Titanium tetrachloride-induced three-component coupling reaction of α-haloacylsilane, allylsilane, and carbonyl compound

Full text of DOI:10.1021/jo9602332

J . Org. Chem. 1996, 61, 4483-4486
4483
mmol)at -78 °C for 30 min gave 1-undecen-4-one 2 (0.16
g) in 98% yield. The use of R-chloroacylsilane 1b (R′ )
Ph) in place of 1a also gave 2 in 76% yield, while 1c
(R′ ) t-Bu) afforded 5-(tert-butyldimethylsilyl)-1-undecen-
4-one (3a ) (0.22 g)9 in 78% yield upon treatment with
TiCl4 in the presence of allyltrimethylsilane (Scheme 1).
Whereas the trimethylsilyl and dimethylphenylsilyl groups
of the acylsilane moiety have been lost completely under
the reaction conditions, the tert-butyldimethylsilyl group
remained on the products.
Tita n iu m Tetr a ch lor id e-In d u ced
Th r ee-Com p on en t Cou p lin g Rea ction of
r-Ha loa cylsila n e, Allylsila n e, a n d Ca r bon yl
Com p ou n d
Yoshihiro Horiuchi, Koichiro Oshima,* and
Kiitiro Utimoto*
Department of Material Chemistry, Faculty of Engineering,
Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-01, J apan
The partial isomerization of the product 2 into the R,â-
unsaturated ketone took place after prolonged stirring
of the reaction mixture at -78 °C. For instance, stirring
a mixture of 1a , titanium tetrachloride, and allyltri-
methylsilane at -78 °C for 3 h provided 2-undecen-4-
one (25%) in addition to 2 (73%). Coexistence of R-halo-
gen with acylsilane moiety was essential for the forma-
tion of â,γ-unsaturated ketone. In fact, treatment of
acylsilane (n-C6H13CH2C(O)SiMe2Ph) or R-chloroaldehyde
(n-C5H11CHClCHO) with TiCl4 in the presence of allyl-
trimethylsilane afforded homoallylic alcohol (n-C6H13CH2C-
Received February 5, 1996
There has been considerable interest in the chemistry
of acylsilanes1 and many procedures have been developed
for the preparation of many functionalized acylsilanes.2
Only a few reports, however, have been published for the
synthesis of R-haloacylsilanes.3 Recently we have re-
ported a facile approach to R-haloacylsilanes based on
the rearrangement of R-haloepoxysilane and their use for
triethylborane-mediated Reformatsky type reaction giv-
ing â-hydroxyacylsilane.4 Here we describe another
application of R-haloacylsilanes to organic synthesis.
Treatment of an R-chloroacylsilane with titanium tetra-
chloride in the presence of allylsilane5 afforded a â,γ-
unsaturated ketone6 or R-silyl-â′,γ′-unsaturated ketone7
in good yield.
(OH)SiMe2PhCH2CHdCH2) or chlorohydrin (n-C5H11
-
CHClCH(OH)CH2CHdCH2) in 85% or 95% yield, respec-
tively.10
Crotyldimethylphenylsilane, cinnamyldimethylphenyl-
silane, methallyldimethylphenylsilane, and prenyldi-
methylphenylsilane reacted at the γ-position exclusively
to provide the corresponding R-(tert-butyldimethylsilyl)-
â’,γ’-unsaturated ketones 3b, 3c, 3d , 3e in 52%, 50%,
66%, and 33% yields, respectively upon treatment with
TiCl4 in the presence of 1c (Scheme 2). The reaction of
1c with 2,4-pentadienyldimethylphenylsilane afforded
7-(tert-butyldimethylsilyl)-1,3-tridecadien-6-one (3f) ex-
clusively in 63% yield.11
On the basis of these findings, we are tempted to
assume the following reaction mechanism (Scheme 3).
The chloro substituent coordinates titanium to give a
carbonium ion12 at the R position of the acylsilane which
is stabilized by a silicon atom. Participation of silicon
atom might produce a cationic intermediate 4 in which
the silicon bridges13-15 both the carbonyl carbon and the
neighboring carbon atom. Nucleophilic attack of allyl-
Treatment of a dichloromethane solution of R-chloro-
acylsilane 1a (R′ ) Me, 0.23 g, 1.0 mmol) and allyltri-
methylsilane (0.16 mL, 1.0 mmol) with titanium tetra-
chloride8 (1.0 M dichloromethane solution, 2.0 mL, 2.0
(1) (a) Page, P. C. B.; Klair, S. S.; Rosenthal, S. Chem. Soc. Rev.
1990, 19, 147-195. (b) Ricci, A.; Degl’Innocenti, A. Synthesis 1989,
647. (c) Cirillio, P. F.; Panek, J . S. Org. Prep. Proc. Int. 1992, 24, 553.
(2) Preparation: (a) Miller, J . A.; Zweifel, G. Synthesis 1981. 288.
(b) Mandai, T.; Yamaguchi, M.; Nakayama, Y.; Otera, J .; Kawada, M.
Tetrahedron Lett. 1985, 26, 2675. (c) Ireland, R. E.; Norbeck, D. W. J .
Org. Chem. 1985, 50, 2198. (d) Brook, A. G.; Duff, J . M.; J ones, P. F.;
Davis, N. R. J . Am. Chem. Soc. 1967, 89, 4431. (e) Corey, E. J .; Seebach,
D.; Freedman, R. Ibid. 1967, 89, 434. (f) Soderquist, J . A. Org. Synth.
1989, 68, 25. Reaction: (g) Danheiser, R. L.; Fink, D. M. Tetrahedron
Lett. 1985, 26, 2509. Idem. Ibid. 1985, 26, 2513. (h) Nakajima, T.; Segi,
M.; Mituoka, T.; Honda, M.; Naitou, K. Ibid. 1995, 36, 1667. (i)
Kuwajima, I.; Kato, M. J . Chem. Soc., Chem. Commun. 1979, 708. (j)
Reich, H. J .; Rusek, J . J .; Olson, R. E. J . Am. Chem. Soc. 1979, 101,
2225. (k) Kuwajima, I.; Matsutani, T.; Enda, J . Tetrahedron Lett. 1984,
25, 5307. (l) Ager, D. J . Chem. Soc. Rev. 1982, 11, 493.
