Olefin inversion: Stereospecific olefin synthesis from Vicinal alkoxyiodoalkanes with butyllithium by an E2 Syn mechanism

Full text of DOI:10.1021/jo961543n

6770
J . Org. Chem. 1996, 61, 6770-6771
Sch em e 1
Olefin In ver sion : Ster eosp ecific Olefin
Syn th esis fr om Vicin a l Alk oxyiod oa lk a n es
w ith Bu tyllith iu m by a n E2 Syn Mech a n ism
Katsuya Maeda, Hiroshi Shinokubo, and
Koichiro Oshima*
Department of Material Chemistry, Graduate
School of Engineering, Kyoto University,
Sakyo-ku, Kyoto 606-01, J apan
Ta ble 1. 1,2-Elim in a tion of 6-Iod o-7-m eth oxyd od eca n e 1
w ith Bu tyllith iu m a
Received August 9, 1996
The carbon-carbon double bond is a basic structural
unit in organic chemistry, and numerous reports have
been published on the syntheses and chemical reactivities
of alkenes.1 Among many synthetic methods, the 1,2-
elimination reaction is one of the most effective for
forming alkenes.2 The use of vicinal dihalogen com-
pounds as a route to alkenes does have an advantage over
most dehydrohalogenation reactions because the double
bond forms at a specific position. However, the procedure
cannot be applied to olefin inversion3 since anti addition
followed by anti elimination of dihalogen results in the
recovery of the starting alkenes. In the E2 mechanism,
anti elimination is generally favored,4 and syn elimina-
tion has been found only in the cases where the molecule
could not achieve an anti-periplanar transition state
because of steric or conformational factors.5 In this
paper, we show that the reaction of vicinal alkoxyiodoal-
kanes with butyllithium proceeds in syn fashion to afford
alkenes stereospecifically and that the interconversion
of olefinic geometrical isomers has been performed by an
anti addition of an iodine-alkoxy moiety to an alkene
and subsequent syn elimination of these groups (Scheme
1).
methoxyiodoalkane 1
6-dodecene
entry
erythro/ threo
R′-Mtl/solvent
yield (%) (E/ Z)
1
2
3
4
5
6
7
8
1a 97/3
1a 97/3
1a 97/3
1a 97/3
1b 3/97
1b 3/97
1b 3/97
1b 3/97
n-BuLi/hex-Et2O (1:1)
s-BuLi/hex-Et2O (1:1)
t-BuLi/hex-Et2O (1:1)
n-BuLi/DME
n-BuLi/hex-Et2O (1:1)
s-BuLi/hex-Et2O (1:1)
t-BuLi/hex-Et2O (1:1)
n-BuLi/DME
77 (6/94)
82 (4/96)
85 (11/89)
79 (75/25)
65 (96/4)
83 (81/19)
83 (48/52)
85 (11/89)
a
The reactions were performed at -78 °C.
6-dodecene (E/ Z ) 6/94) selectively in 77% yield.9
Meanwhile, threo-isomer 1b (erythro/ threo ) 3/97) af-
forded (E)-6-dodecene with high stereoselectivity (E/ Z
) 96/4) in 65% yield9 under the same reaction conditions
(Table 1, entry 5). These results showed us that the
elimination with butyllithium in hexane-ether proceeded
in syn fashion.10 Thus, (E)-6-dodecene could be converted
into (Z) isomer by sequential treatment with I2/MeOH
and butyllithium and (Z)-6-dodecene could be also trans-
formed into the (E)-isomer in the same way. The use of
sec-butyllithium or tert-butyllithium instead of butyl-
lithium resulted in a decrease of selectivity especially for
the transformation of threo alkoxyiodoalkane into (E)-6-
dodecene (Table 1, entries 6 and 7).11 Among the solvent
systems examined (hexane, hexane-ether (3:1), hexane-
ether (1:1), ether, DME), hexane-ether (1:1) proved to
be the best in terms of the combination of yields and
stereoselectivities. In ether, the yield was improved (2-
7%) but stereoselectivities were decreased slightly (2-
5%). DME also gave better yields of 6-dodecene, but in
somewhat lower specificity with regard to stereochem-
istry (Table 1, entries 4 and 8).
