Regioselective Synthesis of (E)-Alkenes from Aldehydes and Ketones
SHORT COMMUNICATION
starting materials (entry 17) were recovered. This may indi- Experimental Section
cate that a stabilized benzylic carbocation[10] is an inter-
General Method: 1H and 13C NMR spectra were recorded in CDCl3
mediate also in the Yb(OTf)3 catalysed aldol-Grob reaction.
In every reaction the corresponding carboxylic acid could
be recovered in nearly quantitative yield. For example,
pentanoic acid was obtained in 93% yield when 5-nonanone
was condensed with benzaldehyde. The ketone symmetry
does not affect the selectivity and yields of the process; in
fact, the same alkene was obtained when using 5-nonanone
or 2-hexanone as starting ketones, suggesting that
Yb(OTf)3 favours the formation of the more alkylated
thermodynamically stable enolate and its subsequent ad-
dition to the aldehyde.
solution on a Bruker AC 200 spectrometer operating at 200.1 and
50.53 MHz, respectively, in the Fourier transform mode. GC analy-
ses and MS spectra were carried out with an HP 5890 gas chroma-
tograph (dimethyl silicone column 12.5 m) equipped with an HP
5971 Mass Selective Detector. Flash column chromatography was
performed on 0.040Ϫ0.063 mm (230Ϫ400 mesh ASTM) Merck sil-
ica gel. Elemental analysis was performed on a Carlo Erba Model
1106 elemental analyzer. All aldehydes and ketones, and Yb(OTf)3
were purchased from Aldrich Chemical Co. and used without any
purification.
General Procedure: Yb(OTf)3 (0.1 mmol) was added to a mixture
of aldehyde (1.0 mmol) and ketone (1.0 mmol) and stirring was
continued at 60 °C for 8 h. CH2Cl2 (2 mL) was added at room
temperature, the precipitated solid was collected and the filtrate
was diluted with CH2Cl2 (20 mL) and washed twice with a 5% solu-
The best results were obtained using 0.1 equivalents of
Yb(OTf)3 hydrate. Higher loadings did not improve reac-
tion times and yields and, moreover, the minimal quantity
of catalyst employed in our process greatly disfavours the
formation of styrenyl polymerisation by-products, deriving tion of NaHCO3 (10 mL), dried over Na2SO4 and the solvents eva-
porated. The residue was purified by silica gel column chromatog-
raphy, using n-hexane as eluent, to give the desired product. 1H
NMR, 13C NMR and GC/MS data of compounds 1, 2, 4, 5, 7, 8, 9,
10 and 12 were in full agreement with those reported previously.[10d]
directly from the olefinic reaction products. It’s also import-
ant to note that the addition of a few millilitres of CH2Cl2
to the reaction medium precipitated the catalyst allowing
its simple recovery by filtration; the catalyst could therefore
be recycled and used several times without appreciable loss
of activity. The reaction to give alkene 1 was in fact re-
peated three times, washing the catalyst with CH2Cl2 and
drying it at 70 °C for two hours after each run, with the
following yields: 83%, 81% and 81%. Therefore the con-
comitant formation of a carboxylic acid as a reaction prod-
uct, capable of rendering Yb(OTf)3 ineffective as an aldol-
Grob catalyst (by chelation), does not significantly affect its
catalytic activity.
The absence of solvents seems to be crucial in driving the
process to yield the aldol-Grob adduct, while the presence
of solvents like THF, alcohols or water leads to the forma-
tion of only aldol condensation products (α,β-unsaturated
ketones) and the use of dichloromethane, n-hexane or tolu-
ene greatly decreases the catalytic activity of Yb(OTf)3;
starting materials were recovered in almost quantitative
yield.
(E)-1-phenyl-1-pentene (1): Yield: 130 mg (89%) (entry 1, Table 1).
Yield: 120 mg (82%) (entry 13).
(E)-1-(4-methylphenyl)-1-pentene (2): Yield: 145 mg (91%) (entry 2).
Yield: 130 mg (81%) (entry 2).
(E)-1-(4-fluorophenyl)-1-pentene (3): Yield: 140 mg (85%) (entry 3).
