Showing papers on "Piperidine published in 2007"
TL;DR: The intramolecular aza-Michael reaction of carbamates bearing remote alpha,beta-unsaturated aldehydes under organocatalytic conditions took place with good yields and excellent ee's when Jørgensen catalyst IV was used in the process, giving rise to the enantioselective formation of several five- and six-membered heterocycles.
156 citations
TL;DR: An efficient chiral Lewis acid-catalyzed inverse-electron-demand Diels−Alder reaction of 1-azadienes is described, providing highly functionalized piperidine derivatives in good yields with excellent endo-selectivity, and enantioselectivities typically in the range of 77−92% ee.
Abstract: An efficient chiral Lewis acid-catalyzed inverse-electron-demand Diels−Alder reaction of 1-azadienes is described. This procedure is based on the combination of NiII-DBFOX complex as catalyst and the use of a metal-coordinating (8-quinolyl)sulfonyl moiety at the iminic nitrogen of the N-sulfonyl 1-aza-1,3-diene, providing highly functionalized piperidine derivatives in good yields with excellent endo-selectivity, and enantioselectivities typically in the range of 77−92% ee.
154 citations
TL;DR: The poor selectivity observed on activation of the thioglycosides with the 1-benzenesulfinyl piperidine, or diphenyl sulfoxide, and trifluoromethanesulfonic anhydride methods appears to be the result of the formation of a complex mixture of glycosyl donors, as determined by low-temperature NMR work.
Abstract: A 2-O-benzyl-3,5-O-benzylidene-α-d-thioarabinofuranoside was obtained by reaction of the corresponding diol with α,α-dibromotoluene under basic conditions. On activation with 1-benzenesulfinyl piperidine, or diphenyl sulfoxide, and trifluoromethanesulfonic anhydride in dichloromethane at −55 °C, reaction with glycosyl acceptors affords anomeric mixtures with little or no selectivity. The analogous 2-O-benzyl-3,5-O-(di-tert-butylsilylene)-α-d-thioarabinofuranoside also showed no significant selectivity under the 1-benzenesulfinyl piperidine or diphenyl sulfoxide conditions. With N-iodosuccinimide and silver trifluoromethanesulfonate the silylene acetal showed moderate to high β-selectivity, independent of the configuration of the starting thioglycoside. High β-selectivity was also obtained with a 2-O-benzyl-3,5-O-(di-tert-butylsilylene)-α-arabinofuranosyl sulfoxide donor on activation with trifluoromethanesulfonic anhydride. The high β-selectivities obtained by the N-iodosuccinimide/silver trifluoromethane...
98 citations
TL;DR: A monodisperse, spherical mesoporous silica was prepared and then functionalized with two types of Fmoc with a method by which the surface of the porous silica can be functionalized in a well-defined manner and can be used to produce materials for catalysis or drug delivery.
Abstract: A monodisperse, spherical mesoporous silica (Acid-Prepared Mesoporous Spheres, APMS) was prepared and then functionalized with two types of Fmoc (9-fluorenylmethyloxycarbonyl) terminated silanes with variable chain lengths. N2 physisorption experiments indicated that, under some conditions, the pores of the solid were completely filled by the Fmoc-protected organosilanes. These blocked pores were then “reopened” by the cleavage of Fmoc groups with a piperidine solution. In contrast to the solution reaction, this deprotection reaction was much slower within the pores. The rate of deprotection was followed by UV/visible spectroscopy, and a plot of Fmoc released versus time showed a sigmoidal shape. An empirical model was applied to the data, which indicated that the reaction was influenced by the concentration and temperature of the piperidine solution as well as the number of Fmoc moieties within the pores. Using this information, we show that the location of the deprotection reaction in the pores of the s...
93 citations
TL;DR: Amines used as bases in copper-free, palladium-catalyzed Sonogashira reactions play a multiple role and a mechanism involving prior coordination of the alkyne is suggested, followed by deprotonation of the ligatedAlkyne by the amine.
