Search

An efficient synthetic method for coumarin derivatives was developed using a dual organocatalytic reaction. A combination of p -toluenesulfonic acid monohydrate and piperidine was found to efficiently catalyze the cyclization between salicylaldehydes and alkynoic esters to give various coumarin derivatives in good yield and high selectivity. Mechanistic and kinetic data suggested that the conjugate addition between piperidine and alkynoic esters played a crucial role in the reaction mechanism. [ABSTRACT FROM AUTHOR]

Piperidine alkaloids continue to challenge the synthetic community by featuring densely functionalized scaffolds that often require careful chemical orchestration. Streptazone A and abikoviromycin are small and highly functionalized piperidine alkaloids, both accommodating Michael acceptors and a labile epoxide. These moieties are loaded into a [4.3.0] bicyclic core also present in other structurally related natural products, including the well-known piperidine alkaloid streptazolin. Here, we cover ring-closing strategies employed in earlier streptazolin syntheses; provide a concise overview of structures, biological properties, and biosyntheses of selected [4.3.0] piperidine alkaloids; and, finally, provide complete coverage of our recent asymmetric syntheses of streptazone A and abikoviromycin. 1 Introduction 2 Streptazolin Syntheses 3 Epo-[4.3.0] Piperidine Alkaloids 3.1 Streptazones 3.2 Abikoviromycin 3.3 Strepchazolin A and B 3.4 Hatomamicin 3.5 Kobutimycin A and B 3.6 Camporidines A and B 3.7 Epostatin 3.8 N -Hydroxydihydroabikoviromycin 3.9 Dihydroabikoviromycin 3.10 Biosynthesis of Streptazone E and Camporidines 4 Syntheses of the Streptazones and Abikoviromycin 4.1 Retrosynthesis 4.2 Results and Discussion 5 Conclusion [ABSTRACT FROM AUTHOR]

A convenient synthesis of 2′-amino-7′,7′-dimethyl-2,5′-dioxo-1′-(phenylamino)-5′,6′,7′,8′-tetrahydro-1′ H -spiro[indoline-3,4′-quinoline]-3′-carbonitrile derivatives has been designed using different substituted isatins, various 5,5-dimethyl-3-(2-phenylhydrazinyl)cyclohex-2-enones (arylhydrazones of dimedone) and malononitrile in ethanol with piperidine as catalyst at room temperature. The structures of the synthesized compounds have been elucidated by various spectroscopic techniques. The selected compounds have also been evaluated for their antibacterial activities against human pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Novel aminoethyl-, aminopropyl-, and aminobutyl-substituted ed thiazole-4-carboxamides have been prepared which are ring-opened analogues of piperidinyl-thiazole fungicides. Depending of the chain length, completely different synthetic approaches had to be chosen which vary from a Sonogashira coupling with a 2-bromothiazole deriva- tive to a thiazole ring construction from different β- and δ-amino acids. [ABSTRACT FROM AUTHOR]

A copper-catalyzed approach for the synthesis of 1-acyloxy-2,2,6,6-tetramethylpiperidines through the C-C bond cleavage of cyclic or acyclic ketones was developed. In this chemistry, a combination of CuCl2·2H2O, 1,10-phenanthroline monohydrate, and aniline was crucial for the formation of the desired products by the reaction of ketones with TEMPO. This research provides a new strategy for the further transformation of α-aryl cyclic or acyclic ketones. [ABSTRACT FROM AUTHOR]

A variety of different N-[2-chloro-4-(chloromethyl)pent-4-enylidene]amines and N-(2,6-dichlorohex-4-enylidene)amines was prepared for the first time, and their reactivity as eligible building blocks for the synthesis of biologically relevant nitrogen-containing heterocyclic compounds was studied. In this way, a convenient entry into functionalized 1-azabicyclo[3.1.0]hexanes, piperidines, pyridines, pyrroles, and tetrahydroindoles was developed, pointing to the broad synthetic flexibility of these dichlorinated imine substrates. [ABSTRACT FROM AUTHOR]

A novel methodology for the synthesis of 3,3-difluoropiperidines has been developed. The target compounds are prepared in three steps using a robust protocol and simple starting materials. The incorporation of the fluorine is achieved by using the cheap and easily available ethyl 2-bromo-2,2-difluoroacetate as building block. Using this methodology, a new potent in vitro phosphodiesterase 2A (PDE2A) inhibitor containing the functionalized fluorinated piperidine scaffold has been prepared. [ABSTRACT FROM AUTHOR]

