Enamides aromatic

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)... 

Stereochemistry can be interpreted in terms of conformation effects in the 1,4-biradical intermediates.199 Vinyl enol ethers and enamides add to aromatic ketones to give 3-substituted oxetanes, usually with the cis isomer preferred.200... 

High facial diastereoselectivity has been reported in the [2+2] photocycloaddition of aromatic aldehydes with a chiral enamide to give the ds-2,3-disubstituted oxetanes 11 and 12 with only minor amounts of the trans-oxetanes <99TL9003>. The same group of workers have investigated the photocycloaddition of m-substituted benzaldehydes to 3,4-dihydro-l.H-pyridin-2-ones to give mainly 13 <99JA10650>. 

Rhodium-catalyzed hydrogenation of enamides has been successfully performed using monodentate phosphites 17, with enantioselectivities of up to 95% being obtained [53]. The rate of hydrogenation is low in order to reach full conversion with a SCR of 500, hydrogenation is performed at a pressure of 60 bar for 20 h. The use of ligand 17 am in the rhodium-catalyzed hydrogenation of aromatic enamides resulted in ee-values of up to 95%. 

L/Rh = 2 SCR=500 (aromatic enamides), 50 (/i-dehydro amino acid esters) and 1000 for the other substrates. 

A similar reaction of vincinal aromatic or heterocyclic diamines 104 with 2-benzoylamino-3-chloropropenoic acid 102 resulted in sprro-2-oxazolines fused to a pyrazinone nucleus 108. It is believed that the enamide 102 first isomerizes to the A-acyl imine 103 followed by Michael addition of the diamine 104. The resulting Michael adduct 105 cyclizes to 106 or 107 either of which leads to the same oxazoline 108. Single-crystal X-ray confirmed the structure of 108. Unsymmetrical diamines gave two isomeric products with the predominant product... 

It is important to note that a possible photochemical ring expansion by [1,3]- or [l,5]-acyl shifts in the 5-membered vinyl lactams 191 has not been observed,4,116 nor have [l,5]-shifts of acyl groups involving an aromatic ring been reported for either enol esters or enamides. However, an example of a similar [l,5]-alkyl shift, 193 -> 194, in related ketene dialkyl acetals is known.24... 

For examples of Ru-catalyzed hydrogenation of N-(3.4-dihydro-2-naphthalenyl)-acetamide see (a) Renaud. J.L., Dupau, P., Hay. A.-E.. Guingouain. M., Dixneuf P.H. and Brtmeau. C. (2003) Ruthenium-catalysed enantioselective hydrogenation of trisubstituted enamides derived from 2-tetralone and 3-chromanone Influence of substitution on the amide ai m and the aromatic ring. Adv. Synth. Catal.. 345. 230-238. 

F-Teda BF4 is effective for the selective addition of fluorine to steroids in good yield, re-gioselectively and, in many cases, stereoselectively at the 6- and 16-positions, under very mild reaction conditions (Table 7).92 Further, 6 will also efficiently fluorinate silyl and alkyl enolates, enamides, carbanions, a-alkenes and actived aromatic compounds (Table 8). As an extension of this method F-Teda BF+ has been used for the electrophilic fluorination of (fluorovinyl)tin compounds affording terminal fluoroalkenes (see Table 9).88... 

It is reported that the palladium-catalysed intramolecular aromatization of 1,1 -dichloro-9/T-fluoren-9-yIidene (15) may lead to the formation of fullerene fragments.89 The amiulation reaction, under palladium catalysis, between iodoanflines and ketones may yield indole derivatives.90 There have also been studies of the palladium-catalysed carbonylation of o-iodophenols with allenes which may lead to l-benzopyran-4-one derivatives,91 of the intramolecular coupling of phenols with aryl halides,92 and of the intramolecular Heck aiylation of cyclic enamides.93... 

Chiral benzo[t/ thiepine fused to pyrrole ring 163 was obtained via a tandem dehydrogenation/intramolecular arylation <2001TL573>. Treatment of ct-hydroxylactam 160 with trifluoroacetic acid (TFA) at 25 °C gave a separable mixture of 163 and 165 in 64% and 22% yields, respectively (Scheme 18). Formation of the minor product 165 was a consequence of deprotonation of /V-acyliminium ion 161, followed by isomerization of unstable enamide 164. Formation of benzo[t/ thiepine 163 can be explained by a 71-aromatic intramolecular arylation of... 

Steroidal, alicyclic or aromatic annulated pyridines were prepared via a microwave-assisted, base-catalyzed Henry reaction of /1-formyl enamides and nitromethane on an alumina support [97]. Highly substituted tri- and tetrasubstituted pyridines were synthesized in a Bohlmann-Rahtz reaction from ethyl /3-amino crotonate and various alkynones. The reaction involved a Michael addition-cyclodehydration sequence and was effected in a single synthetic step under microwave heating conditions [98]. An alternative approach towards polysubstituted pyridines was based on a reaction sequence involving an inverse electron-demand Diels-Alder reaction between various enamines 45 and 1,2,4-triazines 44 (Sect. 3.6), followed by loss of nitrogen and subsequent elimination-aromatization. Enamines 45 were formed in situ from various ketones and piperidine under one-pot microwave dielectric heating conditions [99]. Furthermore, a remarkable acceleration of the reaction speed (from hours and days to minutes) was observed in a microwave-assisted cycloaddition. Unsymmetrically substituted enamines 45 afforded mixtures of regioisomers (Scheme 35). 

High enantioselectivity for various aromatic enamides Lower enantioselectivities of alkyl enamides Rapid rates Ligand synthesis difficult and in low yields... 

Rhodium-Catalyzed Hydrogenation of Aromatic Enamides Using Monodentate Phosphoramidite Ligands... 

Bach, T., Bergmann, H., and Harms, K. (1999) High facial selectivity in the photocycloaddition of chiral aromatic aldehyde and enamide induced by intermolecular hydrogen bonding. Journal of the American Chemical Society, 121, 10650-10651. 

A three component coupling reaction of A-acetyl-2-azetine, aromatic imines and aromatic amines allows a rapid stereoselective entry to 2,3,4-trisubstituted tetrahydroquinolines, via fused tricyclic azetidines 1 <02CC444>. Fused heterocycles 1 were formed through an aza Diels-Alder reaction between aromatic imines and A-acetyl-2-azetine, which acts as an enamide substrate. This strategy has been used for the formal synthesis of luotonin A <02TL5469>. 

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