Piperidine-2-ones

Piperidin-4-one N-oxide, 2,2,6,6-tetramethyl-solvent effects, 2, 146 Piperidinones stability, 2, 159-161 synthesis, 2, 81, 95 from S-aminopentanoic acids, 2, 402 Piperidin-2-ones IR spectroscopy, 2, 130 synthesis... 

Z)][],3]thiazin-6-one with 2.5 equiv of HSnBu3 in the presence of AIBN in boiling benzene for I.5h yielded 4-(2-methoxyphenyl)-l-[3-(tributylstan-nylthio)propyl]piperidin-2-one (01 SI35). 

CN ( )-r-[3-(3-chloro-10,l I-dihydro-5//-dibenz[6/ azepin-5-yI)propyl]hexahydrospiro[imidazo[l,2-a]pyridine-3(2//),4 - piperidin]-2-one... 

We will now consider supidimide (5.66) as an example of a molecule containing a six-membered lactam ring. The piperidin-2-one ring of this potential sedative underwent slow chemical hydrolysis in buffer solution to yield 5.67, but was resistant to metabolic hydrolysis. The other amide bond was stable [175], Supidimide was primarily metabolized by oxidation of the pi-peridin-2-one ring to yield a glutarimide ring, which then was hydrolyzed as described in Sect. 4.4. 

Sphingomonas sp. HXN-200 was also able to accept a six-member ring substrate. Hydroxylation of A/-benzyl- and A/-/ert-butoxycarbonyl-2-piperidinone gave the corresponding (/J)-4-hydroxy-piperidin-2-ones in 31% and 68% ee, respectively (Figure 15.4). This provides a simple synthesis of such types of useful synthons. 

When oxazine 9 was hydrogenated over Pt02 catalyst in the presence of CaC03 and the primarily formed perhydropyrido[l,2-b][l,2[oxazin-8-one 10 suffered an N-O cleavage to give piperidin-2-one 11 (09S655). 

Piperidin-2-ones have also been prepared by the insertion of ammonium ion <2004TL6221> (Equation 108), with chiral versions also being reported (Scheme 52) <2002CC526>. 

A large-scale synthesis of 2-methylthiochromone has been devised from thiosalicylic acid <2000SC1193>, while the reaction of thiosalicylic acids with various 2-substituted A) AAlialky I acetamides is effected by POCl3 which generates an electrophilic iminium salt. The products are 3-substituted 2-aminothiochromones 523 (Equation 183). Application of this protocol to cyclic amides such as piperidin-2-ones leads to tetrahydro[l]benzothiopyrano[2,3-/dpyridinc-5-oncs <2005AJC864>. 

Acylation of iV-phenyl-3-oxobutanethioamide with 3-arylpropenoyl chlorides gives rise to a separable mixture of piperidin-2-ones and 2,3-dihydrothiopyran-4-ones 536 in approximately equal amounts. Acylation at C-2 is considered to compete with N-acylation and is followed by an intramolecular Michael addition (Equation 192) <2005RJ0283>. 

Similar reactions with piperidin-2-one and 4,4-dimethyl-2-oxazolid-inone have been carried out using 3-(4-bromophenyl)-3,6-dimethoxyin-... 

Novel methods for functionalizing piperidines at the 3- and 4-positions were also introduced. Mete and co-worker synthesized 3-diazo-piperidin-2-one and characterized its reactivity in transition-metal catalyzed reactions, particularly H-X insertion reactions and cyclopropanation reactions <02T3137>. Christoffers and co-workers developed an asymmetric Michael addition reaction with a chirally modified 4-piperidone-enamine. They were able to create a quaternary carbon center in >95% de and elaborate the compound on through classical means to the functionalized piperidine 107 (Scheme 21) <02EJ01505>. 

Cyclization of alkyl radicals derived from acryl enamides gives piperidin-2-ones (Equation (10)).51 Radical carbonyla-tions have become a promising tool for the introduction of carbon monoxide into organic molecules. Macrocyclic compounds are prepared by intramolecular cyclization via radical carbonylation (Equation (1l)).53... 

A first example shows the enantioselective reductive radical cyclisation reaction of 3-(5 -iodopentylidene)-piperidin-2-one (24) (Scheme 9). After the primary cyclisation step the hydrogen abstraction leads to the formation of a stereogenic centre. The complexing agent (+)-12 was used as source of chirality (Aechtner et al. 2004 Dressel et al. 2006). 

Reaction of arylhydrazones 216 of piperidin-2-ones with methyl chloro-formate, phosgene, or thiophosgene yielded (80USP4213773) the fused-ring system 217. Reaction of 2,2 -azopyridine (218) with diazoalkanes afforded [66JCS(C)78 73LA2088] the 2-(pyrid-2-yl)-l,2,4-triazolo[4,3-a]-... 

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