(3) (a) Kuwajima, I.; Abe, T.; Minami, N. Chem. Lett. 1976, 993. (b)
Nowick, J . S.; Danheiser, R. L. J . Org. Chem. 1989, 54, 2798. (c) Page,
P. C. B.; Rosenthal, S. Tetrahedron Lett. 1986, 27, 5421. Idem
Tetrahedron 1990, 46, 2573. (d) Hewkin, C. T.; J ackson, R. F. W. J .
Chem. Soc., Perkin Trans 1 1991, 3103. (e) Kuwajima, I.; Matsumoto,
K. Tetrahedron Lett. 1979, 20, 4095. (f) Kuwajima, I.; Matsumoto, K.;
Inoue, T. Chem. Lett. 1979, 41. (g) Kuwajima, I.; Matsumoto, K.;
Sugahara, S. Ibid. 1980, 525.
(9) TiCl4 was added at 0 °C instead of -78 °C, and the resulting
mixture was stirred for 30 min at 25 °C. The reaction at -78 °C gave
3 (53%) along with the recovered starting acylsilane 1c (39%).
(10) (a) Hosomi, A.; Sakurai, H. Tetrahedron Lett. 1976, 1295. (b)
Hayashi, T.; Kabeta, K.; Hamachi, I.; Kumada, M. Ibid. 1983, 24, 2865.
(11) The reaction of 1-propynyltrimethylsilane with 1c provided
5-(tert-butyldimethylsilyl)-2-undecyn-4-one (3g) in 33% yield.
(12) Treatment of R-iodoacylsilane (n-C6H13CHIC(O)SiMe2-t-Bu)
with silver tetrafluoroborate in the presence of allyltrimethylsilane also
provided 3a in 67% yield. In this case, the use of iodide was critical
for the successful reaction. The reaction of 1c with AgBF4 in the
presence of allyltrimethylsilane resulted in complete recovery of
starting material 1c.
(4) (a) Horiuchi, Y.; Taniguchi, M.; Oshima, K.; Utimoto, K. Tetra-
hedron Lett. 1995, 36, 5353. (b) Morihata, K.; Horiuchi, Y.; Taniguchi,
M.; Oshima, K.; Utimoto, K. Ibid. 1995, 36, 5555.
(5) Allylation with allylmetals: (a) Yanagisawa, A.; Habaue, S.;
Yamamoto, H. J . Org. Chem. 1989, 54, 5198. (b) Sato, T.; Matsumoto,
K.; Abe, T.; Kuwajima, I. Bull. Chem. Soc. J pn. 1984, 57, 2167. (c)
Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207. (d) Yanagisawa,
A.; Habaue, S.; Yamamoto, H. Tetrahedron 1992, 48, 1969.
(6) (a) Brown, H. C.; Soundararajan, R. Tetrahedron Lett. 1994, 35,
6963. (b) Takeuchi, S.; Ohira, A.; Miyoshi, N.; Mashio, H.; Ohgo, Y.
Tetrahedron Asymmetry 1994, 5, 1763. (c) Yasui, K.; Fugami, K.;
Tanaka, S.; Tamaru, Y. J . Org. Chem. 1995, 60, 1365.
(7) (a) Obayashi, M.; Utimoto, K.; Nozaki, H. Bull. Chem. Soc. J pn.
1979, 52, 2646. (b) Misra, R. N.; Withers, G. P.; Hudrlik, A. M.; Rona,
R. J .; Arcoleo, J . P. Tetrahedron Lett. 1976, 1453. (c) Larson, G. L;
Hernandez, D.; de Lopez-Cepero, I. M.; Torres, L. E. J . Org. Chem.
1985, 50, 5260. (d) Corey, E. J .; Ru¨cker, C. Tetrahedron Lett. 1984,
25, 4345. (e) Yamamoto, Y.; Ohdori, K.; Nakatani, M.; Akiba, K. Chem.
Lett. 1984, 1967. (f) Fu¨rstner, A.; Kollegger, G.; Weidmann, H. J .
Organomet. Chem. 1991, 414, 295.
(13) (a) Panek, J . S.; Yang, M. J . Am. Chem. Soc. 1991, 113, 9868.
(b) Panek, J . S.; Beresis, R. J . Org. Chem. 1993, 58, 809. (c) Panek, J .
S.; J ain, N. F. Ibid. 1993, 58, 2345. (d) Danheiser, R. L.; Dixon, B. R.;
Glenson, R. W. Ibid. 1992, 57, 6094. (e) Yamazaki, S.; Katoh, S.;
Yamabe, S. Ibid. 1992, 57, 4.
(14) The possibility of ketene formation was suggested by a reviewer.
The reaction of R-chloroacylsilane 1c with TiCl4 in the presence of
PhCHdN-n-Pr did not give any lactam. Thus we assume that ketene
is not an intermediate. In contrast, the reaction with a fluoride source
might proceed via ketene intermediate, since treatment of R-chloroa-
cylsilane with n-Bu4NF in the presence of alcohol (R′OH) afforded ester
RCH2COOR′ in 76% (R′ ) PhCH2) or 75% (R′ ) CH2dCHCH2) yield.
(15) The following crossover experiment was performed. Treatment
of a 1:1 mixture of 1 (R ) n-C3H7, R′ ) t-Bu) and 1b (R ) n-C6H13, R′
) Ph) with TiCl4 in the presence of allyltrimethylsilane provided only
two products, n-C3H7CH(SiMe2-t-Bu)COCH2CHdCH2 and n-C6H13CH2-
COCH2CHdCH2 which suggested that the silane remained attached
to the carbon skeleton throughout the reaction.
(8) The use of BF3‚OEt2 and TMSOTf as Lewis acids resulted in a
recovery of 1a , and no allylation product was detected in the reaction
mixture.
S0022-3263(96)00233-2 CCC: $12.00 © 1996 American Chemical Society

4484 J . Org. Chem., Vol. 61, No. 13, 1996
Notes
Sch em e 1
TiCl4. The use of furan instead of methoxybenzene
furnished only poor yield of Friedel-Crafts type adduct
(<4%).