Abstract: Amines used as bases in copper-free, palladium-catalyzed Sonogashira reactions play a multiple role. The oxidative addition of iodobenzene with [Pd 0 (PPh 3 ) 4 ] is faster when performed in the presence of amines (piperidine > morpholine). Amines also substitute one ligand L in trans-[PdI(Ph)(L) 2 ] (L=PPh 3 , AsPh 3 ) formed in the oxidative addition. This reversible reaction, which gives [PdI(Ph)L(R 2 NH)], is favored in the order AsPh 3 > PPh 3 and piperidine> morpholine. Two mechanisms are proposed for Sonogashira reactions, depending on the ligand and the amine. When L=PPh 3 , its substitution by the amine in trans-[PdI(Ph)(PPh 3 ) 3 ] is less favored than that of the alkyne. A mechanism involving prior coordination of the alkyne is suggested, followed by deprotonation of the ligated alkyne by the amine. When L=AsPh 3 , its substitution in trans-[PdI(Ph)-(AsPh 3 ) 2 ] by the piperidine is easier than that by the alkyne, leading to a different mechanism: substitution of AsPh 3 by the amine is followed by substitution of the second AsPh 3 by the alkyne to generate [PdI(Ph)(amine)-(alkyne)]. Deprotonation of the ligated alkyne by an external amine leads to the coupling product. This explains why the catalytic reactions are less efficient with AsPh 3 than with PPh 3 as ligand.
82 citations
TL;DR: In this paper, the authors studied the catalytic properties of the LiN(SiMe3)2/TMEDA with primary and secondary amines and showed that the selectivity for the mono-hydroamination products could be improved with a two-fold excess of the amine.
75 citations
TL;DR: A series of substituted pyridine derivatives were prepared from 3-acetylpyridine, which was prepared from the corresponding nicotinic acid as a natural starting material.
Abstract: A series of substituted pyridine derivatives were prepared from 3-acetylpyridine, which was prepared from the corresponding nicotinic acid as a natural starting material. Reaction of 3-acetylpyridine with indole-3-carboxaldehyde afforded the corresponding 3-β-(3-indolyl)acryloylpyridine, which was reacted with hydroxylamine hydrochloride in pyridine or acetic acid in the presence of sodium acetate to afford 3-β-(3-indolyl)acryloylpyridine oxime and oxazole derivatives. The oxime was treated with ethyl isothiocyanate or toluene-3,5-diisocyanate in refluxing dioxane to give the corresponding ethyl thiosemicarbazide and 3,5-bissemicarbazide derivative. 3-β-(3-Indolyl)acryloylpyridine was condensed with malononitrile in refluxing ethanol in the presence of piperidine as a catalyst to give cyanoaminopyrane, while it was condensed with ethyl cyanoacetate or malononitrile in the presence of ammonium acetate to yield cyanopyridone and cyanoaminopyridine derivatives. Cyclization of acryloylpyridine with o-phenylenediamine in refluxing butanol led to the formation of the corresponding benzodiazipine via the intermediate A. Finally, cycloaddition reaction of acryloylpyridine with thiourea yielded thioxopyrimidine, which was treated with chloroacetic acid to yield thiazolopyrimidine. An arylmethylene derivative was prepared by reacting thiazolopyrimidine with indole-3-carboxaldehyde or by reacting thioxopyrimidine with indole-3-carboxaldehyde and chloroacetic acid in one step. The pharmacological screening showed that many of these obtained compounds have good analgesic and anticonvulsant activities comparable to Valdecoxib® and Carbamazepine® as reference drugs.
56 citations
TL;DR: A series of 6-mono-, di-, and trifluoro analogs of S-phenyl 2,3,4-tri-O-benzyl-D- or L-thiorhamnopyranoside is synthesized and used as donors in glycosylation reactions, with activation by the 1-benzenesulfinyl piperidine/triflic anhydride system.
