ORGANIC - CLUTCH CH CONDENSATION CHEMISTRY.

Transcription

1 !!

2 CNCEPT: CNDENSATIN REACTINS A condensation reaction spontaneously combines two or more molecules with the loss of a smaller molecule. Instead of just reacting with electophiles, enolates are able to react with themselves to self-condensate bviously, are required for this type of reaction to take place Example Reactions: Page 2

3 CNCEPT: ALDL CNDENSATIN Via enolates, ketones and aldehydes will react with to condensate into The final products are called aldols because they are part and part Mechanism: 1. Form the enolate 2. Nucleophilic attack the other carbonyl (which we will call the electrophile) 3. Protonate the tetrahedral intermediate: β-hydroxy carbonyls are to dehydrate than typical alcohols due to Many times, we will simply assume that the condensation product dehydrated on its own, without requiring an explanation. Page 3

4 PRACTICE: What product can be isolated from the following aldol condensation reaction? H Page 4

5 PRACTICE: Provide the mechanism for the following transformation. H H H Page 5

6 CNCEPT: DIRECTED CNDENSATINS When we run condensation reactions with asymmetrical ketones, two enolates may be possible. We can use different bases to direct the direction of deprotonation The thermodynamic enolate is the substituted one. Favored by bases. The kinetic enolate is the substituted one. Favored by bases. EXAMPLE: Predict the products of the following self-condensation. Page 6

7 CNCEPT: CRSSED ALDL When we run condensation reactions on two different ketones or aldehydes, mixed products are difficult to avoid. In general, condensation reactions with two different carbonyls work best when one carbonyl is nonenolizable. Nonenolizable Carbonyls: Page 7

8 PRACTICE: Give the structure of the aldehydes or ketones used to create the product prepared by a crossed aldol condensation reaction. PRACTICE: Give the structure of the aldehydes or ketones used to create the product prepared by a crossed aldol reaction. H PRACTICE: What product can be isolated from the following aldol condensation reaction? H H Page 8

9 CNCEPT: CLAISEN-SCHMIDT REACTIN When a crossed aldol contains an enolizable aldehyde and a ketone, one product does predominate. Aldehydes are more susceptible toward nucleophilic addition than ketones, favoring a single enolate. EXAMPLE: Predict the major product of the following condensation. Page 9

10 CNCEPT: CLAISEN CNDENSATIN Via enolates, esters will react with to condensate into Mechanism: 1. Form the enolate 2. Nucleophilic attack the other carbonyl (which we will call the electrophile) 3. Kick out the good leaving group: Example Application: Page 10

11 PRACTICE: Draw the structure of the Claisen condensation product for each of the following compounds. NaEt Et Et EtH PRACTICE: Draw the structure of the Claisen condensation product for each of the following compounds. NaMe MeH PRACTICE: Give the structure of the ester precursor for the following Claisen condensation product. Page 11

12 CNCEPT: INTRAMLECULAR CNDENSATIN Dicarbonyl compounds have the ability to self-condensate through cyclization if it will generate a or -membered ring. When a diketone or dialdehyde self-condensate, the resulting product is called a cyclic enone When a diester self-condensates, the resulting product is called a cyclic β-ketoester This is known as a Dieckmann Condensation Page 12

13 PRACTICE: Consider the following reaction. Provide a stepwise mechanism to explain the given transformation. Page 13

14 CNCEPT: CNJUGATE ADDITIN F ENNES nce an aldol condensation is completed, an electrophilic carbonyl still remains. Enones remain susceptible to nucleophilic attack, however they now have two electrophilic regions: Also known as 1,2 vs. 1,4 addition of enones, or nucleophilic addition vs. conjugate addition of carbonyls. Nucleophilic Addition vs. Conjugate Addition Page 14

15 CNCEPT: THE MICHAEL REACTIN The Michael Reaction is a 1,4-conjugate addition of an enone with an enolate. Basically Always forms 1,5-dicarbonyls Mechanism: Page 15

16 PRACTICE: Determine the product in the following conjugated addition reaction. PRACTICE: Determine the product in the following conjugated addition reaction. PRACTICE: Determine the product in the following conjugated addition reaction. Page 16

17 CNCEPT: RBINSN ANNULATIN 1,5-dicarbonyl compounds have the ability to undergo intramolecular self-condensation into 6-membered enones. When the 1,5-dicarbonyl is generated via Michael Reaction (enone + enolate), it is called a Robinson Annulation ` Basically EXAMPLE: Predict the major product of the following Robinson Annulation. Page 17

18 PRACTICE: Provide the product for the following Robinson Annulation Reaction. PRACTICE: How would you prepare the following compound using a Robinson annulation reaction between a di-ketone and an alpha, beta unsaturated ketone? PRACTICE: How would you prepare the following compound using a Robinson annulation reaction between a ketone and an alpha, beta unsaturated ketone? Page 18