The loss of the trimethylsilyl and dimethylphenylsilyl
groups during the reaction might be attributed to a facile
transformation17,18 of the R-silyl ketone to the corre-
sponding silyl enol ether under the reaction conditions,
which then collapsed to â,γ-unsaturated ketone or heptyl
2,4-dimethoxyphenyl ketone upon aqueous workup. Thus,
it was anticipated that the sequential treatment of 1a
or 1b with allyltrimethylsilane in the presence of TiCl4
followed by carbonyl compounds would provide three-
component coupling products. The representative results
which realized this expectation are shown below (Scheme
5). For instance, an addition of acetaldehyde to the
reaction mixture derived from 1a and allyltrimethylsi-
lane gave aldol type product 7a in 70% yield, and
therefore, R-chloroacylsilane 1a or 1b can be regarded
as a synthon of -C-C+(dO).
Sch em e 2
Sch em e 5
Sch em e 3
Sch em e 4
In summary, a simple procedure has been devised for
the preparation of an R-silylacyl cation equivalent. Ad-
ditionally, a convenient and efficient three component
coupling reaction of R-chloroacylsilane, allyltrimethylsi-
lane and carbonyl compound has been achieved which
further enhances the synthetic utility of R-haloacylsi-
lanes.
silane on the carbonyl carbon affords â,γ-unsaturated
ketone 3 which is apparently produced by migration of
silyl group16 to adjacent carbon followed by allylation.
Exp er im en ta l Section
P r ep a r a tion of r-Ch lor oa cylsila n es. 2-Chloro-1-(trimeth-
ylsilyl)-1-octanone (1a ), 2-Chloro-1-(dimethylphenylsilyl)-1-oc-
tanone (1b), 2-chloro-1-(tert-butyldimethylsilyl)-1-octanone (1c),
and 2-chloro-1-(tert-butyldimethylsilyl)-1-pentanone (1d ) were
prepared according to the reported procedure.4 1-(Dimethylphe-
nylsilyl)-1-octanone was produced following the literature.2a The
physical data are as follows.
The intermediary acyl cation equivalent 4 has been
expected to react with electron-rich aromatic compounds
such as methoxybenzene or m-dimethoxybenzene via
Friedel-Crafts type reaction. This was indeed the case,
and an addition of these aromatic compounds instead of
allylsilane gave the corresponding acylated products
(Scheme 4). Trimethylsilyl group was lost under the
reaction conditions and tert-butyldimethylsilyl group
remained on the products as in the case of the reaction
with allylsilane. Thiophene could be used as a trapping
reagent of acyl cation to give the corresponding adduct
in moderate yield (46%) upon treatment with 1a and
1-(Dim eth ylp h en ylsilyl)-1-octa n on e: 1.2 g, 80% yield; Bp
113 °C (0.5 Torr); IR (neat) 2954, 2924, 2852, 1643, 1429, 1250,
1
1111 cm-1; H NMR (CDCl3) δ 0.48 (s, 6H), 0.85 (t, J ) 6.8 Hz,
3H), 1.06-1.34 (m, 8H), 1.43 (m, 2H), 2.55 (t, J ) 7.4 Hz, 2H),
7.34-7.46 (m, 3H), 7.52-7.59 (m, 2H); 13C NMR (CDCl3) δ -4.76,
14.02, 22.13, 22.53, 29.03, 29.12, 31.59, 48.84, 128.13, 129.84,
133.98, 134.63, 246.78. Found: C, 73.23; H, 10.14%. Calcd for
C
16H26OSi: C, 73.22; H, 9.98%.
(16) 1,2-Silyl migration: (a) Bideau, F. L.; Gilloir, F.; Nilsson, Y.;
Anbert, C.; Malacria, M. Tetrahedron Lett. 1995, 36, 1641. (b) Kno¨lker,
H-J .; Graf, R.; Synlett 1994, 131. (c) Monti, H.; Audran, G.; Monti, J .-
P.; Leandri, G. Synlett 1994, 403. (d) Kno¨lker, H.-J .; Foitzik, N.;
Goesmann, H.; Graf, K. Angew. Chem., Int. Ed. Engl. 1993, 32, 1081.
(e) Sato, T.; Otera, J .; Nozaki, H. J . Org. Chem. 1990, 55, 6116.
(17) â-Ketosilanes have been known to undergo a facile thermal
rearrangement to silyl enol ethers. Brook, A. G. Acc. Chem. Res. 1974,
7, 77. See also ref 7e and 7f.
(18) Aldol reaction of â-ketosilane with aldehyde in the presence of
a Lewis acid have been reported. Kuwajima, I.; Inoue, T.; Sato, T.
Tetrahedron Lett. 1978, 4887.

Notes
2-Ch lor o-1-(tr im eth ylsilyl)-1-octa n on e (1a ).3a Diisobuty-
J . Org. Chem., Vol. 61, No. 13, 1996 4485
(ddt, J ) 10.2, 17.1, 6.9 Hz, 1H); 13C NMR (CDCl3) δ -7.17,
-5.83, 14.02, 17.82, 22.58, 26.81, 28.38, 29.16, 30.90, 31.64,
44.68, 49.89, 118.26, 131.23, 210.55. Found: C, 72.19; H,
12.42%. Calcd for C17H34OSi: C, 72.27; H, 12.13%.
laluminum hydride (18.7 mL, 105 mmol) was added dropwise
to a solution of 1-(trimethylsilyl)-1-octyne (17.3 g, 95 mmol) in
ether (95 mL) at 25 °C under argon atmosphere. The mixture
was heated at reflux for 3 h. The resulting solution was cooled
to -15 °C (dry ice-ethylene glycol) and N-chlorosuccinimide
(14.0 g, 105 mmol) was added portionwise. Exothermic reaction
took place. After completion of the addition, the mixture was
warmed to 25 °C and stirred for 30 min. Then the mixture was
poured into ice-cold 1 M HCl. Extraction with hexane followed
by purification by silica gel column (hexane) chromatography
gave (E)-1-(trimethylsilyl)-1-chloro-1-octene (18.5 g, 85 mmol).
m-Chloroperoxybenzoic acid (19.4 g, 80% purity, 90 mmol) was
added to a solution of (E)-1-(trimethylsilyl)-1-chloro-1-octene
(18.5 g) in dichloromethane (100 mL) at 25 °C, and the resulting
mixture was stirred for 8 h. The mixture was poured into
saturated NaHCO3 and extracted with hexane (60 mL × 3).
