Enamides reactions

Electrochemistry (Continued) purely organic compounds, 342 sulfide oxidation, 361 Electrode materials, 342 Electrophilic allylation, 192 attractive interaction, 196 mechanism, 192, 197 turnover-limiting step, 197 Electroreaction, asymmetric, 342 Electrostatic interaction, 328 Elimination and insertion, 3 Enamide reactions ... 

Isocyanophosphonates, aldol reactions, 227 Isoquinoline synthesis, enamide reactions, 33 Isomerization allylic amines, 9, 95 olefins, 118, 171 see also specific compounds Isopulegol, 102 Isotactic polymers, 174 chloral, 182 photoirradiation, 347 methacrylates, 181 propylene, 174 Isotacticity, 177... 

The enamine cyclization reaction has not been utilized in organic synthesis to the same extent as the corresponding enamide reaction. Schultz and Chiu have utilized this reaction in an approach to the synthesis of the aspidosperma alkaloids21. Irradiation of compound 37 produces tetracyclic compound 38 in 71% yield (equation 11). 

Feldgus, S. Landis, C. R. Large-scale computational modeling of [Rh(DuPHOS)]-catalyzed hydrogenation of prochiral enamides Reaction pathways and the origin of enantioselection. /. Am. Chem. Soc. 2000, 122, 12714-12727. 

Thermal decomposition of capsaicin yields capsaicin dimer ( )-JV-vanillyl-di(8-methylnon-6-en)imide (10-35), various amides, acids, hydrocarbons and phenols. The main product is E)-S-methylnon-6-enamide, nonanamide, pentanamide and other amides, ( )-8-methylnon-6-enoic acid, nonanoic acid, ( )-hept -2-ene, vanillin and other substituted phenols (2-methoxy-4-methylphenol and 2-methoxyphenol), which are produced by decomposition of vanillin. Roasting of peppers in oil may produce fatty acid amides. For example, reaction with oleic acid yields (Z)-N-vanillyloctadec-9-enamide reaction of oleic acid with ammonia, originating from capsaicin, gives rise to (Z)-octadec-9-enamide (oleamide). 

T ribenzenesulj enamide Reactions with trisulfenamides Pyrimidines from pyrroles... 

Asymmetric cyclization using chiral ligands has been studied. After early attempts[142-144], satisfactory optical yields have been obtained. The hexahy-dropyrrolo[2,3-6]indole 176 has been constructed by the intramolecular Heck reaction and hydroaryiation[145]. The asymmetric cyclization of the enamide 174 using (S j-BINAP affords predominantly (98 2) the ( )-enoxysilane stereoisomer of the oxindole product, hydrolysis of which provides the ( l-oxindole aldehyde 175 in 84% yield and 95% ec. and total synthesis of (-)-physostig-mine (176) has been achieved[146]. 

Fluorocylatwn of enarnines and enamides has been intensively studied by different groups [78, 79, 80 SI] The effectiveness of this particular electrophilic substitution reaction becomes obvious when the nitrogen atom of the enamine moiety is engaged in an aromatic system [82 S3] or when the olefinic system is part of an aromatic nucleus [84] (equations 37 and 38) A further extension of this reaction is demonstrated by the tnfluoracetylation of aldehyde dialkyl hydrazones [S5 86] (equation 39)... 

Reactions of benzoylperoxide with morpholinocyclohexene and morpho-linocyclopentene furnished the corresponding a-benzoyloxyketones in modest yields (480,481). This oxidation has also been applied to some vinylogous amides (482), and the expected faster rate of reaction of the enamine system as compared with enamides has been noted in derivatives of 20-ketosteroids, in reactions with perbenzoic acid (59,483). 

The most extensive use of enamine halogenations has, hctwever, been in the attachment of fluorine to the steroid skeleton (499-503). The formation of a ]6-fluoro-17-ketosteroid by the reaction of perchlorofluoride with a 17-enamide has also been reported (504). 

The intramolecular cycloaddition reaction of enamides has been exploited in alkaloid synthesis (81JOC3763). One successful application is provided by the total synthesis of the fused indolizidine 5 from 4 as a 1 1 mixture of epimers in 43% total yield 5 is a key intermediate in aspidosperma alkaloid synthesis (79JA3294). 

A series of chiral binaphthyl ligands in combination with AlMe3 has been used for the cycloaddition reaction of enamide aldehydes with Danishefsky s diene for the enantioselective synthesis of a chiral amino dihydroxy molecule [15]. The cycloaddition reaction, which was found to proceed via a Mukaiyama aldol condensation followed by a cyclization, gives the cycloaddition product in up to 60% yield and 78% ee. 

A possible side reaction in A-acyliminium chemistry is caused by deprotonation, giving rise to the formation of an enamide. Though this tautomerization is in principle reversible in acid media, this is not always the case. The enamide may react as a nucleophile with the /V-acyliminium ion still present, to produce dimers14. 

Diels-Alder reaction of dienophiles, N-allylic enamides and a,/l-unsaturated lactam derivatives with open chain and inner ring dienes is promoted by iodine [98]. Thus the cycloaddition of N-benzyl-N-methallyl acrylamide 147 with cyclo-pentadiene (1) proceeds smoothly in DMF at —78 °C in the presence of I2 (2 eq.) to give a prevalence of endo adduct l Vd) in 88% yield (Equation 4.17). 

Diels-Alder reaction of N-allylic enamides and lactam derivatives through iodine-mediated activation [98]... 

Oxidative Heck arylation of enamides with arylboronic acids, using oxygen gas as a reoxidant for Pd(0) and 2,9-dimethyl-1,10-phenanthroline as a chelating regiocontrolling ligand, yielded a (= internally) arylated reaction product as the major compound with a very good a//3 selectivity [92]. Microwave irradiation with prepressurized sealed vials proved useful in reducing the reaction time (Scheme 82). 

Oxetanes are present in several biologically active natural compounds as, for example, the taxol ring skeleton. An interesting method used to obtain this particular ring is the thermal [2 -i- 2] cycloaddition reaction. Longchar and co-workers reported a novel [2-1-2] cycloaddition of /1-formil enamides 5, often used in other cycloaddition and condensation processes, with acetylenic dienophiles 6 under microwave irradiation (in a domestic oven) to afford ox-etenes 7 in 80% yields [29]. This reaction was directed towards the synthesis of D-ring annelated heterosteroids (Scheme 2). 

Enamide hydrogenations have become a routine test reaction for evaluation of the effectiveness of new chiral Hgands [5,11,20,56,59,104]. In addition to being a test reaction, it stands as one of the most powerful and economic methods for the production of enantiomerically pure a-amino acid derivatives. Our group... 

Scheme 24. Examples of Rh-catalyzed asymmetric hydrogenation reactions of enamide derivatives...

Several enamines also participate in these cycloaddition reactions. For example, the addition of methyl lithium to benzaldehyde 5 and the sequential introduction of the vinylogous amide and magnesium bromide results in the cycloaddition elimination product chromene 63 (method G, Fig. 4.33).27 The introduction of methyl magnesium bromide to a solution of the benzaldehyde 5 and two equivalents of the morpholine enamine produces the cycloadduct 64 in 70% yield with better than 50 1 diastereoselectivity (method F). Less reactive enamides, such as that used by Ohwada in Fig. 4.4, however, fail to participate in these conditions. 

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