Yield: 135 mg (81%) (entry 18). Colourless oil. 1H NMR: δ ϭ 0.98
(t, J ϭ 7.1 Hz, 3 H), 1.52Ϫ1.74 (m, 2 H), 2.15Ϫ2.27 (m, 2 H),
6.11Ϫ6.23 (m, 1 H), 6.48 (d, J ϭ 12.0 Hz, 1 H), 7.08Ϫ7.48 (m, 4
H) ppm. 13C NMR: δ ϭ 13.7, 22.5, 36.1, 115.0, 127.2, 127.3, 128.7,
130.6, 134.1, 152.5 ppm. MS (EI): m/z (%) ϭ 164 (33), 135 (100),
122 (27), 115 (25), 109 (27). C11H13F (164.2): calcd. C 80.45, H
7.98; found C 80.47, H 7.96.
(E)-1-(4-chlorophenyl)-1-pentene (4): Yield: 150 mg (83%) (entry 4).
Yield: 140 mg (83%) (entry 19).
(E)-1-(4-bromophenyl)-1-pentene (5): Yield: 160 mg (71%).
(E)-1-(4-phenylphenyl)-1-pentene (6): Yield: 170 mg (77%). colour-
1
less oil. H NMR: δ ϭ 1.02 (t, J ϭ 7.0 Hz, 3 H), 1.51Ϫ1.82 (m, 2
H), 2.22Ϫ2.34 (m, 2 H), 6.27Ϫ6.35 (m, 1 H), 6.49 (d, J ϭ 12.5 Hz,
1 H), 7.32Ϫ7.74 (m, 9 H) ppm. 13C NMR: δ ϭ 13.8, 22.6, 35.2,
126.3, 126.9, 127.1, 127.2, 128.8, 129.3, 131.2, 137.0, 139.5,
140.9 ppm. MS (EI): m/z (%) ϭ 222 (84), 193 (100), 178 (93), 165
(36), 152 (16), 115 (16). C17H18 (222.3): calcd. C 91.84, H 8.16;
Conclusions
In this paper we have shown that Yb(OTf)3 hydrate is an
effective catalyst in promoting the reaction between ketones found C 91.85, H 8.15.
and aromatic aldehydes, affording only (E)-alkenes. The
(E)-1-(4-nitrophenyl)-1-pentene (7): Yield: 30 mg (15%).
main difference in our methodology compared to BF3-cata-
lysed reactions is the Lewis acid/substrate ratio, the optimal
value of which was found to be 0.1:1; in the other cases a
1:1 ratio or even an excess of Lewis acid is needed to effec-
tively promote the coupling reaction. Furthermore, product
yields, easy workup procedure, absence of solvent, simple
recovery, very high recyclability and easy handling of the
catalyst are other important features of our methodology.
Finally, the different reactivity of methylene- and methyl-
derived enolates could allow the use of readily available
methyl ketones.
(E)-1-(4-methoxyphenyl)-1-pentene (8): Yield: 20 mg (11%).
(E)-1-(3-chlorophenyl)-1-pentene (9): Yield: 125 mg (70%).
(E)-1-(3-nitrophenyl)-1-pentene (10): Yield: 10 mg (5%).
(E)-1-(2-methylphenyl)-1-pentene (11): Yield: 130 mg (81%).
Colourless oil. 1H NMR: δ ϭ 1.08 (t, J ϭ 7.0 Hz, 3 H), 1.51Ϫ1.68
(m, 2 H), 2.17Ϫ2.32 (m, 2 H), 2.42 (s, 3 H), 6.07Ϫ6.19 (m, 1 H),
6.68 (d, J ϭ 12.3 Hz, 1 H), 7.25 (m, 3 H), 7.12Ϫ7.54 (m, 1 H) ppm.
13C NMR: δ ϭ 13.8, 19.8, 22.6, 35.4, 125.5, 126.0, 126.8, 127.8,
130.2, 132.4, 134.9, 137.1 ppm. MS (EI): m/z (%) ϭ 160 (46), 131
Eur. J. Org. Chem. 2003, 1631Ϫ1634
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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