Concentration of the dried combined organic layers followed by
silica gel column chromatography afforded R-chloroepoxysilane
(17.3 g, 74 mmol) in 78% overall yield from 1-(trimethylsilyl)-
1-octyne. A catalytic amount of zinc chloride (3 g, 22 mmol) was
added to a solution of R-chloroepoxysilane (17.3 g, 74 mmol) in
ether (50 mL) at 0 °C and the mixture was stirred at 25 °C for
1 h. Extractive workup (EtOAc-H2O) followed by purification
by silica gel column chromatography provided the title compound
(16.6 g, 71 mmol) in 96% yield.
5-(ter t-Bu tyldim eth ylsilyl)-3-m eth yl-1-u n decen -4-on e (3b):
0.15 g, 52% yield; Bp 108 °C (0.5 Torr); IR (neat) 2952, 2926,
2854, 1694, 1466, 1257, 1135, 915, 839, 822, 769 cm-1; 1H NMR
(CDCl3) δ -0.05 (s, 3H), 0.02 (s, 3H), 0.85 (t, J ) 6.9 Hz, 3H,
major), 0.86 (t, J ) 6.9 Hz, 3H, minor), 0.93 (s, 9H, minor), 0.94
(s, 9H, major), 1.08-1.43 (m, 12H, including, 1.12 (d, J ) 6.6
Hz, 3H, major), 1.18 (d, J ) 7.2 Hz, 3H, minor)), 1.99 (m, 1H),
2.61 (dd, J ) 1.8, 11.7 Hz, 1H, minor), 2.73 (dd, J ) 1.8, 11.7
Hz, 1H, major), 3.10 (m, 1H), 5.00-5.23 (m, 2H), 5.59 (ddd, J )
8.7, 9.9, 17.4 Hz, 1H, major), 6.02 (ddd, J ) 8.1, 10.5, 17.1 Hz,
minor); 13C NMR (CDCl3) δ -7.24, -7.18, -5.99, -5.22, 14.04,
14.83, 17.59, 17.91, 22.61, 26.79, 26.90, 28.33, 28.57, 29.21, 29.31,
30.77, 31.15, 31.69, 42.96, 43.73, 52.28, 53.50, 115.33, 117.23,
137.90, 138.18, 212.08, 213.94. Found: C, 72.98; H, 12.09%.
Calcd for C18H36OSi: C, 72.90; H, 12.23%.
5-(ter t-Bu tyldim eth ylsilyl)-3-ph en yl-1-u n decen -4-on e (3c):
0.18 g, 50% yield; Bp 150 °C (0.5 Torr); IR (neat) 2952, 2926,
2854, 1692, 1466, 1455, 1253, 1132, 1079, 914, 823, 806, 699
cm-1 1H NMR (CDCl3) δ -0.13 (s, 3H, minor), 0.02 (s, 3H,
;
minor), 0.05 (s, 6H, major), {0.74-1.55 (m, 13H) including 0.77
(t, J ) 7.2 Hz, 3H, major), 0.86 (t, J ) 6.9 Hz, minor), 0.92 (s,
9H, minor), 0.96 (s, 9H, major)}, 1.93 (m, 1H), 2.56 (dd, J ) 1.8,
11.7 Hz, 1H, major), 2.78 (dd, J ) 2.1, 11.7 Hz, 1H, minor), 4.19
(d, J ) 7.8 Hz, 1H, major), 4.29 (d, J ) 9.3 Hz, 1H, minor), 4.94-
5.25 (m, 2H), 6.02 (ddd, J ) 9.3, 9.6, 16.8 Hz, 1H, minor), 6.40
(ddd, J ) 7.8, 10.2, 17.1 Hz, major), 7.20-7.37 (m, 5H); 13C NMR
(CDCl3) δ -7.17, -7.05, -5.22, 13.99, 14.05, 17.90, 17.95, 22.38,
22.60, 26.83, 26.86, 27.82, 28.60, 28.96, 29.23, 29.49, 30.98, 31.57,
31.67, 43.44, 43.80, 64.82, 65.16, 116.43, 117.82, 126.92, 127.31,
128.34, 128.61, 128.73, 128.79, 128.86, 136.96, 137.69, 209.42,
209.83. Found: C, 76.98; H, 10.65%. Calcd for C23H38OSi: C,
77.03; H, 10.68%.
2-Ch lor o-1-(d im eth ylp h en ylsilyl)-1-octa n on e (1b): 15.3 g,
53% overall yield; Bp 137 °C (0.5 Torr); IR (neat) 2952, 2926,
2856, 1652, 1466, 1429, 1251, 1111, 838, 820, 784, 734, 699, 646
1
cm-1; H NMR (CDCl3) δ 0.58 (s, 3H), 0.59 (s, 3H), 0.85 (t, J )
6.9 Hz, 3H), 1.00-1.39 (m, 8H), 1.61 (m, 1H), 1.80 (m, 1H), 4.29
(dd, J ) 5.4, 8.7 Hz, 1H), 7.36-7.48 (m, 3H), 7.56-7.62 (m, 2H);
13C NMR (CDCl3) δ -3.66, -3.60, 13.95, 22.42, 25.77, 28.56,
31.41, 31.74, 68.28, 128.14, 130.07, 134.03, 134.18, 235.25.
Found: C, 65.02; H, 8.82%. Calcd for C16H26OSiCl: C, 64.73;
H, 8.49%.
2-Ch lor o-1-(ter t-bu tyld im eth ylsilyl)-1-octa n on e (1c): 20
g, 65% overall yield; Bp 98 °C (0.5 Torr); IR (neat) 2952, 2926,
2856, 1652, 1465, 1251, 839, 824, 778 cm-1; 1H NMR (CDCl3) δ
0.24 (s, 3H), 0.26 (s, 3H), 0.86 (t, J ) 6.7 Hz, 3H), 0.93 (s, 9H),
1.17-1.51 (m, 8H), 1.67 (m, 1H), 1.87 (m, 1H), 4.31 (dd, J ) 5.4,
8.5 Hz, 1H); 13C NMR (CDCl3) δ -5.88, 14.00, 16.97, 22.49, 26.05,
26.46, 28.74, 31.26, 31.51, 67.12, 236.30. Found: C, 61.00; H,
10.82%. Calcd for C14H29OSiCl: C, 60.72; H, 10.56%.
