Page 293 - Advanced Organic Chemistry Part B - Reactions & Synthesis

sterically hindered than the TBDMS group and can be used when added stability is 265
required. The triphenylsilyl (TPS) and t-butyldiphenylsilyl (TBDPS) groups are also
used. 201 The hydrolytic stability of the various silyl protecting groups is in the order SECTION 3.5
TMS < TBDMS < TIPS < TBDPS. 202 All the groups are also susceptible to TBAF Installation and Removal
of Protective Groups
cleavage, but the TPS and TBDPS groups are cleaved more slowly than the trialkylsilyl
groups. 203 Bromine in methanol readily cleaves TBDMS and TBDPS groups. 204

3.5.1.4. Esters as Protective Groups. Protection of an alcohol function by esterifi-
cation sometimes offers advantages over use of acetal or ether groups. Generally,
esters are stable under acidic conditions, and they are especially useful in protection
during oxidations. Acetates, benzoates, and pivalates, which are the most commonly
used derivatives, can be conveniently prepared by reaction of unhindered alcohols with
acetic anhydride, benzoyl chloride, or pivaloyl chloride, respectively, in the presence
of pyridine or other tertiary amines. 4-Dimethylaminopyridine (DMAP) is often used
as a catalyst. The use of N-acylimidazolides (see Section 3.4.1) allows the acylation
reaction to be carried out in the absence of added base. 205 Imidazolides are less reactive
than the corresponding acyl chloride and can exhibit a higher degree of selectivity in
reactions with a molecule possessing several hydroxy groups.

O
Ph O CHCl 3 , Ph O
O O + PhC O O
HO N HO
HO Δ O
OCH 3 OCH 3
N
PhCO Ref. 206
78%
Hindered hydroxy groups may require special acylation procedures. One approach
is to increase the reactivity of the hydroxy group by converting it to an alkoxide ion
with strong base (e.g., n-BuLi or KH). When this conversion is not feasible, a more
reactive acylating reagent is used. Highly reactive acylating agents are generated in situ
when carboxylic acids are mixed with trifluoroacetic anhydride. The mixed anhydride
exhibits increased reactivity because of the high reactivity of the trifluoroacetate ion as
a leaving group. 207 Dicyclohexylcarbodiimide is another reagent that serves to activate
carboxy groups.
Ester groups can be removed readily by base-catalyzed hydrolysis. When basic
hydrolysis is inappropriate, special acyl groups are required. Trichloroethyl carbonate
esters, for example, can be reductively removed with zinc. 208

Zn
ROCOCH CCl 3 ROH + H C CCl + CO
2
2
2
2
O
201 S. Hanessian and P. Lavallee, Can. J. Chem., 53, 2975 (1975); S. A. Hardinger and N. Wijaya,
Tetrahedron Lett., 34, 3821 (1993).
202
J. S. Davies, C. L. Higginbotham, E. J. Tremeer, C. Brown, and R. S. Treadgold, J. Chem. Soc., Perkin
Trans., 1, 3043 (1992).
203
J. W. Gillard, R. Fortin, H. E. Morton, C. Yoakim, C. A. Quesnelle, S. Daignault, and Y. Guindon, J.
Org. Chem., 53, 2602 (1988).
204 M. T. Barros, C. D. Maycock, and C. Thomassigny, Synlett, 1146 (2001).
205
H. A. Staab, Angew. Chem., 74, 407 (1962).
206
F. A. Carey and K. O. Hodgson, Carbohydr. Res., 12, 463 (1970).
207 R. C. Parish and L. M. Stock, J. Org. Chem., 30, 927 (1965); J. M. Tedder, Chem. Rev., 55, 787 (1955).
208
T. B. Windholz and D. B. R. Johnston, Tetrahedron Lett., 2555 (1967).