SmI2-Induced 2,3-Wittig Rearrangement: Regioselective Generation of α-Allyloxy Carbanions via 1,5-Hydrogen Transfer of Vinyl Radicals

Full text of DOI:10.1021/jo9714223

7542
J . Org. Chem. 1997, 62, 7542-7543
Sch em e 1
Sm I2-In d u ced 2,3-Wittig Rea r r a n gem en t:
Regioselective Gen er a tion of r-Allyloxy
Ca r ba n ion s via 1,5-Hyd r ogen Tr a n sfer of
Vin yl Ra d ica ls
Munetaka Kunishima,*,† Kazuhito Hioki,†
Kazuhiro Kono,† Akira Kato,‡ and Shohei Tani*,†
Faculty of Pharmaceutical Sciences,
Kobe Gakuin University, Nishi-ku, Kobe 651-21,
J apan, and Niigata College of Pharmacy,
Kamishin’ei-cho, Niigata 950-21, J apan
Received August 1, 1997
2,3-Wittig rearrangement of allyl ethers is widely used
in organic synthesis.1 Numerous studies have focused on
their stereochemistry,1-3 but there are few methods for
generating an R-allyloxy anion regioselectively and under
mild reaction conditions.4 In this communication, we
report a novel 2,3-Wittig rearrangement involving regi-
oselective metalation at carbon R to the ethereal oxygen
via 1,5-hydrogen atom transfer5 by the reaction of γ-ha-
loallyl ethers with SmI2 in benzene-HMPA.6,7
Treatment of benzyl γ-iodomethallyl ether 1a with 2.5
equiv of SmI2 in benzene containing 10% HMPA under
nitrogen atmosphere at room temperature for 10 min
gave homoallyl alcohol 2 in 81% yield (Table 1, run 1,
conditions A).8 The reaction also proceeded with the
corresponding bromide, but a higher temperature (condi-
tions C) or a longer reaction time (conditions D) was
required (runs 3, 4). Both (E)- and (Z)-vinyl halides were
found to be effective for the reaction.
six-membered transition state to give R-allyloxy carbon
radicals 17 followed by reduction with SmI2 to give the
corresponding carbanions 18.10,11 2,3-Sigmatropic rear-
rangement of the anions gives homoallyl alcohols 19.
Lower yields of the product are obtained in THF (runs
2, 5), which has R-hydrogen-donating ability, than in
benzene, and this can be attributed to the competition
between intermolecular hydrogen abstraction and in-
tramolecular 1,5-hydrogen atom transfer. The hydrogen
undergoing 1,5-shift should be observed at the C-2
position of the product in the proposed mechanism.
Thus, we carried out the reaction by using 1b which was
99% deuterium-labeled at the benzylic methylene as
illustrated in eq 1. The 1H NMR spectrum of the product
indicated that one of the two deuteriums was present at
Intramolecular 1,5-hydrogen atom transfer plays an
important part in this reaction.9 As outlined in Scheme
1, a single electron transfer from SmI2 to vinyl halides
15 generates reactive vinyl radicals 16, which abstract
a hydrogen at the R′-carbon to the etheral oxygen via a
C-2, and the other at C-1 (both 98% D).12,13 On the other
hand, both deuteriums were found to remain at the
benzylic position (99% D) in the alkene 1c with none at
the terminal vinylic position.13
† Kobe Gakuin University.
‡ Niigata College of Pharmacy.
(1) For reviews on 2,3-Wittig rearrangement, see: (a) Nakai, T.;
Mikami, K. Chem. Rev. 1986, 86, 885-902. (b) Marshall, J . A. Compre-
hensive Organic Synthesis; Trost, B. M., Ed.; Pergamon Press: Oxford,
1991; Vol. 3, pp 975-1014. (c) Nakai, T.; Mikami, K. Org. React. 1994,
46, 105-210.
(2) For recent reports, see: (a) Konno, T.; Umetani, H.; Kitazume,
T. J . Org. Chem. 1997, 119, 137-150. (b) Nakai, T.; Tomooka, K. Pure
Appl. Chem. 1997, 69, 595-600. (c) Kress, M. H.; Yang, C.; Yasuda,
N.; Grabowski, E. Tetrahedron Lett. 1997, 38, 2633-2636.
