A-Piperidones

PA-5 can be synthesized by die anionic ring-opening polymerization of a-piperidone.12 First the catalyst, A -acetyl piperidone, is prepared. Then the polymerization is performed anionically, well below its melting temperature. 

Lactams are named in several ways. They are named as alkanolactams by the IUPAC substitutive system, such as 3-propanolactam, 4-butanolactam, 5-pentanolactam, and 6-hexano-lactam, respectively, for the 4-, 5-, 6-, and 7-membered rings, respectively. An alternate IUPAC method, the specialist heterocyclic nomenclature system, names these lactams as 2-azetidinone, 2-pyrrolidinone, 2-piperidinone, and hexahydro-2f/-azepi n-2-one, respectively. These lactams are also known by the trivial names fl-propiolactam, a-pyrrolidone (y-butyrolactam), a-piperidone (8-valerolactam), and e-caprolactam, respectively. 

Systems which can react by either 5-exo or 6-endo cyclization normally produce the five-membered ring system. Exceptions result when equilibration of the initially formed five-membered ring is facile and substitution electronically favors the 6-endo mode of cyclization. Several examples have been found in amidoselenation reactions.41158 216 216 232 For example, halocyclization of thioimidate (17) produced only the pyrrolidone product,217b 217c 233 while selenocyclization of amide (18) produced only the piperi-done product.232 Note that the cyclization of (18) to a piperidone also involves regioselectivity in the cyclization of an amide functionality to a lactam rather than an imidate. Both the ring size and type of product can be explained by equilibration. 

In 2001, Magnus and co-workers reported a straightforward synthesis of racemic rhazinilam by initial construction of the pyrrole ring from a piperidone, Fig. (33) [154]. The sequential alkylation of piperidone 155 with iodoethane and allyl bromide furnished piperidone 156, having the requisite C-20 substitution of rhazinilam. After formation of the thiophenyl iminoether 157, A-alkylation with allyl bromide 158 furnished the corresponding iminium intermediate which underwent 1,5-... 

The scope of kinetic resolution of this type is not limited to alcohol derivatives but can be extended to N-tosylamino derivatives when the titanium-tartrate catalyst modified with calcium hydride and silica gel is used. Resolution of AT-tosylamines 47 is effected with high efficiency but the configuration of the slow reacting isomer is opposite to that expected from the empirical rules for kinetic resolution (Scheme 11) The (R)-isomer of 47 is oxidized prior to the (S)-isomer when (-i-)-DIPT is used as a chiral auxiliary. Again, the A -piperidone 49 of high enantiopurity can be obtained by oxidation of the enantioenriched furylamines 48 with ra-CPBA [79]. 

A construction of functionalised glutarimides relies on the doubly nucleophilic dianion that can be generated by C- and N-deprotonation, from a 2-tosyl-acetamide. Regioselective reduction to a piperidone can be achieved via formation of the stabilized enolate. 

Azimic acid (218) was synthesized in eleven steps from (25,65)-6-hydroxy-2-methyl-N-tosyl-A -piperidone-3 [497], (+)-Carpamic acid (219), along with 218, was synthesized using the same approach as for spicigerine methyl ester, 214 and 217, in which a Ni (II) catalyzed reaction is used to attach the side chain to a bromopyridine [495]. 

The most common and versatile route to bispidines is a variant of the Mannich condensation (see Scheme 1). The reaction of a component with C H acidic hydrogen atoms, an aldehyde, and a primary amine or ammonia in the ratio 1 2 1 leads to a piperidone, which in some cases can be further condensed with an aldehyde (usually formaldehyde) and a primary amine to yield a bispidone. For symmetric bispidine derivatives, the preparation can be conducted in one step with the aldehyde, the C H acidic component, and the amine in a 4 1 2 ratio. 

Synthetic work in this area includes a new, stereospecific synthesis of sparteine and a synthesis of isosophoramine. The reduction of quinolizidone (16) by means of lithium aluminium hydride affords, as noted previously, a dimeric product (17), presumably via condensation of the initially formed enamine (18) with the corresponding immonium cation (19). With di-isobutyl aluminium hydride the yield of (17) can be increased to 85%. Analogous reduction of the dilactam (20), prepared by base-catalysed condensation of the bromo-lactam (21) with a-piperidone, gave an intermediate (22), in which the enamine and immonium ion units are present within the same molecule. Intramolecular cyclization of (22), via a transition state derived from the conformation (23), spontaneously gave the... 

Several reports have dealt with the reductive cyclization of enynes where the alkyne component undergoes addition to an adjacent carbonyl group. Typical of this is irradiation of 155, in the presence of the SET sensitizer trie thy lamine, which affords the bicyclic product 156, a piperidone, that was used in a synthesis of z o-oxyskyanthine. Unsaturated aldehydes such as 157 also undergo this photo-electron transfer-induced cyclization to afford a mixture of alcohols 158 (Scheme 6) . Pete and his coworkers have extended their study of this reductive cyclization of unsaturated ketones in a synthesis of hirsutene 159. The reaction involves the irradiation of the ketone 160 at 254 nm in the presence of triethylamine, whereby the tricyclic compound 161 is formed in 58% yield. This is subsequently transformed into hirsutene ... 

Cryst. M.p. anhyd. 2Q6°. Sol. 460 parts H,0 at 40 . Spar. sol. EtOH, EtjO. FeCl3- -> reddish-brown ool. Heat— a-piperidone- -carboxylic acid. ... 

Nylon 5 or poly(a-piperidone) can be prepared by ring opening anionic polymerization of valerolactam [53]. The reaction requires very pure monomer to yield a high molecular weight polymer [53] ... 

In 2003, a highly enantioselective hydrogenation of a piperidone hydrochloride constituted the key step of an efficient enantioselective synthesis of an NMDA 2B receptor antagonist, Ro 67-8867. The chiral diphosphine ligand belonged to the MeOBIPHEP family, as depicted in Scheme 2.30. 

Benzopyridooxazaborinines 130a—e have been synthesized in 32—54% yields by the cyclocondensation of a piperidone derivative with boronic acids in refluxing AcOH (Scheme 46) (2008CHC1527). 

Needles or prisms from EtOH-Et20. M.p. 126-7° (121-2°). Hygroscopic. At 130-60°—> i T-methyl-a-piperidone. 

We also note here the synthesis of (70) and (71) by condensation of a tetrahydrothiapyran-4-one or a piperidone with benzaldehyde and ammonium acetate, of the sulphonamide (72), and of the products of reaction of phosphonous chlorides with the diamines (73)—(75). The synthesis and X-ray structural analysis of (76) are reported. ... 

Method Four, Fischer and Zempl n (313, 314). Piperidine N-ben-zoylpiperidine 8-benzpylvaleric acid a-bromo-8-benzoylamino-valeric acid -> o-amino-8-benzoylaminovaleric acid -> proline. The synthesis through the corresponding m-nitrobenzoyl derivatives was described by Fischer and Zempl (314). The preparation of o-bromo-8-benzoylaminovaleric acid (A) from cyclopentanone oxime throu the intermediates a-piperidone, 8-aminovaleric acid and 8-benzoylamino-vaieric acid has been reported by Schniq >p and Marvel (688). Mayeda and Nozoe (564) sjmthemzed (A) essentially by the method of Schniepp and Marvel. Copper prolinate dibydrate was prepared from (A). 

Method Five. Heymans (395). The N-benzoyl or N-m-nitrobenzoyl derivative of j8,j9-dibromo-a-piperidone, formed as side reaction product in the synthesis of a-bromo-8-benzoylaminovaleric acid, or o-bromo-8- MS p. 361. 

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