Page 1187 - Advanced Organic Chemistry Part B - Reactions & Synthesis

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Multistep Syntheses

Introduction

The reactions discussed in the preceding chapters provide tools for synthesizing
new and complex molecules, but a strategy for using these reactions is essential for
successful multistep syntheses. The sequence of individual reactions must be planned
so that the reactions are mutually compatible with the final synthetic goal. Certain
functional groups can interfere with prospective reactions and such problems must be
avoided either by a modification of the sequence or by temporarily masking (protecting)
the interfering group. Protective groups are used to temporarily modify functionality,
which is then restored when the protecting group is removed. Another approach is to
use a synthetic equivalent group in which a particular functionality is introduced as an
alternative structure that can subsequently be converted to the desired group.
Protective groups and synthetic equivalent groups are tactical tools of multistep
syntheses. They are the means, along with the individual synthetic methods, to reach
the goal of a completed synthesis, and these tactical steps must be incorporated
into an overall synthetic plan. A synthetic plan is normally created on the basis of
a retrosynthetic analysis, which involves identification of the particular bonds that
can be formed to obtain the desired molecule. Depending on the complexity of the
synthetic target, the retrosynthetic analysis may be obvious or intricate. A synthetic plan
identifies potential starting materials and reactions that can lead to the desired molecule,
and most such plans involve a combination of linear sequences and convergent steps.
Linear sequences construct the target molecule step-by-step by incremental additions
and functional group transformations. Convergent steps bring together larger segments
of the molecule that have been created by linear sequences. As the overall synthetic
yield is the multiplication product of the yield of each of the individual steps in the
synthesis, incorporation of a convergent step improves overall yield by reducing the
length of the linear sequences. After discussing some general aspects of synthetic
analysis and planning, we summarize several syntheses that illustrate application of
multistep synthetic methods to representative molecules. In the final sections of the
chapter, we consider solid phase synthesis and its application to polypeptide, poly-
nucleotide, and combinatorial syntheses.
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