1400
R. S. Coleman, J. A. Shah
SHORT PAPER
chromatography (silica gel, 5% CH3OH/CH2Cl2) provided the cor-
responding acid as a white solid.
benzyl group, and the parent compound was isolated di- 1H NMR (400 MHz, CDCl3): d = 1.96 (s, 3H, CH3), 5.21 (s, 1H,
aryl bromides such as the benzyl ether of 1-bromo-2-
naphthol (entry 5), hydrogenolysis was selective for the
C=CH), 5.36 (s, 1H, C=CH), 5.66 (s, 1H, C2-H), 7.44 (t, 2H, J = 7.7
Hz, ArH); 7.57 (t, 1H, J = 7.7 Hz, ArH); 8.08 (d, 2H, J = 8.3, ArH);
10.6 (br s, 1H, CO2H).
13C NMR (100 MHz, CDCl3): d = 174.6, 166.1, 137.9, 134.0, 130.4,
129.6, 129.0, 118.3, 76.4, 19.2.
rectly in moderate yield. In this instance and on occasion
in others, some starting material remained, and forcing the
reaction to completion allowed hydrogenolysis of the aryl
bromide to compete with benzyl ether cleavage. This was
a greater problem with less crowded aryl bromides such as
HRMS (EI), m/z calcd for C12H12O4:220.0743; found:220.0735.
the benzyl ether of p-bromophenol or benzyl ester of
p-bromobenzoic acid, where bromide hydrogenolysis was
fully competitive with benzyl group cleavage (data not
shown), thus establishing a limitation of this methodolo-
gy. With phenolic substrates, we observed the corre-
sponding O-triethylsilylphenol as the intermediate
product of the reaction, necessitating a separate desilyla-
tion reaction, which could be accomplished upon workup
Acknowledgement
This work was supported by the U.S. National Institutes of Health
(CA 65875). R.S.C. was an Sloan Foundation Research Fellow
(1995–1998).
by treatment with either Bu4NF or acetic acid under stan- References
dard conditions.7
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley: New York, 1991.
(2) Kocienski, P. J. Protecting Groups; Thieme: Stuttgart, 1994.
(3) Sakaitani, M.; Ohfune, Y. J. Org. Chem. 1990, 55, 870.
(4) Birkofer, L.; Bierwirth, E.; Ritter, A. Chem. Ber. 1961, 94,
821.
(5) Coleman, R. S. Synlett 1998, 1031.
Coleman, R. S.; Richardson, T. E.; Carpenter, A. J. J. Org.
Chem. 1998, 63, 5738.
In summary, we have delineated the scope of the selective
removal of benzyl groups using triethylsilane catalyzed
by palladium acetate. We found complete selectivity for
benzyl ester and carbamate removal in the presence of
alkenes and cyclopropanes. In the presence of aryl chlo-
rides, we could selectively remove a benzyl ether, but
with aryl bromides, the selectivity was substrate depen-
dent. In any event, this methodology increases the utility
and orthogonality of benzyl protecting groups.
Coleman, R. S.; Kong, J.-S. J. Am. Chem. Soc. 1998, 120,
3538.
Coleman, R. S.; Carpenter, A. J. Tetrahedron 1997, 53,
16313.
Coleman, R. S.; Carpenter, A. J. J. Org. Chem. 1992, 57,
5813.
Cleavage of Benzyl Groups (Entry 1); General Procedure
A solution of Pd(OAc)2 (11.7 mg, 0.052 mmol), Et3SiH (0.25 mL,
1.6 mmol) and Et3N (22 mL, 0.157 mmol) in anhyd CH2Cl2 (4 mL)
was stirred at 23 °C under N2 for 15 min. A solution of benzyl 2-
benzoyloxy-3-methylbut-3-enoate (0.360 g, 1.16 mmol) was added
dropwise. The mixture was stirred at 23 °C under N2 for 12 h before
quenching by the addition of sat. aq NH4Cl (15 mL). The aqueous
layer was extracted with Et2O (2 x 15 mL) and the combined organ-
ic extracts were washed with brine (25 mL), dried (Na2SO4), and
concentrated in vacuo to give a yellow oil. Purification by flash
(6) Raj, T. T.; Eftink, M. R. Synth. Commun. 1996, 26, 3503.
(7) Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94,
6190.
Article Identifier:
1437-210X,E;1999,0,SI,1399,1400,ftx,en;C03099SS.pdf
Synthesis 1999, No. SI, 1399–1400 ISSN 0039-7881 © Thieme Stuttgart · New York