3.4.5.6- Tetrahydropyridine-l-oxide

A novel rearrangement of suitably 2-substituted side-chain perhy-dro-isoxazolo[2,3-a]pyridines has been shown to afford indolizine and quinolizine derivatives (86TL1727). Thus, 2-spirocyclopropylperhydro-isoxazolo[2,3-a]pyridine (61), obtained as a mixture with the 3-spiro isomer from the reaction between 3,4,5,6-tetrahydropyridine-l-oxide and methylene cyclopropane, undergoes thermal rearrangement (400°C, 0.2 mmHg) to the quinolizidin-2-one (62). 

The perhydro-isoxazolo[2,3-fl]pyridine system offers a route to 2,6-disubstituted piperidines. For example, the reaction between styrene and the substituted 3,4,5,6-tetrahydropyridine-l-oxide (69) gives the isoxa-zolidine (70) which, on benzylation, gives 71. This was subjected to reductive cleavage of the N—O bond with lithium aluminum hydride, followed by mesylation of the aminodiol produced. Treatment of the mesylate with lithium triethylborohydride gave the trans-2,6-disubstituted piperidine... 

Hydrogenations of acetylpyridines were carried out similarly, and yielded various products depending on the reaction conditions and especially on the catalyst used. Thus 4-acetylpyridine was hydrogenated over palladium oxide to form the corresponding alcohol, 4-(l-hydroxyethyl)pyridine, with a small amount of the pinacol (4), but it was converted mainly to the pinacol using palladium on charcoal or rhodium on alumina. However, under different conditions, the pyridyl ring of 3-acetylpyridine was reduced to a mixture of 3-acetyl-l, 4,5,6-tetrahydropyridine and 3-acetylpiperidine. 

Nitropyrimidine (147) underwent a Diels-Alder-type addition by the enam-ine, l-acetyl-4-(pyrrolidin-l-yl)-l,2,3,6-tetrahydropyridine (146), and subsequent reactions to afford 6-methyl-3-nitro-5,6,7,8-tetrahydro-l,6-naphthyridine (148, R = Ac) (reactants, EtOH, reflux, 3 h 48%) and thence deacetylation to 3-nitro-5,6,7,8-tetrahydro-l,6-naphthyridine (148, R = H) (6M HC1, reflux, 90 min 89%) and oxidation to 3-nitro-l,6-naphthyridine (substrate, AcOH, EtOH, reflux, I2/EtOH I2EtOHJ, dropwise, reflux. 2 h 64%)656... 

TL1489). An alternative route to a 2,6-disubstituted piperidine (74) involves the reductive cleavage of the N—O bond of the isoxazolidine (73) (from 2-methyl-2,3,4,5-tetrahydropyridin-l-oxide and undec-l-ene) by zinc in acetic acid (86CC1287). 

TRIFLUORO-2-BUTYNOATE. C-Acylation of an enolate using methyl cyanoformate provides a convenient source of the a-carbometh-oxyoctalone, METHYL (la,4Ap,8Aa)-2-OXO-DECAHYDRO-l-NAPH-THOATE and represents a good example of generating jS-keto esters under mild conditions. The nitrone functionality is featured in a procedure which makes it in a single step from secondary amines and 6-METHYL-2,3,4,5-TETRAHYDROPYRIDINE N-OXIDE is the example described. Finally, the synthesis of phospholes l-PHENYL-2,3,4,5-TETRAMETHYLPHOS-PHOLE is described as an example of the versatility of zirconocene chemistry. 

The oxidation of 1,4-dihydropyridines with dimethyldioxirane provides dimeric tetrahydropyridines fused as a 1,4-dioxane. These products can be converted to useful iminium ion precursors and 2-substituted-3-hydroxy-l,2,3,4-tetrahydropyridines <97CC213>. The cycloaddition of 1,4-dihydro- and 1,4,5,6-tetrahydro-nicotinates with cyanoalkenes gives a mixture of regioisomers. No isomerization of the cis/trans relationship is observed with Z- or -but-2-enenitrile indicating a consorted cycloaddition mechanism. Low diastereoselectivity in... 

Heck arylation of AMrenzyloxycarbonyl-l, 2,3,6-tctrahydropyridinc 247 with aryldiazonium salts results in formation of a mixture of unstable ct-hydroxy carbamates, which can be isolated, after oxidation, as the stable lactam derivatives. Arylation occurs preferentially at the 5-position to give lactam 248 and tetrahydropyridine 249 with 4-aryl lactam 250 being formed to a lesser extent (Equation 23) <2002TL741>. 

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