Novel ring contraction of dioxepanes to tetrahydropyrans. Reaction of dioxepanes with trimethylsilyl trifluoromethanesulfonate

Article abstract of DOI:10.1016/S0040-4039(00)00126-X

Reaction of 5-methylene-1,3-dioxepanes derived from oxaphospholanes and paraformaldehyde with trimethylsilyl trifluoromethanesulfonate in the presence of a base yielded novel, exo formyl tetrahydropyran derivatives in good yields. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00126-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2171–2174
Novel ring contraction of dioxepanes to tetrahydropyrans.
Reaction of dioxepanes with trimethylsilyl
trifluoromethanesulfonate
Kentaro Okuma,a,∗ Tetsuji Hayano,a Kosei Shioji a and Haruo Matsuyama b
aDepartment of Chemistry, Faculty of Science, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan
bDepartment of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan
Received 7 December 1999; revised 5 January 2000; accepted 14 January 2000
Abstract
Reaction of 5-methylene-1,3-dioxepanes derived from oxaphospholanes and paraformaldehyde with trimethyl-
silyl trifluoromethanesulfonate in the presence of a base yielded novel, exo formyl tetrahydropyran derivatives in
good yields. © 2000 Elsevier Science Ltd. All rights reserved.
Cyclic ethers are important compounds for the synthesis of natural products. Because their synthetic
utility in the formation of tetrahydropyrans appears promising, many reports on the synthesis of sub-
stituted derivatives of tetrahydropyrans have appeared. Typical recent methods include acid-catalyzed
cyclization of epoxy alcohols,1 acid-catalyzed cyclization of terminal alkenols,2 Pd-catalyzed intramol-
ecular 1,4-dialkoxyalkylation of terminal dienals,3 and reaction of hydroxyallylsilane with aldehydes
in the presence of TMSOTf.4 However, there is no report on the synthesis of tetrahydropyrans by
ring contraction of seven-membered cyclic acetals (dioxepanes). Recently, we have reported a general
synthesis of 5-methylene-1,3-dioxepanes (1) from oxaphospholanes with paraformaldehyde.5 These
results prompted us to investigate the reactivity of these relatively unknown compounds. We report herein
a completely different strategy for the formation of six-membered cyclic ethers (tetrahydropyrans) from
exo-methylene-dioxepanes.
Substituted 5-methylene-1,3-dioxepanes (1) were previously synthesized by the reaction of oxaphos-
pholanes with paraformaldehydes.5 Since oxaphospholane was easily hydrolyzed to give the corres-
ponding diphenylphosphine oxide, we first tried a one-pot synthesis of 1. Treatment of methylene-
triphenylphosphorane obtained from methyltriphenylphosphonium bromide and sodium hydride with
styrene oxide followed by the addition of paraformaldehyde afforded 1a in 56% yield (Scheme 1). Other
reactions were carried out in a similar manner (Table 1).
∗
Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00126-X
tetl 16405

2172
Scheme 1.
Table 1
One-pot synthesis of 5-methylene-1,3-dioxepanes 1
By using this improved method, dioxepanes 1 were synthesized in large scale and can be used for
further investigation.
Since the dioxepanes 1 are acetals, we first attempted the acid hydrolysis of 1 in the hope of
obtaining diols. By using catalytic amount of HCl, trifluoromethanesulfonic acid, and trifluoroacetic
acid, dioxepanes 1 led to unidentified polymeric mixtures. Thus, some other new reaction must be
devised for their synthetic use. Gassman et al. found that the reaction of acetals with trimethylsilyl
trifluoromethanesulfonate (TMSOTf) in the presence of diisopropylethylamine gave vinyl enol ethers
in good yields.6 In view of these results, we then applied this method to dioxepanes. Dioxepane (1a)
was treated with TMSOTf in the presence of diisopropylethylamine at room temperature to give the
corresponding six-membered cyclic silyl enol ether (E:Z=1:1) (Scheme 2, Table 2).
Scheme 2.
When this silyl enol ether 2a was treated with trifluoroacetic acid, 4-formyl-tetrahydropyran (3) was
obtained quantitatively (trans:cis=3:1). These isomers were easily separated by using gel HPLC (Scheme
3).
How do we account for the formation of 2? Gassman et al. reported that the reaction of acetals with
TMSOTf followed by the addition of diisopropylethylamine afforded the corresponding vinyl ethers
in good yields. In view of this result, we proposed the following mechanism. Initial attack of 1 with
TMSOTf resulted in the formation of an oxonium ion intermediate (4), which was further attacked by a

2173
Table 2
Reaction of 5-methylene-1,3-dioxepanes 1 with TMSOTf7
Scheme 3.
double bond to give six-membered cyclic carbocation (5), which finally produced the silyl enol ether, 2,
by abstraction of a proton with diisopropylethylamine (Scheme 4).
Scheme 4.
To confirm this reaction mechanism, we carried out this reaction by using 1 with an electron-
withdrawing group. Treatment of 1f with TMSOTf in the presence of diisopropylethylamine resulted
in the formation of diene 3 (13%) along with 2f (42%), which confirmed the presence of oxonium ion
intermediate 4 (Scheme 5).
The present reaction is quite different from others. Gonzalez et al. have reported the synthesis of 3-
deoxy-3-nitroheptoseptanosides by the reaction of 1,4-dioxepanes with nitromethane in the presence of
potassium fluoride as catalyst.8 Fukuzawa et al. reported the effective transformation of aldoximes of
1,3-dioxepanes to nitriles by dehydration in the presence of scandium(III) triflate.9 However, there is no
report on the ring contraction from methylene-1,3-dioxepanes.

2174
Scheme 5.
Since there are numerous natural products containing a tetrahydropyran moiety,10 the present method
provides another approach to the synthesis of tetrahydropyrans. We are currently continuing further
investigation on the reaction and synthetic application of these compounds.
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CHH), 4.17 (m, 2H, CHH), 4.26 (br d, 2H, J=8 Hz, PhCH), 6.18 (s, 2H, _CH), 7.24–7.42 (m, 12H, Ph). 13C NMR (CDCl3)
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CHH), 2.63 (tt, 1H, J=4, 13 Hz, CH), 3.61 (dt, 1H, J=2, 13 Hz, OCHH), 4.24 (dd, 1H, J=4, 13 Hz, OCHH), 4.38 (dd, 1H,
J=2, 13 Hz, PhCH), 9.62 (s, 1H, CHO). 13C NMR (CDCl3) δ=25.50 (CH2), 33.23 (CH2), 48.17 (CH), 67.37 (OCH2), 78.77
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