A New and Mild System for the Generation of Nonstabilized Carbonyl Ylides: Synthetically Practical Use in Reactions with Electron-Deficient Dipolarophiles

Full text of DOI:10.1021/jo971420i

8610
J . Org. Chem. 1997, 62, 8610-8611
Communications
A New a n d Mild System for th e Gen er a tion
of Non sta bilized Ca r bon yl Ylid es:
Ta ble 1
Syn th etica lly P r a ctica l Use in Rea ction s
w ith Electr on -Deficien t Dip ola r op h iles
Makoto Hojo, Hidenori Aihara,
Yoshifusa Suginohara, Kyosuke Sakata,
Shin-ya Nakamura, Chikara Murakami, and
Akira Hosomi*
Department of Chemistry, University of Tsukuba, Tsukuba,
Ibaraki 305, J apan
Received August 1, 1997
Extensive study has been devoted to the chemistry of
carbonyl ylides, and considerable attention has focused
on their use for the selective construction of oxygen-
containing five-membered heterocycles.1 We recently
found the generation of nonstabilized carbonyl ylides2
from iodohydrin silyl ethers or bis(chloromethyl) ethers
through the 1,3-elimination pathway using samarium
diiodide as a reductant.3 This protocol realized the
practical generation of carbonyl ylides bearing only alkyl
substituents that react intermolecularly with alkenes and
alkynes to afford stereodefined tetrahydrofurans and
dihydrofurans, respectively, in high yields. On the other
hand, in cycloadditions to electron-deficient dipolaro-
philes, the yields for cycloadducts were low because of
the competitive direct-reduction of these dipolarophiles
by the samarium reagent.4 We report a new system that
does not reduce dipolarophiles for the generation and
reactions of nonstabilized carbonyl ylides using a man-
ganese species where alkenes, aldehydes, ketones, and
aldimine can be used as dipolarophiles.5
At the outset of our investigation, samarium diiodide
was the only reductant known to generate nonstabilized
carbonyl ylides. We searched for other effective reduc-
tants in cycloadditions of carbonyl ylides with carbon
dipolarophiles. Alkali metals, alkaline earth metals,
lithium naphthalenide, CrCl2, and Rieke zinc were not
effective for the generation of the carbonyl ylide from bis-
(chloromethyl) ether 1a .6,7 Of all the reductants exam-
ined, only manganese metal successfully afforded the
corresponding cycloadducts. In the reaction with 3-bu-
tenyl 3-phenylpropyl ether (2a ), cycloadduct 3a was
a
Conditions A: a suspension of manganese (6 mmol) and PbCl2
(0.12 mmol) in THF (1 mL) was stirred at rt for 1 h. A dipolarophile
(0.5 mmol), NaI (4 mmol), and bis(chloromethyl) ether (1a ) (2
mmol) were successively added to the flask, and the mixture was
stirred at rt for 4 h. Conditions B: Rieke manganese (2.5 mmol)
was prepared from MnBr2 (2.5 mmol) and lithium naphthalenide
(5 mmol) in THF (2 mL). A dipolarophile (0.5 mmol) and bis(chlo-
romethyl) ether (1a ) (3 mmol) were added to the refluxing
suspension, and the mixture was stirred at reflux temperature
for 3.5 h. Conditions C: Rieke zinc (3 mmol) was prepared from
ZnCl2 (3 mmol) and lithium naphthalenide (6 mmol) in THF (4.5
mL). A dipolarophile (1 mmol) and bis(chloromethyl) ether (1a )
(2 mmol) were added to the suspension, and the mixture was
stirred at reflux temperature for 3 h. Isolated yield. c After the
manganese reagent was prepared (conditions A), the reagents and
THF (4 mL) were added at 0 °C and the mixture was stirred at 0
°C to rt for 2 h and then at rt for 2 h.
b
obtained in 44% yield using manganese activated by the
Rieke method.8 The manganese species prepared by the
Takai method9 was better as a reductant and gave the
tetrahydrofuran 3a in 76% yield (eq 1, Table 1).10
The ylide generated in this way reacted with cis-alkene
2c to produce the syn-substituted tetrahydrofuran 3c. We
(1) (a) Huisgen, R. In 1,3-Dipolar Cycloaddition Chemistry; Padwa,
A., Ed.; Wiley-Interscience: New York, 1984; pp 1-176. For synthetic
use of stabilized carbonyl ylides, see: (b) Padwa, A.; Weingarten, M.
