Page 296 - Advanced Organic Chemistry Part B - Reactions & Synthesis

268 most general way of masking nucleophilicity is by acylations, and carbamates are
particularly useful. A most effective group for this purpose is the carbobenzyloxy
CHAPTER 3 (Cbz) group, 215 which is introduced by acylation of the amino group using benzyl
Functional Group chloroformate. The amine can be regenerated from a Cbz derivative by hydrogenolysis
Interconversion
by Substitution, of the benzyl C–O bond, which is accompanied by spontaneous decarboxylation of
Including Protection and the resulting carbamic acid.
Deprotection
O O
H 2
CH OCNR 2 HOCNR 2 CO 2 +HNR 2
2
cat
+ toluene
In addition to standard catalytic hydrogenolysis, methods for transfer hydrogenolysis
using hydrogen donors such as ammonium formate or formic acid with Pd-C catalyst
are available. 216 The Cbz group also can be removed by a combination of a Lewis acid
and a nucleophile: for example, boron trifluoride in conjunction with dimethyl sulfide
or ethyl sulfide. 217
The t-butoxycarbonyl (tBoc) group is another valuable amino-protecting group.
The removal in this case is done with an acid such as trifluoroacetic acid or
p-toluenesulfonic acid. 218 t-Butoxycarbonyl groups are introduced by reaction of
amines with t-butylpyrocarbonate or a mixed carbonate-imidate ester known as
“BOC-ON.” 219
O O O CN
(CH ) COCOCOC(CH ) (CH ) COCON CPh
3 3
3 3
3 3
“BOC – ON”
t-butyl pyrocarbonate 2-(t-butoxycarbonyloxyimino)-
2-phenylacetonitrile
Another carbamate protecting group is 2,2,2-trichloroethyloxycarbonyl, known as Troc.
2,2,2-Trichloroethylcarbamates can be reductively cleaved by zinc. 220
Allyl carbamates also can serve as amino-protecting groups. The allyloxy group
is removed by Pd-catalyzed reduction or nucleophilic substitution. These reactions
involve formation of the carbamic acid by oxidative addition to the palladium.
The allyl-palladium species is reductively cleaved by stannanes, 221 phenylsilane, 222
formic acid, 223 and NaBH , 224 which convert the allyl group to propene. Reagents
4
215 W. H. Hartung and R. Simonoff, Org. React., 7, 263 (1953).
216 S. Ram and L. D. Spicer, Tetrahedron Lett., 28, 515 (1987); B. El Amin, G. Anantharamaiah, G. Royer,
and G. Means, J. Org. Chem., 44, 3442 (1979).
217
I. M. Sanchez, F. J. Lopez, J. J. Soria, M. I. Larraza, and H. J. Flores, J. Am. Chem. Soc., 105, 7640
(1983); D. S. Bose and D. E. Thurston, Tetrahedron Lett., 31, 6903 (1990).
218 E. Wunsch, Methoden der Organischen Chemie, Vol. 15, 4th Edition, Thieme, Stuttgart, 1975.
219
O. Keller, W. Keller, G. van Look, and G. Wersin, Org. Synth., 63, 160 (1984); W. J. Paleveda,
F. W. Holly, and D. F. Weber, Org. Synth., 63, 171 (1984).
220 G. Just and K. Grozinger, Synthesis, 457 (1976).
221 O. Dangles, F. Guibe, G. Balavoine, S. Lavielle, and A. Marquet, J. Org. Chem., 52, 4984 (1987).
222
M. Dessolin, M.-G. Guillerez, N. T. Thieriet, F. Guibe, and A. Loffet, Tetrahedron Lett., 36, 5741
(1995).
223 I. Minami, Y. Ohashi, I. Shimizu, and J. Tsuji, Tetrahedron Lett., 26, 2449 (1985); Y. Hayakawa,
S. Wakabashi, H. Kato, and R. Noyori, J. Am. Chem. Soc., 112, 1691 (1990).
224
R. Beugelmans, L. Neville, M. Bois-Choussy, J. Chastanet, and J. Zhu, Tetrahedron Lett., 36, 3129
(1995).