R. Almansa et al. / 19 (2008) 1376–1380
1379
C5 of the pyrrolidine ring of the ligand was detrimental to the
enantioselectivity, giving only 48% ee (Table 3, entry 12). The latter
ee is rather lower than the one that was obtained for the same
reaction at room temperature (60%).10
washed with brine (5 mL), and then dried (Na
2
SO
4
). After filtration
and evaporation of the solvents, the crude residue was purified by
column chromatography (silica gel, hexane/acetone) to give prod-
ucts 4 in the yields and enantiomeric excesses indicated in Tables 2
and 3. Compounds 4 were characterised by comparison of their
physical and spectroscopic data with the ones reported in the liter-
Since most of the results of these microwave-heated reactions
show the same trends for the influence of the ligand substituents
on the enantioselectivity as for the reactions stirred at room tem-
perature without microwave irradiation, we assume that the same
mechanism could be operative in both cases. The acceleration of
the reactions observed could just be a result of the fast heating
caused by microwaves. This fast heating could also accelerate the
reaction between the dialkylzinc reagent and the imine without
any participation of the ligand, which could explain the small loss
of ee that was observed in most cases in comparison to the reac-
tions at room temperature.
1
0b
ature.
These products were analysed by HPLC on a ChiralCel OD-
H column using a 254 nm UV detector, 10% i-PrOH in hexane as
eluent and a flow rate of 0.5 mL/min or on a Chiralpak AD column
using a 254 nm UV detector, 20% i-PrOH in hexane as eluent and a
flow rate of 1.0 mL/min. The retention times were reported in our
1
0b
previous article.
The absolute configuration of the major enan-
9
c
tiomer of 4aa was determined by hydrolysis of it and comparison
of the sign of the specific rotation of the free amine obtained with
9
c
the reported data. The absolute configuration of the major enan-
tiomer of 4ab–ad was tentatively assigned according to the order
of elution of the two enantiomers in the HPLC analysis on the
analogy of product 4aa. For addition products 4b–d, the absolute
configuration of the major enantiomer was tentatively
assigned according to the HPLC data described in the literature
3
. Conclusions
In conclusion, we have reported that microwave irradiation is a
very efficient technique to accelerate the addition of dialkylzinc
reagents to N-(diphenylphosphinoyl)imines in the presence of
several b-aminoalcohols with the prolinol skeleton. Very fast
enantioselective addition reactions can be achieved using 0.5 equiv
of the ligand. Reaction times are very short (20–30 min) and the
expected addition products are obtained with improved yields
and with ees very similar to the ones previously observed in the
same reactions performed at room temperature without micro-
wave irradiation. This procedure is especially useful for the addi-
tion of dimethylzinc, since both yield and ee improved in the
microwave-promoted reaction and the reaction time was only
15
for similar compounds under the same conditions. The retention
times of the two enantiomers of compound 4e have already been
15
described.
Acknowledgements
This work was generously supported by the Dirección General
de Enseñanza Superior (DGES) of the current Spanish Ministerio
de Educación y Ciencia (MEC; grant nos. Consolider Ingenio
2
010/CSD2007-00006 and CTQ200765218) and the Generalitat
Valenciana (GV/2007/036). R.A. thanks the Spanish Ministerio de
Educación y Ciencia for a predoctoral fellowship. We also thank
MEDALCHEMY S.L. for a gift of chemicals.
3
0 min.
4
4
. Experimental
References
.1. General
1.
(a) Volkmann, R. A. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
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13
were prepared according to literature procedures. Commercially
2
D
0
available compound 1b {Aldrich, 99%, ½
a
ꢀ
¼ ꢁ72:2 ðneatÞ} was
used as received. The rest of the ligands 1a and 1c–l were prepared
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3.
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.
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(
1
b) Erdik, E. Organozinc Reagents in Organic Synthesis; CRC Press: Boca Raton,
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1
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4
.2. Addition of dialkylzinc reagents to imines 2 catalysed by
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3
28.
The dialkylzinc reagent (0.75 mmol) was added to a stirred
solution of imine 2 (0.25 mmol) and ligand 1 (0.13 mmol) in anhy-
drous toluene (1.3 mL) under argon at room temperature. The reac-
tion vessel was placed into the microwave reactor and was heated
to 50 °C (constant microwave irradiation at 70 W, 0.8 bar, with air
stream cooling) for 20 or 30 min (see Tables 2 and 3). The reaction
9.
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1
999, 5, 1692–1699; (g) Jimeno, C.; Reddy, K. S.; Solà, L.; Moyano, A.; Pericàs, M.
was then hydrolysed with an aqueous saturated solution of NH
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with ethyl acetate (3 ꢂ 10 mL). The combined organic layers were
4
Cl
A.; Riera, A. Org. Lett. 2000, 2, 3157–3159; (h) Pinho, P.; Andersson, P. G.
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(