Pyridinium ylides, addition reactions

Another example with porphyrinic dipolar species uses pyridinium salt derivatives as precursors of porphyrinic pyridinium ylides (Scheme 18) <05TL5487>. The procedure involves the reaction of porphyrin 58 with methyl bromoacetate, in refluxing chloroform, to give pyridinium salt 59. The latter, in the presence of K2CO3, reacts with 1,4-benzoquinone to yield only the mono-addition compound 60. Notably, when the reaction was performed in the presence of DBU, bis-addition occurred and the porphyrinic dimer 61 was the only isolated addition product. 

Yields from 1,3-dipolar addition reactions with pyridinium ylides are enhanced by the addition of phase-transfer catalysts [60]. The ylides are produced in situ under basic two-phase conditions and react at room temperature with acetylenic dipolarophiles. 

In a one-pot reaction (Scheme 126) the iminophosphorane of 6-aminoura-cil (346) (92AHC129) is transformed with isocyanate in the presence of pyridine into a nonisolable carbodiimide. Spontaneous addition of pyridine follows to give a 1,6-dipolar pyridinium ylide (347), which cyclizes to the... 

CHMe, cyclopropylidene, and CMe2 to activated double bonds.1075 Similar reactions have been performed with phosphorus ylides, 076 with pyridinium ylides,1077 and with the compounds (PhS)3CLi and Me3Si(PhS)2CLi.1078 The reactions with ylides are of course nucleophilic addition. 

The reactions of (aryhnethylene)isoxazol-5-ones (97) with pyridinium ylides (98) leads to the diastereoselective formation of olates (99) as a result of preferential Michael addition rather than 1,3-cycloaddition (Scheme 22). The stereoselectivity of the reaction has been rationalized by the involvement of the preferential transition state [(100) over (101)].86... 

Dipolar addition reactions of iV-ylides with 2,2-difluorovinyl tosylate provides a convenient route to moderate yields of monofluorinated indolizines and related structures. A -Ylides derived from pyridinium, isoquinolinium, and bezimidazolium salts were generated in situ from halide salts (Fig. 3.31)7 ... 

Indolizines have been made via carbene addition to 2-vinylpyridine or dipolar addition of pyridinium ylides. 3-substituted indolizines have been obtained in a one step procedure from reaction of chlorocarbenes with 2-vinylpyridine (94CC509). Microwave irradiation has been used in 1,3-dipolar cycloaddition of pyridinium dicyanomethylide with alkynes <94H(38)785>. 

This reaction was first reported by Krohnke et al. in 1961. It is the synthesis of 2,4,6-trisubstituted pyridine derivatives involving the formation of pyridinium ylide from pyridine and a-bromoketone, which undergoes the 1,4-Michael addition to an a, -unsaturaled compound to form 1,5-dicarbonyl compounds and cyclizes with ammonium acetate. Therefore, it is generally known as the Krohnke pyridine synthesis or Krohnke reaction. In this reaction, the intermediate 1,5-dicarbonyl compounds do not need to be isolated from reaction mixture. Because three different substituents can be introduced into pyridine ring, this reaction becomes the ideal model for combinatorial synthesis, and a library pool containing pyridine from 9 to over 200 has been generated by this reaction. 

Thermolysis of 1-imidoyliminopyridinium N-ylides 109 gave the pyrido-triazines 110 in addition to 111 and 112 (76CL413 77JOC443). Compounds 109 were obtained by the reaction of pyridinium salts 107 with 108. 

Af-ylides (prepared from their corresponding pyridinium salts 241) with aromatic aldehydes 242 and malonodinitrile 21 to give tetracychc 1,10-phenanthrohne derivatives 243 (Scheme 13.57) [93]. The reaction is complete within 15min and provides the desired products in high yields over 80%. The 4CR of phenanthridine 245, aromatic aldehydes 244, malonodinitrile 21, and several isonitriles 246 gives tetracychc phenanthridine derivatives 247 in excellent yields over 90% and reaction times between 16 and 48h at rt, as published by Marandi et al. [94], Both reactions follow a Knoevenagel con-densation/Michael addition/cychzation mechanism. 

The reactions of cyclobutene-1,2-diones are the subject of continuing studies. The dione (411) undergoes Michael addition with appropriate nucleophiles. With the stabilized nitrogen ylide (412) the substitution product (413) is formed. The intermediate pyridinium betaine has been isolated. With arylsulphinic acids, 4-aryl-sulphonylcyclobutanediones (414) are produced. The diones (414) exist in the... 

In addition to direct insertion of perfluorinated gronp at position 1, there are plenty of methods how to introduce such a group via cycloaddition reaction. Thus, convenient method to perfluoroalkylated indolizinyl-phosphonates 31 was reported [19]. The reaction proceeded regioselectively via the 1,3-cycloaddition of pyridinium N-ylide and perflnoroalkynyl phosphonate in 49-77 % yields. Similar reaction was proposed to obtain pyrrolo[l,2-a]isoquinolinyl phosphonates in 48-78 % yields [20]. 

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