Imines cyclic, synthesis

Hydrocyanic acid - [CYANIDES] (Vol 7) -atmospheric synthesis [IMINES, CYCLIC] (Vol 14)... 

Enamines and imines, cyclic, 6, 147 Enamines as synthons in the synthesis of heterocycles, 72, 283 /j-Enamino esters, heterocyclic, as heterocyclic synthons, 38, 299 -Excessive heteroannulenes, medium-large and large, 23, 55... 

Fifty years of established views of the Ugi reaction have been challenged by results of a theoretical study which suggests, for example, that the intermediate imine is not in equilibrium with its isocyanide adduct." An asymmetric three-component Ugi reaction has applied chiral cyclic imines in synthesis of morpholino- or piperazine-keto-carboxamide derivatives." ... 

A wide variety of /3-lactams are available by these routes because of the range of substituents possible in either the ketene or its equivalent substituted acetic acid derivative. Considerable diversity in imine structure is also possible. In addition to simple Schiff bases, imino esters and thioethers, amidines, cyclic imines and conjugated imines such as cinnamy-lidineaniline have found wide application in the synthesis of functionalized /3-lactams. A-Acylhydrazones can be used, but phenylhydrazones and O-alkyloximes do not give /3-lactams. These /3-lactam forming reactions give both cis and /raMS-azetidin-2-ones some control over stereochemistry can, however, be exercised by choice of reactants and conditions. 

Fischer s original method for conversion of the nitrile into an aldehyde involved hydrolysis to a carboxylic acid, ring closure to a cyclic ester (lactone), and subsequent reduction. A modern improvement is to reduce the nitrile over a palladium catalyst, yielding an imine intermediate that is hydrolyzed to an aldehyde. Note that the cyanohydrin is formed as a mixture of stereoisomers at the new chirality center, so two new aldoses, differing only in their stereochemistry at C2, Tesult from Kiliani-Fischer synthesis. Chain extension of D-arabinose, for example, yields a mixture of D-glucose and o-mannose. 

Azirines (three-membered cyclic imines) are related to aziridines by a single redox step, and these reagents can therefore function as precursors to aziridines by way of addition reactions. The addition of carbon nucleophiles has been known for some time [52], but has recently undergone a renaissance, attracting the interest of several research groups. The cyclization of 2-(0-tosyl)oximino carbonyl compounds - the Neber reaction [53] - is the oldest known azirine synthesis, and asymmetric variants have been reported. Zwanenburg et ah, for example, prepared nonracemic chiral azirines from oximes of 3-ketoesters, using cinchona alkaloids as catalysts (Scheme 4.37) [54]. 

As a part of the total synthesis of (+ )-corydalic acid methyl ester (12), a reaction of a cyclic enolate with an imine has been applied. The 2-toluamide enolate 9, which in this case is substituted at the methyl group, adds stereospecifically to imine 10, affording mainly tram-iso-quinolone 11 with a d.r. (transjds) > 95 525. 

Dipolar cycloaddition of azides with olefins provides a convenient access to triazolines, cyclic imines, and aziridines and hence is a valuable technique in heterocyclic synthesis. For instance, tricyclic -lactams 273 - 276 have been synthesized using the intramolecular azide-olefin cycloaddition (lAOC) methodology (Scheme 30) [71]. 

Asymmetric hydrogenation of a cyclic enamide (Approach B) had very sparse literature precedents [7]. It should also be noted that preparation of these cyclic imines and enamides is not straightforward. The best method for the synthesis of cyclic imines involves C-acylation of the inexpensive N-vinylpyrrolidin-2-one followed by a relatively harsh treatment with refluxing 6M aqueous HC1, which accomplishes deprotection of the vinyl group, hydrolysis of the amide, and decarboxylation (Scheme 8.6) [8]. 

Hoppe, I., Schollkopf, U., Nieger, M., and Egert, E., Asymmetric addition of a chiral cyclic phosphite to a cyclic imine — synthesis of phosphonic acid analogues of d- and L-penicillamine, Angew. Chem., Int. Ed. Engl., 24, 1067, 1985. 

Formation of nitrones can be achieved in the first stage of a Krohnke type reaction in which p-n trosodi methy 1 an dine reacts with 2-oo-bromoacetylphenoxathiin in alkaline medium (336). The synthesis of a series of cyclic nitrones of structure (182) has been achieved by regioselective, and by an unusual [3 + 2] cycloaddition of a-nitrosostyrenes (181) to 1,3-diazabuta-l,3-dienes (180) (Scheme 2.64) (337a). Theoretical studies of the substitution effect at the imine nitrogen on the competitive [3 + 2] and [4 + 2] mechanisms of cycloaddition of simple acyclic imines with nitrosoalkenes have been reported (337b). 

Allylation of imines using this type of reagent has been extensively studied, and this transformation has become important for the synthesis of acyclic and cyclic amine derivatives. 

One of the interesting application of 12 (R= allyl, X=Br) will be the synthesis of cyclic amino acid, (S)-pipecolic acid, as its tert-butyl ester 271251 Monoalkylation of the O Donnell imine 23 with l-chloro-4-iodobutane afforded the alkylated product 26 with 99 % ee. The conversion of 26 to the tert-butyl ester of pipecolic acid 27 was achieved in high yield by the sequence imine reduction, cyclization, and hydrogenolytic removal, as shown in Scheme 8. 

Allene-substituted lactams or cyclic imines are useful intermediates in the synthesis of indolizine derivatives. While the former are stable and need a Pd(0) catalyst and the presence of phenyl iodide to react < 1997TL6275>, the latter are produced in situ and react immediately (Scheme 37) <2001JA2074>. 

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