3.4.5.6- Tetrahydropyridine-1 -oxide

These results indicate that the sulfinyl group seems to be much more efficient in the control of the stereoselectivity of 1,3-dipolar cycloadditions (endo or exo adducts are exclusively obtained in de> 80%) than in Diels-Alder processes (mixtures of all four possible adducts were formed). Additionally, complete control of the regioselectivity of the reaction was observed. Despite these clearly excellent results, the following paper concerning asymmetric cycloaddition of cyclic nitrones and optically pure vinyl sulfoxides was reported nine years later [154]. (Meanwhile, only one paper [155], related to the synthesis of /1-nicotyri-nes, described the use of reaction of nitrones with racemic vinyl sulfoxides, but these substrates were merely used as a masked equivalent of acetylene dipolaro-phile). In 1991, Koizumi et al. described the reaction of one of the best dipolarophiles, the sulfinyl maleimide 109, with 3,4,5,6-tetrahydropyridine 1-oxide 194 [154]. It proceeded in CH2C12 at -78 °C to afford a 60 20 10 6 mixture of four products in ca. 90 % yield (Scheme 92). 

The proposed biogenetic pathways (See Section 3) to 3-alkylpiperidine sponge alkaloids that have complex structures and nitrogen heterocycles at the piperidine or tetrahydropyridine oxidation states all proceed through a partially reduced Ws-3-alkylpyridine... 

Hofmann degradation of l,l-dimethyl-2-methylenepyrrolidinium hydroxide furnishes dimethylamine and dimethyl-3-pentynylamine 198). 1,1,4,4-Tetramethyltetrahydropyridinium hydroxide was obtained from l-dimethylamino-4,5-dibromopentane by means of silver oxide. Hofmann degradation of the product gives I,4,4-trimethyl-/j -tetrahydropyridine 199). 

Lavilla et al. have reported several stereocontrolled oxidative electrophilic additions to A-alkyl-l,4-dihydropyridines 34 leading to the synthesis of 3-halo-2-substituted-l,2,3,4-tetrahydropyridines 67 (98JOC2728). Adding a stoichiometric amount of iodine or NIS (A-iodosuccinimide) to a methanolic solution of 1 -methy 1-... 

Alkyl-1,4-dihydropyridines on reaction with peracids undergo either extensive decomposition or biomimetic oxidation to A-alkylpyridinum salts (98JOC10001). However, A-methoxycarbonyl derivatives of 1,4- and 1,2-dihydro-pyridines (74) and (8a) react with m-CPBA to give the methyl tmns-2- 2>-chlorobenzoyloxy)-3-hydroxy-1,2,3,4-tetrahydropyridine-l-carboxylate (75) and methyl rran.s-2-(3-chlorobenzoyloxy)-3-hydroxy-l,2,3,6-tetrahydropyridine-l-carboxylate (76) in 65% and 66% yield, respectively (nonbiomimetic oxidation). The reaction is related to the interaction of peracids with enol ethers and involves the initial formation of an aminoepoxide, which is opened in situ by m-chlorobenzoic acid regio- and stereoselectively (57JA3234, 93JA7593). 

Addition of allyltrimethylsilane 82 to 3,4,5,6-tetrahydropyridine-N-oxide (readily accessible, primarily as the dimer, on HgO-oxidation of N-hydroxypiperidine) in the presence of BU4NF 2-3H2O in TH Faffords 2-propenyl-N-hydroxypiperidine [72 a]. 

Using trimethylsilyl triflate, a one-pot reaction of acetoxyallylation and O-silylation of nitrones, gave silylated hydroxylamines (673). Enantiomers of the naturally occurring alkaloid dihydropinidine, potential antifeedants against the pine weevil Hylobius abietis, were prepared by diastereoselective, dimethylzinc mediated addition of pinacolyl 2-propenylboronate to (/ )- and to (S )-2-methyl tetrahydropyridine-A-oxide, obtained from D-alanine and L-alanine, respectively (Scheme 2.190) (674). 

Recently, a series of cycloadducts possessing unusual flipping modes have been isolated from the 1,3-dipolar cycloaddition of 3,4,5,6-tetrahydropyridine IV -oxide to piperidides of cinnamic acid and para-substituted cinnamic acids (791). 

Mabic S, Castagnoli N, Jr. Assessment of structural requirements for the monoamine oxidase-B-catalyzed oxidation of l,4-disubstituted-l,2,3,6-tetrahydropyridine derivatives related to the neurotoxin l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine. J Med Chem 1996 39( 19) 3694—... 

Salach JI, Singer TP, Castagnoli N, Jr, et al. Oxidation of the neurotoxic amine l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) by monoamine oxidases A and B and suicide inactivation of the enzymes by MPTP. Biochem Biophys Res Commun 1984 125(2) 831-835. 

Reaction of pure (5ir,/ c)-9 with nitrones IV or V followed by the addition of an excess of n-Bu4NBr (Scheme 21) gives the corresponding 3,5-crt(io-isoxazolidines in quantitative yield. Table 5 collects the ee values obtained for the two nitrones. Comparison of the results of Table 5 with those of Table 4 indicates that, whereas a mixture of epimers complex 9 (67% / ir,/ c/33% 5ir,/ c, molar ratio) reacts with nitrones 2,3,4,5-tetrahydropyridine /V-oxide (IV) or 3,4-dihydroisoquinoline... 

Oxidation of Secondary Amines to Nitrones 6-Methy1-2,3,4,5-Tetrahydropyridine N-Oxide... 

Desilylative cyclization of oxime silyl ethers 319 in the presence of TBAT (tetra-butylammonium triphenyldrflnorosiliconate)/THF or benzene afforded tetrahydropyridine A-oxides 320 in 67-71% yields (equation 138) . 

Figure 6.5 Hydrogen-bond donors (50mol% loading) screened for the reaction of nitrone 6-methyl-2,3,4,5-tetrahydropyridine N-oxide and TMSCN at -78°C. The yields and reaction times are given for the resulting adducts.

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