Abstract: A series of 6-mono-, di-, and trifluoro analogs of S-phenyl 2,3,4-tri-O-benzyl-D- or L-thiorhamnopyranoside has been synthesized and used as donors in glycosylation reactions, with activation by the 1-benzenesulfinyl piperidine/triflic anhydride system. The stereochemical outcome of the glycosylation reactions was found to depend on the electron-withdrawing capability of the disarming substituent at the 6-position, i.e., on the number of fluorine atoms present. The results are explained with regard to the increased stability of the glycosyl triflates, shown to be intermediates in the reaction by low-temperature 1H NMR experiments, with increased fluorine content.
52 citations
TL;DR: A new approach for the stereoselective synthesis of the piperidine alkaloid (+)-alpha-conhydrine and its pyrrolidine derivative has been developed using a palladium(II)-catalyzed, MOM-ether-directed aza-Claisen rearrangement and ring-closing metathesis to effect the key steps.
51 citations
TL;DR: In this article, a short and efficient stereoselective synthetic approach toward substituted piperidines, involving (2 S,3 S )-3-hydroxypipecolic acid 1, (2 R,3S )-1,2-dibenzyl ethers 13 and 14 using chlorosulfonyl isocyanate (CSI), was developed.
46 citations
TL;DR: The versatility of this hydrazone addition-RCM protocol has been further exemplified by the conversion of the unsaturated heterocycle 5b into the piperidine alkaloid (S)-(+)-coniine.
TL;DR: Piperidine and 1,1, 1-3, 3,3,3 hexafluoro-2-propanol (HFIP) have been co-crystallized and X-ray crystal structure has been explored as discussed by the authors.
TL;DR: In this article, 1-Arylhydrazonopyruvaldehydes 1 react with α,β-unsaturated nitriles 2 to yield 6-amino-1,4-dihydropyridazines 4 that are converted into pyridazinones 5 via refluxing in an acetic acid/hydrochloric acid mixture and into the ethylidenemalononitrile derivatives 6 on reflux with malononiitrile in ethanolic/piperidine solution.
TL;DR: Anti-inflammatory activity screening of the prepared compounds using in vivo acute carrageenan-induced paw oedema in rats exhibited that all the tested compounds possess considerable activity.
TL;DR: In this article, rate constants for a series of 1-chloro-, 1-fluoro, and 1-phenoxy-nitrobenzenes activated by CF3 or CN groups or by ring-nitrogen with n-butylamine, pyrrolidine or piperidine in acetonitrile.
Patent•
29 Aug 2007
TL;DR: In this paper, the authors provided a formula for compounds having the formula (1) wherein X is oxygen or sulphur; Y is oxygen and sulphur, and Z is a bond or a chain of 1-5 carbon atoms and/or heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur forming ring.
Abstract: The present invention provides compounds having the formula (1) wherein X is oxygen or sulphur; Y is oxygen or sulphur; (A) is a 5-membered heterocyclic ring containing one to three heteroatoms, each independently selected from the group consisting of oxygen, nitrogen and sulphur; P is CR12 or N; Q is CR13 or N; S is CR14 or N; T is CR15 or N; Z is a bond or a chain of 1-5 carbon atoms and/or heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulphur forming ring (B), wherein (B) may contain one or more unsaturated bonds and may be optionally substituted wherein B is not an unsubstituted pyrrolidine, an unsubstituted piperidine, an unsubstituted morpholine or an unsubstituted 3-pyrroline or a pyrrolidine, piperidine, morpholine or 3-pyrroline each substituted with 1-2 C1-C2 alkyl. The present invention further relates to methods used to prepare these compounds, to compositions which comprise these compounds and to their use in agriculture or horticulture for controlling undesirable vegetation.
TL;DR: In this paper, an efficient and a general approach to chiral 2-substituted N -tosylpiperidines was developed starting from chiral α-sub-stitution-N -to-aziridines.
TL;DR: In this paper, a piperidine series of γ-secretase inhibitors, potentially useful for the treatment of Alzheimer's disease, is disclosed, which is optimized to provide inhibitors with IC 50s in the single-digit nanomolar range.
