ABSTRACT
We report here the construction of quinolizidine ring systems by intramolecular cyclization of suitable functionalized piperidines via a reductive amination sequence. This reaction proceeds with a total stereocontrol at C4. The preparation of the piperidine precursors is based on a chain elongation of a piperidine aldehyde either by aldolization or by Wittig reaction. We applied this second route to the total synthesis of quinolizidine (-)-217A from (S)-methyl 2-((S)-1-((R)-1-phenylethyl)piperidin-2-yl)propanoate 5.
Subject(s)
Aldehydes/chemistry , Piperidines/chemistry , Quinolizines/chemical synthesis , Molecular Structure , Quinolizines/chemistry , StereoisomerismABSTRACT
An efficient formal total synthesis of (+)-gephyrotoxin is described. The key step of our strategy relies on the diastereoselective reduction of a chiral pyrrolidine beta-enamino ester obtained by condensation of ( S)-phenylglycinol on a protected 8-hydroxy-3,6-dioxooctanoate.
Subject(s)
Alkaloids/chemical synthesis , Amphibian Venoms/chemical synthesis , Ethanolamines , Glycine/analogs & derivatives , Glycine/chemistry , Pyrrolidines/chemical synthesis , Pyrrolidines/chemistry , StereoisomerismABSTRACT
We report here two approaches for the preparation of new N-substituted beta-enamino ester piperidines featuring an exocyclic tetrasubstituted double bond, based either on the direct alkylation of piperidine beta-enamino esters bearing an exocyclic trisubstituted double bond or on the intramolecular cyclization of linear amino beta-keto esters. The target compounds were obtained as unusual (Z)-stereoisomers in high yields. The key role of ammonia as reagent, acting both as a nucleophile and a base, was underlined. The diastereoselective formation of the products was rationalized on the basis of an ammonia addition-syn elimination catalytic process.
Subject(s)
Ammonia/chemistry , Piperidines/chemical synthesis , Catalysis , Esters , StereoisomerismABSTRACT
[reaction: see text] The preparation of new chiral 6-carbonyl 2,3,8,8a-tetrahydro-7H-oxazolo[3,2-a]pyridines by an efficient two-step procedure is described.
ABSTRACT
We report the results of a study aimed at the diastereoselective synthesis of chiral 2-alkoxy-5-/6-methoxycarbonylmethylidenepyrrolidines/-piperidines by condensation of chiral amines onto omega-oxo alkynoates and omega-oxo beta-keto esters.
ABSTRACT
Various chiral pyrrolidine tetrasubstituted beta-enamino esters were reduced catalytically or chemically with good to moderate diastereoselectivity owing to a chiral induction originated from (S)-alpha-methylbenzylamine. With endocyclic double bond compounds, the best result was obtained using PtO(2) as hydrogenation catalyst and led to a major syn addition product (e.d. 90%). In the case of exocyclic double bond compounds, hydrogenation over Pd/C gave rise to the higher diastereoselectivity and mainly afforded the unexpected anti addition product (e.d. 84%). The scope of these reductions has been extended to the synthesis of three pyrrolizidine or indolizidine alkaloids: (+)-tashiromine, (+)-laburnine, and (-)-isoretronecanol. Syntheses of these natural products, starting from chiral beta-enamino diesters, were achieved in a short and convenient manner, leading to enantiopure compounds in good overall yields.