(3) (a) Mikami, K.; Kimura, Y.; Kishi, N.; Nakai, T. J . Org. Chem.
1983, 48, 279-281. (b) Tsai, D. J .; Midland, M. M. J . Org. Chem. 1984,
49, 1842-1843. (c) Goeppel, D.; Mu¨nster, I.; Bru¨ckner, R. Tetrahedron
1994, 50, 3687-3708.
(4) (a) Still, W. C.; Mitra, A. J . Am. Chem. Soc. 1978, 100, 1927-
1928. (b) Broka, C. A.; Shen, T. J . Am. Chem. Soc. 1989, 111, 2981-
2984. (c) Mulzer, J .; List, B. Tetrahedron Lett. 1996, 37, 2403-2404.
(5) We found that R-halovinyl radicals arising from 3-alkoxy-1,1-
dihalo-1-alkenes with SmI2 underwent 1,5-hydrogen atom transfer to
give R-alkoxy radicals in competition with SET from SmI2 to the vinyl
radicals leading to the generation of alkylidenecarbenes, see: Kun-
ishima, M.; Hioki, K.; Kato, A.; Tani, S. Tetrahedron Lett. 1994, 35,
7253-7254.
(6) (a) Kunishima, M.; Hioki, K.; Ohara, T.; Tani, S. J . Chem. Soc.,
Chem. Commun. 1992, 219-220. (b) Kunishima, M.; Hioki, K.; Kono,
K.; Sakuma, T.; Tani, S. Chem. Pharm. Bull. 1994, 42, 2190-2192.
(7) For recent reviews on SmI2, see: (a) Molander, G. A. Org. React.
1994, 46, 211-367. (b) Molander, G. A.; Harris, C. R. Chem. Rev. 1996,
96, 307-338.
When unsymmetrical diallyl ethers are used as a
starting compound for base-induced Wittig rearrange-
ments, control over the regioselectivity of carbanion
formation (R vs R′) becomes important. Nakai and his
co-workers have established that the regioselectivity of
deprotonation by n-butyllithium depends on the differ-
ence in the total number of R- and/or γ-substituents,
which exclusively depress lithiation on the allylic moiety,
between the two allylic moieties.14 These results indicate
the difficulty of realizing the formation of one regioiso-
meric carbanion, independent of the substituents, leading
to the desired product with exclusion of the other via
base-deprotonation. However, these limitations can be
(10) In order to prove the formation of an R-allyloxy carbanion, the
reaction of 1a with SmI2 was performed in the presence of D2O in
THF-HMPA. The formation of 2 was completely depressed, and 1a
and 1c were obtained in 53% and 25% yield, respectively. Incorporation
of deuterium into the benzylic position of 1c (56% D) was observed.
No tetrahydrofuran derivative, which could be formed by radical
cyclization of an R-allyloxy carbon radical, was observed.9b
(11) Organosamariums have been shown to be involved in SmI2-
induced reactions, see: (a) Molander, G. A.; Kenny, C. J . Am. Chem.
Soc. 1989, 111, 8236-8246. (b) Curran, D. P.; Fevig, T. L.; Totleben,
M. J . Synlett 1990, 773-774.
(12) This result indicates that the reaction proceeds by 2,3-rear-
rangement, not by 1,2-rearrangement.
(13) A similar result was obtained for the reaction under conditions
C.
(14) Nakai, T.; Mikami, K.; Taya, S.; Fujita, Y. J . Am. Chem. Soc.
1981, 103, 6492-6494.
(8) Representative procedure for the reaction is as follows. 1a (44.4
mg, 0.154 mmol) in benzene (1.5 mL) was added to a solution of SmI2
(2.76 mL of 0.140 mol/L, 0.385 mmol) in benzene-HMPA under nitro-
gen at rt. After 10 min, the mixture was quenched with K2CO3 solution
and extracted with ether. The crude product was purified by TLC (hex-
ane:AcOEt ) 8:2) to give 20.2 mg of 3-methyl-1-phenyl-3-buten-1-ol
(2, 81%) and the hydrodeiodinated allyl ether (1c: X ) H, 2.9 mg, 12%).
(9) (a) Murakami, M.; Hayashi, M.; Ito, Y. J . Org. Chem. 1992, 57,
793-794. (b) Capella, L.; Montevecchi, P. C.; Navacchia, M. L. J . Org.
