Reactivity of organocerium compounds with allyl alcohols

Full text of DOI:10.1021/jo981130h

J . Org. Chem. 1998, 63, 9559-9560
9559
Ta ble 1. Rea ction s of Oct-1-en -3-ol 1a w ith P r efor m ed
Rea ctivity of Or ga n ocer iu m Com p ou n d s
w ith Allyl Alcoh ols
Bu tylcer iu m Der iva tives w ith Va r iou s
Su bstr a te-Cer iu m (III) Ch lor id e-Bu tyllith iu m Ra tios a t
- 78 °C in THF
Renato Dalpozzo,* Antonio De Nino, and
Antonio Tagarelli
substrate-
CeCl3-BuLi
recvd start.
mater (%)
6-dodecene
(%)
entry
methoda
1
2
3
4
5
6
1:1:1
1:4:4
1:4:4b
1:1:4
1:1:3
1:1:1
A
A
A
A
B
B
83
0
0
0
0
15
Dipartimento di Chimica, Universita` della Calabria,
22c
75c
78c
92
I-87030 Arcavacata di Rende (Cosenza), Italy
Giuseppe Bartoli, M. Cristina Bellucci,
Marcella Bosco, and Letizia Sambri
58
35
a
Dipartimento di Chimica Organica “A. Mangini”,
viale Risorgimento 4, I-40136 Bologna, Italy
Method A: adding oct-1-en-3-ol to the stirred suspension of
BuLi-CeCl3. Method B: adding a THF solution of lithium oct-1-
b
en-3-olate to the stirred suspension of BuLi-CeCl3. Reaction
carried out in DME. c No other characterizable products were
recovered.
Received J une 12, 1998
We were recently interested in the reactivity of elec-
trophiles with organocerium reagents:1 inexpensive, non-
toxic, and nonbasic organometallic reagents introduced
in the 1980s.2 These reagents show low basicity and high
nucleophilicity as opposed to organolithium and Grignard
reagents;2b therefore, they can be used with enolizable
substrates (e.g., benzyl ketones,2a phosphinoyl ketones,1c
enaminones1e,g). However, they have never been tested
with substrates generally inert toward nucleophilic at-
tack such as carbon-carbon double bonds in allyl alco-
hols.
The observation that organometallic compounds can
add to allyl alcohols dates back many years ago,3 but this
interesting reaction has not found general synthetic
applicability. In fact, only primary alkyllithiums are
reported to react with allyl alcohol in the presence of
TMEDA under mild conditions, leading to alcohols in
which the alkyl group binds to the double bond carbon
atom nearer to the hydroxy function.4 On the other hand,
secondary or tertiary alkyllithiums react under drastic
reaction conditions (97 °C in sealed tubes).5 Reactive
(allyl and benzyl) Grignard reagents have been shown
to add to allylic alcohols in refluxing ether in a time range
of 50-96 h.6 The presence of catalytic amounts of
chelating phosphine-nickel and phosphine-palladium
complexes ensures the addition of Grignard reagents to
allyl alcohols in milder conditions, but with poor regio-
selectivity.7
Therefore, we have investigated the reactivity of or-
ganocerium compounds with allyl alcohols. In this paper,
we report results about an efficient and mild reaction to
give alkyl-substituted alkenes.
In preliminary investigations (Table 1) oct-1-en-3-ol 1a
(method A) and oct-1-en-3-olate 2a (method B) were
added to a stirred suspension of BuLi-CeCl3 (3). Various
relative amounts of the reactants (entries 1, 2, 4-6) were
tested in THF, and a run was carried out in DME (entry
3). Most of the starting material is recovered with
equimolecular amounts of CeCl3, BuLi, and 1a (entry 1).