The synthesis of a set of conformationally restricted fluorinated analogues of piperidine, based on a 2-azaspiro[3.3]heptane scaffold, is reported. Different pattern of fluorine substitution within the rigid skeleton make the analogues excellent candidates for use in drug design. The overall simplicity of the experimental procedures and the availability of inexpensive starting materials allow for multigram-scale syntheses of the described compounds. [ABSTRACT FROM AUTHOR]

Starting from a readily available, enantiomerically pure 2,6-disubstituted piperidine the synthesis of pyrido[1,2-a]azepines was accomplished. Key reactions for the ring closure were a photochemically induced acyl radical addition or a SmI2-promoted ketyl radical addition to an α,β-unsaturated ester. En route to the cyclization precursor an epoxidiation/ring opening sequence led to an undesired oxazolidinone which turned out to be useful for the configuration assignment. The compound was successfully converted into (+)-methyl dihydropalustramate. [ABSTRACT FROM AUTHOR]

Herein we report the stereoselective total synthesis of (+)-connine, (+)-β-conhydrine, (+)-8-ethylnorlobelol, and (-)-halosaline via bisnucleophilic substitution with benzylamine as the key step. [ABSTRACT FROM AUTHOR]

A preliminary investigation into the prospect of a common synthetic intermediate for the synthesis of a variety of indole alkaloids has led to a synthesis of substituted piperidinones and the corresponding piperidines. These common natural product cores are accessed via a reductive amination-lactamization sequence of dimethyl 3-ethyl-3-formylpimelate. The synthetic utility of this initial study has been displayed in the formal synthesis of (±)-quebrachamine. [ABSTRACT FROM AUTHOR]

The idea of introducing (cyclo)alkyl substituents at the C-3 atom of the piperidine ring, that is, formal sp3-sp3 retrosynthetic disconnection, is implemented through a two-step reaction sequence including directed ortho metalation of a pyridine derivative and the subsequent quenching with a carbonyl compound, followed by catalytic hydrogenation. This robust but very efficient method allows for multigram preparation of sp3-rich 3-(cyclo)alkylpiperidines, which are valuable building blocks for medicinal chemistry and other areas. [ABSTRACT FROM AUTHOR]

A straightforward and highly selective method has been developed for the nitration of a wide variety of aromatic and aliphatic olefins by using a clay-supported copper nitrate (Claycop) and a catalytic amount of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl, an inexpensive and mild reagent system. High conversions and exclusive E-selectivity, together with the environmentally benign nature of the Claycop reagent, make this a green method and an attractive alternative to established methods. [ABSTRACT FROM AUTHOR]

Enantioenriched heterocyclic piperidines are important structural motifs present in numerous natural products and biologically active molecules. This article outlines our recent efforts to develop a straightforward access to highly functionalized piperidine derivatives with multiple stereogenic centers, in good yields and excellent stereoselectivities, via copper(I)/TF-BiphamPhos-catalyzed asymmetric 1,3-dipolar [6+3] cycloadditions of azomethine ylides with fulvenes. [ABSTRACT FROM AUTHOR]

A series of 4-arylamino-8-(alkyl or aryl)hydrazidepyrimido[ 5,4-d]pyrimidines was obtained efficiently from 6-carbo-hydrazonamidepurines by reaction with piperidine. The 6-carbo-hydrazonamidepurines were generated selectively by the reaction of 6-imidatopurine with hydrazides under acidic conditions. [ABSTRACT FROM AUTHOR]

The direct combination of the desymmetrization of Nheterocyclic meso-diols using lipase from Mucor miehei as biocatalyst and subsequent ring expansion of the optically active products by activation of the remaining hydroxy group gives rise to functionalized nonsymmetrical piperidines in a highly enantio- and diastereoselective manner. [ABSTRACT FROM AUTHOR]

Deprotonative metalation of chlorothiophene takes place with a catalytic amount of cis-2,6-dimethylpiperidine (DMP) and an alkyl Grignard reagent at room temperature for three hours to give the corresponding thienyl Grignard reagent. Polymerization leading to head-to-tail-type poly(3-substituted thiophene) with the thus metalated chlorothiophene proceeds in the presence of a nickel catalyst bearing an N-heterocyclic carbene (NHC) ligand. Palladiumcatalyzed cross-coupling reaction with aryl bromides also gives arylated thiophenes in good to excellent yields while the C-Cl bond remains intact. [ABSTRACT FROM AUTHOR]

