Organic Chemistry: Concepts and Applications - Headley Allan D. 2020

Addition Reactions Involving Carbonyls and Nitriles
9.6 Addition of Ylides to Carbonyl Compounds (The Wittig Reaction)

First, let us define ylides; ylides are neutral compounds that have a negatively charged carbon atom directly bonded to a positively charged atom, typically sulfur, phosphorus, or nitrogen. Two resonance structures for a phosphorous ylide are shown in (9-42).

(9-42)Image

One observation that you will make about ylides is that they are both nucleophilic and electrophilic; a similar observation was made for carbenes that were encountered in the previous chapter. As a result, ylides can undergo an addition reaction with carbonyl compounds in a regiospecific manner, as shown in Reaction (9-43) to give oxaphosphetanes, which readily decompose to form an alkene and phosphine oxide. The phosphine oxide is relatively stable due to the very favorable and strong phosphorus—oxygen double bond.

(9-43)Image

When a phosphorous ylide, which contains the phenyl (Ph, C6H5) groups, is used for Reaction (9-43), the reaction is known as the Wittig reaction. An example of the Wittig reaction is shown in Reaction (9-44).

(9-44)Image

You will recognize that the reaction is a very efficient strategy to convert a carbonyl functionality to an alkene functionality. This type of reaction was discovered in 1954 by Georg Wittig, a German chemist, who shared the Nobel Prize in 1979 with Herbert C. Brown for his discovery.

Problem 9.11

Give the structure of the ylide (Wittig reagent) necessary to carry out the following transformations.

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9.6.1 Synthesis of Phosphorous Ylides

The synthesis of phosphorous ylides is fairly straightforward. First, a substitution reaction is carried out involving triphenylphosphine and alkylbromide in which the bromide is substituted for the triphenylphosphine to form a bromide salt product as shown in the substitution reaction in Reaction (9-45). We have seen a similar reaction in Chapter 6 when we were introduced to substitution reactions. For this reaction, the bromine in the reactant is substituted with the PPh3 molecule to form the product.

(9-45)Image

A second reaction involves an acid-base reaction in which the bromide salt of the product of Reaction (9-45) reacts with strong base, typically butyl lithium, to remove a proton adjacent to the phosphorous to generate the ylide as shown in Reaction (9-46).

(9-46)Image

You will recall from Chapter 7 on acid—base reactions that the butyl lithium is an extremely strong base since its conjugate acid (butane) is an extremely weak acid (pKa ~ 50). One important observation that is made for the synthesis of Wittig ylides that are used for these reactions is that its synthesis depends on having a hydrogen adjacent to the phosphorous atom to be abstracted to form the ylide. Thus, the starting alkyl bromide cannot be tertiary, but methyl, primary or secondary. Reaction (9-47) shows the synthesis of the ylide that is needed to synthesize the alkene shown in Reaction (9-48).

(9-47)Image

(9-48)Image

Problem 9.12

i. Determine the ylides and carbonyl compounds necessary to synthesize the following compounds.Image

ii. Show how to synthesize the ylides of the above question starting from an appropriate alkylbromide and triphenyl phosphine.