Dienamides

An intramolecular palladium-catalyzed tandem cyclization of dienamides 67 in which the amide nucleophile adds twice has been developed (equation 29)60. This reaction constitutes a formal [4+1] cycloaddition and provides a new route to pyrrolizidine and indolizidine alkaloids. Reaction of dienamides 67 in the presence of catalytic amounts of Pd(OAc)2 and CUCI2/O2 as the oxidant afforded bicyclic compounds 68 in good yields. The pyrrolizidine derivative 68 (R = Me, n = 1) was transformed to the alkaloid ( )-heliotridane. 

Metal-catalyzed isomerization of allylamides is slower than that of allylamines. The isomerization was examined at higher temterature (>100°C) using [Rh((+)-BINAP) (cod)]+. Although the enantioselecdvity was high, the yield of the desired enamide was low due to the formation of dienamide (Equation (5)).9... 

Scheme 14.19 Hydrogenation of conjugated a,y-dienamide esters by [((/ ,R)-Et-DuPHOS)-Rh (cod)]OTf (54b) (OTf= triflate) [83].

Piper trichostachyon C.DC. from India contains a variety of pyrrolidine alkaloids in its stem and leaves. Among these one finds trichostachyne (135) (210), its C2 homolog 1-piperettylpyrrolidine (141) (211), tricholein (142) (212), and a long-chain dienamide trichonine or l-pyrrolidinyl-(E, )-eicosa-2,4-di-enamide (143) (213). 

An intramolecular Diels-Alder reaction of allenic dienamide 181 provided the tet-rahydroindole ring system 182, which was oxidized with DDQ or Mn02 to give indole derivatives [147]. 

Natural cis-trikentrin B was synthesized enantioselectively by cycloaddition of the allenic dienamide [149]. 

Cyclic a-amino acids with an enamine pattern can be obtained upon enantioselective hydrogenation followed by a hydroformylation/cyclization sequence in a single-pot version Rh(I)-DuPHOS acts as a catalyst for both steps, the enantioselective hydrogenation of prochiral dienamides and the hydroformylation of the resulting homoallylic amines (Scheme 13) [52,53]. 

Penta-2,4-dienamides have been obtained by stoichiometric Ni(II)-pro-moted oxidative aminocarbonylation of 1,3-butadiene (Eq. 16) [56]. 

Dienamides such as 167 react by a different reaction pathway168, namely by addition of the amide oxygen to the alkene by a radical addition reaction (equation 111). 

Many years later, Fukuhara and Urabe showed that aryl Grignard reagents react with ethyl 2,4-dienoates or 2,4-dienamides, in the presence of iron salts, to give the 1,6-addition products (Scheme 60). This reaction is stereoselective and leads to the (Z)-trisubstituted olefins. 

In 2004, Ley et al. [45] showed a stereoselective enzymatic synthesis of cis-pellitorine [N-isobutyldeca-(2 ,4Z)-dienamide], a taste-active alkamide naturally occurring in tarragon. The reactants were ethyl ( ,Z)-2,4-decadienoate— the pear ester described before—and isobutyl amine. The reaction is catalysed by lipase type B from Candida antarctica (commercially available), which shows a remarkable selectivity towards the 2 ,4Z ester. The yield was about 80%. 

In the presence of a cationic Rh[((/ )-binap)(cod)] complex, geranyl or neryl amides isomerize slowly to give a mixture of the corresponding enamide and dienamide (Scheme 20) (2). The optical purity of the chiral enamide is high, but the chemical yield is low. Certain cyclic allylic amides give the enamide isomers in a high ee. With a DIOP-Rh catalyst, prochiral allylic alcohols are converted to optically active aldehydes with low ee (31). 

Dienamides,3 A key step in a synthesis of m-dihydroxylycoricidine (3) involved in situ generation of a dienamide (a) for an intramolecular (4 + 2]cycloaddition to form 2. 

Another approach to the lycorane skeleton involving an intramolecular Diels-Alder reaction commenced with the conversion of the unsaturated nitrile 138 to the imine 139 by sequential reduction with diisobutylaluminum hydride followed by condensation with but-3-enylamine (Scheme 13) (118). When 139 was acy-lated with chloroethyl chloroformate in the presence of Hiinig base and the resulting dienamide heated at 140°C, the bicyclic carbamate 141 was isolated. If it is assumed that the Diels-Alder reaction proceeded via an exo transition state,... 

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