Enamino-aldehydes

A rather complex reactivity towards the cyclopropenone system is exhibited by N-nucleophiles. Thus, ammonia reacts with diphenyl cyclopropenone to yield either the enamino aldehyde 323222> or a mixture of the cis and trans isomeric diphenyl azetidinones 522223 depending on the reaction conditions these products result from primary addition of the nucleophile at C,(2 ... 

Another interesting example of a photochemi-cally induced domino process is the combination of the photocyclization of aryl vinyl sulfides with an intramolecular addition as described by Dittami et al. [901 as intermediate a thiocarbonyl ylide can be assumed. The domino-Norrish I-Knoevenagel-allyl-silane cyclization developed by us allows the efficient stereoselective formation of 1,2-trans-subsituted five- and six-membered carbocycles.1911 A photochemical cycloaddition of enamino-aldehydes and enamino-ketones with the intermediate formation of an iminium salt followed by addition to allylsilanes gives access to novel bicyclic heterocy-des. New examples of photochemically induced... 

These tautomeric equilibria support the view that in enamino-aldehyde, -ketone and -ester systems generally the relative basicities of the C- and O-protonation sites are comparable, whereas N-protonation is encountered only when steric hindrance to meso-merism is present and, exceptionally, in some solid salts. 

Dihydro-(8//)-5,6-pyridazino[4,5-rf][l,3]oxazin-4-one (153) was prepared from the enamino aldehyde 4-methoxycarbonyl-5-formyl-2,3-dihydro(6//)-1,3-oxazine (152) with hydrazine hydrate in methanol (Equation (20)) <87CCC1773, 87CCC2953). Using the nitrile (154) the resulting pyr-idazinooxazine (155) carries an amino group at position 7 (Equation (21)). 

Although isoxazolines generally undergo photodecomposition to a variety of products, selectivity can be achieved by the introduction of an oxygen atom in the B-position with respect to the isoxazoline oxygen. New examples of this rearrangement leading to the formation of enamino aldehydes have been reported in monocyclic and in bicyclic isoxazolines. Endo- and... 

Further examples of photorearrangeroent of isoxazolines to enamino aldehydes have been reported. 

In that same study, it was found that when C. majus was treated with labeled protopine, labeled sanguinarine and chelidonine were produced. There is, therefore, a possibility that the sequence cw-B/C tetrahydroproto-berberine salt -> protopine A -metho>7,8-dihydroprotoberberine salt -> enamino aldehyde enamine (e.g., 26) -> benzophenanthridine may occur in nature. 

Recent work has shown that they, and the more reactive 2-hydroxytetrahydro-pyridines, can be obtained by photochemical addition of enamino-aldehydes (165) to olefins. The photochemical [2 + 2] cycloaddition proceeds with complete regiospecificity, presumably by the formation of a cyclobutane system, followed by a hetero-retro-aldol reaction and formation of a new enamino-aldehyde, which re-cyclizes to (166). Further treatment with acid provides a useful method for synthesis of benzo[a]quinolizidine alkaloids (167). The last two steps may be completed in one treatment of (166) with BFa EtjO on alumina. 

If a molecule contains both a ketonic and aldehydic carbonyl group, a secondary amine will react with the aldehydic carbonyl group to give a -enamino ketone (15). This has been shown not only for 2-formylcyclo-hexanone (14) (32,33) but also in steroidal systems when the aldehyde and ketone groups are in five- or six-membered rings (34). 

We have previously discussed that keto-aldehydes react with anilines first at the aldehyde carbon to form the aldimine. Subsequent condensation with another aniline formed a bis-imine or enamino-imine. The aniline of the ketimine normally cyclizes on the aldimine (24 —> 26). Conversely, cyclization of the aldimine could be forced with minimal aniline migration to the ketimine using PPA (30 —> 31). The use of unsymmetrical ketones has not been thoroughly explored a few examples are cited below. One-pot enamine formation and cyclization occurred when aniline 48 was reacted with dione 49 in the presence of catalytic p-TsOH and heat. Imine formation occurred at the less-hindered ketone, and cyclization with attack on the reactive carbonyl was preferred. ... 

This is the most common method for the preparation of enamines and usually takes place when an aldehyde or ketone containing an a hydrogen is treated with a secondary amine. The water is usually removed azeotropically or with a drying agent, but molecular sieves can also be used. Stable primary enamines have also been prepared.Enamino-ketones have been prepared from diketones and secondary amines using microwave irradiation on silica gel. ° Secondary amine perchlorates react with aldehydes and ketones to give iminium salts (2, p. 1178). Tertiary amines can only give salts (12). 

The dianions of /S-enamino ketones react with a wide range of electrophiles such as alkyl halides, oxiranes, nitriles, esters, aldehydes and ketones37. Dalpozzo and coworkers reported the generation of the dianion derived from /S-enamino ketones with lithium 2,2,6,6-tetramethylpiperidide and the reaction of the dianion with nitroalkene (Scheme 24)38. The dianion underwent exclusive alkylation at the y-carbon atom to give the monoalkylated product in high yield. This reaction is useful for the introduction of a nitro group into a ketone side chain. 

In contrast, reduction of enamino esters of cyclohexanone resulted in the formation of a series of fragmentation products, among which the a,/ -unsaturated aldehyde is of interest160. The ratio of the products depended on the amount of the reducing agent (Scheme 112). 

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