An efficient synthetic route to the potent and selective ErbB VEGF receptor inhibitor, BMS-690514 (1) is described. Strategic modifications in both approach and procedure addressed several issues, which led to a safe, efficient, and economical process for the preparation of multi-kilogram quantities of 1. The convergent route involves alkylation of a suitably protected (3R,4R)-4-aminopiperidin-3-ol with the triethyl(alkyl)ammonium salt of a functionalized pyrrolotriazine 3a followed by deprotection to provide 1 as the crystalline free base. [ABSTRACT FROM AUTHOR]

The reaction of different 7,8-substituted coumarin 4-acetic acids with 7-diethylaminocoumarin-3-carbaldehyde in the presence of piperidine in methanol gives 1,2-biscoumarinylethenes. These compounds undergo regiospecific Diels-Alder reactions at their electron-rich diene components C3-C4-C10-C9, with electron-deficient dienophiles. The feasibility of normal electron-demand Diels- Alder reactions could be explained on the basis of the HOMO- LUMO gap. All the compounds are new and are intensely colored [ABSTRACT FROM AUTHOR]

Previously, the outcome of the alkylation of cyclen (1,4,7,10-tetraazacyclododecane) with arginine-modified electrophiles was found to be dependent on the solvent used for the reaction as well as on the structure of the electrophile. Herein, we report the alkylation of the related nitrogen macrocycles, TACN (1,4,7-triazacyclononane), cyclam (1,4,8,11-tetraazatetradecane) and the smaller cycles piperidine and piperazine with arginine-modified electrophiles. The products of peralkylation predominate for piperazine and TACN while the product of trialkylation is isolated as a sole product, when cyclam is used as a substrate for the alkylation. The results reported herein provide useful information for chemists involved in the design and synthesis of ligands for MRI (magnetic resonance imaging) contrast agents and for PET (positron emission tomography) imaging agents. [ABSTRACT FROM AUTHOR]

A pyrimidine ring was discovered to aid formation of an azomethine ylide undergoing intramolecular cycloaddition reactions. This method enabled efficient synthesis of a novel tricyclic pyrimidine-piperidine-pyrrolidine scaffold from various pyrimidinemethyl amines and aldehydes in complete stereocontrol and could be rationalized by an S-shaped azomethine ylide intermediate. [ABSTRACT FROM AUTHOR]

While elucidating the inhibitory mechanism of a hydrolytic enzyme by aldehyde-containing natural products, we discovered a reaction involving a rapid 6π-azaelectrocyclization of azatrienes generated from aldehyde with lysine residues. The electrocyclic reaction of the 1-azatriene system, a cyclization precursor, exhibited a substituent effect. Structure-reactivity studies showed that azaelectrocyclization, which usually proceeds in low yield at high temperatures, produced a quantitative yield in less than 5 minutes at room temperature. Asymmetric chiral piperidine synthesis and a one-pot library synthesis of pyridines on solid supports were applied to synthesize pyridine/indole alkaloid-type natural products. Additionally, we developed lysine-based labeling and engineering of biomolecules and living cells based on the rapid 6π-azaelectrocyclization. Both 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (DOTA) as a metal chelating agent and fluorescent groups, as well as oligosaccharide structures were introduced efficiently and selectively into surface lysines within 10 minutes at concentrations as low as 10-8 M. The DOTA-labeled somatostatin and glycoproteins were then radiometallated with 68Ga; the receptor-mediated accumulation of somatostatin in pancreas and the oligosaccharide-dependent circulatory residence of glycoproteins were visualized by microPET for the first time. Furthermore, we succeeded to image the trafficking of the fluorescence-labeled lymphocytes noninvasively, while the N-glycan-engineered lymphocytes targeted the colon carcinoma in tumor mouse model; the tumor-targeting cells were thus synthesized using our 6π-azaelectrocyclization. 1 Introduction 2 Discovery of Smooth 6π-Azaelectrocyclization: Inhibitory Mechanism of Bovine Pancreatic Phospholipase A2 by Unsaturated Aldehyde Terpenoids 3 Renaissance of 6π-Azaelectrocyclization: Remarkable Acceleration by Substituent Effects 3.1 Synthesis of 3-cis-1-Azatriene Derivatives and Their Reactivities toward Azaelectrocyclization 3.2 Rationale for Acceleration of 6π-Azaelectrocyclization by Computational Analysis 4. 6p-Azaelectrocyclization as a New Strategy for Natural Products Synthesis 4.1 One-Pot Pyridine Synthesis: Formal Synthesis of the Ocular Age Pigment A2-E 4.2 Library-Directed One-Pot Solution and Solid-Phase Synthesis of 2,4-Disubstituted Pyridines 4.3 Highly Stereoselective Asymmetric 6π-Azaelectrocyclization 4.4 Application to Natural Alkaloid Synthesis: Formal Synthesis of 20-Epiuleine 5 6π-Azaelectrocyclization-Based Microgram-Scale Labeling of Peptides and Proteins: Biomolecule-Based In Vivo Imaging 5.1 Development of Non-Destructive Lys-Labeling Kit 'Stella+' by 6π-Azaelectrocyclization 5.2 Positron Emission Tomography (PET) of Biomolecules: First Visualization of Somatostatin Accumulation to Pancreas and Sialic Acid Dependent Circulatory Residence of Glycoproteins 6 Labeling and Engineering of Living Cells by Azaelectrocyclization 6.1 Fluorescence Labeling of Living Cell Surfaces 6.2 Chemical Engineering of Cell Surfaces by Functional Molecules 6.3 In Vivo Fluorescence Imaging of Lymphocytes and Effects of Cell Surface Engineering by N-Glycan 7 Site-Selective and Non-Destructive Protein Labeling via Azaelectrocyclization-Induced Cascade Reactions 8 Conclusion. [ABSTRACT FROM AUTHOR]

