Page 301 - Advanced Organic Chemistry Part B - Reactions & Synthesis

O R O CH 2 273
H + C
2
CH OH + H O
RCR′ + HOCH 2 2 SECTION 3.5
R′ O CH 2
Installation and Removal
of Protective Groups
Scandium triflate is also an effective catalyst for dioxolane formation. 246
Dimethyl or diethyl acetals can be prepared by acid-catalyzed exchange with an
acetal such as 2,2-dimethoxypropane or an orthoester. 247

O OCH 3
H +
RCR′ + (CH O) C(CH ) R C R′ + (CH ) C O
3 2
3 2
2
3
OCH 3
O OCH 3
H +
RCR′ + HC(OCH ) R C R′ + HCO CH 3
2
3 3
OCH 3
Acetals can be prepared under very mild conditions by reaction of the carbonyl
compound with a trimethylsilyl ether, using trimethylsilyl trifluoromethylsulfonate as
the catalyst. 248

Me SiO SCF 3
3
3
R C O + 2 R'OSi(CH ) R C(OR') 2 + (CH ) SiOSi(CH )
3 3
3 3
3 3
2
2
The carbonyl group can be deprotected by acid-catalyzed hydrolysis by the general
mechanism for acetal hydrolysis (see Part A, Section 7.1). A number of Lewis acids
have also been used to remove acetal protective groups. Hydrolysis is promoted by
LiBF in acetonitrile. 249 Bismuth triflate promotes hydrolysis of dimethoxy, diethoxy,
4
and dioxolane acetals. 250 The dimethyl and diethyl acetals are cleaved by 0.1–1.0 mol %
of catalyst in aqueous THF at room temperature, whereas dioxolanes require reflux.
Bismuth nitrate also catalyzes acetal hydrolysis. 251
If the carbonyl group must be regenerated under nonhydrolytic conditions, -halo
alcohols such as 3-bromopropane-1,2-diol or 2,2,2-trichloroethanol can be used for
acetal formation. These groups can be removed by reduction with zinc, which leads
to -elimination.

R
O R Zn
R C O + HOCH CH CH 2
2
2
BrCH 2 O
Ref. 252
246
K. Ishihara, Y. Karumi, M. Kubota, and H. Yamamoto, Synlett, 839 (1996).
247 C. A. MacKenzie and J. H. Stocker, J. Org. Chem., 20, 1695 (1955); E. C. Taylor and C. S. Chiang,
Synthesis, 467 (1977).
248 T. Tsunoda, M. Suzuki, and R. Noyori, Tetrahedron Lett., 21, 1357 (1980).
249
B. H. Lipshutz and D. F. Harvey, Synth. Commun., 12, 267 (1982).
250 M. D. Carrigan, D. Sarapa, R. C. Smith, L. C. Wieland, and R. S. Mohan, J. Org. Chem., 67, 1027
(2002).
251 N. Srivasta, S. K. Dasgupta, and B. K. Banik, Tetrahedron Lett., 44, 1191 (2003).
252
E. J. Corey and R. A. Ruden, J. Org. Chem., 38, 834 (1973).