Wittig rearrangement of allyl and propargyl furfuryl ethers leading to 2-furylmethanol derivatives

Article abstract of DOI:10.1039/a907312d

The first example of the Wittig rearrangement of furfuryl ethers is presented and its application to the preparation of 3-(2-furyl)-3-hydroxy-2- methylpropionates is described.

Full text of DOI:10.1039/a907312d

Wittig rearrangement of allyl and propargyl furfuryl ethers leading to
2-furylmethanol derivatives
Masayoshi Tsubuki,* Teruyoshi Kamata, Hiroyuki Okita, Mayumi Arai, Atsushi Shigihara and Toshio
Honda*
Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 142-8501, Japan.
E-mail: tsubuki@hoshi.ac.jp; honda@hoshi.ac.jp
Received (in Cambridge, UK) 9th September 1999, Accepted 5th October 1999
The first example of the Wittig rearrangement of furfuryl
ethers is presented and its application to the preparation of
3-(2-furyl)-3-hydroxy-2-methylpropionates is described.
deprotonation at the a position was generally effected by ButLi
in THF at 278 °C, thus providing 2,3-rearrangement products
2a–e as major isomers. In contrast, weaker bases, such as BuLi
and BusLi, favoured aA over a deprotonation in the reactions of
1a–d, giving 2,3-rearranged products 5a–d together with
1,2-rearranged products 4a,b. (Z)-Crotyl furfuryl ether 1d
afforded syn product5 2d with high diastereoselectivity,
whereas (E)-crotyl ether 1c yielded anti isomer5 2c, albeit in
moderate selectivity. It is noteworthy that the (E)-crotyl ether 1c
underwent [2,3] Wittig rearrangement furnishing the anti
isomer 2c as a major compound, while the corresponding (E)-
crotyl benzyl ether afforded a mixture in which the syn isomer
was favoured.2
In order to gain an understanding of the relative thermody-
namic stabilities of 1a and 1aA anions, we undertook ab initio
calculations involving full optimisations using the GAUSSIAN
92 quantum mechanical package.§ As one might expect, the
calculations suggest that the energy minimums of the 1a–e a
anions were favoured by 12.0-28.5 kJ mol21 over the energy
minimums of the 1a–e aA anions at the RHF/6-31+G* level. It
became apparent that the energy minimum of the prenyl ether 1e
a anion was predicted to be 9.7 kJ mol21 lower than that of the
allyl ether 1a a anion. These results support the idea that the
Wittig rearrangement of allyl furfuryl ethers 1a–e proceeded
through deprotonation mainly at the a position, giving 2,3-re-
arrangement products 2a–e.
We have recently shown that the Wittig rearrangement of
3-furylmethyl ethers could proceed to give 2,3- and 1,2-re-
arrangement products.1 An advantage of this Wittig rearrange-
ment is that the deprotonation occurred selectively at the allylic
position, and either 2,3- or 1,2-rearrangement occurred prefer-
entially depending on the base used. Our interest in defining the
scope, limitations and utility of this rearrangement in fur-
ylmethyl ethers has directed our attention to Wittig rearrange-
ment of furfuryl ethers. Although the Wittig rearrangement of
arylmethyl ethers has been widely studied,2 there has been no
successful report on the rearrangement of a furfuryl ether.3
Herein, we report the first example of the Wittig rearrangement
of allyl and propargyl furfuryl ethers to provide a variety of
furyl alcohols, especially 2-furylmethanol derivatives.
The Wittig rearrangement of allyl furfuryl ethers 1a–e†‡ was
initially investigated under the conditions1 described before.
Allyl furfuryl ether 1 can theoretically produce both 2,3-re-
arrangement products 2 and 4 and 1,2-rearrangement products 3
and 5 depending on the position, a and aA, of deprotonation4
(Scheme 1). The results are summarised in Table 1. Selective
Table 2 shows that the diastereoselectivity in the Wittig
rearrangement of crotyl ethers 1c,d was influenced by the
solvent used. Surprisingly, changing the solvent from THF to
Et2O caused the opposite diastereoselectivity in the reaction of
Table 1 Wittig rearrangement of furfryl ethers 1a–e
Product Distributionb (%)
Yield
Substrate
Basea (%)
2
3
4
5
1a R1 = R2 = R3 = H
BuLi 53
BusLi 61
ButLi 61
31c
30c
63c
23c
23c
67c
19 50
16 54
17 20
23 54
15 62
14 19
1b R1 = R2 = H, R3 = Me BuLi 71
BusLi 55
ButLi 69
1c R1 = R3 = H, R2 = Me BuLi 79
74 (66/34)d
45 (75/25)d
93 (73/27)d
82 (9/91)d
52 (10/90)d
90 (10/90)d
82
—
—
—
—
—
—
5
—
—
—
—
—
—
—
—
—
26
55
7
18
48
10
13
5
BusLi 66
ButLi 73
1d R1 = Me, R2 = R3 = H BuLi 59
BusLi 70
ButLi 64
1e R1 = R2 = Me, R3 = H BuLi 57
BusLi 57
56
91
39
2
ButLI 79
7
a Reactions were carried out with base in THF at 278 °C. BuLi (10 equiv.)
was employed and the reaction was allowed to warm to 220 °C. BusLi (3
equiv.) was employed.ButLi (5 equiv.) was employed. b Determined by 270
MHz NMR analysis of the crude products. c [2,3] Rearranged products 2a,b
are equal to [1,2] rearranged products 3a,b. d In parentheses: the ratio of the
anti to the syn product.
Scheme 1
Chem. Commun., 1999, 2263–2264
This journal is © The Royal Society of Chemistry 1999
2263

