From Amino Acids to Fused Chiral Pyrrolidines and Piperidines via the INOC Route (original) (raw)
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Allylamines possessing a properly positioned aldoxime or ketoxime chain undergo thermally induced dipolar cycloaddition to bicylic isoxazolidines, with stereospecific introduction of three stereo centers. This provides an entry into stereospecifically functionalized pyrrolidines. Intramolecular nitrile oxide olefin cycloadditions (INOC) have been of considerable synthetic and mechanistic interesta, especially since the resulting isoxazoline ring can serve as a precursor to hydroxy ketones3 or
Chemistry – A European Journal, 2006
Phenylglycinol‐derived oxazolopiperidone lactams are exceptionally versatile building blocks for the enantioselective construction of structurally diverse piperidine‐containing natural products and bioactive compounds. These lactams are readily available in both enantiomeric series by cyclocondensation of the chiral amino alcohol with a δ‐oxo acid derivative and allow the substituents to be introduced at the different ring positions in a regio‐ and stereocontrolled manner, providing access to enantiopure polysubstituted piperidines bearing virtually any type of substitution pattern, and also quinolizidines, indolizidines, perhydroquinolines, hydroisoquinolines, as well as complex indole alkaloids. Of particular interest are cyclocondensation reactions with racemic or prochiral δ‐oxo (di)acid derivatives in processes involving dynamic kinetic resolution and/or differentiation of enantiotopic or diastereotopic ester groups, as they directly lead to lactams that already incorporate the...
Molecules, 1998
Enantiomerically pure, five membered cyclic nitrones, easily obtained in large amounts from protected hydroxyacids and aminoacids such as D-and L-tartaric, L-malic, and L-aspartic acids, give cycloaddition reactions with a good diastereocontrol. The adducts of L-malic and L-aspartic acids derived from addition of nitrones to dimethyl maleate and γcrotonolactone were easily converted into enantiopure pyrrolizidinones, which can be transformed into polyhydroxypyrrolidines or polyhydroxypyrrolizidines, both interesting compounds as potential glycosidase inhibitors. The method is suitable for natural products synthesis as exemplified by a straightforward and convenient access to the pyrrolizidine alkaloid necine base (-)-hastanecine, as well as to indolizidine alkaloids, i.e. (+)lentiginosine.
Synthesis, 2000
Epoxidation reactions of chiral 2-and 2,6-substituted 1,2,5,6-tetrahydropyridines 6, 11, 12 and 21 proceed with good to high stereoselectivity and excellent yields using pertrifluoroacetic acid as reagent. Epoxides such as 15, 16 and 19 are unstable but they can be deprotonated by LDA to give allylic alcohols such as 28, 30 or 32. These alcohols turned out to be potentially useful synthons, whose further oxidation or conversion to enones (29, 31) allows, in principle, introduction of a number of substituents on the piperidine ring. In particular, this is exemplified by a five-steps synthesis, from chiral tetrahydropyridine 6, of tetrasubstituted piperidine 7 in 26% overall yield.
Synthesis of enantiopure trisubstituted piperidines from a chiral epoxyaziridine and α-amino esters
Arkivoc, 2009
A new method to obtain enantiopure trisubstituted piperidines 1 by reaction of chiral epoxyaziridine 2 with α-amino esters 3 in the presence of a Lewis acid is reported. This synthesis took place through the successive opening of both oxirane and aziridine rings of 2 by the amino group of the corresponding α-amino ester 3 with total chemo-and regioselectivity. The time of reaction depended on the α-amino ester employed. Moreover, lithium and ytterbium salts were tested to catalyze the reaction, obtaining the best results with ytterbium triflate in comparison with lithium perchlorate.