2-Ch lor o-1-(ter t-bu tyld im eth ylsilyl)-1-p en ta n on e (1d ):
15 g, 60% overall yield; Bp 45 °C (0.5 Torr); IR (neat) 2954, 2930,
5-(ter t-Bu tyldim eth ylsilyl)-2-m eth yl-1-u n decen -4-on e (3d):
0.20 g, 66% yield; Bp 104 °C (0.5 Torr); IR (neat) 2952, 2926,
1
2854, 1691, 1466, 1252, 890, 833, 823, 808, 770 cm-1; H NMR
(CDCl3) δ -0.01 (s, 3H), 0.04 (s, 3H), 0.86 (t, J ) 6.8 Hz, 3H),
0.93 (s, 9H), 0.99-1.43 (m, 9H), 1.76 (s, 3H), 1.96 (m, 1H), 2.59
(dd, J ) 1.8, 11.7 Hz, 1H), 3.00 (d, J ) 14.4 Hz, 1H), 3.09 (d, J
) 14.4 Hz, 1H), 4.78 (s, 1H), 4.91 (s, 1H); 13C NMR (CDCl3) δ
-7.17, -5.67, 14.03, 17.88, 22.58, 22.72, 26.81, 28.29, 29.16,
30.73, 31.67, 43.97, 54.41, 114.71, 139.47, 210.10. Found: C,
72.64; H, 12.16%. Calcd for C18H36OSi: C, 72.90; H, 12.23%.
5-(ter t-Bu t yld im et h ylsilyl)-3,3-d im et h yl-1-u n d ecen -4-
on e (3e): 0.10 g, 33% yield; Bp 118 °C (0.5 Torr); IR (neat) 2954,
2926, 2854, 1683, 1466, 1254, 1137, 1067, 1006, 916, 841, 822,
810, 788, 769, 687 cm-1; 1H NMR (CDCl3) δ -0.10 (s, 3H), 0.03
(s, 3H), 0.86 (t, J ) 6.8 Hz, 3H), 0.92 (s, 9H), 1.16-1.49 (m, 15H,
including 1.18 (s, 3H), 1.21 (s, 3H)), 1.90 (m, 1H), 2.90 (dd, J )
1.8, 11.7 Hz, 1H), 5.10-5.18 (m, 2H), 6.00 (dd, J ) 10.5, 17.4
Hz, 1H); 13C NMR (CDCl3) δ -6.91, -4.45, 14.05, 18.26, 22.60,
23.47, 24.40, 27.09, 29.34, 31.07, 31.43, 31.69, 38.06, 51.20,
113.81, 143.59, 216.72. Found: C, 73.29; H, 12.53%. Calcd for
1
2854, 1651, 1465, 1365, 1252, 839, 823, 811, 779, 679 cm-1; H
NMR (CDCl3) δ 0.26 (s, 3H), 0.28 (s, 3H), 0.939 (t, J ) 7.4 Hz,
3H), 0.943 (s, 9H), 1.28-1.56 (m, 2H), 1.69 (m, 1H), 1.85 (m,
1H), 4.34 (dd, J ) 5.3, 8.6 Hz, 1H); 13C NMR (CDCl3) δ -5.90,
-5.86, 13.51, 16.96, 19.36, 26.46, 33.23, 66.79, 236.26. Found:
C, 56.29; H, 10.06%. Calcd for C11H23OSiCl: C, 56.26; H, 9.87%.
Gen er a l P r oced u r e for th e Rea ction of 1 a n d Allyltr i-
m eth ylsila n e in th e P r esen ce of TiCl4. The reaction of 1a
with allyltrimethylsilane is representative. Under an argon
atmosphere, a dichloromethane solution of TiCl4 (1.0 M, 2.0 mL,
2.0 mmol) was added dropwise to a solution of R-chloroacylsilane
1a (0.24 g, 1.0 mmol) and allyltrimethylsilane (0.16 mL, 1.0
mmol) in dichloromethane (5 mL) at -78 °C. After being stirred
for 30 min at the same temperature, the mixture was poured
into saturated aqueous NaCl. Extraction with EtOAc (20 mL
× 3) followed by purification by silica-gel column chromatogra-
phy afforded 1-undecen-4-one (2, 165 mg) in 98% yield: Bp 110
°C (13 Torr); IR (neat) 2954, 2924, 2852, 1718, 918 cm-1; 1H NMR
(CDCl3) δ 0.87 (t, J ) 6.8 Hz, 3H), 1.12-1.47 (m, 8H), 1.57 (m,
2H), 2.42 (t, J ) 7.5 Hz, 2H), 3.16 (d, J ) 6.6 Hz, 2H), 5.13 (dd,
J ) 1.2, 17.1 Hz, 1H), 5.17 (dd, J ) 1.2, 10.2 Hz, 1H), 5.92 (ddt,
J ) 10.2, 17.1, 6.6 Hz, 1H); 13C NMR (CDCl3) δ 13.92, 22.48,
23.59, 28.95, 29.04, 31.56, 42.31, 47.65, 118.72, 130.84, 209.26.
Found: C, 78.23; H, 12.09%. Calcd for C11H20O: C, 78.51; H,
11.98%.
C
19H38OSi: C, 73.48; H, 12.33%.
7-(ter t-Bu tyldim eth ylsilyl)-1,3-tr idecadien -6-on e (3f): 0.19
g, 63% yield; Bp 118 °C (0.5 Torr); IR (neat) 2952, 2926, 2854,
1693, 1466, 1252, 1087, 1003, 835, 824, 805, 770 cm-1; 1H NMR
(CDCl3) δ -0.04 (s, 3H), 0.03 (s, 3H), 0.85 (t, J ) 6.9 Hz, 3H),
0.93 (s, 9H), 1.10-1.46 (m, 9H), 1.97 (m, 1H), 2.52 (dd, J ) 2.1,
11.7 Hz, 1H), 3.08 (dd, J ) 7.2, 16.5 Hz, 1H), 3.18 (dd, J ) 7.2,
16.5 Hz, 1H), 5.04 (d, J ) 9.9 Hz, 1H), 5.14 (d, J ) 16.8 Hz, 1H),
5.79 (dt, J ) 15.3, 7.2 Hz, 1H), 6.09 (dd, J ) 10.2, 15.3 Hz, 1H),
6.34 (ddd, J ) 9.9, 10.2, 16.8 Hz, 1H); 13C NMR (CDCl3) δ -7.32,
-5.93, 13.94, 17.72, 22.50, 26.71, 28.36, 29.06, 30.81, 31.58,
44.61, 48.61, 116.47, 126.74, 134.32, 136.73, 210.61. Found: C,
73.99; H, 11.83%. Calcd for C19H36OSi: C, 73.95; H, 11.76%.
