Dienamines synthesis

Alkylation of dienamines with alkyl halides has been found to take place at the oc carbon (288-290). The reaction was used in the synthesis of steroid analogs (291). 

Olefins are also the products of hydroboratlon of enamines, followed by treatment of the organoborane products with hot acid (543,544). The reduction of enamines with sodium borohydride and acetic acid (545) and the selective reduction of dienamines with sodium borohydride to give homo-allylic tertiary amines (138-140,225,546,547), has been applied to the synthesis of conessine (548) and other aminosteroid analogs (545,549-552). Further examples of the reduction of imonium salts by sodium borohydride can be found in the reduction of Bischler-Napieralski products, and other cyclic imonium salts (102). 

Soon thereafter, the Yamamoto group reported an extension of this work to the highly diastereo- and enantioselective synthesis of nitroso Diels-Alder-type bicycloketones using dienamines in the presence of the BINOL derivative 44 (Scheme 5.61) [115]. This reaction was thought to proceed through a sequential N-NA/ hetero-Michael reaction mechanism. Support for this mechanism was provided from an experiment employing bulkyl 4,4-diphenyl dienamine where the N-NA... 

Enamines or imines can form pyridines by cyclization to a nitrile group, as shown in the production of compound (48). Alternatively, the nitrogen atpm of the nitrile can be made more nucleophilic by attack on the carbon atom by an external nucleophile. Ammonia causes cyclization of the dienamines (53) (77JHC1077) and (54) (78JAP(K)786878l) in both cases, elimination of the amine introduces the extra double bond. Dimethylamine or piperidine cause cyclization of l-cyano-2,5,5-trimethylhex-l-en-3-yne to the f-butyl-pyridine (55). There are a few other examples of the synthesis of bicyclic compounds from... 

There are numerous studies on the synthesis of pyrrolizines from enam-ines. In these reactions, one of the step is the closure to a new hydrogenated pyrrole ring. In polar solvents, the reaction of enamines with dimethyl acetylenedicarboxylate follows two different pathways, the formation of cycloadducts (18) and Michael adducts (19) (81T3525). Subsequent studies of this reaction have demonstrated (by low-temperature NMR) that compounds of the type 20 are intermediates in this cyclization (83JA4775). On the basis of this information (83JA4775), the authors then studied this type of cyclization using dienamines (21). The reaction follows the scheme shown, with a [1,6] antarafacial hydrogen shift and the formation of a dipo-... 

The reaction of dienamines and sulfonyl azides provides a method for the synthesis of vinyldiazomethanes.233,431 Likewise, the pyrolysis of a fluo-rinated 1-benzyltriazoline over a nickel surface yields difluorodiazometh-ane.145 The formation of diazo compounds from the reaction of azides with alkylidene phosphoranes apparently originates from an intermediate triazoline compound (Scheme 145)408,411 412,415,441... 

The Batcho-Leimgruber indole synthesis is probably the most important and widely used method for the preparation of lH-2,3-unsubstituted indoles. In an attempt to extend the utility of the process to the preparation of 3-substituted indoles, functionalisation of the specific intermediate enamine 1 was explored. Treatment of 1 with ethyl chloroformate in refluxing chloroform in the presence of AT,JV-diethylaniline failed to give the expected ester. Instead, a product was obtained the spectral data for which suggested that it was a dienamine. The same product could be obtained in 52% yield simply by treatment of 1 with half an equivalent of TsOH in toluene at 90°C, and catalytic hydrogenation of this dienamine gave 2 in 58% yield. 

A general synthesis of C-alkyl-dehydroberberines (88) by acid-catalysed cyclization of acyl-dienamines (87) is the subject of a recent patent.96 The synthesis... 

A versatile synthesis of enamines350,351 and dienamines has been developed from aldehydes via a-aminonitriles (equation 23). 

Among the heterocyclic dienamines dihydropyridines are a very important class of compounds. Dihydropyridines play an essential role in biochemistry and they have many applications in pharmacology. They are indispensable intermediates in the synthesis of natural products, mainly alkaloids555-558. These aspects as well as the preparation of dihydropyridines were dealt with exhaustively in several recent reviews559-562. 

A similar [4 + 2] cycloaddition across the a, -positions has been observed in the reaction of isophorone dienamines with electrophilic alkenes (vide infra), and a similar ring opening has been postulated in the reaction of methyl vinyl ketone with dienamines in aprotic media (Section VII.C). Confirmatory evidence for the role of the C-3 methyl group in the above reaction was obtained from reaction of 8-methyl-A 1,8a-2-octalone dienamine with methyl acrylate only the /Talkylated product was obtained in protic and aprotic solvents14. The reaction of dienamines with electrophilic alkenes is discussed further in the section on carbocyclic synthesis (Section VII.C). 

Sodium borohydride reduction of dienamines in the presence of a weak acid (acetic acid or methanol) results in kinetically favoured C-/ protonation followed by rapid hydride addition at C-a17. The method therefore provides a convenient method for converting an a,/ -unsaturated ketone into a y,<5-unsaturated amine as in the synthesis of con-nessine17 (Scheme 11). 

An approach to the synthesis of B-norsteroids involves -alkylation of dienamine 65 with m-methoxybenzyl bromide and ring closure with H3P04 and P2Os53 (Scheme 34). The use of 2-(m-methoxyphenyl)allyl bromide gave access to 6-methyl- 19-norsteroids54. 

Enamines. A new route to enamines involves alkylation of an a-amino nitrile (1) derived from an aldehyde to give an a-amino nitrile of type 2. When 2 is treated with potassium t-butoxide (or KOH), hydrogen cyanide is eliminated with formation of an enamine (3). The sequence is also applicable to synthesis of dienamines. 

Acyclic dienamines are relatively unstable, but very reactive towards electron-poor dienophiles as describe in a review article (1984). A more recent example shows the preparation of sterically encumbered 1-amino-1,3-diene (125) and its, nevertheless, efficient and highly stereoselective [4 + 2] cycloaddition to dimethyl fumarate (Scheme 32). Elimination of pyrrolidine, by heating the non-iso-lated cycloadduct with acetic anhydride, afforded hexahydronaphth ene (126), a key intermediate for a synthesis of drimane-type sesquiterpenes. 

As shown in Scheme 49, the cyclohexylimine of 10-methyl-l(9)-octalin-2-one has been methylated at C-3 via the kinetically formed cross-conjugated dienamine anion (95) or monomethylated at C-1 via the thermodynamically more stable extended anion (96). Steroidal and simpler enones have also been monoalkylated at the a-position via their corresponding hetero- or homo-annular extended dienamine anions. Likewise, a-alkylations are the rule for liAiated a,3-unsaturated aldimines. The thermodynamically controlled procedure for the synthesis of a-methyl a,3-unsaturated ketones is a vast improvement over conventional methodology using extended metal dienolates where a,a-dimethylation is a severe... 

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