Electrophilic addition reactions Enals

The carbanion -type reactivity of dienamine activation can be promoted by a silyl-protected diarylprolinol catalyst in the presence of reactive electrophilic species, such as nitroolefins or diarylmethanols (Scheme 2.10) [20]. Although both direct addition (a-addition) and vinylogous addition (y-addition) are viable reaction pathways, the a-reactivity is the more typical one and usually provides better selectivities due to more effective shielding of the a-position by the aminocatalyst. Interestingly, the a-/y-selectivity of dienamine-mediated carbanion -type addition reactions seems to be strongly influenced by the substitution pattern of the enal reactant For example, it was demonstrated that y,y-disubstituted enals favor the a-addition product while y-functionaUzation is the predominant reaction pathway for y-monosubstituted enals. 

The thermodynamic control of conjugate addition allows even enals that are very electrophilic at the carbonyl carbon to participate successfully. Any aldol reaction, which must surely occur, is reversible and 1,4-addition eventually wins out Acrolein combines with this five-membered diketone under very mild conditions to give a quantitative yield of product, The mechanism is analogous to that shown above,... 

In the second example, the electrophile is an anhydride with two reactive carbonyl groups tha nearly but not quite the same. This is a recipe for bad selectivity - reaction will occur at carbonyls. In addition, stereoselectivity will not be so good as the alkenes are trisubstituted there is not as much difference in stability between cis and trans as there was in the disubstitc enal. 

The addition of l,l-bis(seleno)alkyllithiums at the C-3 site of enals and enones produces enolates which can be trapped with various electrophiles (Scheme 140, b-d Schemes 149 and 150). Silylation of the litiiium enolates with trimethylsilyl chloride leads to the corresponding silyl enol ethers (Scheme 140, c), which can then be subjected to further reactions. 

The Jorgensen group also applied the parent cinchona alkaloids as catalysts to the aza-Michael addition of hydrazones 8 to cyclic enones 9 [4] and the asymmetric deconjugative Michael reaction of alkylidene cyanoacetates 10 with acrolein (11) [5], However, only a moderate level of enantioselectivity was obtained in both reactions (Scheme 9.4). Of note, for the deconjugative Michael reaction, the delocalized allylic anion 12 could be generated via the deprotonation of 10 by the cinchona base and might attack the electrophilic enal at either the a- or the y-position. However, in this study, only the a-adducts were produced. 

In the last chapter we introduced the Heck reaction as a way to add nucleophiles to electrophilic alkenes. The details of the mechanism are discussed there. The reaction also occurs with allylic alcohols 218 and is a good way to make carbonyl compounds, particularly aldehydes, 219 as the alternative conjugate addition of an organometallic compound to an enal often shows poor regioselectivity (chapter 9). 

Finally, there is also a relevant example of an intermolecular conjugate Friedel-Crafts/electrophilic amination cascade developed very recently by Melchiorre in which 2-methyl-IH-indole reacted with a variety of a,p-unsatu-rated aldehydes and dialkyl azodicarboxylates in the presence of a primary amine catalyst, leading to the formation of a family of products containing two contiguous stereocenters, one of them a quaternary one (Scheme 7.43). This reaction started with the conjugate addition of 2-methyl-lH-indole to the enal... 

Lewis acid complexes of p-substituted a,p-unsaturated ketones and aldehydes are unreactive toward alkenes. Crotonaldehyde and 3-penten-2-one can not be induced to undergo ene reactions as acrolein and MVK do. 34 The presence of a substituent on the p-carbon stabilizes the enal- or enone-Lewis acid complex and sterically retards the approach of an alkene to the p-carbon. However, we have found that a complex of these ketones and aldehydes with 2 equivalents of EtAlQ2 reacts reversibly with alkenes to give a zwitterion. 34 This zwitterion, which is formed in the absence of a nucleophile, reacts reversibly to give a cyclobutane or undergoes two 1,2-hydride or alkyl shifts to irreversibly generate a p,p-disubstituted-o,p-unsaturated carbonyl compound (see Figure 19). The intermolecular addition of an enone, as an electrophile, to an alkene has been observed only rarely. The specific termination of the reaction by a series of alkyl and hydride shifts is also very unusual. 35 The absence of polymer is remarkable. 

---