TL;DR: In this paper, it is shown that if a C=C double bond is present in the molecule, an intramolecular cyclization process takes place in an exo mode with additional generation of a hydroxy group at the terminal position of the original olefin moiety to render a series of pyrrolidine and piperidine derivatives.
TL;DR: Sulfinimine-derived, differentially protected, 2,3-diamino esters are useful building blocks for the asymmetric synthesis of heterocycles and is illustrated by an efficient synthesis of amino piperidine (+)-CP-99,994.
TL;DR: Tetrahydroisoquinolines underwent tandem piperidine ring enlargement in the presence of activated alkynes in acetonitrile or methanol, producing tetrahydronzo[d]azocines in high yields as discussed by the authors.
TL;DR: The Shapiro reaction of acetophenone is the key in a convenient three-step access to a divinyl ketone which is further transformed by double aza-Michael reactions with primary amines into N-substituted 3-phenyl-4-piperidones as mentioned in this paper.
TL;DR: In this article, an efficient enantioselective synthesis of (+)- l -733,060 from cinnamyl alcohol is described, where the key steps include a Sharpless asymmetric epoxidation, a regiose-lective allyl opening of an epoxide and piperidine ring formation via a one pot Staudinger/aza-Wittig reaction.
Abstract: An efficient enantioselective synthesis of (+)- l -733,060 from cinnamyl alcohol is described. The key steps include a Sharpless asymmetric epoxidation, a regioselective allyl opening of an epoxide and piperidine ring formation via a one pot Staudinger/aza-Wittig reaction.
TL;DR: Fully established catalytic cycles are now proposed for the Pd-catalyzed allylic amination of (E)-PhCHCHCH CH(Ph)OAc by piperidine and morpholine with fully established rate and equilibrium constants determined in DMF.
TL;DR: In this paper, the stability constants relevant to the formation of amine/p-nitrophenol ion pairs have been determined in [bmim][BF4] solution, in the presence of butylamine, piperidine, and triethylamine by using spectrophotometric measurements.
TL;DR: In this article, a route to 3-arylpiperidines involving radical 1,4-and 1,2-aryl migrations has been explored, which requires a xanthate addition to an N-allylarylsulfonamide, followed by acetylation and treatment with lauroyl peroxide.
TL;DR: (R)-1,2-epoxypentane is used in this 5 + 3 - 2 overall ring expansion sequence, one final step involving delta-lactam to piperidine reduction yields natural (-)-halosaline and (-)-epihalosaline in five steps and 12% and 23% overall yields, respectively.
TL;DR: An asymmetric synthesis for the preparation of both enantiomers of trans-methylpipecolic acids is described, based on Sharpless epoxidation as a chirality source, regioselective ring opening with allylamine, and ring-closing metathesis to construct the piperidine ring.
Abstract: An asymmetric synthesis for the preparation of both enantiomers of trans-methylpipecolic acids is described. It is based on Sharpless epoxidation as a chirality source, regioselective ring opening with allylamine, and ring-closing metathesis to construct the piperidine ring. The stereogenic center at C-4 is set by stereoselective hydrogenation that is directed by the alcohol functionality of an intermediate and proceeds with good diastereomeric control (trans/cis 16/1). Crystallization of the Boc-protected amino acid afforded the target products with excellent chemical (98% de) and enantiomeric purity (99% ee).
TL;DR: In this article, a copper ion catalyzed carbon-carbon bond forming reaction of Nacyliminium ions with diaryl malonates was achieved with high enantioselectivity, achieving an enantiomeric excess of 97% when di-p-chlorophenyl malonate was used as a nucleophile.
TL;DR: The hydroaminocarbonylation of terminal alkynes with carbon monoxide and pyrrolidine or piperidine catalyzed by rhodium complexes affords 1,4-diamide derivatives in good to high yields as mentioned in this paper.
Abstract: The hydroaminocarbonylation of terminal alkynes with carbon monoxide and pyrrolidine or piperidine catalyzed by rhodium complexes affords 1,4-diamide derivatives in good to high yields.