Page 208 - Arrow Pushing in Inorganic Chemistry A Logical Approach to the Chemistry of the Main Group Elements

THE HEAVIER PNICTOGENS
188

REVIEW PROBLEM 5B.20 *
As for the Wittig reaction, a catalytic version of the Appel reaction is a worthy goal.
British chemists have achieved this goal by substituting CCl with oxalyl chloride as
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the chlorine source (Denton, R. M. et al. 2011, 76, 6749–6767) and using a catalytic
amount of triphenylphosphine oxide (typically 15 mol%). The overall process may
be depicted as follows:

Cl
R 2
+
P CO + CO 2
H Ph − Ph Ph
R 1
OH Cl

−
R 2 O Cl O
+
P
Ph
Cl Ph
R 1 Ph O Cl
H
Oxalyl chloride
Explain the role of the oxalyl chloride in mechanistic terms.

5B.13* THE MITSUNOBU REACTION

The Mitsunobu reaction, discovered by Oyo Mitsunobu (1934–2003) in 1967, is one of
the most important among modern synthetic reactions. It allows the replacement of the OH
group of primary and secondary alcohols with a variety of nucleophiles, with clean inver-
sion of stereochemistry and under mild conditions. The key reagents are triphenylphosphine
and a dialkyl azodicarboxylate; the latter is very often diethyl azodicarboxylate (DEAD).
In addition, a key requirement is that the nucleophile should be acidic (for reasons you’ll
see below); carboxylic acids, phenols, thiols, imides, and activated carbon acids are all
appropriate nucleophiles.

HO H H Nu
HNu (5B.71)
C C
R 1 R 2 PPh 3 , DEAD R 1 R 2

How does one come up with a cocktail such as the above—an alcohol, a nucleophile,
PPh , and DEAD? Insight, a lucky observation or two, and tinkering all surely played
3
a role.
The key objective here is to convert the OH group, normally a lousy leaving group, to
an excellent one that can be displaced by the added nucleophile. This is where PPh and
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