A bifunctional polystyrene bearing both DMAP and piperidine groups has been prepared and used as an organocatalyst for decarboxylative Doebner-Knoevenagel reactions of arylaldehydes and monoethyl malonate. Isolated yields of the resulting cinnamates were very high, and in all cases only the E-isomer was detected. When a polystyrene catalyst functionalized with only DMAP or piperidine groups was used in these reactions, catalysis was much less efficient. Furthermore, catalysis using a combination of the monofunctional polymers was also less efficient than with the bifunctional polystyrene. Thus, it appears that there is a synergistic effect obtained by co-locating the two different catalytic amine groups on the same polymer backbone. [ABSTRACT FROM AUTHOR]

This account reports on the use of (R)- or (S)-phenylglycinol-and (S)-tryptophanol-derived oxazolopiperidone lactams as building blocks for the enantioselective synthesis of structurally diverse indole alkaloids. [ABSTRACT FROM AUTHOR]

Reaction of 9-methylene-3-azabicyclo[3.3.1]nonanes with trifluoroperacetic acid results in stereoselective epoxidation to give the SYN-epoxide. Intermolecular hydrogen bonding between the protonated tertiary amine and the peracid is responsible for the high levels of stereoselectivity. [ABSTRACT FROM AUTHOR]

An efficient approach to hydroxylated pyrrolidine and piperidine derivatives through the intramolecular hydroamination catalyzed by a Cu(I)-Xantphos system is described. The transformation allows for the short synthesis of N-alkylated aza-sugars without a protection-deprotection event of the hydroxy groups. [ABSTRACT FROM AUTHOR]

Two unnatural conformationally constrained cyclic amino acid derivatives with the piperidine skeleton were synthesized in enantiomerically pure forms. The key step in the synthesis of these amino acids is the highly diastereoselective functionalization of the oxo group in a 4-oxo-pipecolic acid derivative. [ABSTRACT FROM AUTHOR]

The synthesis of 3-substituted L-fuco-azafagomines from D-lyxose is reported. They represent the first example of aza-C-glycosides having a biimino (-NH-NH-) moiety. The key step of the synthesis is the introduction of the hydrazine moiety by reductive hydrazination of a 1-deoxy-ketohexose with tert-butyl carbazate. Their glycosidase inhibitory properties are also reported. [ABSTRACT FROM AUTHOR]

The letter describes a novel approach for immobilization of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) derivatives by cation-exchange reaction of TEMPO ammonium salts in a commercially available saponite. The organic-inorganic hybrid material is readily prepared and characterized by solid-state �H NMR spectroscopy. The hybrid material can be used as recyclable catalyst for oxidation of various alcohols. High catalytic activity for up to 10 runs is obtained. Leaching of the nitroxide salt out of the saponite occurs to a small extent. However, original high activity of the hybrid material can be restored by simply reloading the hybrid material with nitroxide salt by cation exchange. [ABSTRACT FROM AUTHOR]

