Chapter 11. Multistep Syntheses

Carbon compounds that also contain nitrogen, such as the cimines, play a significant peirt of any Organic 11 course. You encounter more acid-base chemistry with the amines, along with some more reactions. We hit this topic in Chapter 13 and give you some tips for multistep synthesis. 

Multistep synthesis problems are useful for exercising your knowledge of organic reactions, and in Chapter 8 we illustrated a systematic approach to synthesis. Now we apply this approach to a fairly difficult problem emphasizing alkyne chemistry. The compound to be synthesized is cA-2-methylhex-4-en-3-ol. (The 3-ol means there is an alcohol —OH group on C3.)... 

The goal of this chapter is to extract some of the conceptual underpinnings of the idea of synthesis and of the different aspects that constitute its practice. In so doing, we show why chemical synthesis should be of interest to metaphysicians and philosophers of science. To this end we (1) provide a provisional characterization of synthesis (2) describe what chemists have understood to be the "logical" structure that underlies the modern practice of multistep synthesis (3) explore the notions of molecular and synthetic complexity and the relationship between them (4) analyze the use of similarity judgments in the categorization of compounds and, related to this, (5) undertake a scrutiny of the notion of a natural kind in the context of the possibility of chemical synthesis. 

Ring closure by reaction between an amino and a fluoro function is a frequently used method (see Chapter 9) it is sometimes convenient to use a heterocyclic carbonyl group as a precursor of the amine, and thus reduce the number of compounds that have to be isolated and purified in a multistep synthesis. Pyrimidinediones are susceptible to this type of conversion as is demonstrated in the synthesis of a diaza-acridinone. 

Chapter 6 covers the reactions of alkynes—hydrocarbons that contain carbon-carbon triple bonds. Because alkenes and alkynes both have reactive carbon-carbon tt bonds, you will discover that their reactions have many similarities. This chapter will also introduce you to some of the techniques chemists use to design syntheses of organic compounds, and you will then have your first opportunity to design a multistep synthesis. 

CHAPTER 6 Reactions of Alkynes Introduction to Multistep Synthesis... 

Osmylation of the chirally masked 2-alkoxypent-3-enal 1 and subsequent functional group manipulations furnished enantiopure 5-deoxy-L-lyxose and -xylose derivatives. A new preparation of 5-deoxyribonolactone derivative 2 from ribonolactone by tributyltin hydride reduction of a 5-chloro-5-deoxy intermediate has been published. Conversion of compound 2 to a 5 -deoxy-nucleoside analogue is covered in Chapter 20. A multistep synthesis of methyl 5-0-benzoyl-2,3-dideoxy-P-D-g/ycero-pentofuranose (4) from D-xylose involving Raney nickel desulfurization of compound 3 (see Chapter 11) has been described. Several deoxy-ketoses have been prepared by Raney nickel desulfurization of 1-thio-ketose derivatives obtained by enzyme-catalysed aldol condensations (see Vol. 29, Chapter 2, Scheme 1). An example is given in Scheme 1. ... 

In designing a multistep synthesis, one must consider aspects of stereochemistry as well as functionality. In the chapters dealing with individual reactions, many examples were given in which the aspects of stereochemistry were a direct consequence of the reaction mechanism. For example, hydroboration-oxidation involves a syn addition followed by oxidation with retention of configuration. The generalization, widely but not universally correct, that reagents attack molecules from the sterically less hindered side was also illustrated on numerous occasions. 

Updated End-of-Chapter Problems There are plentiful end-of-chapter problems, with the majority categorized by topic. A red problem number indicates an applied, real-world problem. There are numerous multistep synthesis problems, many dealing with the synthesis of important pharmaceuticals, and Reactions in Context problems dealing with functional group transformations of more complex molecules. 

In the previous few chapters, we developed several synthesis strategies that enable us to move the location of a functional group or change its identity. Let s briefly review these techniques, as they will be extremely helpful when solving multistep synthesis problems. 

In conclusion, the multistep synthesis of (/f)-K-13975, presented here, is a typical example of improvement of the critical synthetic steps in new drug synthesis to provide robustness, i.e. reproducibility of the process, easy separation of the product, and the required high yield. This is always a challenge for the synthetic organic chemist when a stmcturally well-defined lead molecule emerges and a workable synthetic route is needed. In view of the expectation that lead compound would be required in multi-kilo quantities, the synthetic chemists developed a process, presented in this chapter, that meets many criteria for alternative scale-up. 

CHAPTER 7 The Reactions of Alkynes An Introduction to Multistep Synthesis 299... 

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