O. Sirkecioglu et al. / Tetrahedron Letters 44 (2003) 8483–8485
8485
However, iso-propyl alcohol and 3-butyn-2-ol did not
yield corresponding ethers as in the case of cyclic
alcohols. This result can be attributed to the low boil-
ing point of the alcohols used, since, the reaction yields
decreased when benzylations reactions were performed
using THF as solvent,9 as seen in Table 1.
4. Boyer, B.; Keramane, J. L.; Roque, J. P.; Pavia, A. A.
Tetrahedron Lett. 2000, 41, 2891–2894.
5. (a) Keramane, E. M.; Boyer, B.; Roque, J. P. Tetrahedron
2001, 57, 1917–1921; (b) Falck, J. R.; Barma, D. K.;
Venkataraman, S. K.; Baati, R.; Mioskowski, C. Tetra-
hedron Lett. 2002, 43, 963–966.
(v) Benzylic ethers on primary alcohol groups were
selectively formed from di or tri hydroxy alcohols. It is
noteworthy that, when the benzylation reactions were
carried out with an excess of benzyl chloride, the same
ether products which were synthesized before were iso-
lated.
(vi) Benzylation of cholesterol was carried out in
PhCH2Cl as reactant and solvent on a large scale. The
driving force for this reaction was the higher boiling
point of benzyl chloride which was higher than the
melting point of cholesterol. A similar result has been
reported by Yamashita6 using a nickel catalyst.
6. Yamashita, M.; Takegami, Y. Synth. Commun. 1977, 803.
7. Preparation of benzyl ethers with bis[acetylaceto-
nato]copper. General procedure:
Method 1: Benzyl chloride (1 mmol), alcohol (1 mmol) and
bis[acetylacetonato]copper (0.025 mmol) were heated under
reflux for 2–5 h. The reaction mixture was cooled then
passed through a short column of neutral aluminum oxide
to remove the catalyst. The crude product was distilled
under vacuum to give the benzyl ether in high yield.
8. Selective benzylation: Method 2: Excess benzyl chloride,
alcohol (1 mmol) and bis[acetylacetonato]copper (0.075
mmol) were heated under reflux for 2–5 h. The reaction
mixture was cooled then passed through a short column of
neutral aluminum oxide to remove the catalyst. The crude
product was distilled under vacuum to give the benzyl ether
in high yield.
References
1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 2nd ed.; John Wiley & Sons: New York,
1991; (b) Schelhaas, M.; Waldmann, H. Angew. Chem., Int.
Ed. Engl. 1996, 35, 2056–2083.
2. (a) Madsen, J.; Viuf, C.; Bols, M. Chem. Eur. J. 2000, 6,
1140–1146; (b) Hori, H.; Nishida, Y.; Ohrui, H.; Meguro,
H. J. Org. Chem. 1989, 54, 1346–1353.
3. Kocienski, P. J. In Protective Groups; Enders, D.; Noyori,
R.; Trost, B. M., Eds.; Georg Thieme Verlag: New York,
1994.
9. Preparation of benzyl ethers with bis[acetylaceto-
nato]copper in THF. General procedure:
Method 3: A solution of benzyl chloride (1 mmol), alcohol
(1 mmol) and bis[acetylacetonato]copper (0.025 mmol) in
dry THF (30 ml) was heated under reflux for 2–10 h. The
reaction mixture was cooled then passed through a short
column of neutral aluminum oxide to remove the catalyst.
The crude product was distilled under vacuum and to give
the benzyl ether in high yield.