A four-carbon unit reagent for the regiospecific synthesis of 2-alkyl- substituted 1,3-butadienes

Article abstract of DOI:10.1021/jo9818881

2-Alkyl-substituted butadienes are synthesized starting from a masked butadiene reagent, which allows the regiospecific synthesis of 2- alkylbutadienes by lithiation and subsequent reaction with alkyl halides or aliphatic aldehydes. The regioselectivity of the reaction with allylic halides and aliphatic and aromatic aldehydes is studied.

Full text of DOI:10.1021/jo9818881

1
888
J . Org. Chem. 1999, 64, 1888-1892
A F ou r -Ca r bon Un it Rea gen t for th e Regiosp ecific Syn th esis of
2
-Alk yl-Su bstitu ted 1,3-Bu ta d ien es
Alan R. Katritzky,* Larisa Serdyuk, Dorin Toader, and Xiaojing Wang
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received September 16, 1998
2
-Alkyl-substituted butadienes are synthesized starting from a masked butadiene reagent, which
allows the regiospecific synthesis of 2-alkylbutadienes by lithiation and subsequent reaction with
alkyl halides or aliphatic aldehydes. The regioselectivity of the reaction with allylic halides and
aliphatic and aromatic aldehydes is studied.
In tr od u ction
Numerous studies have been performed on the re-
Sch em e 1
giospecific synthesis of 2-substituted 1,3-butadienes due
to their use in the Diels-Alder reaction for the construc-
tion of complex molecules.1 The recent syntheses of
2
Bacatin III-steroid hybrid by Danishefsky and (()-
3
Ipsenol by Najera demonstrate the utility of such strate-
gies.
Previous syntheses of 2-alkyl-substituted 1,3-dienes
can be divided into two categories. The first uses pre-
formed 1,3-butadien-2-yl reagents which are prepared (i)
by nickel(II)-catalyzed coupling of diethyl 1-methylene-
2
-propenyl phosphates with Grignard reagents4 or (ii)
from 2-lithio-1,3-butadiene synthesized via a Shapiro
5
reaction or by lithium-halogen exchange upon 2-chloro-
1
,3-butadiene.1a,6 These are excellent approaches, but
Zr,12 and palladium-catalyzed 1,2-elimination of meth-
1
3
2,3,14
15
sometimes require starting materials which are not
readily available and occasionally afford the rearranged
allene as a byproduct.1
ylvinylcarbinol acetates; (v) silicon-
directed synthesis of dienes.
and tin -
a,6b
We have recently shown that easily accessible 2-ben-
zotriazolylethylsilanes undergo vicinal elimination of
silicon and the benzotriazole residue under various
conditions to afford ethylenes.16 We now describe the use
of 1-{1-[(trimethylsilyl)methyl]prop-2-enyl}-1H-benzo-
triazole (2) (Scheme 1) as a four-carbon unit for regio-
specific synthesis of 2-alkyl-substituted 1,3-butadienes.
The second category of syntheses of 2-alkyl-substituted
1
,3-butadienes build the backbone of the diene by a
variety of multistep approaches: (i) elaboration of 1-sub-
stituted 2,3-butadienes using boronate reagents devel-
7
oped by Brown, trimethylsilyl reagents developed by
8
9
Takano or diethyl phosphate esters; (ii) elaboration of
propargylic ethers;10 (iii) addition of bromomethane-
sulfonyl bromide to 2-substituted propenes followed by
Resu lts a n d Discu ssion
a Ramberg-B a¨ cklund elimination of sulfur dioxide and
hydrogen bromide;11 (iv) transition metal-catalyzed meth-
1-Allyl-1H-benzotriazole (1) (Scheme 1) was prepared
from allyl bromide and benzotriazole by the previously
reported procedure.17 Lithiation of 1 was accomplished
with BuLi in THF at -78 °C for 30 min. 1-{1-[(Trimeth-
ods including â-vinylation of R-olefins catalyzed by Ni and
(
1) (a) Bloch, R.; Chaptal-Gradoz, N. J . Org. Chem. 1994, 59, 4162.
b) Hatakeyama, S.; Sugawara, K.; Takano, S. J . Chem. Soc., Chem.
Commun. 1992, 953.
2) Alaimo, C. A.; Coburn, C. A.; Danishefsky, S. J . Tetrahedron Lett.
994, 35, 6603.
(
(11) (a) Block, E.; Eswarakrishnan, V.; Gebreyes, K. Tetrahedron
Lett. 1984, 25, 5469. (b) Block, E.; Aslam, M.; Eswarakrishnan, V.;
Gebreyes, K.; Hutchinson, J .; Iyer, R.; Laffitte, J .-A.; Wall, A. J . Am.
Chem. Soc. 1986, 108, 4568.
(12) Ibragimov, A. G.; Zolotarev, A. P.; Muslukhov, R. R.; Lomakina,
S. I.; Dzhemilev, U. M. Russ. Chem. Bull. 1995, 44, 113.
(13) Carpita, A.; Bonaccorsi, F.; Rossi, R. Tetrahedron Lett. 1984,
25, 5193.
(
1
(
(
3) N a´ jera, C.; Sansano, J . M.Tetrahedron Lett. 1993, 34, 3781.
