Addition of organocerium reagents to homoallyl alcohols

Article abstract of DOI:10.1016/S0040-4039(01)01917-7

Alkylcerium reagents and hydride ions add to multiple bonds of homoallyl alcohols under mild conditions, leading to saturated alcohols in good yields.

Full text of DOI:10.1016/S0040-4039(01)01917-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8833–8835
Addition of organocerium reagents to homoallyl alcohols
Giuseppe Bartoli,a Renato Dalpozzo,b,* Antonio De Nino,b Antonio Procopio,b Letizia Sambria and
Antonio Tagarellib
aDipartimento di Chimica Organica ‘A. Mangini’, Universita` di Bologna, viale Risorgimento 4, I-40136 Bologna, Italy
bDipartimento di Chimica, Universita` della Calabria, ponte Bucci, I-87030 Arcavacata di Rende (Cs), Italy
Received 12 October 2001
Abstract—Alkylcerium reagents and hydride ions add to multiple bonds of homoallyl alcohols under mild conditions, leading to
saturated alcohols in good yields. © 2001 Elsevier Science Ltd. All rights reserved.
We were recently interested in the reaction of allyl
alcohols with organocerium regents:1,2 inexpensive,
non-toxic and non-basic organometallic reagents intro-
duced about 20 years ago.3–6
homoallyl alcohols (the reaction of allyl Grignard
reagent with 1,1-diphenyl-3-buten-1-ol,12 3-cyclopenten-
1-ol and 3-cyclohexen-1-ol,13 the titanium-mediated
addition of alanes or organolithiums,14 and, more
recently, the zirconium-catalyzed carbomagnesation)15
always give low yields and conspicuous amounts of
regioisomers, stereoisomers and elimination product
mixtures.
Addition of organometallic reagents to a double bond
always represented an unreachable target for organic
chemists, since carbonꢀcarbon double bonds are gener-
ally inert toward nucleophilic attack. Few reactants and
substrates are reported to give fair yields in extreme
reaction conditions and most examples are restricted to
allyl alcohols.7–11 Much more rare reactions involving
Organocerium reagents promise to be more widely
applicable and efficient than previous reported proce-
dures as in the case of homoallyl alcohols.
Table 1. Reactions of homoallyl alcohols with organocerium reagents
1) LiH
2) R4Li/CeCl3 (2)
OH
R2
3) HCl dil
OH
R2
R3
R4
R3
R1
R1
1
3
Entry
Product
R1
R2
R3
Reagent
R4
Reaction time (h)
Yield (%)
1
2
3
4
5
6
7
1a
1a
1a
1a
1b
1c
1d
H
H
H
H
Et
H
H
Ph
Ph
Ph
Ph
Ph
Ph
Pr
H
H
H
H
H
Ph
Ph
2a
2b
2c
2d
2b
2d
2d
H
72
72
24
24
72
72
72
86
94
85
86
Me
Ph
Bu
Me
Bu
Bu
93
90a
14b,c
a 68/32 Isomer ratio.
b 66/34 Isomer ratio.
c Together with 47% yield of 1-phenyl-1,3-heptadiene.
Keywords: cerium reagents; unsaturated alcohols; alkylation reactions.
* Corresponding author. Tel./fax: 390984492055; e-mail: dalpozzo@unical.it
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01917-7