Table 3 Wittig rearrangement of furfuryl propargyl ethers 6a,b
Table 2 Wittig rearrangment of crotyl furfuryl ethers 1c,d with ButLi in
different solvents at 278 °C
Substrate
Solvent
syn+anti
Yield (%)
1c
1c
1c
1c
1d
1d
1d
1d
THFa
Et2O
toluene
hexane
THFa
Et2O
toluene
hexane
b
27+73
87+13
74+26
78+22
90+10
94+6
73
72b
69
58b
64
66
51
60b
92+8
> 99+ < 1
a
The results from Table 1. Based on the recovery of the starting
material.
Product Distributionb (%)
Yield
Substrate
Basea (%)
7
8
9
10
6a R = H
6a R = H
6a R = H
6b R = Me BuLi
6b R = Me BusLi 64
6b R = Me ButLi 52
BuLi
73
—
—
—
9
12
9
45
65
89
—
—
—
6
49
21
11
21
3
BusLi 62
14
—
70
85
82
ButLi 61
67
9
Scheme 2 Reagents and conditions: i, TESCI, Pri2EtN, CH2Cl2 (87% for
11c, 89% for 11d); ii, OsO4, NMO, acetone–H2O; iii, NalO4, CH2Cl2–H2O
(2 steps: 54% for 12c, 47% for 12d); iv, NaClO2, 2-methylbut-2-ene,
NaH2PO4, ButOH, H2O; v, Mel, NaHCO3, DMF; vi, TsOH, MeOH (3 steps:
65% for 13c, 59% for 13d).
a Reactions were carried out with base in THF at 278 °C. BuLi (10 equiv.)
was employed and the reaction was allowed to warm to 220 °C. BusLi (3
equiv.) was employed. ButLi (5 equiv.) was employed. b Determined by 270
MHz NMR analysis of the crude products.
Notes and references
† Furfuryl ethers 1a–e and 6a,b were prepared by reaction of furfuryl
alcohol with the corresponding halides in DMF using 2 equiv. of sodium
hydride (ref. 7).
(E)-crotyl ether 1c. The same trend was observed even in a non-
polar solvent. On the other hand, better results were found in
Et2O, toluene and hexane, where 84–98% de was obtained in
the reactions of (Z)-crotyl ether 1d. A trace amount of 5c,d was
formed in all cases.
‡ All new compounds exhibited satisfactory elemental analyses and/or
1
HRMS and H and 13C NMR and IR spectral data. In general furans with
The promising results for the Wittig rearrangement of allyl
furfuryl ethers prompted us to examine the rearrangement of
propargyl ethers 6a,b (Table 3). For propargyl ether 6a
deprotonation with BusLi or ButLi proceeded through the
dianion at the a and terminal alkyne positions to give
1,2-rearrangement product 8a preferentially. In contrast,
propargyl ether 6b was deprotonated at the aA position to
produce mainly 2,3-rearrangement product 9b.
Employing anti and syn alcohols 2c,d we prepared
3-(2-furyl)-3-hydroxy-2-methylpropionates 13c,d, key inter-
mediates for the synthesis of several natural products.6
Protection of the hydroxy group in 2c,d as a TES ether afforded
11c,d, which were oxidised to aldehydes 12c,d by dihydroxyla-
tion of the alkene followed by glycol cleavage in 47 and 42%
yield, respectively. Oxidation of 12c,d with sodium chlorite
gave the carboxylic acids, which were esterified and then
deprotected with TsOH to furnish propionates 13c,d in 65 and
59% yield, respectively.
low molecular weight are volatile.
§ MO calculations were performed using the IBM RS/6000 version of the
GAUSSIAN 92 suite of programs.
1 M. Tsubuki, H. Okita and T. Honda, J. Chem. Soc., Chem. Commun.,
1995, 2135.
2 J. A. Marshall, in Comprehensive Organic Synthesis, ed. B. M. Trost and
I. Fleming, Pergamon, New York, 1991, vol. 3, p. 975; R. Brückner, in
Comprehensive Organic Synthesis, ed. B. M. Trost and I. Fleming,
Pergamon, New York, 1991, vol. 6, p. 873; T. Nakai and K. Mikami, Org.
React., 1994, 46, 105.
3 Marshall et al. have reported a [2,3] Wittig rearrangement of a
macrocyclic furan diether, in which the allyl furfuryl ether moiety did not
react via [2,3] Wittig rearrangement: J. A. Marshall and D. J. Nelson,
Tetrahedron Lett., 1988, 29, 741.
4 pKa values for 2-methylfuran and MeCHNCH2 are 43 and 44, re-
spectively. See F. G. Bordwell, Acc. Chem. Res., 1988, 21, 456.
5 P. G. M. Wuts and G. R. Callen, Synth. Commun., 1986, 16, 1833; G.
Cahiez and P.-Y. Chavant, Tetrahedron Lett., 1989, 30, 7373.
6 H. Akita, H. Koshiji, A. Furuichi, K. Horikoshi and T. Oishi, Chem.
Pharm. Bull., 1984, 32, 1242; S. F. Martin and D. E. Guinn, J. Org.
Chem., 1987, 52, 5588.
In summary, Wittig rearrangement of furfuryl ethers offers a
new route for the synthesis of furyl alcohols, especially
2-furylmethanol derivatives.
This work was supported by a Grant-in-Aid for Scientific
Reseach (C) from the Ministry of Education, Science, Sports
and Culture, Japan.
7 J. E. Zanetti, J. Am. Chem. Soc., 1927, 49, 1061; W. R. Kirner, J. Am.
Chem. Soc., 1928, 50, 1955.
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Chem. Commun., 1999, 2263–2264