28
LETTERS
SYNLETT
In conclusion, the synthesis of simple alkenes using the one-pot Julia
olefination is both more efficient and more stereoselective using
phenyltetrazolyl sulfones as coupling partners. We have shown that
yield and stereoselectivity of the reaction can be optimised by varying
the solvent and base with sodium or potassium hexamethyldisilazide in
DME being generally the most effective. Furthermore, the enhanced
stability of the PT sulfone anions allows the metallation step to take
place prior to the addition of the aldehyde component thereby extending
the scope of the reaction to base-sensitive substrates. We predict that the
one-pot variant of the Julia olefination will become one of the premiere
fragment linkage reactions in the construction of functionally complex
targets and no doubt further enhancements in stereoselectivity and
efficiency will be discovered in due course.
2.40-2.24 (1H, m), 1.60-1.20 (8H, m), 1.15 (3H, d, J 6.8), 0.88 (3H, t, J
6.6); δ (67.5 MHz, CDCl ) 154.2 (C), 133.2 (C), 131.5 (CH), 129.8
C
3
(CH), 125.3 (CH), 62.0 (CH ), 36.6 (CH ), 31.7 (CH ), 28.4 (CH), 26.1
2
2
2
(CH ), 22.6 (CH ), 19.8 (CH ), 14.1 (CH ).
2
2
3
3
5.
Stock solutions of lithium hexamethyldisilazide (LiHMDS, 0.45
M in hexanes), NaHMDS (0.54 M in toluene) and KHMDS (0.44 M in
toluene) were dispensed.
6.
The isomer ratio of alkene 8 was determined by GC analysis using
a DB-225 fused silica capillary column (50% cyanopropylphenyl
silicone, 30 m x 0.32 mm x 0.25 µm) at 50 → 90°C; helium carrier gas
–1
–1
1.5 ml min ; make-up gas 25 ml min ; split ratio 300:1. The isomer
ratio of alkenes 9, 12 and 13 was determined with an SGE HT5 capillary
column (5% phenyl equivalent polysiloxane-carborane, 12 m x 0.22 mm
Notes
–1
–1
x 0.1 µm); helium carrier gas 1.4 ml min ; make-up gas 25 ml min
;
1.
The one-pot olefination of Sylvestre Julia is operationally simpler
split ratio 75:1. A flame ionisation detector (FID) was used throughout.
The identity of each alkene isomer was verified by GC-MS.
and more amenable to scaleup than the classical 3/4-step variant
originally reported by Marc Julia
7,8
.
7.
Authentic samples of the isomeric alkenes rich in the (Z)-isomer
10
2.
A recent synthesis of 1,2-disubstituted alkenes using the one-pot
were obtained via the Schlosser modification of the Wittig reaction
.
Julia olefination showed that the stereochemistry of the reaction was
9
dependent on the base and solvent .
8.
In the classical Julia olefination based on the reductive elimination
of β-acyloxy sulfones, chain branching dramatically improves the
11,12
3.
All of the other heterocycles examined gave the desired alkene
stereoselectivity of the reaction
.
products but the yields and/or stereoselectivity were generally inferior
to the benzothiazolyl system.
Acknowledgements. We thank the EPSRC and Rhône-Poulenc Rorer
for a CASE studentship (PRB).
4.
The BT sulfones 6 and 10 and the PT sulfones 7 and 11 were
prepared from the commercially available (Aldrich) benzothiazole-2-
thiol and 1-phenyl-1H-tetrazole-5-thiol (14) as illustrated in the
following example:
References
(1) Baudin, J. B.; Hareau, G.; Julia, S. A.; Ruel, O. Tetrahedron Lett.
1991, 32, 1175.
(2) Baudin, J. B.; Hareau, G.; Julia, S. A.; Ruel, O. Bull. Soc. Chim.
Fr. 1993, 130, 336.
(3) Baudin, J. B.; Hareau, G.; Julia, S. A.; Lorne, R.; Ruel, O. Bull.
Soc. Chim. Fr. 1993, 130, 856.
(4) Smith, N. D.; Kocie ski, P. J.; Street, S. D. A. Synthesis 1996,
652.
6 δ (200 MHz, CDCl ) 8.21 (1H, dm, J 8.0), 8.02 (1H, dm, J 7.0),
(5) Bellingham, R.; Jarowicki, K.; Kocie ski, P.; Martin, V. Synthesis
1996, 285.
H
3
7.69-7.53 (2H, m), 3.54-3.45 (2H, m), 1.97-1.79 (2H, m), 1.50-1.22
(4H, m), 0.86 (3H, t, J 7.0); δ (50 MHz, CDCl ) 165.9 (C), 152.8 (C),
C
3
(6) Campbell, J. B.; Molander, G. A. J. Organomet. Chem. 1978, 156,
136.8 (C), 128.1 (CH), 127.7 (CH), 125.5 (CH), 122.5 (CH) 54.8 (CH ),
2
71.
30.3 (CH ), 22.1 (CH ), 22.0 (CH ) 13.8 (CH ). 7 δ (200 MHz,
2
2
2 ,
3
H
(7) Julia, M.; Paris, J.-M. Tetrahedron Lett. 1973, 4833.
CDCl ) 7.75-7.54 (5H, m), 3.78-3.68 (2H, m), 2.02-1.87 (2H, m), 1.57-
3
(8) Kocienski, P. In Comprehensive Organic Synthesis; B. M. Trost
1.32 (4H, m), 0.92 (3H, t, J 7.0); δ (50 MHz, CDCl ) 153.6 (C), 133.2
C
3
and I. Fleming, Ed.; Pergamon: Oxford, 1991; Vol. 6; pp 975.
(C), 131.6 (CH), 129.8 (CH), 125.2 (CH), 56.1 (CH ), 30.3 (CH ), 22.2
2
2
(9) Charette, A. B.; Lebel, H. J. Am. Chem. Soc. 1996, 118, 10327.
(CH ), 21.8 (CH ), 13.8 (CH ). 10 δ (270 MHz, CDCl ) 8.18 (1H, dm,
2
2
3
H
3
J 7.5), 7.99 (1H, dm, J 7.3), 7.62 (1H, t, J 6.4), 7.56 (1H, t, J 7.3), 3.55
(1H, dd, J 14.3, 4.6), 3.33 (1H, dd, J 14.3, 7.9), 2.40-2.15 (1H, m), 1.55-
(10) Schlosser, M.; Schaub, B.; de Oliveira-Neto, J.; Jeganathan, S.
Chimia 1986, 40, 244.
1.10 (8H, m), 1.12 (3H, d, J. 6.8), 0.81 (3H, d, J 6.8); δ (67.5 MHz,
C
(11) Kocie ski, P.; Lythgoe, B.; Ruston, S. R. J. Chem. Soc., Perkin
Trans. 1 1978, 829.
CDCl ) 166.8 (C), 152.7 (C), 136.8 (C), 128.1 (CH), 127.7 (CH), 125.4
3
(CH), 122.4 (CH), 60.8 (CH ), 36.6 (CH ), 31.6 (CH ), 28.6 (CH), 26.0
2
2
2
(12) Kocie ski, P.; Lythgoe, B.; Waterhouse, I. J. Chem. Soc., Perkin
Trans. 1 1980, 1045.
(CH ), 22.5 (CH ), 19.9 (CH ), 14.0 (CH ). 11 δ (270 MHz, CDCl )
2
2
3
3
H
3
7.70-7.54 (5H, m), 3.81 (1H, dd, J14.5, 4.6), 3.58 (1H, dd, J 14.5, 7.9),