4) Sahlberg, C.; Quader, A.; Claesson, A. Tetrahedron Lett. 1983,
2
4, 5137.
(5) Brown, P. A.; J enkins, P. R. Tetrahedron Lett. 1982, 23, 3733.
6) (a) Wada, E.; Fujiwara, I.; Kanemasa, S.; Tsuge, O. Bull. Chem.
(
Soc. J pn. 1987, 60, 325. (b) Bloch, R.; Chaptal-Gradoz, N. Tetrahedron
Lett. 1992, 33, 6147.
(14) (a) Brown, P. A.; Bonnert, R. V.; J enkins, P. R.; Selim, M. R.
Tetrahedron Lett. 1987, 28, 693. (b) Oertle, K.; Beyeler, H.; Duthaler,
R. O.; Lottenbach, W.; Riediker, M.; Steiner, E. Helv. Chim. Acta 1990,
73, 353. (c) Brown, P. A.; Bonnert, R. V.; J enkins, P. R.; Lawrence, N.
J .; Selim, M. R. J . Chem. Soc., Perkin Trans. 1 1991, 1893.
(15) Ueno, Y.; Sano, H.; Aoki, S.; Okawara, M.Tetrahedron Lett.
1981, 22, 2675.
(16) Katritzky, A. R.; Toader, D. J . Am. Chem. Soc. 1997, 119, 9321.
(17) Katritzky, A. R.; Li, J .; Malhotra, N. Liebigs Ann. Chem. 1992,
843.
(
7) (a) Soundararajan, R.; Li, G.; Brown, H. C. Tetrahedron Lett.
995, 36, 2441. (b) Soundararajan, R.; Li, G.; Brown, H. C. J . Org.
Chem. 1996, 61, 100.
8) (a) Hatakeyama, S.; Sugawara, K.; Kawamura, M.; Takano, S.
1
(
Tetrahedron Lett. 1991, 32, 4509. (b) Hatakeyama, S.; Sugawara, K.;
Takano, S. Tetrahedron Lett. 1991, 32, 4513.
(
(
9) Djahanbini, D.; Cazes, B.; Gore, J . Tetrahedron 1984, 40, 3645.
10) Yamashita, K.; Sato, F. Tetrahedron Lett. 1996, 37, 7275.
1
0.1021/jo9818881 CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/25/1999

Synthesis of 2-Alkyl-Substituted 1,3-Butadienes
J . Org. Chem., Vol. 64, No. 6, 1999 1889
Sch em e 2
Sch em e 4
Sch em e 3
for 6 h, and starting material was recovered; at 135 °C
for 6 h, 60% of the starting material 3d and unidentified
products were obtained. However, 5a is formed by mixing
N-phenylmaleimide with 3d under acidic condition
(Scheme 3). Here, the role of TFA is to protonate
benzotriazole which then leaves and forms a carbocation
that is quaternary, allylic, and â to a silicon (highly
stabilized). The trifluoroacetate anion acts as a nucleo-
phile to react with the trimethylsilyl group, and the
elimination is then accomplished. Thus the isolation of
intermediates 3 is superfluous if the preparation of dienes
ylsilyl)methyl]prop-2-enyl}-1H-benzotriazole (2) was ob-
tained in 88% yield as a colorless stable oil by nucleophilic
substitution of chlorine in chloromethyltrimethylsilane
by the anion derived from 1. Reagent 2 can be lithiated
with BuLi, and the resulting carbanion behaves as a
4
has been carried out for the sole purpose of reacting
masked 1,3-butadien-2-yl reagent. Reagent 2 is similar
them with a dienophile in a Diels-Alder protocol.
The reaction of lithiated 2 with aliphatic aldehydes
afforded alcohols 8a -c as a mixture of diastereomers in
good yields (Scheme 4). However, when the reaction
to some others previously used1
a,5,6
for the synthesis of
2
-alkyl-substituted dienes, but importantly rearrange-
ment to allenes is suppressed with reagent 2 because the
second double bond is formed by vicinal elimination of
silicon after the reaction with electrophiles. A regiospe-
cific synthesis of 2-alkyl-substituted 1,3-butadienes is
thus possible as illustrated in Scheme 1 without the
drawback of side-product formation. Elimination of sili-
con is in most cases accomplished thermally by heating
the intermediate adducts 3 neat at 75-135 °C for 6-8
h. Dienes 4 were obtained pure after the byproduct
benzotriazole was removed by washing with dilute aque-
ous sodium hydroxide solution.
(without isolation of the intermediate alkoxide derived
from 6a -c) was performed in THF solution and refluxed
for 3-5 h, dienes 7a -c were isolated in good yields. This
outcome is the result of a [1,4]-C f O silicon migration
followed by hydrolysis of the intermediate silyl ether.
The regiochemistry of the reaction 2 f 3 (Scheme 1)
is dependent upon the nature of the electrophile, as
shown by a study of the reactions of the anion derived
from 2 with electrophiles under the reaction conditions
used for alkyl halides. The adducts 3 or 8 and 11a -e
were obtained as mixtures in high yields and analyzed
Thus, lithiation of 2 followed by reaction with alkyl
halides afforded the corresponding adducts 3a -e in
excellent yields. The vicinal elimination of silicon worked
well with medium and long chain alkyl groups in the
1
by GC-MS and H NMR. The results are summarized in
Scheme 5.