8834
G. Bartoli et al. / Tetrahedron Letters 42 (2001) 8833–8835
Addition of organocerium reagents to homoallyl alco-
hols was carried out under the same reaction conditions
previously set up for allyl alcohols.2
double bond terminus farthest from the alcohol func-
tion. Spectroscopic and chemical evidences support this
unexpected finding. The product arising from the reac-
tion of 1,4-diphenyl-3-buten-1-ol (1c) and butylcerium
(2d) shows a peak at 2.81 in the 1H spectrum, the
As shown in Table 1, these conditions can be efficiently
extended to the present reaction, but reaction times are
considerably longer than with allyl alcohols.
integration of which accounts for a benzylic proton. 13
C
NMR spectrum confirms this assignment: the signal at
31.6 ppm accounts for a benzylic CH as demonstrated
by a DEPT experiment. Moreover, we found2 that
addition of iodine should result in decomposition to
alkene and aldehyde according to the pathway depicted
in Scheme 1. The reaction of 1c and 2d was treated with
iodine‡ and the product distribution confirms that the
alkyl framework is bound to the double-bond terminus
farthest from the alcohol function.
The combination of both organolithiums and lithium
aluminium hydride with cerium chloride works very
well. Products are obtained in good or satisfactory
yields and chromatographic separation of the product
was often unnecessary.†
Conversely from allyl alcohols, where addition depends
on substituents on the double bond,1 the alkyl frame-
work of the organocerium reagent always binds to the
The most remarkable drawback of this reaction is
elimination to alkene in the presence of substituents
enhancing allylic proton acidity. In fact, allowing 1,2-
diphenyl-3-buten-1-ol (1e) to react both with methyl-
cerium (2b) and 2d, the exclusive formation of
1,2-diphenyl-1,3-butadiene was observed.¶ Despite the
declared non-basicity of cerium reagents (at least for a
1/1 ratio between cerium chloride and organolithium),2
we observed that the elimination prevailing over addi-
tion was very likely caused by the low tendency of
double bond to undergo nucleophilic attack and by the
simultaneous presence of allylic and benzylic protons.
Moreover, 1-phenyl-1,3-heptadiene is exclusively recov-
ered in the reaction of 2b with 1-phenyl-1-hepten-4-ol
(1d), while reaction of 1d with 2d led to a mixture of
addition and elimination products (Table 1, entry 7),
probably due to a higher basicity of the methyl complex
with respect to the butyl one. Finally, from reaction of
1c and 2d the expected addition product was recovered
in very high yield (Table 1, entry 6), very likely because
phenyl group is less encumbering that an alkyl chain.
OLi
Li
1) LiH
2) BuLi/CeCl3
OH
Ph
Bu
Ph
Ph
Ph
I2
I
Li
O
Ph
+ PhCHO
Ph
Bu
Ph
Bu
Scheme 1.
† General procedure: Cerium(III) chloride was dried according to the
classical procedure.6 The resulting white THF slurry was then
cooled to −78°C and the titrated organolithium reagent (16.5 mmol)
was added dropwise from a syringe [or lithium aluminium hydride
(7.5 mmol) was poured in] and the mixture allowed to stir for 2 h.
Lithium hydride (5.5 mmol) was poured into a THF solution of
homoallyl alcohol la–e (5 mmol) with stirring at 0°C under a
nitrogen atmosphere. After 1.5 h the mixture was syringed into the
organocerium reagent with stirring at −78°C under a nitrogen
atmosphere. The reaction was allowed to stand in a freezer for the
requested time (Table 1) before quenching with 4% HCl solution,
extraction with diethyl ether, and washing with water. The dried
(Na2SO4) extracts were concentrated under reduced pressure and
characterized without further purification except for reaction of
entry 7 in Table 1, which was purified by flash chromatography on
a silica gel column [light petroleum (40–60°C)/diethyl ether, 7:3 as
eluant]. Yields of the recovered products are listed in Table 1. All
compounds gave satisfactory microanalyses and were fully charac-
terised by NMR, and mass spectroscopy. 1-Phenyl-1-pentanol,16
3-phenyl-3-heptanol,17 1-phenyl-1,3-heptadiene,18 1,2-diphenyl-1,3-
butadiene,19 1-phenyl-1-octanol,20 1-phenyl-1-butanol,21 1,4-
diphenyl-1-butanol22 gave physical data identical to those reported
in the literature. 1,4-Diphenyl-1-octanol (68/32 mixture of
diastereomers, determined by GC): oil. lH 0.73 (t, 3H, CH3, J=
6.45), 0.85–1.30 (m, 8H), 1.55–1.90 (m, 2H), 2.00 (brs, 1H, OH),
2.81 6.80–7.30 (m, 10H, Ar); m/z (%): (major isomer) 264 (M+−18,
1), 176 (73), 133 (7), 107 (100), 92 (55), 91 (77), 79 (39), 77 (28).
(Minor isomer) 281 (M+−1, 1), 264 (1), 176 (60), 133 (6), 107 (100),
92 (53), 91 (76), 79 (42), 77 (28). 7-Phenyl-4-undecanol: (66/34
mixture of diastereomers, determined by GC): oil. lH 0.60–0.95 (m,
6H, 2CH3), 1.00–1.50 (m, 12H), 1.55–1.95 (m, 2H), 2.57 (tt, 1H,
J1=6.21, J2=3.63), 3.55–3.75 (m, 1H, CHOH), 7.10–7.40 (m, 5H,
ArH); m/z (%): (major isomer) 230 (M+−18, 7), 173 (10), 160 (100),
117 (48), 104 (77), 91 (68). (Minor isomer) 230 (M+−18, 39), 173
(59), 160 (19), 117 (53), 104 (30), 91 (100).
In conclusion, the addition of organoceriums to
homoallyl alcohols appears to be a valid improvement
in the field of nucleophilic addition to functionalized
double bonds. In fact, this reaction employs easily
available starting materials and mild experimental con-
ditions. However, a question arises from this reaction:
are organoceriums completely nucleophilic and non-
basic reagents? The answer seems to be ‘no’, when
nucleophilic attack is very fast, it largely prevails over
proton abstraction, but in stressing the reaction condi-
tions also cerium reagents can act as a base.
‡ When formation of 1,4-diphenyl-1-octanol was detected by GC/MS,
a THF solution of iodine (16 mmol) was added. The reaction was
allowed to stand in freezer overnight and then treated with HCl
(4%) and extracted with ether. The organic layer was washed with
a NaHSO3 solution and water, dried (Na2SO4). GC/MS analysis
showed benzaldehyde and 3-phenyl-1-heptene [m/z=174 (M+), 117
(base), 104, 91].
¶ Elimination does not take place before addition of organocerium
reagent. In fact 1c–e are quantitatively recovered after allowing
them to react for 24 h with lithium hydride, instead of the 1.5 h
generally used for the preparation of the lithium alcoholate.

