20.1: Common Synthetic Sequences For OChem I
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Students frequently get overwhelmed by the increasingly large number of organic reactions and mechanisms they must learn. This task is made particularly difficult by the perception that it is just “busy work,” and that it serves no purpose other than to meet an academic requirement. It is true that a lot of organic reactions seem to lack meaning in and of themselves, but obviously they are not useless. Unfortunately students do not get exposed to the contexts in which this information comes to life until later, or sometimes never. The context of most immediate relevance from the point of view of the organic chemistry student is in the application of these reactions in synthesis.
A synthesis is a series of two or more reactions designed to obtain a specific final product. A synthetic step (not to be confused with a mechanistic step, which is something entirely different) is a single reaction that must be conducted separately from the others in a synthesis. Therefore the number of steps in a synthetic sequence is the same as the number of reactions that must be conducted separately, that is to say, the number of reactions that make up the sequence. The concept of synthetic strategy refers to the design of the most efficient combination of reactions that will yield the desired final product. This concept is widely used in R&D departments in the pharmaceutical industry to obtain synthetic drugs of many kinds. This type of research brings together widely different fields of science such as biochemistry, organic chemistry, biology, and even computer science into a single integrated task: the task of drug discovery.
Another context in which organic reactions acquire meaning is in biochemistry. Many of the reaction types discussed in introductory organic chemistry, such as nucleophilic substitutions, eliminations, and oxidations and reductions actually take place in biological systems. There are some differences in the way these reactions happen in biological systems as opposed to the organic chemistry lab. For example most biological reactions take place in water as the medium, not in organic solvents like methylene chloride. Another difference is in the catalysis. In the vast majority of biological systems reactions are catalyzed by enzymes, which are organic macromolecules that have a high degree of specificity and precision. For example, at the stereochemical level they are capable of distinguishing one enantiomer from another. They can catalyze the formation of a specific stereoisomer with 100% efficiency. By way of contrast, one can use many catalysts in the organic chemistry lab that could not possibly be used in biological systems. However, it is surprising that the same mechanistic principles studied in organic chemistry courses, such as the rules of proton transfers, nucleophilic attacks, and steric interactions actually apply in almost the same form in bioorganic mechanisms. Thus, an understanding of the physiology of an organism at the molecular level requires a solid understanding of organic mechanisms and reaction types.
With that in mind, we now turn to the task of learning a few basic synthetic sequences that a beginning organic chemistry student can use to get started in the art of synthetic design. A typical synthetic problem requires the design of a specific molecule or functional group from simple starting materials that can be obtained commercially, or which are readily available in the lab. It is then up to the synthetic chemist to choose from a variety of organic reactions those that will accomplish the task most effectively. Needless to say, this is an art as much as it is a science, and only experience can bring about improved synthetic skills.