The carbanion derived from 2 has an ambident char-
acter: it can react either R to the benzotriazolyl group
(carbanion 9 in Scheme 5) or γ to the benzotriazolyl group
(carbanion 10 in Scheme 5). In contrast to the simple
halides of Scheme 2, cinnamyl bromide 12 reacted
predominantly in the γ position. Moderately hindered
aldehydes 13 and 14 reacted predominantly at the
R-position, similar to their simple analogue of Scheme
4. However, highly hindered 15 prefers the γ-orientation
in a ratio of 1:9.5. Under the same reaction conditions
4-chlorobenzaldehyde shows an intermediate position
with a 1:0.66 ) R:γ ratio (Scheme 5).
2
-position to yield 2-alkyl-1,3-butadienes 4a -c in excel-
lent yields after simple heating at 120-135 °C for 6-8 h
Scheme 2). When short chain alkyl adducts 3d and 3e
(
were heated under similar conditions, polymers were the
only observed products. However, these difficulties were
overcome by trapping the corresponding 3d and 3e in
the presence of a dienophile. This approach is depicted
in Scheme 3 where reagent 1 is transformed into Diels-
Alder adduct 5b by heating the corresponding adduct 3e
with N-phenylmaleimide at 75-80 °C for 6 h. N-Phenyl-
maleimide does not react with 3d on heating at 95 °C

1
890 J . Org. Chem., Vol. 64, No. 6, 1999
Katritzky et al.
Sch em e 5
7.42 (t, J ) 7.5 Hz, 1H), 7.53 (d, J ) 8.3 Hz, 1H), 8.03 (d, J )
8
1
.3 Hz, 1H); 13C NMR δ -1.5 (3C), 22.2, 59.9, 110.2, 116.7,
20.0, 123.7, 126.8, 131.9, 138.0, 146.4. Anal. Calcd for
13 19 3
C H N Si: C, 63.63; H, 7.80; N, 17.12. Found: C, 63.37; H,
8
.15; N, 17.42.
Gen er a l P r oced u r e for th e Syn th esis of Com p ou n d s
a -e a n d 11a . To a solution of 2 (0.98 g, 4 mmol) in THF (50
3
mL) at -78 °C under argon was added n-BuLi (1.52 M, 2.9
mL, 4.1 mmol). After the mixture was stirred for 15 min, a
solution of the appropriate alkyl halide (4.1 mmol) in THF (5
mL) was added. The reaction mixture was allowed to warm to
room temperature overnight, before being washed with water
(
(
2 × 20 mL), extracted with ethyl ether (2 × 20 mL), and dried
Na SO ). The crude oil left after the solvent was removed
2
4
under reduced pressure was subjected to column chromatog-
raphy with hexanes:ethyl acetate ) 8:1 to give the pure
product.
1
-{1-Hexyl-1-[(tr im eth ylsilyl)m eth yl]p r op -2-en yl}-1H-
1
1
,2,3-ben zotr ia zole (3a ): colorless oil (1.00 g, 82%): H NMR
δ -0.26 (s, 9H), 0.72 (t, J ) 6.8 Hz, 3H), 1.09-1.20 (m, 8H),
1
2
1
7
-
1
.70 (d, J ) 14.8 Hz, 1H), 1.79 (d, J ) 14.9 Hz, 1H), 2.18-
.38 (m, 2H), 5.16 (d, J ) 17.6 Hz, 1H), 5.27 (d, J ) 11.0 Hz,
H), 6.12 (dd, J ) 17.6 and 10.8 Hz, 1H), 7.18-7.29 (m, 2H),
1
3
.52 (d, J ) 8.0 Hz, 1H), 7.95 (d, J ) 8.0 Hz, 1H); C NMR δ
0.1 (3C), 13.9, 22.4, 23.5, 26.9, 29.2, 31.5, 39.2, 69.1, 112.7,
15.1, 119.9, 123.3, 126.1, 132.3, 142.2, 147.0. Anal. Calcd for
Si: C, 69.24; H, 9.50; N, 12.75. Found: C, 68.92; H,
.75; N, 12.71.
-{1-Decyl-1-[(tr im eth ylsilyl)m eth yl]p r op -2-en yl}-1H-
19 31 3
C H N
9
1
1
1
,2,3-ben zotr ia zole (3b): colorless oil (1.39 g, 90%): H NMR
δ -0.18 (s, 9H), 0.84 (t, J ) 5.7 Hz, 3H), 1.12-1.28 (m, 16H),
1
2
1
7
.78 (d, J ) 14.9 Hz, 1H), 1.87 (d, J ) 14.9 Hz, 1H), 2.25-
.42 (m, 2H), 5.24 (d, J ) 17.4 Hz, 1H), 5.35 (d, J ) 10.7 Hz,
H), 6.20 (dd, J ) 17.4 and 10.7 Hz, 1H), 7.26-7.36 (m, 2H),
1
3
.60 (d, J ) 7.9 Hz, 1H), 8.03 (d, J ) 7.9 Hz, 1H); C NMR δ
Con clu sion s
-0.1 (3C), 14.0, 22.6, 23.5, 26.9, 29.2, 29.3, 29.4, 29.6, 29.7,
1.8, 39.2, 69.1, 112.7, 115.0, 120.0, 123.3, 126.1, 132.3, 142.3,
147.0. Anal. Calcd for C H N Si: C, 71.63; H, 10.19; N, 10.90.
3
A four-carbon unit reagent for the regiospecific syn-
2
3
39
3
theses of 2-alkyl and 2-(hydroxyalkyl)butadienes has
been developed. This new approach shows advantages
over the previously described methods in its high regio-
selectivity, easily available precursors and stable masked
butadienes which can be deprotected thermally during
the Diels-Alder process. The regiochemistry of the
reaction of the allyl carbanion with electrophiles is
influenced by steric and electronic factors.
