Unique methodological considerations

In contrast to considerations of 50 years ago, today carbene and nitrene chemistries are integral to synthetic design and applications. Always a unique methodology for the synthesis of cyclopropane and cyclopropene compounds, applications of carbene chemistry have been extended with notable success to insertion reactions, aromatic cycloaddition and substitution, and ylide generation and reactions. And metathesis is in the lexicon of everyone planning the synthesis of an organic compound. Intramolecular reactions now extend to ring sizes well beyond 20, and insertion reactions can be effectively and selectively implemented even for intermolecular processes. 

Equivalence and noninferiority trials are quite different from superiority trials in their design, analysis, and interpretation (although exactly the same methodological considerations apply to collect optimum quality data in these trials). Superiority trials continue to be our focus in this book, but it is important that you are aware of other designs too. Therefore, in Chapter 12 we discuss some of the unique features of these other design types. 

The first chapter, High Pressure Synthesis of Heterocycles Related to Bioactive Molecules by Kiyoshi Matsumoto, presents a unique high-pressure synthetic methodology in heterocyclic chemistry. Basic principles and fruitful examples for pericyclic reactions, such as Diels-Alder reactions, 1,3-dipolar reactions, and also for ionic reactions, such as Sn and addition reactions, are discussed. The review will be of considerable interest to heterocyclic chemists and synthetic chemists. 

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