6110
M. André et al. / Tetrahedron Letters 53 (2012) 6107–6110
2. Giessert, A. J.; Snyder, L.; Markham, J.; Diver, S. T. Org. Lett. 2003, 5, 1793–1796.
3. Piantadosi, C.; Hirsch, A. F.; Yarbro, C. L.; Anderson, C. E. J. Org. Chem. 1963, 28,
2425–2428.
4. Craig, J. C.; Hamon, D. P. G.; Brewer, H. W.; Härle, H. J. Org. Chem. 1965, 30, 907–
910.
5. Cabianca, E.; Chéry, F.; Rollin, P.; Tatibouët, A.; De Lucchi, O. Tetrahedron Lett.
2002, 43, 585–587.
6. Feugeas, C. Bull. Soc. Chim. Fr. 1963, 421, 2568–2579.
7. Park, H. S.; Kim, S. H.; Park, M. Y.; Kim, Y. H. Tetrahedron Lett. 2001, 42, 3729–
3732.
8. Naruse, Y.; Yamamoto, H. Tetrahedron Lett. 1986, 27, 1363–1366.
9. Kaino, M.; Naruse, Y.; Ishihara, K.; Yamamoto, H. J. Org. Chem. 1990, 55, 5814–
5815.
10. Gassman, P. G.; Burns, S. J.; Pfister, K. B. J. Org. Chem. 1993, 58, 1449–1457.
11. Farschtschi, N. Chem. Biodiv. 2004, 1, 402–414.
12. Matysiak, S.; Fitznar, H.-P.; Schnell, R.; Pfleiderer, W. Helv. Chim. Acta 1998, 81,
1545–1566.
13. Munro, T. A.; Duncan, K. K.; Xu, W.; Wang, Y.; Liu-Chen, L.-Y.; Carlezon, W. A.,
Jr.; Cohen, B. M.; Béguin, C. Bioorg. Med. Chem. 2008, 16, 1279–1286.
14. Wuts, P.G.M.; Greene T.W. in Greene’s Protective Groups in Organic Syntheses,
4th ed., Wiley (Ed.), Wiley & Sons: Hoboken, New Jersey, 2007; pp. 165–222.
15. Schlenk, W.; Schlenk, W. Ber. Dtsch. Chem. Ges. 1929, 62, 920–924.
16. Smith M. B.; March J., In March’s Advanced Organic Chemistry–Reactions,
Mechanisms and Structure 6th ed., Wiley & Sons: Hoboken, New Jersey, 2007,
pp. 260–261.
fractional distillation) of such compounds is delicate as they spon-
taneously cyclize into their corresponding dioxolanes.
Finally, ring-opening in anhydrous conditions enabled us to
investigate in situ protection of the generated alkoxide to produce
easily isolable compounds (Scheme 4).
Adding benzoyl chloride after triethylamine and before final
addition of water gave the desired b-hydroxy-protected vinyl ether
in satisfactory yield after purification (55%). This procedure22 was
then successfully extended to other brominated dioxolanes as
shown in Table 4. Both primary and secondary a-brominated diox-
olanes were compatible under our reaction conditions. Moderate
to good yields (55ꢁ62%) of the corresponding b-hydroxy-protected
vinyl ethers were obtained, even in the case of aromatic or bulky
dioxolanes (entries 18 and 19, respectively). Other protecting
groups were also tested: tert-butyldiphenylsilyl (TBDPS) gave an
even better yield than its benzoate-protected analogue (entry 24
vs. 17) while 4,40-dimethoxytrityl (DMT) and acetate induced
slightly lower yields (entries 25 and 26 respectively).
In summary, the ring-opening of a-brominated ketals involving
17. Gauvin, R. M.; Buch, F.; Delevoye, L.; Harder, S. Chem. Eur. J. 2009, 15, 4382–
4393.
18. Maughan, M. A. T.; Davies, I. G.; Claridge, T. D. W.; Courtney, S.; Hay, P.; Davis,
B. G. Angew. Chem., Int. Ed. 2003, 42, 3788–3792.
19. Salinger, R. M.; Mosher, H. S. J. Am. Chem. Soc. 1964, 86, 1782–1786.
20. Ashby, E. C.; Parris, G. E. J. Am. Chem. Soc. 1971, 93, 1206–1213.
21. Krasovskiy, A.; Knochel, P. Angew. Chem., Int. Ed. 2004, 43, 3333–3336.
22. General procedure for the preparation of hydroxy-protected vinyl ethers,
Ribbon magnesium (295 mg, 12.2 mmol) was chemically polished by the
following sequential washes: 6% aqueous HNO3, H2O, EtOH and anhydrous
ether. Washed pieces were activated in a 2% I2 solution in anhydrous THF for 2
minutes then rinsed with anhydrous THF. Activated magnesium was placed
under argon atmosphere in anhydrous THF (5 mL), catalytic dibromoethane (2
Grignard reaction conditions has been optimized and we proposed
a hypothetical mechanism for the organomagnesium ring opening
based on both experimental observations and literature data. We
have developed a reproducible medium-scale one-pot three-step
process using inexpensive non-hazardous reagents, yielding stable
and easily isolable b-hydroxy-protected monovinyl ethers derived
from ethylene glycol. These conditions are versatile enough to pro-
vide benzoate-, TBDPS-, DMT-, or acetate-protected compounds,
providing compatibility with numerous protection/deprotection
strategies.
drops) was added and a solution of
a-brominated dioxolane (11.0 mmol) in
anhydrous THF (10 mL) was added under argon atmosphere. The reaction was
initiated by warming with a heating gun and the soft reflux was maintained by
Acknowledgements
continuous addition of the a-brominated dioxolane solution. The mixture was
stirred at 50 °C for 1 h after addition ended and NEt3 (4.7 mL, 33.1 mmol) was
added under argon atmosphere. The mixture was then stirred at room
temperature for 1 h and cooled down to 0 °C. A solution of BzCl (1.708 g,
12.2 mmol) in anhydrous THF (10 mL) was added under argon atmosphere, the
mixture was stirred at room temperature overnight and poured in CH2Cl2
(300 mL). The mixture was washed with water (2 ꢂ 100 mL) and the combined
aqueous layers were extracted with CH2Cl2 (50 mL). Combined organic layers
were washed with brine (2 ꢂ 100 mL), dried over MgSO4, filtered and the
solvent was evaporated under reduced pressure. The crude oil was purified by
flash chromatography using a mixture of cyclohexane/ethyl acetate (4–12%
ethyl acetate) as the eluent to afford the hydroxy-protected vinyl ethers as
colorless or slight yellow fragrant oils.
We are grateful to Bertrand Légeret (Service de Spectrométrie
de Masse, Université Blaise Pascal, Clermont-Ferrand) and Sébast-
ien Tarrit (Laboratoire de Chimie Analytique et de Spectrométrie
de Masse) for recording and processing GC–MS spectra.
Supplementary data
Supplementary data associated with this article can be found, in
23. Visweswariah, S.; Prakash, G.; Bhushan, V.; Chandrasekaran, S. Synthesis 1982,
309–310.
References and notes
1. Liu, W.; Nichols, P. J.; Smith, N. Tetrahedron Lett. 2009, 50, 6103–6105.