Subject Lactam acetals

The unsaturated amides (RCH=CHCONH2, where R = aryl or heteroaryl) in the presence of sodium acetate and NBS gave 3-bromoazetidin-2-ones 67 in moderate yield, probably by cyclization of 68 <99JCS(P1)2435>. The mesylate 69 cyclized in the presence of base to 70 and, after deprotection, the racemic P-lactam was subjected to lipase-mediated resolution to yield 71 (R = Et, ee 99%) and the amino acid 72 (R = Et, ee 98%) . 

An alternative synthesis of ( )-a- and ( )--y-lycoranes (57 and 93) commenced with the 2-oxocyclohexyl acetic acid derivative 114 obtained by the alkylation of the enamine derived from 113 (Scheme 10) (116). Refluxing the oxime of 114 with zinc dust in glacial acetic acid afforded a mixture of the lactams 115, 116, and 117 in an approximate ratio of 4 6 3. The structure of 115 was verified by catalytic hydrogenation to give the lactam 118, which had previously been converted to ( )-a-lycorane (57). When the lactam 116 was subjected to sequential catalytic hydrogenation, hydride reduction, and Pictet-Spengler cyclization, ( )-y-lycorane (93) was obtained. A more efficient route to ( )-a-lycorane (57) involved refluxing the ketone 114 first with benzylamine in xylene and then with 87% formic acid to furnish the unsaturated lactam 119. 

Verazine (37) has been the subject of a formal total synthesis (Scheme 1) based on the earlier reported versatile syntheses of solanidine and tomatidenol. As in the earlier work, Michael addition of the anion of the configurationally pure nitro-ester (30) to (29) gave the C-22 epimeric mixture (31), from which the individual diastereomers were isolated after acetylation. The (22S)-acetate (32) was converted via thioketal (34) and lactam (35) into the piperidine derivative (36). Base treatment of the N-chloro-derivative of (36) then gave verazine (37). 

Imino aldol reaction of ketene silyl acetals with the chiral imine derived from tartaric acid 83 in the presence of a cation-exchange resin provided the corresponding /i-amino esters 84 in a good yield and high diastereose-lectivity [68]. The esters 84, thus obtained, were subjected to the Grignard reagent which promoted S-lactam formation. After a sequence of reactions compound 84 was transformed into the ester 85 [68] which in the past was... 

As a special case, the formation of hemiacetals 2 (lactolization) during the hydroformylation of hydroxy-functionalized olefins, such as allyl or homoallyl alcohols, has to be mentioned (1, Y= O, Scheme 5.70). With these substrates, the reaction occurs in an intramolecular manner. In the presence of an external alcohol, the cyclic hemiacetal can further react to give a nonsymmetric cyclic acetal 3. Hemiacetals can be subjected to hydrogenation to afford diols 4. Under reducing conditions and in the presence of amines, amino alcohols 5 are formed both are valuable building blocks in fine chemistry. Alternatively, oxidation gives lactones 6 [5]. By dehydration of hemiacetals, cychc vinyl ethers 7 are formed. The same transformation with allylamines (Y=NR) gives cyclic hemiaminals, A/ ,0-acetals, lactames, or vinyl amines. 

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