A tellurium-triggered domino reaction for the synthesis of a 1-substituted-3-vinyl-1,3-dihydroisobenzofuran

Article abstract of DOI:10.1016/S0040-4039(00)01047-9

Telluride ion reacts with an oxiranemethanol toluenesulfonate in toluene under phase-transfer conditions to give an allylic alkoxide anion that is trapped by addition to an adjacent α,β-unsaturated ester to yield a furan derivative. Use of a non-racemic oxiranemethanol tosylate gives two furan diastereomers in a ratio of 56:44. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01047-9

Tetrahedron Letters 41 (2000) 6001±6004
A tellurium-triggered domino reaction for the synthesis of a
1-substituted-3-vinyl-1,3-dihydroisobenzofuran1
Bin Chao and Donald C. Dittmer*
Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA
Received 23 May 2000; revised 20 June 2000; accepted 21 June 2000
Abstract
Telluride ion reacts with an oxiranemethanol toluenesulfonate in toluene under phase-transfer conditions
to give an allylic alkoxide anion that is trapped by addition to an adjacent a,b-unsaturated ester to yield a
furan derivative. Use of a non-racemic oxiranemethanol tosylate gives two furan diastereomers in a ratio
of 56:44. # 2000 Elsevier Science Ltd. All rights reserved.
Previously, a tellurium process has been applied to the conversion of both racemic and non-racemic
epoxyalcohols, the latter being obtained by Sharpless±Katsuki asymmetric epoxidation, to
racemic and non-racemic secondary and tertiary allylic alcohols (Scheme 1).2 Elemental tellurium
is relatively non-toxic.3 It is reduced to telluride ions Te2n^ (n=1,2,3), which trigger the hypothetical
reaction sequence shown in Scheme 1, which results in the formation of the desired product with
the release of tellurium which can be reused. Still open is the question of whether the putative
epitelluride intermediate (1) in Scheme 1 might be formed by a more-or-less simultaneous attack
on two carbon atoms, displacing two leaving groups, the epoxide oxygen and the tosylate. The
process may be performed under no-solvent or phase transfer conditions4 and can be catalytic in
tellurium.5
Scheme 1.
* Corresponding author. Tel: (315) 443-3151; fax: (315) 443-4070; e-mail: dcdittme@syr.edu
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01047-9

6002
In our previous work exempli®ed in Scheme 1, the alkoxide ion from a ring-opening of the
epoxide by telluride is trapped by protonation. If, however, the oxygen anion is generated in
proximity to an electron-de®cient group such as a Michael acceptor (Scheme 2), a heterocyclic
ring is obtained. Intramolecular Michael-type additions of oxyanions to a,b-unsaturated esters
have been previously observed.6 Domino, tandem, or cascade reactions such as that shown in
Scheme 2 are not uncommon in the synthesis of heterocyclic compounds and include Michael-type
reactions.7 They are especially useful in the one-step synthesis of complex molecules with
excellent regio-, chemo-, diastereo- and enantioselectivity.8,9
Scheme 2.
The starting material 2 (Scheme 3) is obtained by way of a double Heck reaction with methyl
acrylate on o-dibromobenzene.10,11 Selective reduction of one ester group of 2 (Scheme 3) by
diisobutylaluminum hydride (DIBALH) (2 equiv.) is easiest on a small-scale, and over-reduction
to the insoluble bis-allylic alcohol can be minimized by use of a mixture of toluene and
dichloromethane (80/20) at ^78ꢀC. The carbon±carbon double bond of the allylic alcohol is
epoxidized selectively with m-chloroperoxybenzoic acid (m-CPBA). Conversion of the
epoxyalcohol to its tosylate and reaction with telluride ions under phase-transfer conditions gave
the dihydroisobenzofuran. Certain dihydrobenzo [c] furans are said to have medicinal uses.12
Scheme 3.
Sharpless±Katsuki asymmetric epoxidation of allylic alcohol 3 and subsequent conversion of
the optically active epoxyalcohol to the dihydroisobenzofuran (Scheme 4) results in a mixture of
two diastereomers of 6 in a 56:44 ratio according to the proton NMR spectrum which shows two
non-equivalent methyl groups. Other similar non-equivalencies in the proton spectra indicate
nearly equal amounts of the two diastereomers. The 13C NMR spectrum (126 MHz) shows
slightly unequal doublings for the two aliphatic carbon atoms of the dihydrofuran ring and for
the two CH2 groups (one alkene and one aliphatic). Thus, the e€ect of the chiral center
introduced by asymmetric epoxidation is not very great in selecting one face of the acrylate
carbon±carbon double bond over the other in the formation of the isobenzofuran derivative.

6003
Scheme 4.
Relatively low diastereoselectivity has been observed in domino reactions involving addition of
lithium benzyl (trimethylsilyl) amide without Lewis acid additives to a,b-unsaturated esters13
although a single diastereomer was reported for the reactions of 2,11 and high stereocontrol was
observed in non-domino Michael reactions of arylmenthyl crotonates when good p-stacking can
occur between the aryl group of the crotonate ester and the carbon±carbon double bond.14
Experimentalꢀprocedure: An aqueous suspension (3 mL) of Te powder (101 mg, 0.790 mmol)
.
was heated (60 C) for 2 h under argon with rongalite (HOCH2SO2Na 2H2O) (0.280 g, 3.27
mmol) and NaOH (0.0950 g, 2.37 mmol). The original black suspension of Te was transformed
into a deep red±purple solution containing telluride ions (Te2n^). The solution was cooled to room
temperature and the quaternary ammonium phase transfer catalyst Adogen 464 (20 mg) in
toluene (1 mL) and the tosylate of (2S,3S)-4 (0.243 g, 0.680 mmol) in toluene (4 mL) were
added.15 Black elemental Te began to precipitate after about 15 min. The mixture was stirred for
2 h, and the layers were allowed to separate. Air was bubbled through the mixture to facilitate
oxidation of excess telluride ions. The toluene layer was removed, dried (MgSO4), and ®ltered
through a pipet of silica gel to remove Teo followed by evaporation of the solvent to give the
20
1
nearly pure isobenzohydrofuran 6 (0.133 g, 0.610 mmol, 90%) ‰ꢀŠD =^53.4 (c 0.52, CHCl3): H
NMR (500 MHz) ꢁ 2.81 (9-line multiplet, 2H), 3.74 (s, 0.44H), 3.75 (s, 0.56H), 5.22 (ddd, J=9.1,
1.1, 1.1 Hz, 0.49H), 5.26 (ddd, J=8.8, 1.1, 1.1 Hz, 0.51H), 5.43 (ddd, J=17, 1.5, 1.1 Hz, 0.56H),
5.41 (ddd, J=17, 1.5, 1.1 Hz, 0.44H), 5.56 (br d, 0.5H), 5.65 (br m, 1H), 5.74 (br td, 0.5H), 5.91
(m, 1H), 7.10±7.30 (m, 4H). 13C NMR (126 MHz) 42.3, 43.0, 52.5, 80.3, 80.4, 85.4, 85.7, 117.5,
117.6, 121.8, 121.9, 122.6, 128.6, 128.7, 138.3, 139.0, 141.3, 171.9. HRMS (FAB): calcd for
C13H14O3Na (M+Na): 241.0841; found: 241.0842.
Acknowledgements
Acknowledgement is made to the donors of The Petroleum Research Fund, administered by
the American Chemical Society for the partial support of this research. We are indebted to
Professor Franklin Davis for the mass spectra and to Professor John Baldwin for the use of a
polarimeter. The drawings were done by Aphichart Rodchanarowan.
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1
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