our original intention to develop a method for the
ring expansion of small vinylic oxacycles to larger oxa-
cycles via an oxonium ylide mediated [2,3] sigmatropic ring
expansion. Specifically, a vinyl-oxirane, oxetane, or tetrahy-
drofuran precursors would undergo the ring expansion to
form dihydropyran, tetrahydrooxepine, or tetrahydrooxocine
† Cornell University.
‡ The University of Arizona.
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1998.
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C. S. J. Am. Chem. Soc. 1998, 120, 7653–7654. (d) Hodgson, D. M.;
Petroliagi, M. Tetrahedron: Asymmetry 2001, 12, 877–881. (e) Kitagaki,
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r
10.1021/ol203129d
Published on Web 12/21/2011
2011 American Chemical Society