Lactams aminonitriles

In addition to the two asymmetric syntheses above described, two racemic syntheses of tetraponerines based on the 5=6-5 tricyclic skeleton have been published. Thus, Plehiers et al. [199] have reported a short and practical synthesis of ( )-decahydro-5Tf-dipyrrolo[l,2-a r,2/-c]pyrimidine-5-carbonitrile (238), a pivotal intermediate in the synthesis of racemic tetraponerines-1, -2, -5 and -6, in three steps and 24% overall yield from simple and inexpensive starting materials. The key reaction of the synthesis was a one-pot stereoselective multistep process, whereupon two molecules of A pyrroline react with diethylmalonate to afford the tricyclic lactam ester 239, possessing the 5-6-5 skeleton (Scheme 10). Hydrolysis of the carboethoxy group of 239 followed by decarboxylation yielded lactam 240, that was converted into a-aminonitrile 238 identical in all respects with the pivotal intermediate described by Yue et al. [200] in their tetraponerine synthesis. 

Amines. Chiral a-amino acids are obtained from cyanohydrins via a Mitsunobu reaction employing A-f-butoxycarbonyl-A-(2-trimethylsilyl)ethylsulfonamide as the nucleophile. The a-aminonitrile derivatives thus generated are hydrolyzed with acid. By means of an intramolecular displacement (3-hydroxy acids are transformed into (3-amino acids. Thus, subjecting the derived 0-benzylhydroxamides to Mitsunobu reaction conditions leads to (3-lactams which are readily processed (LiOH H, Pd/C). 

In addition to several general reviews on enamine chemistry, all of which include heterocyclic syntheses, there is an extensive survey by Hickmott which is entirely concerned with the formation of heterocycles. More specialized reviews deal with heterocyclic enamines, enaminones, the photochemistry of enamides , heterocyclic jS-enamino esters , enamino thiones , the synthesis of indole alkaloids via enamines , formation of pyrimidines, pyridopyrimidines, pyridines and pyrrolizines from enamines , synthesis of lactams , formation of heterocycles from cyclic enamino ketones and 2-acetylcyclohexen-l-ones, the synthesis of 3-cyano-2(l -pyrimidine-thiones and -selenones from jS-enamino ketones and the chemistry of cyclic en-aminonitriles. ... 

Synthesis from L-threitol The L-threitol derivative 24, obtained from D-(-)-diethyl tartarate in three steps and 90% overall yield, was used as a starting material for the synthesis of nectrisine (1) (Scheme 5). " Swern oxidation of 24 produced the L-threose derivative 25, which was transformed into the aminonitrile 26 in 96% overall yield from 24, as an inseparable diastereomeric mixture. Removal of the silyl protecting group from 26 followed by oxidation of the resulting primary hydroxyl group with TPAP afforded the lactam 27, which was treated with sodium methoxide to produce the methyl ester 28 in 62% yield from 26. Lithium borohydride reduction of 28 afforded a chromatographically separable mixture of the lactams 29 and 30 in a ratio of 56 44 and 87% total yield. Silylation... 

A -Cyano-A -(methoxycarbonylalkyl)amino groups attached to 1,3,5-triazines have been reacted with hydrazine to give imidazolyltriazines <89AKZ192>. The same author also reacted an aminonitrile with a chloroacetamide to give the same imidazolyltriazine structure with a phenyl substituent. Hydrazones (117) are available from hydrazinotriazines on reaction with benzaldehyde and have been converted into jS-lactams (118) by reaction with chloroacetyl chloride and base (Scheme 29) <91MI612-03>. 

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