Page 299 - Advanced Organic Chemistry Part B - Reactions & Synthesis

The 4-pentenoyl group is easily removed from amides by I and can be used as a 271
2
protecting group. The mechanism of cleavage involves iodocyclization and hydrolysis
of the resulting iminolactone (see Section 4.2.1). 239 SECTION 3.5
Installation and Removal
of Protective Groups
O
I 2 O H O
2
RNCCH CH CH CH 2 RN CH 2 I RNH 2
2
2
H
Sulfonamides are very difficult to hydrolyze. However, a photoactivated reductive
method for desulfonylation has been developed. 240 Sodium borohydride is used in
conjunction with 1,2- or 1,4-dimethoxybenzene or 1,5-dimethoxynaphthalene. The
photoexcited aromatic serves as an electron donor toward the sulfonyl group, which
then fragments to give the deprotected amine. The NaBH reduces the radical cation
4
and the sulfonyl radical.
hν
R NSO Ar + CH 3 O OCH 3 R N – + CH O + . OCH + ArSO 2 .
3
2
2
2
3
Table 3.2 summarizes the common amine-protecting groups. Reagents that permit
protection of primary amino groups as cyclic bis-silyl derivatives have been developed.
Anilines, for example, can be converted to disilazolidines. 241 These groups are stable to
a number of reaction conditions, including generation and reaction of organometallic
reagents. 242 They are readily removed by hydrolysis.
CH 3
CsF, HMPA Si CH 3
ArNH + (CH ) SiCH CH Si(CH ) 100°C Ar N
3 2
2
3 2
2
2
Si
H H CH 3 CH 3
CH CH 3
(CH ) SiH (PPh ) RhCl 3 Si
3 2
3 3
ArNH 2 + Ar N
(CH ) SiH Si
3 2
CH 3 CH 3
Amide nitrogens can be protected by 4-methoxy or 2,4-dimethoxyphenyl groups.
The protecting group can be removed by oxidation with ceric ammonium nitrate. 243
2,4-Dimethoxybenzyl groups can be removed using anhydrous trifluoroacetic acid. 244
239 R. Madsen, C. Roberts, and B. Fraser-Reid, J. Org. Chem., 60, 7920 (1995).
240
T. Hamada, A. Nishida, and O. Yonemitsu, Heterocycles, 12, 647 (1979); T. Hamada, A. Nishida,
Y. Matsumoto, and O. Yonemitsu, J. Am. Chem. Soc., 102, 3978 (1980).
241 R. P. Bonar-Law, A. P. Davis, and B. J. Dorgan, Tetrahedron Lett., 31, 6721 (1990); R. P. Bonar-Law,
A. P. Davis, B. J. Dorgan, M. T. Reetz, and A. Wehrsig, Tetrahedron Lett., 31, 6725 (1990); S. Djuric,
J. Venit, and P. Magnus, Tetrahedron Lett., 22, 1787 (1981); T. L. Guggenheim, Tetrahedron Lett., 25,
1253 (1984); A. P. Davis and P. J. Gallagher, Tetrahedron Lett., 36, 3269 (1995).
242
R. P. Bonar-Law, A. P. Davis, and J. P. Dorgan, Tetrahedron, 49, 9855 (1993); K. C. Grega,
M. R. Barbachyn, S. J. Brickner, and S. A. Mizsak, J. Org. Chem., 60, 5255 (1995).
243 M. Yamaura, T. Suzuki, H. Hashimoto, J. Yoshimura, T. Okamoto, and C. Shin, Bull. Chem. Soc. Jpn.,
58, 1413 (1985); R. M. Williams, R. W. Armstrong, and J.-S. Dung, J. Med. Chem., 28, 733 (1985).
244
R. H. Schlessinger, G. R. Bebernitz, P. Lin, and A. J. Pos, J. Am. Chem. Soc., 107, 1777 (1985);
P. DeShong, S. Ramesh, V. Elango, and J. J. Perez, J. Am. Chem. Soc., 107, 5219 (1985).