Synthesis problems working backwards

Now we are one step closer to solving this problem. The next step is to ask if there is a way to turn the starting material into this double bond. And there is. We just do an elimination reaction to get the double bond. So now we have solved our synthesis by working backward ... 

In this final section of the chapter, we will combine the skills from the previous two sections and work on synthesis problems that involve functional group interconversion and C—C bond formation. Recall from Chapter 12 that it is very helpful to approach a synthesis problem work ing forward as well as working backward (retrosynthetic analysis). We will use all of these skills in the following example. 

Do synthesis problems working both from the starting material forward and, using retrosynthesis, from the target backwards. 

During our previous discussion of strategies for working synthesis problems in Section 8.9, we said that ids usually best to work a problem backward, or retrosyntheticnlly. Look at the target molecule and ask yourself, "What is an immediate precursor of this compound " Choose a likely answer and continue working backward, one step at a time, until you arrive at a simple starting material. Let s try some examples. 

When you see a synthesis problem for the first time, you are not expected to immediately know the answer. I cannot stress this enough. It is so common for students to get overly anxious when they see synthesis problems that they cannot solve. Get used to it. This is the way it is supposed to be. Going back to our chess analogy, you don t need to make a move as soon as it is your turn. You are allowed to think about it first. In fact, you are supposed to think about it first. So, how do you begin thinking about a multistep synthesis problem where you do not immediately see the solution The most powerful technique is called retro synthetic analysis. This means that you analyze the problem backward. Let s see how this works with an example ... 

The synthesis problem above is a multistep synthesis problem, because we do not have a single reaction that allows us to do this transformation in just one step. So the best way to start is to first look at the product and work our way backward. 

To do any synthesis problem, you must know your reactions backwards and forwards. This takes time and effort. To learn them thoroughly, you need to practice over and over. During an exam, you don t have time to work out every possibility, so you must know the reactions. 

Retrosynthetic analysis is a method for tackling synthesis problems, especially multistep synthesis problems. The application of this technique involves working the problem backwards, starting at the final product and ending up with the initial reactants. 

When applying retrosynthetic analysis to a multistep synthesis problem, you must work backwards. If you become lost, as a last resort you may want to look at the forward reactions. However, the forward process often goes off on a tangent or leads to a cul-de-sac. 

So the synthesis could be done in one step by making the anion of methyl acetate and reacting it with bromocyclohexane. The polarities of the reaction partners match nicely, but the problem is that alkylations of secondary bromides with enolates often give poor yields. The enolate is a strong base, which promotes elimination in the secondary bromide rather than giving the substitution product needed in the synthesis. Thus elimination from cyclohexyl bromide to cyclohexene would be a major process if the reaction were attempted. While the retrosynthetic step seems reasonable, the synthetic step has known difficulties. It is important to work backward in the retrosynthetic analysis and then check each forward step for validity. 

The disconnection approach to synthesis essentially involves working backwards from a target compound in a logical manner (so-called retrosynthesis), so that a number of possible routes and starting materials are suggested. This approach has been applied mainly to alicyclic, carbocyclic, and saturated heterocyclic systems. Retrosynthetic analyses are presented in this text not as an all-embracing answer to synthetic problems, but rather as an aid to understanding the actual construction of unsaturated heterocycles. 

The synthesis problems in the early chapters anf ridiculously easy. No problem is easy to a person who cannot do it. In addi-tion, this is the place where the ground work for the question-answer format, described above, is laid. The format of working problems backwards is difficult for most students to comprehend therefore, the first exposure to this format should be as simple as possible. 

Remember that it helps to use retrosynthetic analysis in synthesis problems. This means working backward to simpler and simpler compounds until an available compound is reached. These problems offer an additional clue in that the starting material is specified. In such cases it is often useful to identify which carbons in the target come from the carbons of the starting material. It is usually advisable to change these carbons as little as possible. It is also useful to identify which carbon-carbon bonds must be formed in the synthesis and how any functional groups need to be modified. In some cases the entire path will be apparent after this examination. In others it will be neces-... 

Problems that require the synthesis a specific target molecuie shauld always be worked backward. Look at the target, identify its functional... 

To use the Heck reaction in synthesis, you must determine what alkene and what organic halide are needed to prepare a given compound. To work backwards, locate the double bond with the aryl, COOR, or CN substituent, and break the molecule into two components at the end of the C = C not bonded to one of these substituents. Sample Problem 26.3 illustrates this retrosynthetic analysis. 

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