However, adventitious water8 seems to have no influence
in the reaction because even with a 1:1 cerium-alkyl-
lithium ratio the reaction occurs if the alcohol is 1:4 with
respect to the organometallic reagent (entries 2, 3). An
excess of cerium trichloride is not necessary to allow its
addition to the substrate (entries 4-6). On the other
hand, as in the reaction of epoxides with cerium re-
agents,9 higher yields are obtained with a large excess
of the lithium derivative with respect to both the cerium
trichloride and the substrate. In fact, the reaction
requires a 4-fold excess of lithium reagent starting from
the alcohol (entry 4), or a 3-fold excess starting from the
alcoholate (entry 5).10 The latter methodology gives the
product in higher yields.
* Corresponding author, email dalpozzo@pobox.unical.it.
(1) (a) Bartoli, G.; Sambri, L.; Marcantoni, E.; Petrini, M Tetrahe-
dron Lett. 1994, 8453. (b) Bartoli, G.; Sambri, L.; Marcantoni, E.; Bosco,
M. Tetrahedron Lett. 1994, 8651. (c) Bartoli, G.; Sambri, L.; Marcan-
toni, E.; Tamburini, M. Angew. Chem., Int. Ed. Engl. 1995, 34, 2046.
(d) Bartoli, G.; Bosco, M.; Van Beck, J .; Sambri, L.; Marcantoni, E.
Tetrahedron Lett. 1996, 1293. (e) Bartoli, G.; Marcantoni, E.; Petrini,
M.; Sambri, L. Chem. Eur J . 1996, 2, 913. (f) Bartoli, G.; Bosco, M.;
Sambri, L.; Marcantoni, E.; Nobili, F. J . Org. Chem. 1997, 62, 4183.
(g) Bartoli, G.; Bosco. M.; Dalpozzo, R.; De Nino, A.; Marcantoni, E.;
Sambri, L. J . Org. Chem. 1998, 63, 3745.
(2) For reviews see: (a) Imamoto, T. Pure Appl. Chem., 1990, 62,
747. (b) Imamoto, T. In Comprehensive Organic Chemistry; Trost, B.
M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 1, p 231. (c)
Imamoto, T. Lanthanides in Organic Synthesis; Academic Press: New
York, 1994.
(3) Che`rest, M.; Felkin, H.; Frajerman, C.; Lion. C.; Roussi, G.;
Swierczewski, G. Tetrahedron Lett. 1966, 875.
(4) Felkin, H.; Swierczewski, G.; Tambute`, A. Tetrahedron Lett.
1969, 710.
(5) (a) Crandall, J . K.; Clark, A. C. J . Org. Chem. 1972, 37, 4236.
(b) Eisch, J . J .; Merkeley, J . H.; Galle, J . E. J . Org. Chem. 1979, 44,
587. (c) Richey, H. G., J r.; Wilkins, C. W., J r. J . Org. Chem. 1980, 45,
5027.
(6) (a) Crandall, J . K.; Clark, A. C. Tetrahedron Lett. 1969, 325. (b)
Dimmel, D. R.; Huang, S. J . Org. Chem. 1973, 38, 2756. (c) Eisch, J .
J .; Merkeley, J . H. J . Am. Chem Soc. 1979, 101, 1148.
These findings strongly support alcoholate 2 as the key
intermediate of the reaction. Moreover, allyl ethers do
not react with organocerium reagents, and starting
material is recovered at the end of the reaction.
On the basis of the above-reported results, the reaction
was carried out as follows and extended to various
(7) (a) Chuit, C.; Felkin, H.; Frajerman, C.; Roussi, G.; Swierczewski,
G. J . Organomet. Chem. 1977, 127, 371. (b) Hayashi, T.; Konishi, M.;
Kumada, M. J . Organomet. Chem. 1980, 186, C1. (c) Consiglio, G. B.;
Morandini, F.; Piccolo, O. Helv. Chim. Acta 1980, 63, 987. (d) Consiglio,
G. B.; Morandini, F.; Piccolo, O. J . Am. Chem Soc. 1981, 103, 1847. (e)
Felkin, H.; J oly-Goudket, M.; Davies, S. G. Tetrahedron Lett. 1981,
22, 1157. (f) Hayashi, T.; Konishi, M.; Yokota, K.-I.; Kumada, M. J .