5-(ter t-Bu tyld im eth ylsilyl)-2-u n d ecyn -4-on e (3g): 92 mg,
33% yield; Bp 120 °C (0.5 Torr); IR (neat) 2952, 2926, 2854, 2216,
5-(ter t-Bu tyld im eth ylsilyl)-1-u n d ecen -4-on e (3a ): 0.22 g,
78% yield; Bp 112 °C (0.5 Torr); IR (neat) 2954, 2926, 2856, 1693,
1651, 1467, 1252, 1167, 838, 825, 810, 770 cm-1 1H NMR
;
(CDCl3) δ 0.06 (s, 3H), 0.07 (s, 3H), 0.87 (t, J ) 6.6 Hz, 3H),
0.93 (s, 9H), 1.14-1.52 (m, 9H), 2.00 (s, 1H), 2.08 (m, 1H), 2.54
(dd, J ) 1.8, 11.7 Hz, 1H); 13C NMR (CDCl3) δ -6.82, -6.38,
3.95, 14.03, 17.96, 22.54, 26.75, 28.00, 29.05, 30.76, 31.58, 48.69,
81.30, 88.97, 190.68. Found: C, 72.53; H, 11.41%. Calcd for
1
1466, 1252, 834, 823, 807, 771 cm-1; H NMR (CDCl3) δ -0.04
(s, 3H), 0.03 (s, 3H), 0.85 (t, J ) 6.8 Hz, 3H), 0.92 (s, 9H), 1.02-
1.46 (m, 9H), 1.97 (m, 1H), 2.51 (dd, J ) 2.1, 12.0 Hz, 1H), 3.05
(dd, J ) 6.9, 16.2 Hz, 1H), 3.14 (dd, J ) 6.9, 16.2, Hz, 1H), 5.09
(dd, J ) 1.5, 17.1 Hz, 1H), 5.15 (dd, J ) 1.5, 10.2 Hz, 1H), 5.91
C
17H32OSi: C, 72.79; H, 11.50%.

4486 J . Org. Chem., Vol. 61, No. 13, 1996
Notes
4-(Dim eth ylp h en ylsilyl)-1-u n d ecen -4-ol: 0.26 g, 85% yield;
Bp 127 °C (0.5 Torr); IR (neat) 2926, 2852, 1429, 1248, 1112,
914, 831, 812, 772, 734, 701, 648 cm-1; 1H NMR (CDCl3) δ 0.38
(s, 3H), 0.39 (s, 3H), 0.88 (t, J ) 6.8 Hz, 3H), 1.11 (bs, 1H), 1.15-
1.35 (m, 10H), 1.52 (m, 2H), 2.33 (d, J ) 7.2 Hz, 2H), 5.03-5.12
(m, 2H), 5.79 (ddt, J ) 10.2, 16.8, 7.2 Hz, 1H), 7.33-7.42 (m,
3H), 7.56-7.63 (m, 2H); 13C NMR (CDCl3) δ -4.52, -4.45, 14.03,
22.58, 23.46, 29.12, 30.28, 31.74, 37.78, 41.58, 68.14, 118.44,
127.73, 129.18, 133.80, 134.59, 137.05. Found: C, 75.03; H,
10.72%. Calcd for C19H32OSi: C, 74.93; H, 10.59%.
1.35 (m, 10H, including, 0.16 (d, J ) 6.3 Hz, 3H, erythro) 0.20
(d, J ) 6.6 Hz, 3H, threo)), 1.48-1.76 (m, 3H), 2.25 (bs, 1H,
erythro), 2.42 (bs, 1H, threo), 2.54-2.65 (m, 1H, mainly, 2.62,
ddd, J ) 4.5, 4.8, 9.2 Hz, erythro), 3.21 (dq, J ) 6.9, 17.1 Hz,
1H), 3.29 (dd, J ) 6.9, 17.1 Hz, 1H), 3.93 (m, 1H, threo), 3.96
(dq, J ) 4.8, 6.3 Hz, 1H, erythro), 5.09-5.21 (m, 2H), 5.83-5.97
(m, 1H); 13C NMR (CDCl3) δ 13.91, 20.47, 21.68, 22.46, 26.85,
27.16, 27.87, 29.10, 29.34, 29.45, 31.49, 49.06, 49.21, 57.32, 58.05,
67.89, 68.56, 119.04, 119.08, 130.24, 213.32. Found: C, 73.46;
H, 11.44%. Calcd for C13H24O2: C, 73.54; H, 11.39%.
1-(4-Meth oxyp h en yl)-1-p en ta n on e (5a ): 0.15 g, 77% yield;
Bp 113 °C (0.5 Torr); IR (neat) 2956, 1679, 1602, 1577, 1510,
1460, 1311, 1259, 1213, 1171, 1031, 840 cm-1; 1H NMR (CDCl3)
δ 0.94 (t, J ) 7.4 Hz, 3H), 1.40 (tq, J ) 7.8, 7.4 Hz, 2H), 1.70 (tt,
J ) 7.5, 7.8 Hz, 2H), 2.91 (d, J ) 7.5 Hz, 2H), 3.87 (s, 3H), 6.93
(d, J ) 9.0 Hz, 2H), 7.94 (d, J ) 9.0 Hz, 2H); 13C NMR (CDCl3)
δ 13.91, 22.50, 26.70, 37.99, 55.42, 113.64, 130.19, 130.32, 163.30,
199.30. Found: C, 74.84; H, 8.58%. Calcd for C12H16O2: C,
74.97; H, 8.39%.