The reaction of other various vicinal methoxyiodoal-
kanes with butyllithium was studied (Table 2). Several
comments are worth noting. (1) The regioisomeric
mixture 2a afforded (Z)-3-dodecene almost exclusively
upon treatment with butyllithium in hexane-ether at
-78 °C (Table 2, entry 1). On the other hand, treatment
of a regioisomeric mixture of 2b with butyllithium
provided (E)-3-dodecene as a single product (Table 2,
entry 2). Thus, the interconversion of olefinic geometrical
We examined a â elimination reaction6,7 of methoxy-
iodoalkane8 1a and 1b with organometallic reagents
(Table 1). Treatment of erythro-6-iodo-7-methoxydode-
cane (1a , erythro/ threo ) 97/3) with butyllithium in
hexane-ether (1:1) at -78 °C for 30 min provided (Z)-
(1) The Chemistry of Alkenes; Patai, S., Ed.; Interscience: New York,
1964. The Chemistry of Alkenes; Zabicky, J ., Ed.; Interscience: New
York, 1968; Vol. 2.
(2) Krebs, A.; Swienty-Busch, J . Comprehensive Organic Synthesis;
Pergamon Press: Oxford, 1991; Vol. 6, Chapter 5.1, pp 949-974.
Kocienski, P. Comprehensive Organic Synthesis; Pergamon Press:
Oxford, 1991; Vol. 6, Chapter 5.2, pp 975-1010.
(3) Sonnet, P. E. Tetrahedron 1980, 36, 557 and references cited
therein. cis-Chlorotelluration-trans-dechlorotelluration: Ba¨ckvall, J .-
E.; Engman, L. Tetrahedron Lett. 1981, 22, 1919. vic-Bromohydrin
trifluoroacetate with NaI: Sonnet, P. E. J . Org. Chem. 1980, 45, 154.
vic-Bromochloride with NaI: J ie, M. S. F. L. K.; Chan, M. F. J . Am.
Oil Chem. Soc. 1985, 62, 109.
(4) Bach, R. D.; Badger, R. C.; Lang, T. J . J . Am. Chem. Soc. 1979,
101, 2845. McLennan, D. J .; Lim, G. C. Aust. J . Chem. 1983, 36, 1821.
Ogawa, S.; Takagaki, T. J . Org. Chem. 1985, 50, 2356.
(5) Cis E2 reaction of trans-2-arylcyclopentyl tosylate: Depuy, C.
H.; Morris, G. F.; Smith, J . S.; Smat, R. J . J . Am. Chem. Soc. 1965,
87, 2421. Cis-1,2-elimination of 1,2-dibromo compounds with bis(tri-
methylsilyl)mercury: Bennett, S. W.; Eaborn, C.; J ackson, R. A.;
Walsingham, R. W. J . Organomet. Chem. 1971, 27, 195.
(6) Nicolaou, K. C.; Duggan, M. E.; Ladduwahatty, T. Tetrahedron
Lett. 1984, 25, 2069. Wender, P. A.; Keenan, R. M.; Lee, H. Y. J . Am.
Chem. Soc. 1987, 109, 4390. Rao, A. V. R.; Reddy, E. R.; J oshi, B. V.;
Yadav, J . S. Tetrahedron Lett. 1987, 28, 6497. Ireland, R. E.; Ha¨bich,
D.; Norbech, D. W. J . Am. Chem. Soc. 1985, 107, 3271. The stereo-
chemical outcome has not been discussed in the foregoing literature.
(7) The stereoselective conversion of iodo acetals into alkenyl ethers
has been reported. Maeda, K.; Shinokubo, H.; Oshima, K.; Utimoto,
K. J . Org. Chem. 1996, 61, 2262.
(9) SN2 Reaction product n-C5H11CH(n-Bu)CH(OMe)-n-C5H11 was
also obtained in 5-10% yield.
(10) Stereospecific â-elimination of conformationally rigid bromo
ethers with Na or Zn has been reported in the synthesis of natural
products. Schlessinger, R. H.; Nugent, R. A. J . Am. Chem. Soc. 1982,
104, 1116. Kato, T.; Aoki, M.; Uyehara, T. J . Org. Chem. 1987, 52,
1803.