Found: C, 71.95; H, 10.47; N, 10.66.
1-{1-Dod ecyl-1-[(t r im et h ylsilyl)m et h yl]p r op -2-en yl}-
1
1
H-1,2,3-ben zotr ia zole (3c): colorless oil (1.33 g, 86%):
H
NMR δ -0.16 (s, 9H), 0.87 (t, J ) 6.1 Hz, 3H), 1.18-1.27 (m,
2
2
0H), 1.80 (d, J ) 14.9 Hz, 1H), 1.89 (d, J ) 14.9 Hz, 1H),
.26-2.44 (m, 2H), 5.26 (d, J ) 17.5 Hz, 1H), 5.38 (d, J ) 10.8
Hz, 1H), 6.22 (dd, J ) 17.5 and 10.8 Hz, 1H), 7.30 (t, J ) 6.6
Hz, 1H), 7.36 (t, J ) 6.6 Hz, 1H), 7.62 (d, J ) 8.1 Hz, 1H),
1
3
8.05 (d, J ) 8.1 Hz, 1H); C NMR δ -0.1 (3C), 14.1, 22.6, 23.5,
2
1
6.9, 29.2, 29.3, 29.4, 29.5, 29.6, 31.8, 39.2, 69.1, 112.7, 115.0,
20.0, 123.3, 126.1, 132.3, 142.2, 147.0. Anal. Calcd for
Exp er im en ta l Section
C
25
H
43
N
3
Si: N, 10.16. Found: N, 10.32.
Gen er a l Meth od s. NMR spectra were recorded in CDCl
3
1-{1-P r op yl-1-[(tr im eth ylsilyl)m eth yl]p r op -2-en yl}-1H-
1
1
with tetramethylsilane as the internal standard for H (300
1,2,3-ben zotr ia zole (3d ): colorless oil (1.50 g, 87%): H NMR
δ -0.10 (s, 9H), 0.91 (t, J ) 6.9 Hz, 3H), 0.97-1.05 (m, 1H),
1.33-1.43 (m, 1H), 1.87 (d, J ) 14.8 Hz, 1H), 1.96 (d, J ) 14.5
Hz, 1H), 2.31-2.52 (m, 2H), 5.33 (d, J ) 17.6 Hz, 1H), 5.44 (d,
J ) 10.7 Hz, 1H), 6.28 (dd, J ) 17.6 and 10.7 Hz, 1H), 7.35-
7.45 (m, 2H), 7.68 (d, J ) 8.2 Hz, 1H), 8.11 (d, J ) 8.0 Hz,
1
3
MHz) or solvent as the internal standard for C (75 MHz).
THF was distilled from sodium/benzophenone under nitrogen
immediately prior to use. All reactions with air-sensitive
compounds were carried out under an argon atmosphere.
1
-Allyl-1H-benzotriazole (1) was prepared according to the
1
7
13
previously reported procedure. All reagents were used as
purchased from commercial suppliers without further purifica-
tion.
1H); C NMR δ -0.2 (3C), 13.9, 16.8, 26.8, 41.3, 69.0, 112.7,
115.0, 119.9, 123.3, 126.1, 132.3, 142.1, 146.9. Anal. Calcd for
C
16
H
25
N
3
Si: C, 66.84; H, 8.78. Found: C, 66.62; H, 8.59.
P r ep a r a tion of 1-{1-[(Tr im eth ylsilyl)m eth yl]p r op -2-
en yl}-1H-1,2,3-ben zotr ia zole (2). To a solution of 1 (5 mmol)
in THF (50 mL) at -78 °C under argon was added n-BuLi (1.52
M, 3.7 mL, 5.2 mmol). After stirring for 30 min, a solution of
chloromethyltrimethylsilane (0.73 mL, 5.2 mmol) in THF (5
mL) was added. The reaction mixture was allowed to warm to
room temperature overnight before being washed with water
1-{1-Ben zyl-1-[(tr im eth ylsilyl)m eth yl]p r op -2-en yl}-1H-
1
1,2,3-ben zotr ia zole (3e): colorless oil (2.90 g, 85%): H NMR
δ -0.11 (s, 9H), 1.62 (d, J ) 14.6 Hz, 1H), 2.06 (d, J ) 14.6
Hz, 1H), 3.59 (s, 2H), 5.36 (d, J ) 17.6 Hz, 1H), 5.47 (d, J )
10.9 Hz, 1H), 6.35 (dd, J ) 10.9 and 17.5 Hz, 1H), 6.61(d, J )
7.3 Hz, 1H), 7.00-7.20 (m, 3H), 7.32-7.40 (m, 2H), 7.58 (d, J
) 8.5 Hz, 1H), 8.06 (d, J ) 7.4 Hz, 1H); 13C NMR δ 0.3 (3C),
27.6, 46.0, 69.1, 112.7, 115.7, 120.0, 123.4, 126.3, 126.8, 127.8,
130.4, 132.7, 135.3, 141.5, 146.9. HRMS (M + 1, FAB) calcd
(
(
2 × 20 mL), extracted with ethyl ether (2 × 20 mL), and dried
Na SO ). The oil remaining after the solvent was removed
2
4
under reduced pressure was subjected to column chromatog-
26 3
for C20H N Si: 336.1896 (M + 1). Found: 336.1898.
