Page 1094 - Advanced Organic Chemistry Part B - Reactions & Synthesis

1070 12.1.2. Other Oxidants

CHAPTER 12 12.1.2.1. Oxidations Based on Dimethyl Sulfoxide. A very useful group of procedures
Oxidations for oxidation of alcohols to ketones employs dimethyl sulfoxide (DMSO) and any
one of several electrophilic reagents, such as dicyclohexylcarbodiimide (DCCI), acetic
22
anhydride, trifluoroacetic anhydride (TFAA), oxalyl chloride, or sulfur trioxide. The
original procedure involved DMSO and DCCI. 23 The mechanism of the oxidation
involves formation of intermediate A by nucleophilic attack by DMSO on the carbodi-
imide, followed by reaction of the intermediate with the alcohol. 24 A proton transfer
leads to an alkoxysulfonium ylide that is converted to product by an intramolecular
proton transfer and elimination.

RNH
C CH
H + R CHOH O NR 3
2
RN C NR RNH C NR H R 2 C O S +
O – + CH O S –
O S(CH ) R 2 CH 2 H : CH 2
3 2
A S(CH ) CH 3 C
+ 3 2 B
O
R C O + (CH ) S + RNHCNHR
3 2
2
The activation of DMSO toward the addition step can be accomplished by other
electrophiles. All of these reagents are believed to form a sulfoxonium species by
electrophilic attack at the sulfoxide oxygen. The addition of the alcohol and the
departure of the sulfoxide oxygen as part of a leaving group generates an intermediate
comparable to C in the carbodiimide mechanism.
+ +
(CH ) S O – + X + (CH ) S O X
3 2
3 2
CH 3
+ + + OX
–
CHOH ) S O X R CHO S O X R CHO S(CH )
R 2 + (CH 3 2 2 2 3 2
CH 3
+
) S + H
R CHO S(CH ) R C O + (CH 3 2 +
3 2
2
2
Preparatively useful procedures based on acetic anhydride, 25 trifluoroacetic
anhydride, 26 and oxalyl chloride 27 have been developed. The last method, known as
the Swern oxidation, is currently the most popular.
Scheme 12.3 gives some representative examples of these methods. Entry 1 is
an example of the original procedure using DCCI. Entries 2 and 3 use SO and
3
CH CO O, respectively, as the electrophilic reagents. Entry 3 is noteworthy in
3
2
successfully oxidizing an alcohol without effecting the sensitive indole ring. Entry 4 is
22
A. J. Mancuso and D. Swern, Synthesis, 165 (1981); T. T. Tidwell, Synthesis, 857 (1990).
23 K. E. Pfitzner and J. G. Moffatt, J. Am. Chem. Soc., 87, 5661, 5670 (1965).
24
J. G. Moffatt, J. Org. Chem., 36, 1909 (1971).
25
J. D. Albright and L. Goldman, J. Am. Chem. Soc., 89, 2416 (1967).
26 J. Yoshimura, K. Sato, and H. Hashimoto, Chem. Lett., 1327 (1977); K. Omura, A. K. Sharma, and
D. Swern, J. Org. Chem., 41, 957 (1976); S. L. Huang, K. Omura, and D. Swern, J. Org. Chem., 41,
3329 (1976).
27
A. J. Mancuso, S.-L. Huang, and D. Swern, J. Org. Chem., 43, 2480 (1978).