Page 291 - Advanced Organic Chemistry Part B - Reactions & Synthesis

aromatic radical anions. 177 Benzyl ethers can also be cleaved using formic acid, cyclo- 263
hexene, or cyclohexadiene as hydrogen sources in transfer hydrogenolysis catalyzed
by platinum or palladium. 178 Several nonreductive methods for cleavage of benzyl SECTION 3.5
ether groups have also been developed. Treatment with s-butyllithium, followed by Installation and Removal
of Protective Groups
reaction with trimethyl borate and then hydrogen peroxide liberates the alcohol. 179 The
lithiated ether forms an alkyl boronate, which is oxidized as discussed in Section 4.5.2.
Li
s-BuLi
B(OCH 3 ) 2 H 2 O 2
ROCH 2 Ph ROCHPh ROCHPh ROCHPh ROH + PhCH O
(CH 3 O) 2 B
OB(OCH 3 ) 2
Lewis acids such as FeCl and SnCl also cleave benzyl ethers. 180
3
4
Benzyl groups having 4-methoxy (PMB) or 3,5-dimethoxy (DMB) substituents
can be removed oxidatively by dichlorodicyanoquinone (DDQ). 181 These reactions
presumably proceed through a benzylic cation and the methoxy substituent is necessary
to facilitate the oxidation.
OH
H 2 O
–2e – +
CH 3 O CH 2 OR CH 3 O COR CH 3 O CHOR ROH
H
–H +
These reaction conditions do not affect most of the other common hydroxy-protecting
groups and the methoxybenzyl group is therefore useful in synthetic sequences that
require selective deprotection of different hydroxy groups. 4-Methoxybenzyl ethers
can also be selectively cleaved by dimethylboron bromide. 182
Benzyl groups are usually introduced by the Williamson reaction (Section 3.2.3).
They can also be prepared under nonbasic conditions if necessary. Benzyl alcohols are
converted to trichloroacetimidates by reaction with trichloroacetonitrile. These then
react with an alcohol to transfer the benzyl group. 183

NH O
ROH
ArCH OH + Cl CCN ArCH OCCCl 3 ROCH Ar + Cl CCNH 2
3
2
2
2
3
Phenyldiazomethane can also be used to introduce benzyl groups. 184
177
E. J. Reist, V. J. Bartuska, and L. Goodman, J. Org. Chem., 29, 3725 (1964); R. E. Ireland,
D. W. Norbeck, G. S. Mandel, and N. S. Mandel, J. Am. Chem. Soc., 107, 3285 (1985); R. E. Ireland
and M. G. Smith, J. Am. Chem. Soc., 110, 854 (1988); H.-J. Liu, J. Yip, and K.-S. Shia, Tetrahedron
Lett., 38, 2253 (1997).
178 B. El Amin, G. M. Anatharamaiah, G. P. Royer, and G. E. Means, J. Org. Chem., 44, 3442 (1979);
A. M. Felix, E. P. Heimer, T. J. Lambros, C. Tzougraki, and J. Meienhofer, J. Org. Chem., 43, 4194
(1978); A. E. Jackson and R. A. W. Johnstone, Synthesis, 685 (1976); G. M. Anatharamaiah and
K. M. Sivandaiah, J. Chem. Soc., Perkin Trans., I, 490 (1977).
179
D. A. Evans, C. E. Sacks, W. A. Kleschick, and T. R. Taber, J. Am. Chem. Soc., 101, 6789 (1979).
180
M. H. Park, R. Takeda, and K. Nakanishi, Tetrahedron Lett., 28, 3823 (1987).
181 Y. Oikawa, T. Yoshioka, and O. Yonemitsu, Tetrahedron Lett., 23, 885 (1982); Y. Oikawa, T. Tanaka,
K. Horita, T. Yoshioka, and O. Yonemitsu, Tetrahedron Lett., 25, 5393 (1984); N. Nakajima, T. Hamada,
T. Tanaka, Y. Oikawa, and O. Yonemitsu, J. Am. Chem. Soc., 108, 4645 (1986).
182
N. Hebert, A. Beck, R. B. Lennox, and G. Just, J. Org. Chem., 57, 1777 (1992).
183 H.-P. Wessel, T. Iverson, and D. R. Bundle, J. Chem. Soc., Perkin Trans., I, 2247 (1985); N. Nakajima,
K. Horita, R. Abe, and O. Yonemitsu, Tetrahedron Lett., 29, 4139 (1988); S. J. Danishefsky, S. DeNinno,
and P. Lartey, J. Am. Chem. Soc., 109, 2082 (1987).
184
L. J. Liotta and B. Ganem, Tetrahedron Lett., 30, 4759 (1989).