A-Pipecoline

On the basis of a comprehensive ECD study of chiral 2-alkyl-substituted piperidines92, such as (S -a-pipecoline [(5 )-2-methylpiperazine, (5 )-102] and their TV-methyl derivatives [(5)-103] in ethanol, the sign of the strong, long-wavelength CE near 200 nm, shifted to... 

Electrolytic reduction using a lead cathode in 20% sulfuric acid converted pyridine a-carboxaldehyde to a mixture of 41% of a-picoline, 25% of a-pipecoline and 11% of 2-methyl-1,2,3,6-tetrahydropyridine [443]. 

The resulting 2,6-xylidide a-pipecolinic acid (2.2.5) is methylated to mepivacaine using formaldehyde with simultaneous reduction by hydrogen in the presence of platinum on carbon catalyst [15]. 

Mtroso-a-pipecoline gives a-methylpiperylhydrazine, a pipecoline and ammonia at the cathode, and at the anode a... 

Pyridine.—Ahrens1 accomplished the electrolytic reduction of pyridine and the derivatives of pyridine, and obtained piperidine from pyridine, and a-pipecoline from a-picoline. In these electrolyses lead cathodes and 10% solutions of sulphuric acid were employed. 

V-Hexylenanthamide gives a 58% yield of A -caproylenantham-ide [940] on treatment with ruthenium tetroxide in carbon tetrachloride at 10-15 °C. Ethyl A -acetyl-a-pipecolinate, when treated with ruthenium dioxide and sodium periodate in aqueous ethyl acetate at room temperature, gives a 95% yield of ethyl l-acetyl-2-piperidone-6-carboxylate (equation 526) [944],... 

In a survey of a number of species of the genus Pinna for alkaloids it was discovered that three species, i.e., P. aabiniana Dougl., P. jejfreyi Balfour, and P. torreyana Parry contained appreciable quantities of an alkaloid that was named pinidine. These three species differed from others in not containing any bicyclic terpenes. P. aabiniana, which was chosen for a detailed study, was found to contain as well as pinidine a low-boiling alkaloid identified as (-(-)-a-pipecoline (77). 

The piperidine ring is probably the most common heterocycle occurring in pharmaceuticals. Piperidine is often used as a secondary amine in the synthesis of drugs. The local anaesthetic bupivacaine 20 (used as the racemate or the ( S)-enantiomer levobupivacaine) is a pipecolinic acid derivative. The antihistamine bamipine 21 and the analgesic fentanyl 22 are derived from 4-aminopiperidines. The ... 

Pyridine—Picoline—Nitro-piperidines—Nitroso-a-pipecoline — Nitroso-aldehyde-capellidine — Quinoline — Quinal-dine.75-76... 

Nitroso-a-pipecoline gives, in addition to ammonia, a-pipecoline and a-methyl-piperylhydrazine. 

Pipecoline. See 3-Methylpiperidine a-Pipecoline. See 2-Methylpiperidine P-Pipecoline. See 3-Methylpiperidine Piperalin CAS 3478-94-2... 

The utility of lOOC reactions in the synthesis of fused rings containing a bridgehead N atom such as pyrrolizidines, indolizidines, and quinolizidines which occur widely in a number of alkaloids has been demonstrated [64]. Substrates 242 a-d, that possess properly positioned aldoxime and alkene functions, were prepared from proline or pipecolinic acid 240 (Eq. 27). Esterification of 240 and introduction of unsaturation on N by AT-alkylation produced 241 which was followed by conversion of the carbethoxy function to an aldoxime 242. lOOC reaction of 242 led to stereoselective formation of various tricyclic systems 243. This versatile method thus allows attachment of various unsaturated side chains that can serve for generation of functionalized five- or six-membered (possibly even larger) rings. 

The key feature of the first total synthesis of (+)-homopumiliotoxin 223G 418 was a Lewis acid-induced, chelation-controlled propargylation of the trifluoroacetate salt of (. )-2-acetyl pi peri dine 415, derived from iV-Cbz-L-pipecolinic acid. Alkyne 416 thus formed was transformed after several steps into 417, which was cyclized by activation of the primary hydroxyl with the carbon tetrabromide-triphenylphosphine system to give the natural product (Scheme 98) <1998TL2149>. 

Ugi five-center three-component reaction of pipecolinic acid and glycol aldehyde dimer with isocyanides gave a 1 1.7-2.1 diastereomeric mixture of l-oxoperhydropyrido[2,Tc][l,4]oxazine-9-carboxamides 397 (Scheme 35) <20010L4149>. Using CF3CH2OH as solvent is critical for the reaction. When 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid was employed, 1,3,4,6,11,11 a-hexahydro-[ l,4]oxazino[4,3+]isoquinoline-4-carboxarnide was formed. 

Some interesting fused 1,2,3-triazole ring systems have been reported. A series of 5-piperidyl-substituted 7-hydroxy-3f/-l,2,3-triazolo[4,5-d]pyrimidines 143 has been synthesized from pipecolinate esters, benzylazides, and cyanoacetamide <06CHE246>. 4-Alkylidene-5,6-dihydro-4//-pyrrolo-[l,2-c][l,2,3]triazoles 144 were prepared from alkylidenecyclopropanes via diiodogenation/Cu(I)-catalyzed 1,3-dipolar cycloaddition/intra-molecular Heck reaction sequence <06SL1446>. 6,6-Dimethyl-2-phenyl-4,5,6,7-tetrahydro-27/-benzotriazol-4-one 145 were prepared from A-(5,5-dimethyl-3-oxocyclohexenyl)-S,S-diphenylsulfilimine and... 

As in the case of the formation of an azepine (Scheme 43), Pro afforded a pyrrolo[l,2-fl]azepine 88, and pipecolinic acid afforded a pyrido[l,2-a]aze-pine 89 (80JHC1593). 

Careful inspection of the reported photocatalytic reactions may demonstrate that reaction products can not be classified, in many cases, into the two above categories, oxidation and reduction of starting materials. For example, photoirradiation onto an aqueous suspension of platinum-loaded Ti02 converts primary alkylamines into secondary amines and ammonia, both of which are not redox products.34) ln.a similar manner, cyclic secondary amines, e.g., piperidine, are produced from a,co-diamines.34) Along this line, trials of synthesis of cyclic imino acids such as proline or pipecolinic acid (PCA) from a-amino acids, ornithine or lysine (Lys), have beer. successfuL35) Since optically pure L-isomer of a-amino acids are available in low cost, their conversion into optically active products is one of the most important and practical chemical routes for the synthesis of chiral compounds. It should be noted that l- and racemic PCA s are obtained from L-Lys by Ti02 and CdS photocatalyst, respectively. This will be discussed later in relation to the reaction mechanism. 

Formamides derived from L-pipecolinic acid act as Lewis base organocatalysts for reduction of A-arylimines with trichlorosilane, giving yields and ees in the high 90s for a wide range of imine substrates.54... 

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