Page 976 - Advanced Organic Chemistry Part B - Reactions & Synthesis

952 The migrating group retains its configuration. Some reaction conditions can lead to
syn-anti isomerization at a rate exceeding rearrangement, and when this occurs, a
CHAPTER 10
mixture of products is formed. The reagents that have been found least likely to
Reactions Involving cause competing isomerization are phosphorus pentachloride and p-toluenesulfonyl
Carbocations, Carbenes, 283
and Radicals as Reactive chloride.
Intermediates A fragmentation reaction occurs if one of the oxime substituents can give rise
to a relatively stable carbocation. Fragmentation is very likely to occur if a nitrogen,
oxygen, or sulfur atom is present to the oximino group.

R
+
X C C N OY X C + RC N + – OY

Fragmentation can also occur when the -carbon can support cationic character.

CH CH C N
PCl 5 2 2
NOH
C CH
CH 3 CH 3 2
CH 3 93%
Ref. 284

Section D of Scheme 10.15 provides some examples of the Beckmann rearrangement.
Section A of Scheme 10.15 contains a number of examples of Curtius rearrange-
ments. Entry 1 is an example carried out in a nonnucleophilic solvent, permitting
isolation of the isocyanate. Entries 2 and 3 involve isolation of the amine after
hydrolysis of the isocyanate. In Entry 2, the dihydrazide intermediate is isolated as
a solid and diazotized in aqueous solution, from which the amine is isolated as the
dihydrochloride. Entry 3 is an example of the mixed anhydride procedure (see p. 948).
The first stage of the reaction is carried out in acetone and the thermolysis of the acyl
azide is done in refluxing toluene. The crude isocyanate is then hydrolyzed in acidic
water. Entry 4 is a reaction that demonstrates the retention of configuration during
rearrangement.
Entries 5 to 8 are synthetic applications in more complex molecules. Entries 5
and 6 illustrate the diphenylphosphoroyl azide method. Entry 7 was used in the late
stages of the synthesis of an antitumor macrolide, zampanolide, to introduce the amino
group. The ultimate target molecule in Entry 8 is himandrine, one of several polycyclic
alkaloids isolated from an ancient plant species.

CH O C
3
2
PhCO 2 OH
CH 3 O
N
himandrine CH 3

283 R. F. Brown, N. M. van Gulick, and G. H. Schmid, J. Am. Chem. Soc., 77, 1094 (1955); J. C. Craig
and A. R. Naik, J. Am. Chem. Soc., 84, 3410 (1962).
284
R. T. Conley and R. J. Lange, J. Org. Chem., 28, 210 (1963).