Enals nucleophilic addition

Various aldehydes 184 and alcohols have been shown to be competent in the redox esterification of unsaturated aldehydes in the presence of the achiral mesityl triazo-lium pre-catalyst 186. Both aromatic and aliphatic enals participate in yields up to 99% (Table 13). Tri-substituted enals work well (entry 3), as do enals with additional olefins present in the substrate (entries 4 and 7). The nucleophile scope includes primary and secondary alcohols as well as phenols and allylic alcohols. Intramolecular esterification may also occur with the formation of a bicyclic lactone (entry 8). 

An investigation of alkylation of 1,1-enediamines with a,/ -unsaturated aldehydes and ketones has been recently conducted by Jones and Hirst36. The reaction of 1,1-enediamine 93 and a,/ -enals affords the fused 1,4-dihydropyridines 133, via a nucleophilic addition and intramolecular dehydration sequence (equation 49). 93 reacts with propenal, however, to give the cyclohexene carboxaldehyde 134 in almost quantitative yield (equation 50). The formation of 134 is most probably due to addition of 93 to two... 

Deprotection of the dienes and oxidation of the resulting alcohols gave CE.Zj-b.S-decadi-enal and (is,Z)-6,8-decadienal13. These were converted to ( , .fc )-l-(phenylsulfonylj-1,7,9-un-decatriene and the corresponding (E,Z.E)-isomer by a nucleophilic addition-elimination sequence. 

The chemical reactivity of propenal is representative of a, -unsaturated carbonyl compounds. The conjugation between a carbon-carbon double bond and a carbonyl group leads to characteristic reactivity, which includes reduced reactivity of the carbon-carbon double bond toward electrophiles and enhanced susceptibility to the addition of nucleophilic reagents at the (3 carbon. The anion formed by addition is a delocalized enolate, with the negative charge shared by oxygen and carbon. The topic of nucleophilic addition to enals and enones is considered further in Section 2.6, Part B. 

The BFa-catalysed reactions of tri-O-acetyl-D-glucal with thiophenol have been reinvestigated. Whereas under anhydrous conditions the expected 2,3-unsaturated phenyl 1-thioglycopyranosides 53 were formed, an isomeric mixture of phenyl 2-deoxy-3-phenylthio-l-thiohexopyranosides 54 was obtained in almost quantitative yield when traces of water were present. It is proposed that these products arise from an intermediate enal. The addition products of TolSCl to tri-O-benzyl-D-galactal formed diastereomeric episulfonium ions on exposure to SnCU. These were opened by C-nucleophiles (TmsCN, AllTms, etc.)... 

The first organocatalytic asymmetric carbon nucleophilic addition to enals was reported by MacMillan in 2001 [15]. MacMillan reported the first Friedel-Craft alkylation between N-substituted pyrroles and enals promoted by catalyst 7. The reaction renders the final compounds in good yields and enantioselectivities (Scheme 33.4). 

Jorgensen and coworkers reported in the same year a (3-phosphonylation of enals by trialkyl phosphites [73]. The key to this reaction was the right choice of nucleophilic additive enabling the P " to P oxidation by means of a SN2-type dealkylation reaction. The optimum reaction conditions employed an excess of benzoic acid and Nal and triisopropyl phosphite (90) as a phosphonylation reagent under diphenylprolinol catalysis. Under these conditions the reaction afforded the final products 91 in good yields and excellent enantioselectivities (Scheme 33.23). 

Quintard and Alexakis developed a double Michael addition reaction of enals, taking advantage of the high reactivity of vinyl sulfone-initiated nucleophilic addition of benzaldoxime, triazole, Angelica lactone, benzyl mercaptan, and 174. The powerful organocascade allows for the rapid construction of highly attractive synthons in high enantioselectivities (typically, 99% ee) [117]. 

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