Synthesis of Enamides

The present methods for the preparation of N acyl a arylenamides include (i) reductive acylation of ketoximes with iron metal [2] or phosphines [3] in the presence of acyl chlorides or acyl anhydrides (Method A) (ii) metal catalyzed coupling of vinyl halides [4], triflates [5], or tosylates [6] with amides (Method B) (iii) reaction of imine intermediates derived from nitriles with acyl chlorides or anhydrides (Method C) [7] and(iv) Pd catalyzed coupling ofaryl tosylates with N acyl vinylamines (MethodD) [8]. 

The enamides with an exocyclic double bond have been extensively used in the 

---

The N,0-acetals are intermediates for the synthesis of enamides 264) and for the production of DL-omithine 265 266) and DL-lysine 267 268>. The amino acid syntheses are not economically competitive with the fermentation methods since they only give the racemates, which then have to be resolved into the antipodes. 

Another method employing nitriles for the synthesis of enamides starts from amino nitriles prepared by Strecker synthesis641. An aminonitrile has been acylated to form the acylaminonitrile, and pyrolysis of the latter under reduced pressure over quartz at 450-650 °C yielded the enamide in approximately 95% yield (equation 45). 

Furstner, A., Brehm, C., Cancho-Grande, Y. Stereoselective Synthesis of Enamides by a Peterson Reaction Manifold. Org. Lett 2001, 3, 3955-3957. 

A simple synthesis of enamides from ketoximes has been described and demonstrated with various steroidal derivatives. Thus, 5a-cholestan-3-one oxime (54a) and its derivatives (54b—e) when refluxing in acetic anhydride and pyridine afforded (55) with 10% of its A-3 isomer. From crude reaction mixture, the enimide (56) could be isolated by crystallization or silica gel chromatography. Compound (55) was obtained by alumina chromatography and led to (56) with acetic anhydride-... 

Klapars reported the synthesis of enamides by the coupling of enol tosylates with amides [181], Here, an i-propyl-derivative of dppf was used as ligand together with the weak bases K3PO4 or K2CO3 in t-AmOH as solvent. Previously, XantPhos and CS2CO3 were used for the same purpose in 1,4-dioxane as solvent by Wallace [182],... 

Carbamido-sulphones could also be deprotonated and alkylated successfully, with a synthesis of enamides being completed by based-induced elimination of the sulphonyl moiety.Four routes leading to the synthesis of (50) which was used in the preparation... 

Formation of C-N bond has raised of interest in the scientific community in the last 10 years. In this context, the formation of enamides is a valuable protocol. In addition to conventional approaches that include condensation of amides and aldehydes, addition of amides to alkynes, acylation of imines, Curtius rearrangement of a,jS-unsaturated acyl azides, amide Peterson olefination, and Wittig and Horner-Wadsworth-Emmons reactions, several transition metal-catalyzed methods have been developed that allow the synthesis of enamides.Inspired by the analogous arylation of amines catalyzed by palladium or copper complexes (Buchwald-Hartwig reaction), a new approach for the synthesis of enamides has been published recently, which allows to prepare enamides from readily available starting materials (amides and vinyl halides) proceeding under very mild conditions. Thus, we decided to test the Porco-Buchwald amidation of vinyl halides in our synthesis [144-146]. 

Later, Buchwald reported a general procedure for the synthesis of enamides under mild conditions that allows the use of substituted vinyl iodides and bromides using Cul and DMEDA (Scheme 4.30) [146]. The coupling required CS2CO3 in... 

Reviews about metal-catalyzed coupling reaction Dehli et al. [142], Evano et al. [143]. Synthesis of enamides starting from 2-pyrrolidine and vinyl triflates Wallaee et al. [147], Klapars et al. [148]. From vinyl ehlorides Hesse and Kirsch [149]. 

Recently, Goopen has reported a new protocol that draws on easily available ruthenium chloride trihydrate (RUCI3 3H2O) as a catalyst precursor instead of the expensive [Ru(cod)(methallyl)2] [189]. In this new protocol, the catalyst is generated in situ, affording comparable yields. Furthermore, in 2007 Kuninobu and Takai reported the synthesis of ( )-enamide by rhenium-catalyzed hydroamination of unactivated terminal alkynes [190]. However, this method proceeds with less efficiency and lower reaction scope with respect to the mthenium one. 

The Wittig reaction can be modified to allow the synthesis of enamides. In Scheme 4.57, the Wittig olefination of A -formyl imide precursor III-85 [204] (pseudo-aldehyde) with a phosphonium ylide III-86 is shown. The A -formyl imide III-85 can be synthesized from the parent lactam unit. 

In 2007, the group of Marquez reported the first synthesis of enamides through the use of 77-formyl imides. [204] These 7/-formyl imides behave as carbonyls due to the presence of a second carbonyl unit, which effectively ties up the nitrogen... 

Scheme 4.61 Witting reaction of 7V-foimyl imide ni-89 and phosphinium bromide ni-87 Synthesis of Enamides by Heck Reaction...

SCHEME 3.115 Copper-catalyzed synthesis of enamides from primary amides [121]. 

SCHEME 3.116 Copper-catalyzed synthesis of enamides using a rubidium carbonate as the base [122]. 

SCHEME 3.122 Synthesis of enamides through vinyl transfer reactions [130]. 

Interestingly, Lam has described a synthesis of enamides via rhodium-catalyzed carbozincation of ynamides [175]. When applied to dialkenylzinc compounds, this reaction leads to the regio- and stereoselective formation of 1-amidodienes 224 (Scheme 87). The regioselectivity of the reaction was explained by the possible formation of a chelated complex 223. 

---