raphy with hexanes:ethyl acetate ) 20:1 to give the pure
1-(1Z,5E)-6-P h en yl-1-[(tr im eth ylsilyl)m eth yl]h exa -1,5-
d ien yl-1H-1,2,3-ben zotr ia zole (11a ): yellow oil (1.21 g,
84%): 1H NMR δ -0.15 (s, 9H), 2.47-2.55 (m, 6H), 5.78 (t, J
) 6.7 Hz, 1H), 6.28-6.39 (m, 1H), 6.54 (d, J ) 15.7 Hz, 1H),
7.24-7.46 (m, 7H), 7.64 (d, J ) 8.0 Hz, 1H), 8.09 (d, J ) 8.0
1
product as a colorless oil (1.08 g, 88%): H NMR δ -0.13 (s,
9
H), 1.52 (dd, J ) 14.6 and 7.1 Hz, 1H), 1.70 (dd, J ) 14.8
and 8.8 Hz, 1H), 5.15 (d, J ) 9.0 Hz, 1H), 5.20 (s, 1H), 5.51 (q,
J ) 7.5 Hz, 1H), 6.09-6.20 (m, 1H), 7.32 (t, J ) 7.5 Hz, 1H),

Synthesis of 2-Alkyl-Substituted 1,3-Butadienes
J . Org. Chem., Vol. 64, No. 6, 1999 1891
Hz, 1H); 13C NMR δ -1.6 (3C), 21.2, 27.5, 32.8, 110.9, 119.9,
2-P h en yl-5-(p h en ylm et h yl)-3a ,4,7,7a -t et r a h yd r o-1H -
1
1
1
20.7, 123.8, 125.9, 127.1, 127.4, 128.4, 129.2, 131.0, 132.1,
isoin d ole-1,3(2H)-d ion e (5b): yellow oil (0.86 g, 54%):
H
35.2, 137.2, 145.9. Anal. Calcd for C22
H
27
N
3
Si: N, 11.62.
NMR δ 2.22-2.34 (m, 2H), 2.58 (d, J ) 15.5 Hz, 1H), 2.69 (dd,
Found: N, 11.62.
Gen er a l P r oced u r e for th e Syn th esis of Com p ou n d s
J ) 15.5 and 6.6 Hz, 1H), 3.15-3.20 (m, 2H), 3.34 (s, 2H),
1
3
5.62-5.66 (m, 1H), 7.09-7.26 (m, 6H), 7.34-7.46 (m, 4H); C
4
a -c. The corresponding 3a -c (2 mmol) was heated under
NMR δ 24.4, 27.6, 39.3, 39.6, 43.7, 121.6, 126.3, 128.4, 128.9,
129.0, 132.0, 138.5, 139.9, 178.7, 179.1. HRMS (M + 1, FAB)
argon and stirred at 130-135 °C for 8-12 h. The cold reaction
mixture was dissolved in diethyl ether (40 mL), washed with
NaOH solution (10%, 2 × 20 mL) and water (2 × 20 mL), and
2
calcd for C21H19NO : 318.1494 (M + 1). Found: 318.1497.
Gen er a l P r oced u r e for th e Syn th esis of Com p ou n d s
8a ,e a n d 11b-e. To a solution of 2 (0.98 g, 4 mmol) in THF
(50 mL) at -78 °C under argon was added BuLi (1.52 M, 2.9
mL, 4.1 mmol). After the mixture was stirred for 15 min, a
solution of the appropriate aldehyde (4.1 mmol) in THF (5 mL)
was added. The reaction mixture was allowed to warm to room
temperature overnight before being washed with water (2 ×
20 mL), extracted with diethyl ether (2 × 20 mL), and dried
2 4
then dried (Na SO ). After the solvent was removed under
reduced pressure, the remaining crude oil was subjected to
column chromatography with hexanes:ethyl acetate ) 40:1 to
afford the pure product.
1
2
2
-Hexylbu ta -1,3-d ien e (4a ): colorless oil (lit. oil) (0.20
1
g, 70%): H NMR δ 0.93 (t, J ) 6.9 Hz, 3H), 1.20-1.45 (m,
6
(
6
2
H), 1.45-1.60 (m, 2H), 2.24 (t, J ) 8.0 Hz, 2H), 5.02-5.03
m, 2H), 5.07 (d, J ) 10.9 Hz, 1H), 5.26 (d, J ) 17.6 Hz, 1H),
2 4
(Na SO ). The crude oil left after the solvent was removed
.40 (dd, J ) 17.6 and 10.7 Hz, 1H); 13C NMR δ 14.1, 22.7,
under reduced pressure was subjected to column chromatog-
raphy to give the pure product.