D. Chem. Rev. (Washington, D.C.) 1996, 96, 223-269.
(7) With simple alkenes, the substrates were mainly recovered when
alkali metals, alkaline earth metals, lithium naphthalenide, CrCl2, and
the Rieke zinc were used. Unidentified polymeric products were
obtained from alkynes and allenes using Zn(0) activated by 1,2-
dibromoethane or Me3SiCl and Bu3MnLi. In the reaction with 2a using
Zn(0) activated by 1,2-dibromoethane or Me3SiCl, the adduct 3a was
obtained in ca. 20-30% yield.
(2) (a) Hojo, M.; Aihara, H.; Hosomi, A. J . Am. Chem. Soc. 1996,
118, 3533-3534. (b) Hojo, M.; Aihara, H.; Ito, H.; Hosomi, A. Tetra-
hedron Lett. 1996, 37, 9241-9244.
(3) For another method to generate nonstabilized carbonyl ylide,
see: Prakash, G. K. S.; Ellis, R. W.; Felberg, J . D.; Olah, G. A. J . Am.
Chem. Soc. 1986, 108, 1341-1342.
(4) (a) Namy, J . L.; Souppe, J .; Kagan, H. B. Tetrahedron Lett. 1983,
24, 765-766. (b) Souppe, J .; Danon, L.; Namy, J . L.; Kagan, H. B. J .
Organomet. Chem. 1983, 250, 227.
(5) During this work, it was learned that Prof. K. Takai et al. also
independently found the generation of nonstabilized carbonyl ylides
using manganese in the course of their work with respect to activated
manganese. We thank Professor Takai for communicating the results
prior to publication. Takai, K.; Kaihara, H.; Higashiura, K.-i.; Ikeda,
N. J . Org. Chem. 1997, 62, 8612.
(6) Buc, S. R. Organic Syntheses; Wiley: New York, 1963; Collect.
Vol. IV, pp 101-103. Caution! Very high carcinogenic activity has been
reported for bis(chloromethyl) ethers. See the hazard note in Organic
Syntheses; Wiley: New York, 1973; Collect. Vol. V, p 218.
(8) Kim, S.-H.; Hanson, M. V.; Rieke, R. D. Tetrahedron Lett. 1996,
37, 2197-2200.
(9) (a) Takai, K.; Ueda, T.; Hayashi, T.; Moriwake, T Tetrahedron
Lett. 1996, 37, 7049-7052. (b) Takai, K.; Ueda, T.; Ikeda, N.; Moriwake,
T. J . Org. Chem. 1996, 61, 7990-7991. (c) Takai, K.; Ueda, T.; Kaihara,
H.; Sunami, Y.; Moriwake, T. J . Org. Chem. 1996, 61, 8728-8729.
(10) PbCl2 (34 mg, 0.12 mmol) and THF (1.0 mL) were added to a
well-dried flask containing manganese (330 mg, 6.0 mmol), and the
mixture was stirred at rt for 1 h. Dipolarophile 2 (0.5 mmol), NaI (600
mg, 4.0 mmol), and bis(chloromethyl) ether 1 (2.0 mmol) were succes-
sively added, and the mixture was stirred for 4 h. Water was added,
and organics were extracted with ethyl acetate (20 mL × 3). After
drying over anhydrous Na2SO4, evaporation of the solvents, and
purification by means of column chromatography on silica gel (hexane/
ethyl acetate), pure cycloadduct 3 was obtained.
