Butadiene cycloaddition with formaldehyde

Ab initio and density functional theoretical studies of the 4 + 2-cycloaddition of 2-azabutadiene with formaldehyde predict a concerted reaction that agrees well with experimental evidence.184 The azadiene A-plienyl-l-aza-2-cyanobuta-l,3-diene reacts with electron-rich, electron-poor, and neutral dipolarophiles under mild thermal conditions.185 5,6-Diliydro-4//-1,2-oxazines have been shown to be usefiil as synthon equivalents of 2-cyano-l-azabuta-1,3-dienes.186 The intramolecular Diels-Alder reaction of 1-aza-l,3-butadienes (106) can be activated by a 2-cyano substituent (Scheme 37).187 Stereoselectivity in the hetero-Diels-Alder reactions of heterobutadienes, nitrosoalkenes, and heterodienophiles has been extensively reviewed.188 The azadiene l-(f-butyldimethylsilyloxy)-l-azabuta-1,3 -diene (107) reacts with halobenzo-quinones, naphthoquinones, and A-phcnylmalcimidc to yield low to good yields of various pyridine heterocycles (108) (Scheme 38).189 The 4 + 2-cycloaddition of homophthalic anhydride with A-(cinnamylidcnc)tritylaminc produces the 3,4-adduct whereas with A -(cinnamylidcnc)bcnzylidinc the 1,2-adduct is produced.190... 

The Regioselectivity ofHetero Diels-Alder Reactions. In a few cases, carbonyl, nitrosyl, cyano, and other double bonds with one or more electronegative heteroatoms have acted as dienophiles in Diels-Alder reactions. The carbonyl group has a HOMO and a LUMO as shown in Fig. 1.51. The energies of both orbitals are relatively low, and most of their Diels-Alder reactions will therefore be guided by the interaction between the HOMO of the diene and the LUMO of the carbonyl compound. This explains the regioselectivity in the cycloaddition of dimethylbutadiene 6.176 and formaldehyde, and between 1-substitituted butadienes 6.177 and nitrosobenzenes. 

Strictly speaking, these variants are no more ene reactions than the cycloaddition reaction of dimethyl azodicarboxylate with 1,3-butadiene is a Diels-Alder reaction. Indeed, the reaction of a carbonyl group, specifically formaldehyde, is separately known as the Prins reaction. The overall characterization of the reaction as a process that fundamentally effects the change illustrated in the basic ene reaction, regardless of the specific atoms involved, is nonetheless useful and will be discussed here. 

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