2-(ter t-Bu tyld im eth ylsilyl)-1-(4-m eth oxyp h en yl)-1-p en -
ta n on e (6a ): 0.20 g, 66% yield; Bp 145 °C (0.5 Torr); IR (neat)
2928, 2854, 1651, 1602, 1509, 1464, 1260, 1246, 1209, 1171, 835,
824 cm-1; 1H NMR (CDCl3) δ -0.26 (s, 3H), 0.03 (s, 3H), 0.85 (t,
J ) 7.2 Hz, 3H), 0.90 (s, 9H), 1.10-1.43 (m, 2H), 1.53 (m, 1H),
2.21 (m, 1H), 3.37 (dd, J ) 2.1, 11.7 Hz, 1H), 3.85 (s, 3H), 6.91
(d, J ) 8.7 Hz, 2H), 7.89 (d, J ) 8.7 Hz, 2H); 13C NMR (CDCl3)
δ -7.27, -5.83, 14.04, 18.12, 24.04, 27.02, 31.19, 38.15, 55.36,
113.54, 130.19, 132.81, 162.92, 202.25. Found: C, 70.60; H,
10.11%. Calcd for C18H30O2Si: C, 70.53; H, 9.86%.
1-(2,4-Dim eth oxyp h en yl)-1-octa n on e (5b): 0.22 g, 84%
yield; Bp 140 °C (0.5 Torr); IR (neat) 2926, 2852, 1665, 1602,
1576, 1465, 1293, 1262, 1212, 1163, 1030 cm-1; 1H NMR (CDCl3)
δ 0.87 (t, J ) 6.8 Hz, 3H), 1.20-1.39 (m, 8H), 1.85 (tt, J ) 7.5,
7.5 Hz, 2H), 2.91 (t, J ) 7.5 Hz, 2H), 3.84 (s, 3H), 3.87 (s, 3H),
6.45 (d, J ) 2.4 Hz, 1H), 6.51 (dd, J ) 2.4, 8.4 Hz, 1H), 7.77 (d,
J ) 8.4 Hz, 1H); 13C NMR (CDCl3) δ 13.94, 22.50, 24.50, 29.09,
29.35, 31.64, 43.57, 55.35, 55.41, 98.37, 104.98, 121.51, 132.64,
160.68, 164.25, 201.22. Found: C, 72.92; H, 9.24%. Calcd for
er yt h r o-5-(1-H yd r oxy-1-p h e n ylm e t h yl)-1-u n d e ce n -4-
on e (7b): 0.16 g, 58% combined yield (erythro and threo isomers);
Bp 153 °C (0.5 Torr); IR (neat) 3396, 2952, 2924, 2854, 1710,
1455, 1053, 918, 763, 701 cm-1; 1H NMR (CDCl3) δ 0.85 (t, J )
6.9 Hz, 3H), 1.05-1.33 (m, 8H), 1.57-1.83 (m, 2H), 2.67 (bs, 1H),
2.84-3.08 (m, 3H), 4.84 (d, J ) 6.0 Hz, 1H), 4.98 (dd, J ) 1.5,
17.1 Hz, 1H), 5.12 (dd, J ) 1.5, 10.2 Hz, 1H), 5.43 (dddd, J )
7.1, 7.1, 10.2, 17.1 Hz, 1H), 7.24-7.38 (m, 5H); 13C NMR (CDCl3)
δ 13.90, 22.42, 27.33, 27.65, 29.36, 31.43, 49.46, 58.62, 74.21,
119.12, 126.23, 127.82, 128.51, 129.93, 142.01, 212.94. Found:
C, 78.83; H, 9.70%. Calcd for C18H26O2: C, 78.79; H, 9.55%.
th r eo-5-(1-H yd r oxy-1-p h en ylm et h yl)-1-u n d ecen -4-on e
(7b): Bp 153 °C (0.5 Torr); IR (neat) 3448, 2952, 2924, 2854,
1711, 1455, 916, 764, 700 cm-1; 1H NMR (CDCl3) δ 0.74 (t, J )
6.8 Hz, 3H), 1.00-1.24 (m, 8H), 1.42-1.56 (m, 2H), 2.73 (bs, 1H),
2.85 (ddd, J ) 4.8, 7.5, 9.1 Hz, 1H), 3.00 (m, 1H), 3.08 (m, 1H),
4.67 (d, J ) 7.5 Hz, 1H), 4.95 (dd, J ) 1.5, 17.1 Hz, 1H), 5.05
(dd, J ) 1.5, 10.2 Hz, 1H), 5.75 (dddd, J ) 6.9, 6.9, 10.2, 17.1
Hz, 1H), 7.15-7.29 (m, 5H); 13C NMR (CDCl3) δ 13.85, 22.35,
27.09, 29.14, 29.39, 31.36, 49.80, 57.98, 75.76, 118.92, 126.28,
127.95, 128.58, 130.09, 142.61, 213.86. Found: C, 78.58; H,
9.35%. Calcd for C18H26O2: C, 78.79; H, 9.55%.
5-(1-Hyd r oxy-1-m eth yleth yl)-1-u n d ecen -4-on e (7c): 0.19
g, 83% yield; Bp 94 °C (0.5 Torr); IR (neat) 3436, 2954, 2926,
2854, 1703, 1467, 1378, 1152, 918 cm-1; 1H NMR (CDCl3) δ 0.87
(t, J ) 6.3 Hz, 3H), 1.13-1.36 (m, 14H, including 1.19 (s, 3H)
and 1.21 (s, 3H)), 1.47-1.80 (m, 2H), 2.64 (dd, J ) 3.3, 10.8 Hz,
1H), 2.69 (bs, 1H), 3.23 (dd, J ) 6.9, 17.5 Hz, 1H), 3.33 (dd, J )
6.9, 17.5 Hz, 1H), 5.13 (dd, J ) 3.0, 17.1 Hz, 1H), 5.20 (dd, J )
3.0, 10.2 Hz, 1H), 5.91 (dddd, J ) 6.9, 6.9, 10.2, 17.1 Hz, 1H);
13C NMR (CDCl3) δ 13.92, 22.47, 26.86, 28.26, 28.32, 29.49,
29.60, 31.49, 51.35, 59.96, 72.04, 119.05, 130.15, 215.59.
Found: C, 74.16; H, 11.83%. Calcd for C14H26O2: C, 74.29; H,
11.58%.
C
16H24O3: C, 72.69; H, 9.15%.
