Dienamides Diene

Chelidonine, a representative benzo[c]phenanthridine alkaloid (1,2), was synthesized as the first application of this reaction in natural product synthesis (145). Initial thermal opening of the four-membered ring in 299 led to the formation of a transient -o-quinodimethane (301), which has a dienamide structure in the diene part and is then trapped by the suitably positioned multiple bond in the same molecule. They applied this intramolecular reaction to the acetylenic cyclobutene 300 for the synthesis of ( )-chelidonine (Scheme 110). 

Chiral auxiliaries may also be used to effect diastereoselective complexations of acyclic dienes. For chiral dienamides (225a-d), the best case employed the sterically demanding (5 )-2-(diphenylhydroxymethyl)pyrrolidine auxiliary. Diene (225d) was complexed with excellent diastereoselectivity but in modest yield (Scheme 64). For substrates (217a-c), diastereomer ratios of the corresponding complexes were poorer (1.5 1 to 4.6 1), likely a result of the increased distance between the auxiliary s chiral center and the diene. 

Dienamides (133) readily undergo intermolecular [4 + 2] cycloadditions, as exemplified by the highly emfo-selective reaction of (136) with maleic anhydride giving (137) (Scheme However, the main advantage of the simple diene preparation (131) — (133) is the facile introduction of an alkenic chain. 

Similar palladium-catalyzed intramolecular dicarborations of dienes using aryl or vinyl halides and tributyl(vinyl)tin as reagents are known39,69. Thus, dienamide 2, containing the chiral pinene skeleton, gives the heterocyclic spiro adduct 3 with complete control of stereochemistry69. 

Reactions of azadienes and dienamides, carrying chiral substituents, are repotted295 to react with [Fe2(CO)9] to afford (T -diene) iron tricarbonyl complexes with good to excellent diasteroselectivity, depending on the nature of the chiral auxiliary employed. Complete selectivity was observed for the dienamide prepared from (5)-2-(diphenylhydroxymethyl)pyrrolidine and sorbic acid, leading to a chiral non-racemic diene complex, the stereochemistry of which was determined by single crystal X-ray methods. 

A totally different mechanism has been shown to apply to the palladium-catalyzed route. The speculated mechanism involves an in situ generated Pd(II)-H entity rather than a Pd(0) complex [77]. This hydride is supposed to add across the triple bond of the alkyne in a syn fashion, leading to a vinylpaUadium intermediate that then behaves as in the classical Heck mechanism toward the olefin and affords the diene [78]. This methodology has allowed the transformation of acrylamide 84 into a series of dienamides 85 in good regio- and stereo-selectivities (Scheme 43). 

Cobalt-mediated stereoselective assembly of 1-dienamides has also been described by VolUiardt recently. The process involves a hydroaminative alkyne coupling of a,(D-diynes and leads to a completely Z-selective formation of the diene moiety with a regiochemistry that depends on the substrate [179]. 

Prandi and coworkers investigated cychzation reactions involving dien-amides they found differential reactivity based on the substitution pattern of the dienamide (Scheme 48 2011OBC2535). For example, treatment of dienamide 211 with TFA led to the formation of 3-pyrrolin-2-one 212. The same reaction with the methyl-containing substrate 213 led to the formation ofimino ether 214. The structures of the 3-pyrrolin-2-one products were confirmed by ROESY NMR experiments the structure of one of the imino ether products (N-naphthyl) was confirmed by single crystal X-ray analysis. 

---