Ketones formation, azodicarboxylate

C-Nucleophiles have recently been added asymmetrically to azodicarboxylates as Michael-acceptors, resulting in a-amination of the nucleophilic component. Examples of this type of reaction, which is based on activation of the aldehyde or ketone component by enamine formation, are summarized in Scheme 4.27. Please note that this type of reaction is covered in more detail in chapter 7 of this book. 

Extension of this proline-catalyzed a-amination to the use of aldehydes as starting materials has been described independently by the Jorgensen and List groups [6, 7]. The principle of the reaction and some representative examples are shown in Scheme 7.4. The practicability is high - comparable with that of the analogous reaction with ketones described above. For example, in the presence of 5 mol% L-proline as catalyst propanal reacts with azodicarboxylate 3a at room temperature in dichloromethane with formation of the a-aminated product 5a in 87% yield and with 91% ee [7]. Good yields and high enantioselectivity can be also obtained by use of other types of solvent, e.g. toluene and acetonitrile. The products of type 5 were isolated simply by addition of water, extraction with ether, and subsequent evaporation. 

The photochemical addition of 2H-azirines to the carbonyl group of aldehydes, ketones and esters is completely regiospecific (77H143). Besides the formation of the isomeric oxazolines 18 from 3 and ethyl cyanoformate, there is also formed the imidazole 19 from addition to the C = N in the expected regioselective manner. Thioesters lead to thiazolines 20, while isocyanates and ketenes produce heterocycles 21 (Scheme 4). The photocycloaddition of arylazirines with a variety of multiple bonds proceeds in high yield and provides a convenient route for the synthesis of five-membered heterocyclic rings. Some of the dipolarophiles include azodicarboxylates, acid chlorides, vinylphospho-nium salts and p-quinones. 

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