Piperidine, derivatives reactions

Ring expansion of ftve-membered ring heterocycHc compounds has been accompHshed to form pyridine derivatives. Reaction of tetrahydrofurfuryl alcohol with ammonia gives pyridine (1) under dehydrogenating conditions, and gives piperidine (18) under reductive conditions. 

Reaction of the chiral piperidine derivative 602 with the activated alkyne 603 afforded the corresponding oxazoloquinoline derivative 604 (98H747) (Scheme 102). 

Other examples were tested and the results are summarized in Table 5.7 [24]. The reactions always proceeded smoothly to afford the corresponding piperidine derivatives in high yields with high enantiomeric excess. In addition, reverse enantio-... 

The ZwKKER reaction involving Co salts is frequently used for the detection of barbituric acid derivatives [31-35], but some purine, pyridine and piperidine derivatives and heterocyclic sulfonamides also yield colored derivatives. The Zwkker reaction is particularly sensitive when it is possible to form a tetrahedral complex [Co(Barb)2 Xj] (X = donor ligand, e.g. amine) [4]. 

Method B involves the preparation of precursor of 2-alkyl-l-benzo-pyrylium salts, as shown in Scheme ll.50 2-Alkylbenzopyrylium salts have been prepared by condensation of salicylaldehyde with appropriate ketone in acetic acid or by alkylation or reduction of coumarin or chromone derivatives. Reaction of 2-alkylbenzopyrylium salts with salicylaldehyde gives directly a spirodibenzopyran or 2-vinynologue benzopyrylium salt 17 which then can be converted into the spirodibenzopyran by piperidine or pyridine. 

Enantiospecific syntheses of amino derivatives of benzo[ ]quinolizidine and indolo[2,3- ]quinolizidine compounds have also been achieved via A-acyliminium ion cyclization reactions, as an alternative to the more traditional Bischler-Napieralski chemistry (see Section 12.01.9.2.2). One interesting example involves the use of L-pyroglutamic acid as a chiral starting material to construct intermediates 240 via reaction with arylethylamine derivatives. Diisobutylaluminium hydride (DIBAL-H) reduction of the amide function in 240 and subsequent cyclization and further reduction afforded piperidine derivatives 241, which stereoselectively cyclized to benzo[ ]quinolizidine 242 upon treatment with boron trifluoride (Scheme 47) <1999JOC9729>. 

A similar strategy served to carry out the last step of an asymmetric synthesis of the alkaloid (—)-cryptopleurine 12. Compound 331, prepared from the known chiral starting material (l )-( )-4-(tributylstannyl)but-3-en-2-ol, underwent cross-metathesis to 332 in the presence of Grubbs second-generation catalyst. Catalytic hydrogenation of the double bond in 332 with simultaneous N-deprotection, followed by acetate saponification and cyclization under Mitsunobu conditions, gave the piperidine derivative 333, which was transformed into (—)-cryptopleurine by reaction with formaldehyde in the presence of acid (Scheme 73) <2004JOC3144>. 

Iodo-2-alkynoates (e.g., compound 380) react with 6-chloropropylamines (e.g., compound 381) to give quinolizine derivatives in a single synthetic operation (Scheme 88). The process comprises a sequence of an Sn2 reaction that yields secondary amine 382, an intramolecular Michael addition to give the piperidine derivative 383, halogen... 

Piperidine derivatives 161 and 164 could be cyclized to hexahydropyridooxadiazines 162, 165 via a dehydrogenation process by six oxidation equivalents of Hg(n)-EDTA. However, in both reactions, side products were also formed. From 161, piperidone derivative 163 was obtained, whereas starting from the amide 164, pyridopyrimidine 166 was isolated via cyclization by the amide nitrogen instead of oxime oxygen (Scheme 21) <1999ZNB632>. 

The thioxotetrazinoquinazoline 7 was reacted with paraformaldehyde and secondary amines, namely diethylamine and piperidine (Mannich reaction), to afford the corresponding derivatives (Equation 2) <1999IJB850>. 

Piperidines. Grieco et al. have described a general synthesis of piperidines by reaction of the acid salt of a primary amine with an allylsilane and 2 equiv. of formaldehyde in water. The reaction involves reaction of iminium ion (a), derived from the amine and formaldehyde, with the allylsilane to form a homoallylamine (b), which can form a second iminium ion (c), which cyclizes with capture of water to the piperidine. 

Fustero has devised an intramolecular version of the iminium ion catalysed conjugate addition of nitrogen in the preparation of a series of simple pyrrolidine and piperidine derivatives [115]. The reactions proceed in chloroform to give the target heterocycles in good yield and excellent levels of stereocontrol (Scheme 32). 

Diazoamides of type 300 rapidly cyclize to form aziridines 302 (342) (Scheme 8.73). It is conceivable that this reaction proceeds through a 1,2,3-triazoline intermediate 301, which is the consequence of a LUMO(dipole)— HOMO(dipolarophile) controlled intramolecular [3 + 2] cycloaddition. Some remarkable steric effects were encountered for this cyclization. While the piperidine derivative [300, = ( 112)4] readily cyclized by diazo group transfer at... 

The reaction of piperidine derivatives with electrophilic and oxidizing agents has been an effective method for functionalizing the positions adjacent to the nitrogen atom. This can be a useful synthetic process and a number of these methods are presented below. 

The mercury(II) acetate oxidation of tertiary amines is frequently used to introduce unsaturation into piperidine derivatives. The iminium ion is believed to be an intermediate in this reaction. These ions can give the enamine or react further with nucleophiles to give more complex heterocycles (Scheme 4). 

The electrolytic oxidation of N- methoxycarbonylpiperidines provides an interesting and potentially valuable method for the functionalization of piperidine derivatives (81JA1172). Anodic oxidation of piperidine (101) gave (102) which reacted, presumably through the acyl imine, with enol ethers to form a carbon-carbon bond a to the nitrogen atom (Scheme 9). The regiochemical control in this reaction is illustrated by the exclusive oxidation at the less substituted carbon atom (55JA439). 

Amines react with perchloryl fluoride. Thus, l-fluoro-2,2,6,6-tetramethylpiperidine (22) is form ed from the piperidine derivative 35 on the other hand, 1-fluoro salts 23 can he prepared by reactions with l-alkylpiperidines.36... 

The quaternization of simple quinolizidine and related alkaloids has attracted much attention, directed primarily at the stereochemistry of the reaction. Methylation of trans-quinolizidine (545) affords the ra-fused 5-methylquinolizidinium salt (546) its isomer (548) is available only by the cyclization of piperidine derivative (547) (51JA3681). 

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