Page 289 - Advanced Organic Chemistry Part B - Reactions & Synthesis

methylthiomethyl chloride is efficient if catalyzed by iodide ion. 161 Alcohols are also 261
converted to MTM ethers by reaction with dimethyl sulfoxide in the presence of acetic
acid and acetic anhydride, 162 or with benzoyl peroxide and dimethyl sulfide. 163 The SECTION 3.5
latter two methods involve the generation of the methylthiomethylium ion by ionization Installation and Removal
of Protective Groups
of an acyloxysulfonium ion (Pummerer reaction).
I –
–
RO M + + CH SCH Cl ROCH SCH 3
2
3
2
CH CO H
3
2
ROH + CH SOCH 3 ROCH SCH 3
3
2
(CH CO) O
3
2
ROH + (CH ) S + (PhCO ) ROCH SCH 3
2
3 2
2 2
The MTM group is selectively removed under nonacidic conditions in aqueous
+
solutions containing Ag or Hg 2+ salts. The THP and MOM groups are stable under
these conditions. 161 The MTM group can also be removed by reaction with methyl
iodide, followed by hydrolysis of the resulting sulfonium salt in moist acetone. 162
Two substituted alkoxymethoxy groups are designed for cleavage involving
-elimination. The 2,2,2-trichloroethoxymethyl groups can be cleaved by reducing
agents, including zinc, samarium diiodide, and sodium amalgam. 164 The -elimination
results in the formation of a formaldehyde hemiacetal, which decomposes easily.
2e –
–
Cl CCH OCH OR Cl + Cl C CH 2 + CH 2 O + OR
–
2
2
2
3
The 2-(trimethylsilyl)ethoxymethyl group (SEM) can be removed by various fluoride
sources, including TBAF, pyridinium fluoride, and HF. 165 This deprotection involves
nucleophilic attack at silicon, which triggers -elimination.
–
–
F + (CH ) SiCH 2 CH OCH OR (CH ) SiF + CH 2 CH 2 + CH 2 O + OR
3 3
3 3
2
2
The SEM group can also be cleaved by MgBr . A noteworthy aspect of this method
2
is that trisubstituted silyl ethers (see below) can survive.
CH
CH 3
CH 3 CH 3 OH 3
S OSEM O O MgBr 2 S O O
OSi(Ph) C(CH )
OSi(Ph) C(CH ) ether/ S 2 3 3
S 2 3 3
nitromethane CH CH
CH 3 CH 3 3 3
Ref. 166
161 E. J. Corey and M. G. Bock, Tetrahedron Lett., 3269 (1975).
162 P. M. Pojer and S. J. Angyal, Tetrahedron Lett., 3067 (1976).
163
J. C. Modina, M. Salomon, and K. S. Kyler, Tetrahedron Lett., 29, 3773 (1988).
164 R. M. Jacobson and J. W. Clader, Synth. Commun., 9, 57 (1979); D. A. Evans, S. W. Kaldor, T. K. Jones,
J. Clardy, and T. J. Stout, J. Am. Chem. Soc., 112, 7001 (1990).
165 B. H. Lipshutz and J. J. Pegram, Tetrahedron Lett., 21, 3343 (1980); B. H. Lipshutz and T. A. Miller,
Tetrahedron Lett., 30, 7149 (1989); T. Kan, M. Hashimoto, M. Yanagiya, and H. Shirahama, Tetrahedron
Lett., 29, 5417 (1988); J. D. White and M. Kawasaki, J. Am. Chem. Soc., 112, 4991 (1990); K. Sugita,
K. Shigeno, C. F. Neville, H. Sasai, and M. Shibasaki, Synlett, 325 (1994).
166
A. Vakalopoulos and H. M. R. Hoffmann, Org. Lett., 2, 1447 (2000).