Page 251 - Advanced Organic Chemistry Part B - Reactions & Synthesis

Scheme 3.1. (Continued) 223

12 l SECTION 3.2
PPh , I 2 Introduction of
3
Functional Groups by
CH O CH OH N Nucleophilic Substitution
3
2
at Saturated Carbon
2
N CH 3 O CH I 75%
H
a. C. R. Noller and R. Dinsomore, Org. Synth., II, 358 (1943).
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g. K. B. Wiberg and B. R. Lowry, J. Am. Chem. Soc., 85, 3188 (1963).
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i. L. A. R. Hall, V. C. Stephens, and J. H. Burkhalter, Org. Synth., IV, 333 (1963).
j. H. Loibner and E. Zviral, Helv. Chim. Acta, 59, 2100 (1976).
k. J. P. Schaefer, J. G. Higgins, and P. K. Shenoy, Org. Synth., V, 249 (1973).
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but no rearrangement was observed under these conditions. Entry 8 illustrates the
use of a chlorobenzoxazolium cation for conversion of a secondary alcohol to a
chloride. This reaction was shown to proceed with inversion of configuration. Entry 9
involves conversion of a primary alcohol to a chloride using SOCl . In this particular
2
example, the tertiary amino group captures the HCl that is formed by the reaction of
the alcohol with SOCl . There is also some suggestion from the procedure that much
2
of the reaction proceeds through a chlorosulfite intermediate. After the reactants are
mixed (exothermic reaction), the material is heated in ethanol, during which time gas
evolution occurs. This suggests that much of the chlorosulfite ester survives until the
heating stage.
O
SOCl 2 heat
+
+
(CH ) NCH CH OH (CH ) N CH CH OSCl (CH ) N CH CH Cl +SO 2
3 2
2
2
2
3 2
2
2
3 2
2
H H
Entry 10 illustrates the application of the Mitsunobu reaction to synthesis of a steroidal
iodide and demonstrates that inversion occurs. Entry 11 shows the use of the isolated
Ph P–Br complex. The reaction in Entry 12 involves the preparation of a primary
3 2
iodide using the Ph P–I -imidazole reagent combination.
3 2
3.2. Introduction of Functional Groups by Nucleophilic Substitution
at Saturated Carbon
The mechanistic aspects of nucleophilic substitution reactions were treated in
detail in Chapter 4 of Part A. That mechanistic understanding has contributed to the
development of nucleophilic substitution reactions as important synthetic processes.
Owing to its stereospecificity and avoidance of carbocation intermediates, the S 2
N
mechanism is advantageous from a synthetic point of view. In this section we discuss