Chem. Soc., Chem. Commun. 1981, 313. (g) Hayashi, T.; Konishi, M.;
Yokota, K.-I.; Kumada, M. J . Organomet. Chem. 1985, 285, 359.
(8) Evans, W. J .; Feldman, J . D.; Ziller, J . W. J . Am. Chem. Soc.
1996, 118, 4581.
(9) (a) Hukaji, Y.; Fujisawa, T. Tetrahedron Lett. 1988, 29, 5165.
(b) Ukaji, Y.; Yoshida, A.; Fujisawa, T. Chem. Lett. 1990, 157.
(10) The reported excesses are presumably enough to allow the
reaction to occur. Actually a further 10% of reagent is added, since
currently no methods to exactly evaluate organocerium concentration
are known.
10.1021/jo981130h CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/14/1998

9560 J . Org. Chem., Vol. 63, No. 25, 1998
Notes
Ta ble 2. Rea ction of Allyl Alcoh ola tes a n d
Or ga n ocer iu m s a t -78 °C (see m eth od B, Ta ble 1)
F ollow ed by Acid ic Qu en ch in g
P r ep a r a tion of th e Or ga n ocer iu m Rea gen t. Commercial
cerium(III) chloride heptahydrate (6 mmol) was placed in a flask
with a stirring bar. The flask was heated in vacuo in an oil bath
to 140 °C/0.2 mmHg for 2 h. Nitrogen was introduced while
the flask was still hot. The flask was cooled in an ice bath, and
dry THF was introduced from a syringe. The suspension was
stirred overnight at room temperature. The resulting white
slurry was then cooled at -78 °C, and the titrated commercial
organolithium reagent (17.5 mmol) was added dropwise from a
syringe.
reaction yield cis:trans
Rea ction of Oct-1-en -3-ol w ith Bu tylcer iu m Ch lor id e.
Meth od A. Butyllithium and anhydrous cerium trichloride
were mixed in the ratios reported in Table 1 in THF or DME,
and the mixture was allowed to stand at -78 °C for 2 h under
a nitrogen atmosphere. Then oct-1-en-3-ol was (5 mmol) added
into the organocerium reagent with stirring at -78 °C.
Meth od B. Lithium hydride (5.5 mmol) was poured into a
THF solution of allyl alcohol (5 mmol) with stirring at 0 °C under
a nitrogen atmosphere. After 1 h the mixture was syringed into
the organocerium reagent prepared as above with stirring at
-78 °C under a nitrogen atmosphere.
entry R in 2 R′ in 3 product time (h)
(%)
ratio
1
2
3
4
5
6
7
8
C5H11
C5H11
C5H11
C5H11
C5H11
C5H11
C5H11
H
Me
Bu
4a
4b
4c
4d
4e
4f
4a
4g
4h
4i
24
2
3
24
3
24
72
3
67
92
79
79
94
76
36b
70
64
70
1:3
1:3
2:3
1:2
1:3
1:5
1:3
-
s-Bu
t-Bu
C6H13
Ph
Mea
C6H13
Ph
9
10
H
Ph
18
18
-
1:1
Bu
After 2 h, the temperature was allowed to rise to -20 °C. The
mixture was then quenched with 4% HCl solution, extracted
with diethyl ether, and washed with water. The dried (Na2SO4)
extracts were concentrated under reduced pressure and purified
by flash chromatography on a silica gel column (light petroleum
ether (40-60 °C):diethyl ether, 9:1 as eluant). Yields of the
recovered 6-dodecene are listed in Table 1. 6-Dodecene was
recognized by comparison of its physical data with those in the
literature.11
Gen er a l P r oced u r e. Lithium hydride (5.5 mmol) was
poured into a THF solution of allyl alcohol (5 mmol) with stirring
at 0 °C under a nitrogen atmosphere. After 1 h the mixture
was syringed into the organocerium reagent (prepared from 5.5
mmol of cerium trichloride and 16.5 mmol of alkyllithium) with
stirring at -78 °C under a nitrogen atmosphere. During the
reaction time (Table 2), the temperature was allowed to rise to
-20 °C. The mixture was then quenched with 4% HCl solution,
extracted with diethyl ether, and washed with water. The dried
(Na2SO4) extracts were concentrated under reduced pressure and
purified by flash chromatography on a silica gel column (light
petroleum ether (40-60 °C):diethyl ether, 9:1 as eluant). Yields
of the recovered products are listed in Table 2. All compounds
were fully characterized by NMR, IR, and mass spectra. 2,2-
Dimethyl-4-decene (4d ),12 6-tetradecene (4e),13 1-phenyl-2-octene
(4f),14 and 1-phenyl-1-heptene (4i)15 had physical data identical
to that reported in the literature. 3-Nonene (4a ), 1-nonene (4g),
and allylbenzene (4h ) were recognized by comparison with
commercial samples (Aldrich).