8.2, 29.3, 31.4, 31.8, 113.0, 115.4, 139.1, 146.7.
2
-Decylbu ta -1,3-d ien e (4b): colorless oil (0.32 g, 64%): 1
H
4-(1H -1,2,3-Ben zot r ia zol-1-yl)-1-p h en yl-4-[(t r im et h yl-
silyl)m eth yl]h ex-5-en -3-ol (8a ): yellow oil (1.52 g, 80%), 1.3:1
mixture of diastereomers (minor diastereomer in square
brackets): 1H NMR δ -0.10 (s, 9H) [-0.24 (s, 9H)], 1.71-2.21
(m, 4 + [4]H), 2.85-2.95 (m, 2H) [3.15-3.30 (m, 2H)], 4.08 (s,
1H) [4.09 (s, 1H)], 4.74-4.79 (m, 1H) [5.10-5.13 (m, 1H)], 5.36
(d, J ) 18.0 Hz, 1H) [5.53 (d, J ) 18.0 Hz, 1H)], 5.58 (d, J )
11.4 Hz, 1H) [5.70 (d, J ) 11.4 Hz, 1H)], 6.32 (dd, J ) 17.5
and 10.8 Hz, 1H) [6.55 (dd, J ) 17.5 and 10.8 Hz, 1H)], 7.34-
7.58 (m, 7 + [7]H), 7.77 (d, J ) 7.8 Hz, 1H) [7.78 (d, J ) 7.8
Hz, 1H)], 8.22 (d, J ) 7.8 Hz, 1 + [1]H); 13C NMR δ -0.1 [-0.8]
(3C), 22.5 [23.0], 32.5 [32.4], 33.0 [32.9], 73.4 [73.2], 75.6 [73.7],
113.1 [112.8], 117.3 [117.6], 119.9, 123.7 [123.8], 125.7 [125.8],
126.7 [126.9], 128.2 [128.3], 128.4 [128.5], 132.6 [132.7], 139.5
NMR δ 0.91 (t, J ) 6.8 Hz, 3H), 1.20-1.40 (m, 14H), 1.49-
1
.54 (m, 2H), 2.22 (t, J ) 8.0 Hz, 2H), 5.01-5.02 (m, 2H), 5.07
(d, J ) 10.8 Hz, 1H), 5.25 (d, J ) 17.6 Hz, 1H), 6.40 (dd, J )
1
2
7.6 and 10.7 Hz, 1H); 13C NMR δ 14.1, 22.7, 28.2, 29.4, 29.6,
9.7, 31.4, 32.0, 113.0, 115.4, 139.1, 146.7; HRMS (EI) calcd
for C14
-Dod ecylbu ta -1,3-d ien e (4c): colorless oil (0.40 g, 90%):
H NMR δ 0.91 (t, J ) 6.5 Hz, 3H), 1.20-1.35 (m, 18H), 1.46-
.53 (m, 2H), 2.22 (t, J ) 7.6 Hz, 2H), 5.00-5.02 (m, 2H), 5.07
H26: 194.2035. Found: 194.2013.
2
1
1
(
1
2
d, J ) 10.8 Hz, 1H), 5.25 (d, J ) 17.6 Hz, 1H), 6.40 (dd, J )
7.6 and 10.8 Hz, 1H); 13C NMR δ 14.1, 22.7, 28.2, 29.4, 29.6,
9.7, 31.4, 32.0, 113.0, 115.4, 139.1, 146.7; HRMS (EI) calcd
for C16H30: 222.2348. Found: 222.2351.
Gen er a l P r oced u r e for th e Syn th esis of Com p ou n d s
[138.2], 141.7 [141.9], 146.2 [146.4]. HRMS calcd for C25
43 3
H N -
5
a ,b. BuLi in hexanes (1.4 M, 3.7 mL, 5.1 mmol) was added
Si: 380.2158 (M + 1). Found: 380.2144 (M + 1, FAB).
to a solution of 1 (0.80 g, 5 mmol) in THF (50 mL) at -78 °C.
