Page 297 - Advanced Organic Chemistry Part B - Reactions & Synthesis

used for nucleophilic cleavage include N,N -dimethylbarbituric acid, 225 and silylating 269
agents, including TMS-N /NH F, 226 TMSN Me , 227 and TMSN CH COCF . 219 The
2
3
4
3
3
silylated nucleophiles trap the deallylated product prior to hydrolytic workup. SECTION 3.5
Installation and Removal
of Protective Groups
O O – RNH + CO + Pd 0 + H
2
2
R 0 R H – D
Pd Pd II
N O N O
Nu – H RNH + CO + Pd 0 + Nu
H H 2 2
Allyl groups attached directly to amine or amide nitrogen can be removed by
isomerization and hydrolysis. 228 These reactions are analogous to those used to cleave
allylic ethers (see p. 266). Catalysts that have been found to be effective include
45
Wilkinson’s catalyst, 229 other rhodium catalysts, 230 and iron pentacarbonyl. Treatment
of N-allyl amines with Pd PPh and N,N -dimethylbarbituric acid also cleaves the

3 4
allyl group. 231
Sometimes it is useful to be able to remove a protecting group by photolysis.
2-Nitrobenzyl carbamates meet this requirement. The photoexcited nitro group
abstracts a hydrogen from the benzylic position, which is then converted to a
-hydroxybenzyl carbamate that readily hydrolyzes. 232
O O
hν
CH OCNR 2 CHOCNR 2 CH O + CO 2 + H NR
2
2
OH
NO 2 NO NO
N-Benzyl groups can be removed from tertiary amines by reaction with chloro-
formates. This can be a useful method for protective group manipulation if the resulting
carbamate is also easily cleaved. A particularly effective reagent is -chloroethyl
chloroformate, which can be removed by subsequent solvolysis, 233 and it has been
used to remove methyl and ethyl groups. These reactions are related to ether cleavage
by acylation reagents (see Section 3.3).

CH CHO CCl
2
3
2
CH 3 O C CH 3 O C O CH O C
2
2
3
Cl CH OH
3
N CH 3 N COCHCH 3 NH
Cl
Simple amides are satisfactory protecting groups only if the rest of the molecule
can resist the vigorous acidic or alkaline hydrolysis necessary for removal. For this
225
P. Braun, H. Waldmann, W. Vogt, and H. Kunz, Synlett, 105 (1990).
226
G. Shapiro and D. Buechler, Tetrahedron Lett., 35, 5421 (1994).
227 A. Merzouk, F. Guibe, and A. Loffet, Tetrahedron Lett., 33, 477 (1992).
228
I. Minami, M. Yuhara, and J. Tsuji, Tetrahedron Lett., 28, 2737 (1987); M. Sakaitani, N. Kurokawa,
and Y. Ohfune, Tetrahedron Lett., 27, 3753 (1986).
229 B. C. Laguzza and B. Ganem, Tetrahedron Lett., 22, 1483 (1981).
230 J. K. Stille and Y. Becker, J. Org. Chem., 45, 2139 (1980); R. J. Sundberg, G. S. Hamilton, and
J. P. Laurino, J. Org. Chem., 53, 976 (1988).
231
F. Garro-Helion, A. Merzouk, and F. Guibe, J. Org. Chem., 52, 6109 (1993).
232 J. F. Cameron and J. M. J. Frechet, J. Am. Chem. Soc., 113, 4303 (1991).
233
R. A. Olofson, J. T. Martz, J.-P. Senet, M. Piteau, and T. Malfroot, J. Org. Chem., 49, 2081 (1984).