a
b
Grignard reagent used instead of organolithium. 63% start-
ing material recovered.
lithium derivatives and alcohols. The allyllithium alco-
holate 2 was preformed from equimolecular amounts of
alcohol and lithium hydride at 0 °C. The organocerium
reagent 3 was prepared from a 3-fold excess of lithium
reagent with respect to “anhydrous” cerium trichloride
(1.2 equiv per equiv of allyl alcohol) at -78 °C. Then 2
was added to 3. During the reaction time, the temper-
ature was allowed to rise to -20 °C, the mixture was
quenched with 4% aqueous HCl, and usual workup
afforded the corresponding olefin 4. The reaction always
occurs in very good yields (Table 2): long, secondary, and
tertiary alkyl chains and aromatic groups can be intro-
duced under mild conditions, with very good regioselec-
tivity at the farthest carbon atom in contrast to simple
alkyllithiums.3-7
The low stereoselectivity of the reaction leads to the
more stable E-olefin only with a slight excess. When the
cerium reagent is prepared from cerium trichloride and
4 mol equiv of a Grignard reagent instead of alkyllithium,
the reaction proceeds more slowly and less efficiently
(Table 2, entry 7).
In conclusion a mild general method to add organo-
metallic reagents to the double bond of allyl alcohols is
now available. This methodology overcomes most of the
drawbacks of the previously reported reactions3-7 such
as long reaction times, high temperatures, and simple
reduction of the double bond via hydride transfer from
the reagent. Studies are in progress to understand the
influence on the addition of substituents on the double
bond and the mechanistic pathway followed.
3-Methyl-5-undecene (4c): cis:trans mixture. 1H NMR (CDCl3)
δ 0.75-0.95 (m, 9H); 1.20-1.50 (m, 9H); 1.70-1.90 (m, 4H, cis-
isomer); 1.90-2.05 (m, 4H, trans-isomer); 5.30-5.40 (m, 2H).
Relevant 13C NMR (CDCl3)
δ 128.42 (CHd cis), 128.79
(CHdtrans), 130.60 (CHd cis), 131.57 (CHd trans). MS m/z 168
(M+), 139, 112, 97, 83, 70 (100), 69, 57, 55, 41. Anal. Calcd for
C
12H24 (168.32): C, 85.63; H, 14.37. Found: C, 85.60; H, 14.40.
J O981130H
(11) Hamatami, T.; Matsubara, S.; Matsuda, H.; Schlosser, M.
Tetrahedron 1988, 44, 2875.
Exp er im en ta l Section
(12) Lehmkuhl, H.; Olbrysch, O.; Reinehr, D.; Schomburg, G.;
Henneberg, D. J ustus Liebig Ann. Chem. 1975, 145.
(13) Barret, A. G. M.; Hill, J . M. Tetrahedron Lett. 1991, 32, 3285.
(14) Yamane, T.; Kikukawa, K.; Takagi, M.; Matsuda, T. Tetrahe-
dron 1973, 29, 955.
THF was dried by refluxing over sodium wire until the blue
color of benzophenone ketyl persisted and then distilling into a
dry receiver under nitrogen atmosphere. DME was dried by
refluxing over sodium wires and then over lithium aluminum
hydride.
(15) Chan, T. H.; Chang, E. J . Org. Chem. 1974, 39, 3264.