The reaction of KBrO 3and NH 2OH?HCl in situ generates NO xand Br anion, which combine with 2,2,6,6-tetramethylpiperidine- N-oxide (TEMPO) to construct a NO-activating dioxygen, Br-assisted, TEMPO-catalyzed aerobic oxidation of alcohols. Catalyzed by KBrO/NH 2OH?HCl/TEMPO, various benzylic alcohols can be oxidized quantitatively to their corresponding carbonyl compounds under mild conditions. The easy handling and simple product separation make the process an attractive candidate for the oxidation of alcohols. [ABSTRACT FROM AUTHOR]

The rapid, high-yielding synthesis of (2 S,3 R)-3-hydroxy-2-phenylpiperidine, a known advanced key intermediate of some non-peptide human NK-1 receptor antagonists such as (+)-CP-99,994, (+)-CP-122,721 and (+)-LP-733,060, is reported. This synthesis involves the stereoselective addition of racemic 3-(methoxymethoxy)allenylzinc bromide to enantiopure ( RS, E)- N-2-benzylidene-2-methylpropane-2-sulfinamide and a ring-closing metathesis reaction as the key steps. Following this procedure, (2 S,3 R)-3-hydroxy-2-phenylpiperidine is obtained in seven steps in 56.2% overall yield. [ABSTRACT FROM AUTHOR]

Compared to other nitrogen heterocycles such as aziridines, pyrrolidines, or piperidines, the chemistry of azetidines is much less developed, probably because of their limited availability. In this account, recent synthetic routes to these strained heterocycles starting from readily available enantiomerically pure starting compounds will be detailed. The ring strain in these heterocycles makes them excellent candidates for nucleophilic ring-opening or ring-expansion reactions yielding higher ring systems or highly substituted acyclic amines. These useful transformations will be described in the second section of this account. 1 Introduction 1.1 Synthesis of Azetidines from ?-Amino Alcohols 2 Synthetic Transformation of 2-Cyanoazetidines 3 Ring Expansion of Functionalized Azetidines 3.1 Ring Expansion to Pyrrolidines 3.2 Ring Expansion to Azepanes 4 Ring Opening of Azetidines and Azetidinium Ions 5 Reactivity of Azetidinium Ylides 6 Synthetic Applications 7 Concluding Remarks [ABSTRACT FROM AUTHOR]

An asymmetric total synthesis of antimalarial alkaloid (+)-febrifugine is accomplished in 23% overall yield over 14 steps from readily available starting materials. The synthesis features a SmI 2-mediated reductive cross-coupling of chiral N- TERT-butanesulfinyl imine with aldehyde. [ABSTRACT FROM AUTHOR]

Fluorinated piperidines bearing an additional functional group at the heterocyclic ring are important building blocks for use in agrochemical or pharmaceutical chemistry. Therefore, for the first time 3-alkoxy-4,4-difluoropiperidines were synthesized by deoxofluorination of 3-alkoxy-4-piperidinones with morpholinosulfur trifluoride and were selectively N- and O-deprotected. In �addition, the oxidation of 4,4-difluoro-3-hydroxy-1-trifluoroacetylpiperidine resulted in the interesting 4,4-difluoro-3,3-dihydroxypiperidine. [ABSTRACT FROM AUTHOR]

In the presence of a catalytic amount of piperidine ?(10 mol%), reaction of ethyl 4,4,4-trifluoro-3-oxobutanoate 3 and ?2-arylidene-indane-1,3-diones 4 gave the unexpected fluorine-?containing multiply substituted dispirocyclohexanes 5 in good yields. The structures of compounds 5 were fully confirmed by spectroscopic methods and elemental analysis. A representative compound 5A was further confirmed by XRD analysis. A plausible reaction mechanism for the formation of compounds 5 was presented. [ABSTRACT FROM AUTHOR]

A synthetic route toward new 1-alkyl-3-aminomethyl-3-fluoropiperidines, which are of high interest as building blocks in medicinal chemistry, is described. The successful approach consists of the fluorination of ethyl 3-chloropropyl-2-cyanoacetate with N-fluorodibenzenesulfonimide (NFSI) and transformation of the ester moiety into different amides, yielding N-alkyl-5-chloro-2-cyano-2-fluoropentanamides. Ring closure was achieved under basic conditions, yielding 1-alkyl-3-fluoro-2-oxopiperidine-3-carbonitriles. After reduction of the obtained lactams with borane, the desired 3-aminomethyl-3-fluoropiperidines were obtained in good yields. [ABSTRACT FROM AUTHOR]

The synthesis of piperidine alkaloids (+)-dihydropinidine (1), (+)-isosolenopsin (2a), (+)-isosolenopsin A (2b), and (2R,6R)-6-methylpipecolic acid (3a) hydrochlorides, based on cross-metathesis of chiral N-tert-butylsulfinyl homoallylamines with methyl vinyl ketone, is presented. [ABSTRACT FROM AUTHOR]

