reaction is determined in this case by the stereoselectivity of the
condensation step, usually not too high in reactions of
phosphonate-stabilised carbanions. For the reaction involving
were recorded on a Bruker AC 300 spectrometer in CDCl , and
3
the chemical shift values (δ) are given in ppm relative to the
7
1
13
31
solvent ( H, δ 7.24; C, δ 77.0). P NMR chemical shifts are
the bisphosphonate carbanion (Scheme 2), on the other hand,
the C᎐C bond making step results in a racemic adduct, for
which two pairs of enantiomeric conformers are possible for the
olefination step to occur (Scheme 3). Since the (R)-X /(S)-X (S)
given relative to 85% H PO as external standard. For struc-
3
4
1
1
13
tural assignments both H-decoupled and H-coupled
C
NMR spectra were recorded. J values are given in Hz.
Diethyl trichloromethylphosphonate 1 was prepared accord-
2
1
8
ing to the literature procedure.
P
P
Li
Cl
General procedure for the preparation of diethyl á-chlorovinyl-
phosphonates 3
A solution of 1 (5.10 g, 0.020 mol) in dry diethyl ether (60 cm )
2
a
3
was cooled to Ϫ78 ЊC and a solution of butyllithium (1.6 mol
RCHO
Ϫ3
3
dm solution in hexane, 13.8 cm , 0.022 mol) was added drop-
wise with stirring. The solution was stirred at Ϫ78 ЊC for 30 min
and a solution of an aldehyde (1.1 equiv.) in diethyl ether (20
H
H
R
R
R
O–
P
R
O–
H
P
O–
P
H
O–
P
Cl
P
Cl
P
3
cm ) was added dropwise at the same temperature. After stir-
Cl
Cl
P
P
ring at Ϫ78 ЊC for 1 h, the mixture was allowed to warm to
room temp. and was stirred for another 20 h. Saturated aqueous
(R)-X1
(R)-X2
(S)-X2
(S)-X1
3
NH Cl (30 cm ) was added, the aqueous layer was extracted
4
3
with dichloromethane (3 × 25 cm ), and the combined organic
solution was dried (MgSO ) and evaporated under reduced
4
P
P
R
H
H
R
pressure. Crude products were purified by column chroma-
tography followed in some cases by bulb-to-bulb distillation or
crystallisation.
Cl
Cl
(Z)-3
(E)-3
Preparation of chlorodiethylphosphonomethylenecycloalkanes 5
The reactions were peformed in the same way as described for
the preparation of product 3.
P
= P(O)(OEt)2
Scheme 3
Chlorodiethylphosphonomethylenecyclopentane 5a
pair involves syn-periplanar (eclipsed) orientation of two pairs
Purified by bulb-to-bulb distillation, oven temp. 85–90 ЊC at
of ‘small’/‘large’ substituents (H/PO Et , Cl/R), those con-
3
2
17
ϩ
0
5
1
7
.15 mmHg. Yield 91%; n 1.4840; m/z 252, 254 (M , 15,
D
ϩ ϩ
formers should be favoured relative to the (R)-X /(S)-X pair
1
2
%), 224, 226 (M Ϫ C H , 14, 5%), 196, 198 (M Ϫ 2C H ,
2
4
2
4
which contains unfavourable ‘large’/‘large’ (R/PO Et ) non-
3
2
ϩ
3
00, 32%), 161 (M Ϫ 2C H Ϫ Cl, 28%); δ 1.32 (6 H, t, J
2
4
H
H H
bonded interactions. In consequence, the stereoselectivity of the
olefination is in our case a function of the conformational equi-
librium of the adduct and, as Table 1 shows, can lead (with a
proper choice of the solvent) to the formation of the alkene
product resulting from a single conformation of the precursor.
The reaction described in Scheme 2 can also be applied to
ketones, but its outcome depends on the structure of the sub-
strate. While cyclopentanone and cyclohexanone reacted
smoothly yielding the corresponding alkenes 5 (Scheme 4),
.1, 2 × Me of POEt), 1.64–1.77 (4 H, m, 3-H , 4-H ), 2.51–
2
2
2
.53 (2 H, m, 2-CH ), 2.73–2.75 (2 H, m, 5-CH ), 4.06 (4 H, dq,
2 2
3
3
JH H 7.1, J 14.3, 2 × CH of POEt); δ 15.8 (d, J 6.5), 24.7
H P
2
C
(s), 27.4 (s), 33.6 (s), 35.5 (d, J 11.9), 62.1 (d, J 5.1), 111.1 (d, J
2
18.6), 164.7 (d, J 18.7); δ 10.06.
P
Chlorodiethylphosphonomethylenecyclohexane 5b
Purified by bulb-to-bulb distillation, oven temp. 95–100 ЊC at
1
7
ϩ
0
2
.15 mmHg. Yield 93%; n 1.4868; m/z 266, 268 (M , 77,
D
ϩ ϩ
5%), 238, 240 (M Ϫ C H , 44, 15%), 210, 212 (M Ϫ 2C H ,
2
4
2
3
4
(
CH2)n PO3Et2
ϩ
i, ii, iii
100, 34%), 175 (M Ϫ 2C
2
H
4
Ϫ Cl, 23%); δ 1.31 (6 H, t, JH H
H
1
7
2
.1, 2 × Me of POEt), 1.53–1.66 (6 H, m, 3-H , 4-H , 5-H ),
2 2 2
Cl
.47–2.52 (2 H, m, 2-CH ), 2.79–2.83 (2 H, m, 6-H ), 4.06 (4 H,
2
2
3
3
5
a n = 1
b n = 2
dq, J
7.1, J 14.3, 2 × CH of POEt); δ 15.8 (d, J 7.3),
H H
H P
2
C
2
5.7 (s), 27.2 (s), 27.9 (s), 32.0 (d, J 3.2), 32.9 (d, J 12.9);
δP 10.89.
Scheme 4 Reagents and conditions: i, BuLi, Et O, Ϫ78 ЊC;
2
(CH2)n
ii,
O (n = 1,2), Ϫ78 ЊC; iii, NH Cl, room temp.
4
Acknowledgements
Financial assistance from the University of Pretoria, the Foun-
dation for Research Development and the Polish Academy of
Sciences is gratefully acknowledged.
reaction with acetophenone led to the isolation of the inter-
mediate 2 in 90% yield. Similarly, for cyclohex-2-enone, no
product resulting either from the 1,2, or 1,4-addition could be
detected. Further studies on the scope and limitations of the
reactions utilising 1 and carbonyl compounds as starting
materials are currently in progress.
References
1
D. Seyferth and R. S. Manor, J. Organomet. Chem., 1973, 59, 237;
P. Coutrot, C. Laurence, J. F. Normant, P. Perriot, P. Savignac and
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Normant, Synthesis, 1978; 29, 31, 33; F. Karrenbrock, H. J. Schäfer
and I. Langer, Tetrahdron Lett., 1979, 2915; D. Villemin, F. Sauvaget
and M. Hajek, Tetrahedron Lett. 1994, 35, 3537; S. Berté-Verrando,
F. Nief, C. Patois and P. Savignac, J. Chem. Soc., Perkin Trans. 1,
Experimental
Solvents and commercially available substrates were purified by
conventional methods. All condensation reactions were per-
formed under dry nitrogen. Merck Kieselgel 60 (0.063–0.200)
was used for column chromatography. Mass spectra were
recorded on a Varian MAT-212 double-focusing direct-inlet
spectrometer at an ionisation potential of 70 eV. NMR spectra
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