S0022-3263(97)01420-5 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 25, 1997 8611
including easily reducible hetero-dipolarophiles. Finally,
we have also shown that this reaction system can be
applied to the generation of methyl-substituted ylide from
1b,12-14 and this protocol leads to the generation of
structural varieties of carbonyl ylides bearing various
substituents (eq 3).
previously reported that, in the reaction with propargyl
ether 2d using a samarium reagent, a double-addition
product of the parent carbonyl ylide was the main product
when excess ylide was used.2b Interestingly, under the
present conditions only the monoadduct 3d was obtained
selectively (81%) and the bis-adduct was not detected
even if a 4-fold excess of ylide was used.11 In the reaction
with electron-deficient alkene 2e, the reduction of the
alkene was suppressed and the corresponding tetrahy-
drofuran-bearing ester function 3e was obtained in high
yield. The addition of NaI gave better results, possibly
because this additive may convert 1a to bis(iodomethyl)
ether that is more reactive than 1a , and manganese
would then reduce the iodomethyl group to generate the
parent carbonyl ylide preferentially to reduction of the
dipolarophile.
Ack n ow led gm en t. This work was partly supported
by Grants-in-Aid for Scientific Research, Grants-in-Aid
for Scientific Research on Priority Areas from the
Ministry of Education, Science, Sports and Culture,
J apan, Teikoku Chemical Industries Inc., and Pfizer
Pharmaceuticals Inc. C.M. and H.A. acknowledge sup-
port by Research Fellowships from the J apan Society
for the Promotion of Science for Young Scientists.
Reactions with hetero-dipolarophiles were also
examined: it was found that this manganese system can
be used with a variety of carbonyl compounds, and even
benzophenone, known as a good electron acceptor, was
used (eq 2, Table 1). As can be seen in Table 1, the parent
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and 1H and 13C NMR, IR, and mass spectral data of
the products (16 pages).
J O971420I
(12) Hall, G. E.; Ubertini, F. M. J . Org. Chem. 1950, 15, 715-719.
See the Supporting Information.
(13) We also examined the reactions of 1b with unsymmetrical
dipolarophiles such as benzyl propargyl ether (2d ), benzaldehyde (2g),
and benzophenone (2h ). In the reaction of 2d with 1b, a 55:45
regioisomeric mixture of cycloadducts (3k + 3k ′) was obtained in 78%
yield. In the reaction with 2g, a regioisomeric mixture of cycloadducts
(3l + 3l′) was obtained in 86% yield where the major regioisomer was
trans- and cis-2-methyl-4-phenyl-1,3-dioxolane ((2R*,4R*)-3l and
(2R*,4S*)-3l) (the regioisomeric ratio was 77:23). With 2h , the
corresponding cycloadducts (3m + 3m ′) were obtained in 78% yield
where 4,4-diphenyl-2-methyl-1,3-dioxolane (3m ′) was a major product
(the regioisomeric ratio was 94:6). For conditions, see the Supporting
Information.
carbonyl ylide reacts with aldehydes 2f-g, ketone 2h ,
and aldimine 2i to produce the corresponding 1,3-
dioxolanes 3f-h and 1,3-oxazolizine 3i, respectively, in
high yields.
We have been able to realize the reactions of the
carbonyl ylide with a wide variety of dipolarophiles,
(14) The diastereoselectivity (2,3-trans:2,3-cis ) 56:44 in 90% yield)
between the unsymmetrical carbonyl ylide derived from 1b and 2c was
almost identical in the case of the SmI2-promoted reaction (2,3-trans:
2,3-cis ) 59:41).2b For conditions, see the Supporting Information.
(11) Although the reason for the differences in reactivity is unclear
at present, it is possible that metals or metal ions may interact (or
coordinate) with carbonyl ylides to directly affect their reactivities.