1.2.3.6- Tetrahydropyridine

Amines undergo aminopalladation to alkynes. The intramolecular addition of amines to alkynes yields cyclic imines. The 3-alkynylamine 273 was cyclized to the 1-pyrroline 274, and the 5-alkynylamine 275 was converted into the 2,3,4,5-tetrahydropyridine 276[137]. Cyclization of o-(l-hexynyl)aniline (277)... 

B. 2,3,4,5-Tetrahydropyridine Trimer. In a 3-1., three-necked, round-bottomed flask equipped with a sealed mechanical stirrer, a dropping funnel, and a reflux condenser fitted with a calcium chloride... 

These IHs have been applied to the synthesis of several pyrroHnes and 2,3,4,5-tetrahydropyridines known as venom constituents from ant species [278]. 

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... 

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.

The simple non-aromatic pyridines discussed in this Section are represented by nine structures (l)-(9). These are the fully saturated piperidine (1), the tetrahydropyridines (2)-(4) and the dihydropyridines (5)-(9). In this section (2), (3) and (4) will be referred to as A5-, A2- and A1-piperideine as well as 1,2,3,6-, 1,2,3,4- and 2,3,4,5-tetrahydropyridine. The former designation is rather archaic but less cumbersome and it has also been used by other authors of the review literature in this area (74HC(14-Sl)i). The latter designation is used by Chemical Abstracts. 

A mixture of silver(I) fluoride and 2,2 -bipyridine replaces chlorine with fluorine in 1-chloro-octane in 86% yield after 45 minutes at 130°C.28 Some heterocyclic polychloro derivatives are also fluorinatcd by silver(I) fluoride. Thus, perfluoro(2,3,4,5-tetrahydropyridine) (1) and per-fluoro(3,4-dihydro-2//-pyrrole) are prepared from 2,2,6-trichloro-3,3,4,4,5,5-hexafluoro-2,3.4,5-tetrahydropyridine and 2,2,5-trichloro-3,3,4.4-tetrafluoro-3,4-dihydro-2//-pyrrole by reaction with silver(l) fluoride at room temperature.31 Since the fluorination of 2,2,5-trichloro-3,3,4,4-tetrafluoro-3,4-dihydro-2//-pyrrole with silver(l) fluoride is slow, recycling is necessary.31... 

When comparing the chemistry of the three tetrahydropyridine isomers, the reactivities of 1,2,3,4- and 2,3,4,5-tetrahydropyridines are similar and these two isomers are often interconvertable. The chemistry of 1,2,3,6-tetrahy-dropyridines is somewhat different, and in particular the influence of the nitrogen atom has the least effect on the reactivity of the alkene, which behaves more like an alkene in a nonheterocyclic system. 

Unsubstituted 2,3,4,5-tetrahydropyridine 152 exists as a monomer in solution where it is somewhat unstable and highly reactive but conveniently exists in air as a stable crystalline solid in its trimeric form 153 <19770S118>. 

Tetrahydropyridine 152, handled as triazine 153, in the presence of metal catalysts, undergoes insertion into spiro-fused cyclopropane 156 to give the tetracyclic adduct 157 in an 86 14 mixture of diastereoisomers. 

Tetrahydropyridine 152 can be inserted into the iron-acyl carbon bond of the Fe(CO)3-bound vinyl ketene 158 to give the iron complex 159, which can be oxidatively cleaved to give bicyclic lactam 160 (Scheme 42)... 

The use of 6-methyl-2,3,4,5-tetrahydropyridine 163 has been widely reported in the synthesis of heterocycles due to its ability to be deprotonated selectively on the o -methyl group using lithium diisopropylamide (LDA). Deprotonation of tetrahydropyridine 163 with LDA followed by addition of a nitrile and propargyl bromide give tetrahydroindolizines 164 in moderate to high yields (Equation 12) <1996JOC2185>. 

IJnsymmetrical diketimines 168, which are widely used as bidentate metal ligands, can be synthesized by deprotonation of 6-methyl-2,3,4,5-tetrahydropyridine 163 followed by addition of imidoyl thioethers 167 (Equation 13) <2005JOC2075>. 

Tetrahydropyridine Ar-oxidc 174 undergoes 1,3-dipolar cycloaddition with (Z)-vinyl sulfoxides 178 to give isoxazolidines 179, which can be desulfurized to give amino alcohols 180 with high enantiomeric selectivity (Scheme 47) <1997TA109>. 

Recent work has focused on developing catalytically controlled asymmetric 1,3-dipolar cycloadditions of cyclic nitrones such as 2,3,4,5-tetrahydropyridine IV-oxide 174. The Lewis acid iron complex 181 catalyzes the cycloaddition of 2,3,4,5-tetrahydropyridine jV-oxide 174 with methacrolein to give (3A,5A)-isoxazolidine 182 in good yield and high enantiomeric selectivity (Scheme 48) <2002JA4968>. The same catalyst 181 however gave (3R,4A,5R)-isoxazolidine 183 with much lower selectivity when crotonaldehyde was used. 

Rhodium complex 184 catalyzes the cycloaddition of 2,3,4,5-tetrahydropyridine Ar-oxidc 174 with methacrolein to give the (iR,5R (-isoxazolidine 185 in quantitative yield and high enantiomeric selectivity (Equation 14) <2005JA13386>. 

Methyl-2,3,4,5-tetrahydropyridine 558 can be deprotonated at the methyl group and thus utilized in heterocyclic ring synthesis, for example, to make 559 <1996JOC2185>. 

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