Aldehydes addition-elimination reactions

Scheme 8.2. Addition-Elimination Reactions of Aldehydes and Ketones...

Villsmeier reaction on the dimethylacetal of methoxyacetaldehyde (141) with phosgene and dimethyIformamide affords the acrolein derivative, 142. Condensation of this with guanidine gives the pyrimidine, 143. (The enamine can be viewed as a latent aldehyde-the dimethylamino group is probably lost in the course of an addition elimination reaction with one of the guanidine groups.) This pyrimidine serves as starting material for sulfameter (111). ... 

This approach offers unique opportunities for the generation of multi-functionalized cyclic 2-azadiene systems. A wide variation of the substitution pattern at the positions N-1 and C-6 can be determined by an appropriate choice of the aldehyde and amine. Various substituents can easily be introduced at the C-3 position via addition/elimination reactions on the sensitive imidoyl chloride moiety [24]. Upon reaction with bi-functional reagent, an adequately AT-protected 2(lH)-pyrazinone was elaborated into C-nucleoside analogues (Scheme 8). The desired skeleton and functionalities were obtained by oxidation-cyclization reaction followed by photochemical removal of the protective o-nitrobenzyl group [25]. 

The solid-phase synthesis of the 2(lff)-pyrazinone scaffold is based on a Strecker reaction of commercially available Wang amide linker with appropriate aldehyde and tetramethylsilyl (TMS) cyanide, followed by cyclization of a-aminonitrile with oxalyl chloride resulting in the resin linked pyrazinones. This approach allows a wide diversity at the C-6-position of pyrazinone scaffold (Scheme 35, Table 1). As it has been shown for the solution phase, the sensitive imidoyl chloride moiety can easily undergo an addition/elimination reaction with in situ-generated sodium methoxide affording the resin-linked... 

In Section 7.7.2 we met enamines as products from addition-elimination reactions of secondary amines with aldehydes or ketones. Enamines are formed instead of imines because no protons are available on nitrogen for the final deprotonation step, and the nearest proton that can be lost from the iminium ion is that at the P-position. 

Aldehydes and ketones undergo nucleophilic addition-elimination reactions with oxygen and nitrogen nucleophiles. 

Overall, the addition of a nitrogen nucleophile to an aldehyde or a ketone is a nucleophilic addition-elimination reaction nucleophilic addition of an amine to form an unstable tetrahedral intermediate, followed by elimination of water. The tetrahedral intermediates are unstable because the newly formed sp carbon is bonded to an oxygen and to a nitrogen—another electronegative atom. Water is eliminated, and loss of a proton from the resulting protonated imine forms a stable imine. 

In contrast, the reaction of an aldehyde or a ketone with a carbon or hydrogen nucleophile forms a stable tetrahedral compound because the newly formed sp carbon is not bonded to a second electronegative atom. Thus, aldehydes and ketones undergo nucleophilic addition reactions with carbon and hydrogen nucleophiles, whereas they undergo nucleophilic addition-elimination reactions with nitrogen nucleophiles. 

The stereocontrolled synthesis of 1,2-aminols is of interest due to the utility of these substances as efficient synthons for a variety of natural products. A highly stereoselective addition of lithium alkyls or Grignard reagents to the 0-protected a-hydroxy-A-trimethylsi-lylimines generated in situ constitutes the path for the preparation of these 1,2-aminols. Thus, the addition-elimination reaction of lithium hexamethylsilylamide with aldehyde 129, easily obtained in two steps from 103, leads to the a-OTBS-A -TMS-imine 130 (Scheme 30). 

HCI + CH2 CH2 CHaCHja An example of nucleophilic addition is the addition of hydrogen cyanide across the carbonyl bond in aldehydes to form cyanohydrins. Addition-elimination reactions are ones in which the addition is followed by... 

SECTION 8.2. ADDITION-ELIMINATION REACTIONS OF KETONES AND ALDEHYDES... 

Some addition-elimination reactions of aldehydes and ketones... 

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