This action might not be possible to undo. Are you sure you want to continue?
Chemistry 342-2008 Lecture 23
Mukund P. Sibi
Formation of alkenes from carbonyl compounds: The Wittig Reaction. Prof. Georg Wittig, Nobel laureate, invented one of the most important organic reactions in the 1950s, the conversion of a carbonyl compound to an alkene. The Wittig reagent is a carbon nucleophile. Generally the reagent contains a phosphorous atom bonded to three phenyl groups and another alkyl group that has a negative charge. The nucleophile adds to the carbonyl carbon and elimination of triphenylphosphine oxide produces the alkene.
Wittig Reaction R R P C R Wittig Reagent
C C Alkene
R R P O R Phosphine oxide
Important characteristics of the Wittig Reaction: • • • • Pure alkene of known structure No regioisomers of alkenes E/Z isomers of alkene (this could be also controlled) C=C double bond in the product is always exactly where the C=O group in the reactant
The Wittig reaction is an addition-elimination reaction. It involves three steps. • • • Step 1- Addition of carbon nucleophile to the carbonyl carbon Step 2-Formation of oxaphosphetane Step 3-Elimination of triphenylphosphine oxide and formation of the alkene
H H C I H
H P SN2 reaction C H H IPhosphonium salt
Strong Base B
H H + H B
Triphenyl phosphine Solid, easy to handle good nucleophile
Both atoms have octets. CH3MgBr H 2. They eliminate phosphine oxide at low temperatures (even at -78 °C). A Wittig reagent has no net charge. a variety of a phosphonium salts can be prepared. It is possible to prepare mono. H3O+ H3C OH C H H2SO4 H3C C Major Dehydration of alcohols gives a mixture of product alkenes H H H + H H + C C H H Minor O C H + H R R P C R H C C R R P O R Phosphine oxide Wittig reaction provides a single alkene product The position of the double bond is unambiguous in the Wittig Reaction The scope of the Wittig Reaction A variety of alkenes can be prepared using the Wittig reaction. di. . and tetrasubstituted alkenes. Both aldehydes and ketones participate in the Wittig reaction.Lecture Notes Chemistry 342-2008 Lecture 23 Mukund P. The oxaphosphetane intermediate cannot be isolated generally. tri. Depending on the starting alkyl halide (primary or secondary only). Sibi Ylide is a specie that contains two oppositely charged atoms [(+) and (-) charges] bonded to each other. The carbon atom in Wittig reagent is nucleophilic We can write two resonance structures for the Wittig reagents Nucleophile P C H H P C H H Ylide Ylide R 3P H C H O C R R P O R Phosphine oxide PH C H H H R R P C R H H R R P C R H + O C step 1 R3P O C C H H Betaine step 2 step 3 H C C + H Alkene Oxaphosphetane Comparison of methods for alkene synthesis Let us compare dehydration of alcohols with Wittig Reaction O C 1.
Sibi One of the major disadvantages of the Wittig reaction is the formation of E and Z alkene isomers. O H + H R R P C R H H C H H mono substituted alkene O C H + H R R P C R H C C H Major Disubstituted alkene H C C H H Minor O + H R R P C R trisubstituted alkene O CH3 + CH3 R R P C R CH3 H3C C CH3 tetrasubstituted alkene CH3 Cannizaro Reaction Carboxylic acid derivatives undergo nucleophilic substitution. On the other hand. An exception to this is the Cannizaro reaction O O H OH O H OH Hydride Migration OH H H O O H H O H O OH . The main reason for this difference is due to nature of the carbonyl group. where as aldehydes and ketones undergo nucleophilic addition. the tetrahedral intermediate formed by nucleophile addition to aldehydes and ketones is stable [lack of a leaving group] and overall process is addition.Lecture Notes Major disadvantage: Chemistry 342-2008 Lecture 23 Mukund P. The E/Z ratio depends on reaction conditions and the nature of the substituents on the phosphorus. The tetrahedral intermediate formed after nucleophile addition to carboxylic acid derivatives is not stable and eliminates a leaving group. The overall process is thus a nucleophilic substitution.
β-unsaturated carbonyl compounds.4-Addition O C Reactions of carbon nucleophiles with α.2-Addition H Reaction occurs on atoms 1 and 2 H C C H 2 H 3 4 1O 1.β-unsaturated carbonyl compounds can react as an electrophile at two sites: the carbonyl carbon and the β-carbon. Overall. Conjugate Addition α. NuO C H H H C 1.2-Addition O 1. OH C 2. etc) are also good for 1. H C C H H 2 3 4 !. Sibi In this reaction.4-addition. . The selectivity depends on reaction conditions as well as the nucleophile itself.4-Addition also known as conjugate addition Reaction occurs on atoms 1 and 4 H O C H C NuH H O C H C Nu H H O C H H3O+ C Nu H H C Nu H H 1. H3O+ H Nu 1. After proton transfer. one obtains benzyl alcohol and benzoic acid. H3O+ 1. hydroxide (nucleophile) adds to benzaldehyde in the first step. (CH3)2CuLi 2.4-addtion.2-addition.Lecture Notes Chemistry 342-2008 Lecture 23 Mukund P. one molecule of benzaldehyde is reduced to benzyl alcohol and the other is oxidized to benzoic acid. On the other hand.4-Addition CH3 O Heteroatom nucleophiles (amines."-Unsaturated aldehyde 1O O C H C O C H C H H H H Electrophilic at C-2 Electrophilic at C-4 Nucleophiles can attack either at C-2 or C-4. HO CH3 CH3MgBr 1. A variety of nucleophiles can be used for reactions with α. Nu2. a hydride (another nucleophile) adds to another molecule of benzaldehyde. After formation of the tetrahedral intermediate. Grignard reagents (carbon nucleophiles) do only 1. copper reagents (carbon nucleophiles) do 1.β-unsaturated carbonyl compounds is important. H3O+ H H C Nu H 1.