Dienamide synthesis

Biolatto B, Kneeteman M et al (1999) Diels-Alder reactions of lV-tosyl-3-nitroindole and dienamides synthesis of intermediates of Aspidospermine alkaloids. Tetrahedron Lett... 

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%. 

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. 

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). 

In a short known reaction sequence, enal 250 was obtained from commercially available material 184). With methylamine and magnesium sulfate imine 251 was formed and combined with acyl chloride 252 185) (>4 steps). The use of low temperatures for this acylation led exclusively to the less substituted dienamide 253. The desired basic skeleton of dendrobine 254 was obtained by cyclizing 253 at 180°C in an acceptable 50% yield, Adduct 254 was accompanied by small amounts of the exo-adduct. Epoxidation led exclusively to exo-epoxide 255, which by means of trimethylsilyltriflate was converted into the allylic silyl ether. Acid treatment liberated the hydroxy group and subsequent oxidation of alcohol 256 led to enone 163, an intermediate of Inubushi s dendrobine synthesis and thus concluded this formal synthesis. The intermediate 163 was obtained from commercially not available materials in seven steps in 22.5% overall yield. To reach ( )-dendrobine according to Inubushi et al. would afford six additional steps, reducing the overall yield to 0.4% without including the preparation of the starting materials from commercially available compounds. 

Naskar, D., Roy, S. Catalytic Hunsdiecker reaction and one-pot catalytic Hunsdiecker-heck strategy synthesis of a,P-unsaturated aromatic halides, a-(dihalomethyl)benzenemethanols, 5-aryl-2,4-pentadienoic acids, dienoates and dienamides. Tetrahedron 2000, 56,1369-1377. 

One of the key steps of the total synthesis of ent-(42) is the formation of the dienamide and uses the palladium-catalyzed cross-coupling [82] between the ( )-vinyl iodide and (Z)-P-tributyltinpropenamide (Scheme... 

The observation by Ma and Lu [53] that 2-alkynylamides, when heated in the presence of /2-BU3P and transition metal complexes, undergo efficient and stereoselective isomerization to 2 , 4 -dienamides was exploited for the synthesis of several naturally occurring aliphatic... 

A terse paper by Kaga et al. reports the synthesis of dienamides in moderate yield by palladium-catalyzed coupling of P-bromoacrylamides with alkenyl boronates. (Scheme 13) [138]. Employing alkenyl boronates derived from appropriate alkynes, the strategy was applied to the synthesis of piperlongumine, 36(n=0), piperine, 42, trichonine, 9(n=14), pellitorine, 5, and the trienyl amide, 48. An alkyl boronate, prepared from l-(3, 4 -methylenedioxyphenyl)-l,5-hexadiene, was similarly used for the synthesis of the non-conjugated dienamide, pipernonaline, 46(n=4) (Scheme 13) [138]. 

Side chain introduction by carbopalladation has been utilized in a total synthesis of an-thramycin methyl ether (32) (Scheme Heck reaction of the alkenyl triflate 30 with acrylamide installs the necessary three-carbon chain in moderate yield. The desired alkene geometry and oxidation state are observed in the dienamide 31 with no need for protection of the primary amide. The organopalladium precursor can also be part of the side chain being introduced as illustrated in a synthesis of prostaglandin E2 33. ... 

A synthesis of substituted dihydropyridin-2(3/f)-ones has been reported from penta-2,4-dienamides in which an intramolecular C-N bond is formed via a thermal 6 r-azaelectrocyclization (Scheme 41). ... 

---