(11) Methyllithium and trimethylaluminum proved to be unreactive
toward alkoxyiodoalkanes, and 1a and 1b were recovered unchanged.
In contrast, treatment of 1a and 1b with Et2Zn provided the same
isomeric mixture of 6-dodecene (E/ Z ) 91/9).
(8) Cambie, R. C.; Noall, W. I.; Potter, G. J .; Rutledge, P. S.;
Woodgate, P. D. J . Chem. Soc., Perkin Trans. 1 1977, 226.
S0022-3263(96)01543-5 CCC: $12.00 © 1996 American Chemical Society

Communications
J . Org. Chem., Vol. 61, No. 20, 1996 6771
Ta ble 2. 1,2-Elim in a tion of Va r iou s Regioisom er ic
Mixtu r es of Vicin a l Meth oxyiod oa lk a n es w ith
Bu tyllith iu m a
Sch em e 2
Ta ble 3. 1,2-Elim in a tion of Va r iou s Vicin a l
Meth oxyiod oa lk a n es w ith Bu tylm a gn esiu m Br om id e
methoxyiodoalkaneb
alkene
erythro/
threo
yield (%)
(E/ Z)
entry
R1
R2
1
2
3
4
5
6
7
8
9
2a n-C8H17 C2H5
2b n-C8H17 C2H5
3a n-C8H17 (CH2)8OCH3
99/1
4/96
88/12
4/96
99/1
5/95
98/2
11/89
1/99
70 (3/97)
64 (96/4)
66 (13/87)
64 (96/4)
83 (25/75)
63 (91/9)
76 (12/88)
77 (89/11)
94c (95/5)
alkoxyiodoalkane
alkene
3b n-C8H17 (CH2)8OCH3
erythro/
threo
yield
(%) (E/ Z)
4a n-C5H11 CH2CH2CH2OCH3
4b n-C5H11 CH2CH2CH2OCH3
5a n-C5H11 CH2CH2CH2Br
5b n-C5H11 CH2CH2CH2Br
entry
R1
R2
1
2
3
4
5
6
7
8
1a n-C5H11 n-C5H11
2a n-C8H17 C2H5
4a n-C5H11 CH2CH2CH2OCH3
5a n-C5H11 CH2CH2CH2Br
1b n-C5H11 n-C5H11
2b n-C8H17 C2H5
4b n-C5H11 CH2CH2CH2OCH3
5b n-C5H11 CH2CH2CH2Br
97/3
99/1
99/1
98/2
3/97
4/96
5/95
11/89
92 (>99/1)
94 (>99/1)
86 (>99/1)
66 (>99/1)
96 (>99/1)
82 (>99/1)
94 (>99/1)
97 (>99/1)
6b
-(CH2)6-
a
b
The reactions were performed at -78 °C for 30 min. 1:1
regioisomeric mixtures. c GC yield.
isomers has been also achieved for the unsymmetrical
alkene. (2) Olefins having a methoxy group at the remote
position such as (E)- and (Z)-1-methoxy-9-octadecene
afforded the inverted alkenes stereospecifically by meth-
oxyiodination and subsequent treatment with butyl-
lithium (Table 2, entries 3 and 4). (3) Dimethoxyiodode-
canes 4a and 4b having two methoxy groups at a closer
position to each other could be also converted into the
corresponding alkenes stereospecifically. However, the
selectivities were slightly inferior to those for 3a and 3b.
The loss of stereoselectivity for the transformation of
erythro dimethoxyiododecanes 4a was larger than that
for the threo regioisomeric mixture 4b. (4) A similar
decrease of stereochemical purity was also observed in
the reaction of 5a prepared from (E)-1-bromo-4-decene.
(5) Iodoetherification of cis-cyclooctene followed by treat-
ment with butyllithium gave trans-cyclooctene (trans/
cis ) 95/5) selectively in 94% yield.
