4009
To meet our project needs, as anticipated, the vinyl dichlorides were easily transformed into their
corresponding terminal alkynes through elimination reactions with strong bases, such as methyllithium
or sodamide/DMSO, as summarized in Table 1. We have applied this procedure to the synthesis of our
target, cyclopropylacetylene (1, entry a in Table 1), on a 100 g scale in approximately 81% yield.
In summary, we have identified an efficient and economical conversion of aldehydes into vinyl
dihalides. It is of great practical significance that this conversion does not involve phosphorous-containing
reagents. Subsequent conversion of the vinyl dichlorides to terminal alkynes was further accomplished
smoothly and in high yields.8
Acknowledgements
We are grateful to the Chemical Process Analytical Group for their support of this work.
References
1. (a) Pierce, M. E.; Parsons, R. L.; Radesca, L. A.; Lo, Y. S.; Silverman, S.; Moore, J. R.; Islam, Q.; Choudhury, A.; Fortunak,
J. M.; Nguyen, D.; Luo, C.; Morgan, S. J.; Davis, W. P.; Confalone, P. N.; Chen, C.; Tillyer, R. D.; Frey, L.; Tan, L.; Xu, F.;
Zhao, D.; Thompson, A. S.; Corley, E. G.; Grabowski, E. J. J.; Reamer, R.; Reider, P. J. J. Org. Chem. 1998, 63, 8536. (b)
Corley, E. G.; Thompson, A. S.; Huntington, M. Org. Synth, 1999, 77, 231. (c) Schoberth, W.; Hanack, M. Synthesis 1972,
703. (d) Liang, S.; Price, T. W.; Nolen, D. B.; Attride, D. C. US Patent 5,502257, 1996; Chem. Abstr. 1996, 125, 10231. (e)
Torihara, M.; Minagawa, Y. Japan Patent Application H08-233884, 1996.
2. Fortunak, J. M.; Wang, Z.; Yin, J. Patent, WO 9906341, 1999.
3. Wang, Z.; Yin, J.; Campagna, S.; Pesti, J. A.; Fortunak, J. M. J. Org. Chem. 1999, 64, 6918.
4. Wang, Z.; Campagna, S.; Xu, G.; Yang, K.; Pierce, M. E.; Fortunak, J. M.; Confalone, P. N. J. Org. Chem. 2000, 65, 1889.
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8. Preparation of 1,1-dichloro-3-cyclopropylethene 4 is a typical example of this procedure. To a stirred solution of
trichloroacetic acid (105 g, 0.642 mol) and cyclopropylcarboxaldehyde (30 g, 0.428 mol) in DMF (300 mL) at 25°C
was added sodium trichloroacetate (119 g, 0.642 mol) in portions. The internal temperature was kept below 35°C by
addition control. After addition was completed, the mixture was stirred at room temperature for 4 h with continuous
evolution of CO2. The solution was cooled to 5°C and acetic anhydride (80.77 mL, 0.856 mol) was carefully added.
Strong CO2 evolution was observed. The mixture was allowed to warm to room temperature and stirred for an additional
hour. The reaction mixture was diluted with acetic acid (400 mL) and cooled to 0°C. To the solution, the zinc powder
(55.9 g, 0.856 mol) was added in one portion. The solution was stirred for 1 h at 60°C and then was cooled to room
temperature. To the solution, water was added and then extracted with hexanes. The combined organic phases were
washed with water and saturated aqueous solution of sodium chloride. The organic phase was dried over MgSO4, filtered
and concentrated by rotary evaporation. The crude 1,1-dichloro-2-cyclopropylethylene was obtained in a relative good
purity. Both flash chromatography (hexane:EtOAc, 9:1) and distillation (bp=47–5°C/2 torr) methods for the purification
of this compound had been applied. Purification by distillation yielded 44.07 g (88%) of the desired compound, 4.
Preparation of cyclopropylacetylene 1 (CPA) is a typical example for this procedure: To a stirred solution of 1,1-dichloro-
2-cyclopropylethylene (29.10 mmol) in dried THF (40 mL) at −30°C was added MeLi (1.4 M in ether, 32 mmol, 1.2
equiv.) dropwise via an additional funnel. After the addition was completed, the solution was allowed to slowly warm to
0°C over a 1 h period. The reaction was quenched with saturated aqueous solution of ammonium chloride and diluted
with heptane. The aqueous phase was extracted with heptane. The combined organic phases were washed with brine and
dried over anhydrous MgSO4. After filtration a 95% solution yield of CPA in THF:heptane (1:6) was obtained. Fractional
distillation at atmosphere pressure (b.p. 54–56°C) afforded neat CPA 1, 1.71 g (89%).