After stirring for 30 min at -78 °C, a solution of chlorometh-
yltrimethylsilane (0.63 g, 5.1 mmol) in THF (5 mL) was added,
and the reaction mixture was allowed to warm to room
temperature overnight. The reaction mixture was cooled to
2-(1H-1,2,3-Ben zotr iazol-1-yl)-1-(4-ch lor oph en yl)-2-[(tr i-
m eth ylsilyl)m eth yl]bu t-3-en -1-ol (8e): hexanes:diethyl ether
) 1:1 (eluent); yellow oil (0.79 g, 52%), 2.7:1 mixture of
diastereomers (minor diastereomer in square brackets):
1
H
NMR δ -0.01 (s, 9H) [-0.13 (s, 9H)], 1.75 (d, J ) 15.0 Hz,
2H) [2.14 (d, J ) 15.0 Hz, 2H)], 5.37 (d, J ) 17.7 Hz, 2H) [5.68
(d, J ) 10.8 Hz, 2H)], 5.78 (s, 1H) [6.11 (s, 1H)], 6.41 (dd, J )
18.0 and 12.0 Hz, 1H) [6.70 (dd, J ) 18.0 and 12.0 Hz, 1H)],
7.17 (d, J ) 8.7 Hz, 2 + [2]H), 7.38-7.64 (m, 4 + [4]H), 7.84
-
78 °C and BuLi in hexanes (1.4 M, 3.6 mL, 5.0 mmol) was
added. After 15 min a solution of 1-iodopropane (0.48 mL, 5.0
mmol), in the case of 5a , or benzyl bromide (0.86 g, 5.0 mmol)
in THF (5 mL), in the case of 5b, was added. After the reaction
reached rt overnight, the mixture was washed with water (2
1
3
(d, J ) 8.0 Hz, 1 + [1]H), 8.27 (d, J ) 8.0 Hz, 1 + [1]H);
C
×
20 mL), extracted with diethyl ether (2 × 20 mL), and dried
NMR δ 0.3 [-0.1] (3C), 24.1 [23.6], 73.4 [73.3], 79.4, 113.8
[113.1], 117.4 [119.2], 120.0 [120.1], 123.8 [124.0], 126.7
[127.0], 127.9 [127.7], 129.7 [130.1], 133.4, 134.0, 136.8, 138.7,
(
Na SO ). After the filtration of the drying agent, the solvent
2
4
was removed from the filtrate, and the remaining oil was
purified as previously described to afford 3d , in the case of
24 3
146.4. Anal. Calcd for C20H N ClOSi: C, 62.24; H, 6.27; N,
10.89. Found: C, 61.86; H, 6.56; N, 11.03.
5
a , or the solution was used without purification, in the case
of 5b. In the case of 5a , N-phenylmaleinimide was added (0.45
g, 2.6 mmol) to a solution of 3d (0.50 g, 1.7 mmol) in methylene
chloride (30 mL) followed by slow addition of trifluoroacetic
acid (0.8 mL, 10 mmol). After being stirred for 2 h at room
temperature, the mixture was washed with sodium hydroxide
6-(1H-1,2,3-Ben zotr iazol-1-yl)-6-[(tr im eth ylsilyl)m eth yl]-
2-m eth ylh ex-5-en -3-ol (11c): hexanes:EtOAc ) 8:1; yellow
1
oil (0.34 g, 22%): H NMR δ -0.20 (s, 9H), 1.01 (d, J ) 6.7
Hz, 6H), 1.75-1.85 (m, 1H), 2.39-2.51 (m, 2H), 2.46 (s, 2H),
3.55-3.60 (m, 1H), 5.87 (t, J ) 7.2 Hz, 1H), 7.36 (t, J ) 7.6
Hz, 1H), 7.47 (t, J ) 7.6 Hz, 1H), 7.67 (d, J ) 8.4 Hz, 1H),
8.05 (d, J ) 8.4 Hz, 1H); 13C NMR δ -1.5 (3C), 17.4, 18.8, 21.3,
32.7, 33.5, 76.3, 111.0, 118.5, 120.0, 124.0, 127.6, 132.2, 136.4,
2 4
aqueous solution (0.5 M, 20 mL) and dried (Na SO ) and had
the solvent removed. In the case of 5b, N-phenylmaleinimide
was added (1.04 g, 6.0 mmol) to the ether solution, and the
mixture was heated under reflux for 1 h. The solvent was
removed by distillation under a stream of nitrogen, and the
remaining oil was heated at 75-80 °C for 6 h. The cold reaction
mixture was dissolved in diethyl ether (40 mL), washed with
sodium carbonate (10%, 40 mL) and water (40 mL), and then
146.0. Anal. Calcd for C17
27 3
H N OSi: N, 13.24. Found: N, 13.35.
6-(1H-1,2,3-Ben zotr iazol-1-yl)-6-[(tr im eth ylsilyl)m eth yl]-
2,2-d im eth ylh ex-5-en -3-ol (11d ): hexanes:EtOAc ) 8:1;
yellow oil (1.37 g, 83%): 1H NMR δ -0.20 (s, 9H), 1.00 (s, 9H),
2.24-2.54 (m, 5H), 3.42 (m, 1H), 5.91 (t, J ) 7.2 Hz, 1H), 7.33
(t, J ) 7.6 Hz, 1H), 7.44 (t, J ) 7.6 Hz, 1H), 7.68 (d, J ) 8.3
Hz, 1H), 8.02 (d, J ) 8.3 Hz, 1H); 13C NMR δ -1.5 (3C), 21.1,
25.7 (3C), 30.0, 35.0, 79.3, 111.1, 119.6, 119.8, 123.9, 127.5,
2 4
dried (Na SO ). In both cases the remaining crude oil was
subjected to column chromatography with hexanes:ethyl ac-
etate ) 2:1 to give the pure product.
2
-P h en yl-5-p r op yl-3a ,4,7,7a -tetr a h yd r o-1H-isoin d ole-
132.1, 135.9, 145.9. Anal. Calcd for C17
Found: N, 12.61.
27 3
H N OSi: N, 12.67.