In order to elucidate the reaction mechanism, the role
of the alkoxy moiety was examined. Replacing the
methoxy group of 1a with the tert-butoxy moiety afforded
6-dodecene in only 43% yield. Nevertheless, the stereo-
selectivity of the product was still high (E/ Z ) 5/95). The
use of a more bulky triisopropylsiloxy group resulted in
the recovery of the starting material almost exclusively.
It should be also mentioned that the reaction of erythro-
6-chloro-7-iodododecane with butyllithium proceeded in
anti fashion to provide (E)-6-dodecene exclusively (E/ Z
) 99/1).
On the basis of these facts, we are tempted to assume
the following reaction mechanism (E2, syn-periplanar).
(1) The oxygen atom of methyl ether coordinates to
lithium of butyllithium to give A, (2) the conformation
of alkoxyiodoalkane changes to B, and (3) syn elimination
of iodine and the methoxy group provides alkene ste-
reospecifically (Scheme 2).12
The use of butylmagnesium bromide instead of butyl-
lithium changed the course of the reaction completely,
and (E)-olefin was produced with high stereoselectivities
irrespective of the stereochemistry of the starting alkoxy-
iodoalkane (Table 3). For instance, treatment of erythro-
Ta ble 4. Con ver sion of
7-Iod o-6-m eth yl-6-m eth oxyd od eca n e in to
6-Meth yl-6-d od eca n e
entry
erythro/ threo
R-Mtl/solvent
yield (%) (E/ Z)
1
2
3
4
7a
7b
7a
7b
95/5
1/99
95/5
1/99
n-BuLi/hex-Et2O
n-BuLi/hex-Et2O
n-BuMgBr/Et2O
n-BuMgBr/Et2O
74 (12/88)
68 (95/5)
70 (75/25)
92 (76/24)
6-iodomethoxydodecane (1a ) or threo-6-iodo-7-methoxy-
dodecane (1b) with butylmagnesium bromide in ether at
25 °C gave the same (E)-6-dodecene exclusively in 92%
or 96% yield, respectively (Table 3, entries 1 and 5).13,14
The reaction of trans-1-iodo-2-methoxycyclooctane de-
rived from cis-cyclooctene afforded a mixture of cis- and
trans-cyclooctene (cis/ trans ) 90/10) in 86% yield.
The elimination reaction was then applied to the
formation of trisubstituted alkenes (Table 4). An addi-
tion of butyllithium to 7a in hexane-ether (1:1) at -78
°C gave (Z)-6-methyl-6-dodecene selectively. On the
other hand, 7b provided (E)-6-methyl-6-dodecene selec-
tively upon treatment with butyllithium. The selectivi-
ties were slightly inferior to those in the formation of
disubstituted alkenes. Treatment of 7a and 7b with
butylmagnesium bromide afforded the same isomeric
mixture consisting of (E)-6-methyl-6-dodecene and (Z)-
isomer in 3:1 ratio.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectral data for all compounds (5 pages).
J O961543N
(13) A radical intermediate might be involved in the course of the
reaction. Single electron transfer from Grignard reagent into iodoal-
kanes followed by departure of iodide would produce the carbon radical.
Second single electron transfer would provide
a carbanion that
collapses to alkene along with the elimination of the methoxide ion.
(14) A mixture of (E)- and (Z)-alkenes could be converted with (E)-
pure alkene by sequential treatment with I2/MeOH and butylmagne-
sium bromide. For instance, trans-cyclododecene (>99/<1) was ob-
tained in 80% overall yield from a commercially available (Nacalai
tesque, Inc.) cis- and trans-cyclododecene (34/66). Moreover, trans-
cyclododecene could be converted into cis-isomer (cis/ trans ) >99/<1)
in 75% overall yield by methoxyiodination and subsequent treatment
with butyllithium in hexane-ether.
(12) Beak, P.; Meyers, A. I. Acc. Chem. Res. 1986, 19, 356. Stanetty,
P.; Krumpak, B.; Rodler, I. K. J . Chem. Res., Miniprint 1995, 2110.
Halogen-metal exchange followed by syn elimination of LiOMe might
be an alternative mechanism. However, this proposed mechanism
could be negated by the fact that the reaction of 1a and 1b with s-BuLi
and t-BuLi gave stereochemical results different from those obtained
in the reaction with n-BuLi.