Chem. 1995, 60, 7424-7432.
S0022-3263(97)01422-9 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 22, 1997 7543
Ta ble 1. Sm I2-Med ia ted 2,3-Rea r r a n gem en t of γ-Ha logen oa llylic Eth er s
overcome by SmI2-mediated metalation as demonstrated
by runs 7-12 in Table 1. Since 1,5-hydrogen atom trans-
fers are favored over 1,3-shifts,15,16 the anion can be gen-
erated regioselectively on an allyl group rather than on
the γ-haloallyl group. The formation of 6 from 5 with Sm-
I2 indicates selective metalation on the allylic moiety pos-
sessing an unfavorable γ-substituent. The regiochemis-
try of carbanion formation of diallyl ethers (7, 9, 11), of
which both allylic moieties have neither R- nor γ-sub-
stituents, can be controlled completely. It is noteworthy
that regioisomeric products 10 and 12 could be obtained
regiospecifically from 9 and 11, respectively. Metalation
of alkyl allyl ether 13 takes place preferentially on the
alkyl group having lower acidic R-protons leading to the
formation of 14.
radicals,18 rapid isomerization between (E)-16 and (Z)-
16 would occur, and the correlation between the geometry
at 15 and 16 would be lost. The 1,5-hydrogen atom trans-
fer is possible only for isomer (E)-16, whose half-occupied
orbital can be directed to a hydrogen undergoing transfer,
and, therefore, this step is responsible for the geometry
of alkene 18. Thus, the stereochemistry of 19 is not deter-
mined by the geometry of the starting vinyl halides. It
has been shown that the Z-form of benzyl crotyl ether
exhibits a high erythro selectivity whereas E-form shows
a low and sometime the opposite sense of diastereose-
lectivity in base-deprotonation.1a,3a Thus, the above re-
sult is compatible with E-geometry of 18 undergoing
rearrangement and, therefore, also supports the reaction
mechanism.
We observed the reactions of benzyl crotyl ether
derivatives 20 with defined stereochemistries. Interest-
ingly, the same distribution of the products 21 from
either of the geometrical isomers was observed (eq 2).17
Unfortunately, the selectivity was low in this case (vide
The present SmI2-induced Wittig rearrangement pro-
ceeds in a regioselective manner under nonbasic condi-
tions. This is the first example, to our knowledge, of a
successful attempt to achieve the regioselective metala-
tion of unsymmetrical diallyl ethers. In addition, the reac-
tion can be effected at room temperature, and the starting
γ-halovinyl ethers are more stable and accessible19 than
are silyl- or stannylmethyl allyl ethers used for the Still-
Wittig rearrangement.4a,c,20 Further detailed studies of
the stereochemistry of the rearrangement and extension
to more complex compounds are under investigation.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectral data for selected compounds (9 pages).
infra), but this result is very important from mechanistic
J O9714223
viewpoint. Because of the low inversion barrier of vinyl
(18) (a) Galli, C.; Guarnieri, A.; Koch, H.; Mencarelli, P.; Rappoport,
Z. J . Org. Chem. 1997, 62, 4072-4077. (b) Fessenden, R. W.; Schuler,
R. H. J . Chem. Phys. 1963, 39, 2147-2195.
(15) Huang, X. L.; Dannenberg, J . J . J . Org. Chem. 1991, 56, 5421-
5424.
(16) (a) Heiba, E. I.; Dessau, R. M. J . Am. Chem. Soc. 1967, 89,
3772-3777. (b) Lathbury, D. C., Parsons, P. J ., Pinto, I. J . Chem. Soc.,
Chem. Commun. 1988, 81-82. (c) Curran, D. P.; Kim, D.; Liu, H. T.;
Shen, W. J . Am. Chem. Soc. 1988, 110, 5900-5902.
(17) In the case of (E)- or (Z)-3-iodocrotyl 2-butynyl ether, the threo-
selectivity was improved to 84:16, 90:10, respectively .
(19) There are so many methods available for the synthesis of alken-
yl halides, see: Larock, R. C. Comprehensive Organic Transformations:
A Guide to Functional Group Preparations; VCH: New York, 1989.
(20) Although Still-type protocols are known to exhibit
a high
regioselectivity, substrates utilized for reported reactions are virtually
restricted to a stannylated methyl ether of allyl alcohols.1