1
1
,3(2H)-d ion e (5a ): colorless oil (0.40 g, 65% yield): H NMR
δ 0.86 (t, J ) 7.1 Hz, 3H), 1.25-1.48(m, 2H), 2.02 (t, J ) 7.4
4-(1H-1,2,3-Ben zotr ia zol-1-yl)-1-(4-ch lor op h en yl)-5-(tr i-
m eth ylsilyl)-3-p en ten -1-ol (11e): hexanes:EtOAc ) 3:1;
yellow oil (0.45 g, 30%): 1H NMR δ -0.22 (s, 9H), 2.39(s, 2H),
2.66-2.81 (m, 2H), 3.00 (br s, 1H), 4.89 (t, J ) 6.6 Hz, 1H),
5.74 (t, J ) 7.2 Hz, 1H), 7.08-7.50 (m, 7H), 8.00 (d, J ) 8.2
Hz, 1H); 13C NMR δ -1.6 (3C), 21.3, 37.5, 73.0, 110.9, 116.9,
119.9, 124.1, 127.2, 127.7, 128.7, 132.1, 133.5, 137.0, 142.4,
Hz, 2H), 2.25-2.32 (m, 2H), 2.61-2.74 (m, 2H), 3.20-3.30 (m,
2
H), 5.62 (m, 1H), 7.23 (d, J ) 8.0 Hz, 2H), 7.36-7.49 (m, 3H);
C NMR δ 13.7, 20.4, 24.3, 27.6, 39.2, 39.4, 39.7, 119.9, 126.3,
28.4, 129.0, 132.0, 140.6, 179.1, 179.3. Anal. Calcd for C17
: C, 75.80; H, 7.12; N, 5.20. Found: C, 75.46; H, 7.24; N,
.42.
1
3
1
19
H -
NO
2
5

1
892 J . Org. Chem., Vol. 64, No. 6, 1999
45.8. Anal. Calcd for C20 OSiCl: C, 62.23; H, 6.28; N,
Katritzky et al.
1
1
H
24
N
3
1H), 6.32 (dd, J ) 18.0 and 11.3 Hz, 1H), 7.15-7.30 (m, 5H);
C NMR δ 32.0, 37.9, 70.6, 114.1, 114.3, 125.8, 128.3, 128.5,
1
3
0.89. Found: C, 61.87; H, 6.61; N, 11.01.
Gen er a l P r oced u r e for th e Syn th esis of Com p ou n d s
a -c. To a solution of 2 (0.98 g, 4 mmol) in THF (50 mL) at
78 °C under argon was added n-BuLi (1.52 M, 2.9 mL, 4.1
136.1, 141.9, 149.1.
7
-
3-Meth yliden e-1,1-m eth ylph en ylpen t-4-en -2-ol (7b): yel-
low oil, 0.45 g, 60%: 1H NMR δ 1.23 (d, J ) 7.1 Hz, 3H), 1.79
(s, 1H), 3.02-3.11 (m, 1H), 4.51 (d, J ) 4.4 Hz, 1H), 5.09 (d, J
) 11.0 Hz, 1H), 5.16 (s, 1H), 5.20 (s, 1H), 5.33 (d, J ) 17.6 Hz,
1H), 6.31 (dd, J ) 17.9 and 11.3 Hz, 1H), 7.17-7.32 (m, 5H);
mmol). After the mixture was stirred for 15 min, a solution of
the appropriate aldehyde (4.1 mmol) in THF (5 mL) was added.
The reaction mixture was allowed to warm to room temper-
ature overnight and then refluxed in THF under argon for 3
h. Upon being cooled, the reaction mixture was washed with
saturated aqueous ammonium chloride solution (40 mL), HCl
1
3
C NMR δ 13.6, 42.9, 75.3, 114.1, 115.3, 126.3, 127.7, 128.3,
136.4, 144.5, 147.0. Anal. Calcd for C H16O: C, 82.93; H, 8.58.
1
3
Found: C, 82.61; H, 8.48.
(
10%, 2 × 20 mL), and water (2 × 20 mL) before being
2-Meth yl-4-m eth ylid en eh ex-5-en -3-ol (7c): yellow oil
(lit.1a oil), 0.56 g, 72%: H NMR δ 0.93 (d, J ) 6.6 Hz, 6H),
1.72 (br s, 1H), 1.80-2.00 (m, 1H), 4.12 (d, J ) 5.8 Hz, 1H),
5.10 (d, J ) 11.1 Hz, 1H), 5.17 (s, 1H), 5.20 (s, 1H), 5.36 (d, J
1
extracted with diethyl ether (2 × 20 mL) and dried (Na
2
SO ).
4
The crude oil left after the solvent was removed under reduced
pressure was subjected to column chromatography to give the
pure product.
1
3
) 17.9 Hz, 1H), 6.33 (dd, J ) 11.0 and 17.6 Hz, 1H); C NMR
δ 16.9, 19.6, 32.0, 77.2, 114.4, 114.6, 136.2, 148.3.
4
-Meth ylid en e-1-p h en ylh ex-5-en -3-ol (7a ): yellow oil
8
a
1
(
2
1
lit. oil), 0.69 g, 74%: H NMR δ 1.80-2.02 (m, 3H), 2.67-
.83 (m, 2H), 4.41 (dd, J ) 7.3 and 3.8 Hz, 1H), 5.05 (d, J )
1.3 Hz, 1H), 5.15 (s, 1H), 5.20 (d, J ) 18.0 Hz, 1H), 5.26 (s,
J O9818881