1-(2,4-Dim et h oxyp h en yl)-2-(ter t-b u t yld im et h ylsilyl)-1-
p en ta n on e (6b): 0.29 g, 87% yield; Bp 154 °C (0.5 Torr); IR
(neat) 2954, 2928, 1644, 1602, 1465, 1255, 1212, 1162, 1135,
1028, 823 cm-1; 1H NMR (CDCl3) δ -0.23 (s, 3H), -0.03 (s, 3H),
0.87 (s, 9H), 0.88 (t, J ) 6.8 Hz, 3H), 1.16-1.53 (m, 3H), 2.23
(m, 1H), 3.80 (dd, J ) 1.2, 9.6 Hz, 1H), 3.84 (s, 3H), 3.85 (s, 3H),
6.43 (d, J ) 2.4 Hz, 1H), 6.50 (dd, J ) 2.4, 8.7 Hz, 1H), 7.68 (d,
J ) 8.7 Hz, 1H); 13C NMR (CDCl3) δ -7.13, -5.75, 14.10, 18.06,
23.82, 27.03, 31.22, 43.08, 55.27, 55.40, 98.54, 104.75, 124.00,
132.94, 159.86, 163.53, 203.25. Found: C, 67.74; H, 9.73%. Calcd
for C19H32O3Si: C, 67.81; H, 9.58%.
1-Th ien yl-1-p en ta n on e: 77 mg, 46% yield; Bp 122 °C (13
Torr); IR (neat) 2956, 2930, 2868, 1661, 1519, 1417, 1266, 1209,
856, 721 cm-1; 1H NMR (CDCl3) δ 0.95 (t, J ) 7.2 Hz, 3H), 1.41
(tq, J ) 7.5, 7.2 Hz, 2H), 1.73 (tt, J ) 7.5, 7.5 Hz, 2H), 2.90 (t,
J ) 7.5 Hz, 2H), 7.12 (m, 1H), 7.62 (m, 1H), 7.71 (m, 1H); 13C
NMR (CDCl3) δ 13.76, 22.35, 26.78, 39.08, 128.10, 131.73, 133.39,
er yth r o-5-(1-Meth oxyeth yl)-1-u n d ecen -4-on e (7d ): 0.14 g,
61% combined yield (erythro and threo isomers); Rf 0.50 (hex/
AcOEt ) 10/1); Bp 90 °C (0.5 Torr); IR (neat) 2924, 2854, 1712,
1459, 1379, 1143, 1116, 1096, 917 cm-1; 1H NMR (CDCl3) δ 0.85
(t, J ) 6.8 Hz, 3H), 1.04 (d, J ) 6.3 Hz, 3H), 1.09-1.34 (m, 8H),
1.43 (m, 1H), 1.65 (m, 1H), 2.76 (ddd, J ) 4.2, 6.3, 9.8 Hz, 1H),
3.17 (dd, J ) 7.2, 17.1 Hz, 1H), 3.31 (dd, J ) 7.2, 17.1 Hz, 1H),
3.32 (s, 3H), 3.39 (dq, J ) 6.3, 6.3 Hz, 1H), 5.10 (dd, J ) 1.5,
17.4 Hz, 1H), 5.15 (dd, J ) 1.5, 10.5 Hz, 1H), 5.90 (ddt, J )
10.5, 17.4, 7.2 Hz, 1H); 13C NMR (CDCl3) δ 13.91, 16.05, 22.45,
27.55, 28.38, 29.35, 31.51, 49.53, 56.42, 78.06, 118.56, 130.76,
211.19. Found: C, 74.54; H, 11.79%. Calcd for C14H26O2: C,
74.29; H, 11.58%.
144.64, 193.76. Found: C, 64.05; H, 7.15%. Calcd for C9H12
OS: C, 64.25; H, 7.19%.
-
th r eo-5-(1-Meth oxyeth yl)-1-u n d ecen -4-on e (7d ): Rf 0.46
(hex/AcOEt ) 10/1); Bp 90 °C (0.5 Torr); IR (neat) 2924, 2854,
Gen er a l P r oced u r e for Th r ee-Com p on en t Cou p lin g
Rea ction . The reaction of 1a , allyltrimethylsilane, and acetal-
dehyde was representative. TiCl4 (2.0 mmol) was added to a
dichloromethane solution of 1a (1.0 mmol) and allyltrimethyl-
silane (1.0 mmol) at -78 °C. After being stirred for 15 min,
acetaldehyde (44 mg, 0.06 mL, 1.0 mmol) was added to the
reaction mixture and the whole was stirred for another 25 min
at -78 °C. The resulting mixture was poured into saturated
aqueous NaCl. Extractive workup followed by purification by
silica-gel column chromatography gave 5-(1-hydroxyethyl)-1-
undecen-4-one (7a , 149 mg) in 70% yield: Bp 158 °C (13 Torr);
IR (neat) 3404, 2954, 2924, 2854, 1707, 1459, 1378, 1143, 1109,
2820, 1717, 1465, 1379, 1145, 1116, 1095, 992, 915 cm-1 1H
;
NMR (CDCl3) δ 0.85 (t, J ) 6.8 Hz, 3H), 1.08-1.39 (m, 12H,
including 1.21 (d, J ) 6.3 Hz, 3H)), 1.55 (m, 1H), 2.60 (ddd, J )
3.6, 8.8, 10.6 Hz, 1H), 3.16 (dd, J ) 6.9, 17.4 Hz, 1H), 3.23 (s,
3H), 3.27 (dd, J ) 6.9, 17.4 Hz, 1H), 3.41 (dq, J ) 8.8, 6.3 Hz,
1H), 5.10 (dd, J ) 1.5, 17.1 Hz, 1H), 5.16 (dd, J ) 1.5, 10.5 Hz,
1H), 5.93 (ddt, J ) 10.5, 17.1, 6.9 Hz, 1H); 13C NMR (CDCl3) δ
13.91, 16.46, 22.45, 27.34, 28.29, 29.37, 31.47, 49.30, 56.52, 58.05,
78.91, 118.39, 130.91, 212.20. Found: C, 74.30; H, 11.75%. Calcd
for C14H26O2: C, 74.29; H, 11.58%.
918 cm-1
;
1H NMR (CDCl3) δ 0.87 (t, J ) 6.6 Hz, 3H), 1.13-
J O9602332