A convergent stereoselective first total synthesis of a novel ten-membered macrolide from l-malic acid and (2R)-2,3-O-cyclohexylideneglyceraldehyde is reported. [ABSTRACT FROM AUTHOR]

The synthesis of piperidine alkaloids (+)-dihydropinidine ( 1), (+)-isosolenopsin ( 2A), (+)-isosolenopsin A ( 2B), and (2 R,6 R)-6-methylpipecolic acid ( 3A) hydrochlorides, based on cross-metathesis of chiral N- TERT-butylsulfinyl homoallylamines with methyl vinyl ketone, is presented. [ABSTRACT FROM AUTHOR]

A [3+3]-annulation approach to piperidines via a tandem iminium ion allylation reaction of bisaminals has been developed. The scope of this process is described as well as preliminary experiments aimed at understanding the mechanism of a competing olefin isomer formation. [ABSTRACT FROM AUTHOR]

A variety of different N-(2,2,3-trichloropropyli?dene)amines, N-(2,2,3-trichlorobutylidene)amines, and N-(2,2,5-trichloropentylidene)amines were synthesized for the first time, and their reactivity with regard to hydride reagents was investigated. In this way, N-(2,2,5-trichloropentylidene)amines were evaluated as substrates for the synthesis of piperidines, and N-(2,2,3-trichloropropylidene)amines and N-(2,2,3-trichlorobutylidene)amines were reduced efficiently into the corresponding novel ?,?,?-trichloro-amines by means of sodium cyanoborohydride in methanol in the presence of acetic acid. Furthermore, N-(2,2,3-trichloropropyli?dene)amines were transformed into 2-(chloromethyl)aziridines by lithium aluminium hydride in Et 2O, and N-(2,2,5-trichloropentylidene)acetamide was used for the first time as a suitable substrate for the addition of oxygen, nitrogen, and sulfur nucleophiles in good yields. [ABSTRACT FROM AUTHOR]

The first asymmetric synthesis of (trifluoromethyl)pipecolic acids is reported. The synthetic strategy involves as key step an intramolecular Mannich reaction of a homochiral α-Tfm-β-amino ketal, prepared with a high stereoselectively in four steps from a fluoral hemiacetal. [ABSTRACT FROM AUTHOR]

The first asymmetric synthesis of (trifluoromethyl)pipecolic acids is reported. The synthetic strategy involves as key step an intramolecular Mannich reaction of a homochiral ?-Tfm-?-amino ketal, prepared with a high stereoselectively in four steps from a fluoral hemiacetal. [ABSTRACT FROM AUTHOR]

The first asymmetric synthesis of (-)-morusimic acid D, a 2,3-trans-2,6-cis-2-methyl-6-substituted piperidin-3-ol containing alkaloid is reported. The key steps are the reductive alkylation of N,O-diprotected 3-hydroxyglutarimide, a stepwise reductive alkylation, and an asymmetric aldol-type reaction using a modified Evans chiral auxiliary. [ABSTRACT FROM AUTHOR]

Proline-promoted Mannich reactions of a series of cycloalkanones with formalin and aniline followed by N-acetylation provided precursors 9- 12 for samarium diiodide mediated cyclizations. The ketyl-aryl coupling of these compounds furnished angularly fused piperidine derivatives such as 13 in good yields. Highly stereoselective dihydroxylation gave compounds of type 14 with five contiguous stereogenic centers. Our modular approach to this type of compounds involves just four simple steps and is fairly general. For the conversion of 10 into 15 we could demonstrate that the toxic and carcinogenic additive HMPA can be successfully replaced by lithium bromide and 1,3-dimethyl-2-imidazolidinone (DMI). [ABSTRACT FROM AUTHOR]

New amino derivatives of porphyrins containing cyclic amino and hydroxypiperidine groups bound through the MESO phen?yl rings are prepared by the Pd-catalyzed amination of MESO-bromophenyl(polyalkyl)porphyrins. The reaction allows for the introduction of piperidine, morpholine, 3- and 4-hydroxypiperidine groups with 50-80% product yields, but in the case of TRANS-3,4-dihydroxypiperidine and TRANS-3-hydroxy-4-(4-hydroxypiperidin-1-yl)piperidine the reaction leads to extensive hydrodebromination of the porphyrin substrate. [ABSTRACT FROM AUTHOR]