G. Bartoli et al. / Tetrahedron Letters 42 (2001) 8833–8835
8835
Acknowledgements
8. Felkin, H.; Swierczewski, G.; Tambute`, A. Tetrahedron
Lett. 1969, 00, 707–710.
9. Crandall, J. K.; Clark, A. C. J. Org. Chem. 1972, 37,
4236–4242.
10. Dimmel, D. R.; Huang, S. J. Org. Chem. 1973, 38,
2756–2759.
A.T. thanks the Italian Ministero dell’Universita` e della
Ricerca Scientifica e Tecnologica (MURST) for his
educational grant.
11. Richey, Jr., H. G.; Wilkins, Jr., C. W. J. Org. Chem.
1980, 45, 5027–5047.
12. Eisch, J. J.; Merkeley, J. H. J. Am. Chem. Soc. 1979, 101,
1148–1155.
13. Eisch, J. J.; Merkeley, J. H.; Galle, J. E. J. Org. Chem.
1978, 44, 587–593.
14. Moret, E.; Schlosser, M. Tetrahedron Lett. 1985, 26,
4423–4426.
References
1. Bartoli, G.; Bellucci, M. C.; Bosco, M.; De Nino, A.;
Sambri, L.; Tagarelli, A. Eur. J. Org. Chem. 2000, 99–
104.
15. Hoveyda, A. H.; Xu, Z.; Morken, J. P.; Houri, A. F. J.
Am. Chem. Soc. 1991, 113, 8950–8952.
16. Arvidsson, P. I.; Davidsson, O.; Hilmersson, G. Tetra-
2. Dalpozzo, R.; De Nino, A.; Tagarelli, A.; Bartoli, G.;
Bellucci, M. C.; Bosco, M.; Sambri, L. J. Org. Chem.
1998, 63, 9559–9560.
hedron: Asymmetry 1999, 10, 527–534.
3. Dalpozzo, R.; De Nino, A.; Bartoli, G.; Sambri, L.;
Marcantoni, E. Recent Res. Devel. Org. Chem. 2001, 5,
181–191.
4. Liu, H. J.; Shia, K. S.; Shjang, X.; Zhu, B. Y. Tetra-
hedron 1999, 55, 3803–3830.
5. Imamoto, T. In Lanthanides in Organic Synthesis; Aca-
demic Press: New York, 1994; section 5.4.
6. Imamoto T. In Comprehensive Organic Synthesis; Trost,
B. M.; Fleming, I.; Schreiber, S. L., Eds.; Pergamon:
London, 1991; Vol. 1, Chapter 1.8.
7. Che`rest, M.; Felkin, H.; Frajerman, C.; Lion, C.; Roussi,
G.; Swierczewski, G. Tetrahedron Lett. 1966, 875–879.
17. Ramon, D. J.; Yus, M. Tetrahedron 1998, 54, 5651–5666.
18. Masuyama, Y.; Maekawa, K.; Kurihara, T.; Kurusu, Y.
Bull. Chem. Soc. Jpn. 1991, 64, 2311–2313.
19. Wang, K. K.; Liu, C.; Gu, Y. G.; Burnett, F. N. J. Org.
Chem. 1991, 56, 1914–1922.
20. Lie, K.; Jie, M. S. F.; Lam, W. L. K.; Lao, H. B. J.
Chem. Soc., Perkin Trans. 1 1989, 1–11.
21. Fleming, I.; Higgins, D.; Lawrence, N. J.; Thomas, A. P.
J. Chem. Soc., Perkin Trans. 1 1992, 3331–3349.
22. Groenwold, G. S.; Ches, E. K.; Gross, M. L. J. Am.
Chem. Soc. 1984, 106, 539–543.