Ylide compounds nitrile ylides

The two major methods of preparation are the cycloaddition of nitrile oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamines. Additional methods include reaction of /3-haloketones and hydroxylamine, the reaction of ylides with nitrile oxides by activation of alkyl nitro compounds from isoxazoline AT-oxides (methoxides, etc.) and miscellaneous syntheses (62HC(i7)i). 

Enolates of aldehydes, ketones, and esters and the carbanions of nitriles and nitro compounds, as well as phosphorus- and sulfur-stabilized carbanions and ylides, undergo the reaction. The synthetic applications of this group of reactions will be discussed in detail in Chapter 2 of Part B. In this section, we will discuss the fundamental mechanistic aspects of the reaction of ketone enolates with aldehydes md ketones. 

A novel pyrolytic method of generating nitrile ylides in situ was reported by Burger [44] (equation 45) Such nitrile ylides react with various dipolarophiles alkynes [44] (equation 46), nitriles [45] (equation 47), dimethyl azodicarboxylate [45], aldehydes [45], and nitroso compounds [46]... 

Recently, Burger devised an improved method of carrying out mild, regiospecific cyclizations that involve an intermediate that acts as a synthon for a nitrile ylide of HCN [47 (equation 48). With this methodology, cycloadditions with activated alkenes, alkynes, and azo compounds were earned out [47] (equation 49). All such reported reactions were regiospecific and had the same orientational preference... 

Syntheses in which a nitrile provides atoms 1 and 2 start from an ylide (82JFC373), or a 1-amino-2-pyridone (82S974) to give compounds 45 and 46. Other two atom fragments used with l-amino-2-pyridones are amides which give compounds such as 47 (86S860). 

Cycloaddition of 2-nitrosopyridine 48 with nitrile oxides can give either di-A -oxides such as 49 or 3-mono-A -oxides such as 50 (93JHC287). In general, greater electron withdrawing character in the aromatic substituent appears to favor formation of the di-A -oxides. Sulfur ylides such as compound 51 are obtained from aryl isothiocyanates and l-amino-2-methylthiopyridinium iodides (84JCS(P1)1891) nitrogen ylides can be obtained from a similar reaction (86H(24)3363). 

Despite the above, there is also considerable evidence to suggest that oxazole formation proceeds via an intermediate nitrile ylide, particularly in the catalysed reactions (see below). Nitrile ylides have been detected in laser flash photolysis studies of diazo compounds in the presence of nitriles, and stable nitrile ylides can be isolated in some cases.<94CRV1091>... 

The role of the rhodium is probably two-fold. Initially due to its Lewis acidity it reversibly forms a complex with the nitrile nitriles are known to complex to the free axial coordination sites in rhodium(II) carboxylates as evidenced by the change of colour upon addition of a nitrile to a solution of rhodium(II) acetate, and by X-ray crystallography. Secondly the metal catalyses the decomposition of the diazocarbonyl compound to give a transient metallocarbene which reacts with the nitrile to give a nitrile ylide intermediate. Whether the nitrile ylide is metal bound or not is unclear. 

Phosphorus ylides C-substituted and stabifized by elements of group 16 are often used for the synthesis of natural substances. For example, the synthesis of simpHfied analogs of artemisinin, used against chloroquine-resistant malaria, has been recently described from methoxymethylphosphonium yhde 120 [127,128]. The later is able to convert afiphatic nitriles into a-functionafized ketones 122 which are the precursors of the target compounds. Starting from the aromatic ni-... 

The 1,3-dipolar cycloaddition reactions to unsaturated carbon-carbon bonds have been known for quite some time and have become an important part of strategies for organic synthesis of many compounds (Smith and March, 2007). The 1,3-dipolar compounds that participate in this reaction include many of those that can be drawn having charged resonance hybrid structures, such as azides, diazoalkanes, nitriles, azomethine ylides, and aziridines, among others. The heterocyclic ring structures formed as the result of this reaction typically are triazoline, triazole, or pyrrolidine derivatives. In all cases, the product is a 5-membered heterocycle that contains components of both reactants and occurs with a reduction in the total bond unsaturation. In addition, this type of cycloaddition reaction can be done using carbon-carbon double bonds or triple bonds (alkynes). 

Reactions of 1,1-difluoropropadiene or monofluoropropadiene and a 1,3-dipolar reagent such as diazo compounds, nitrones, nitrile oxides and carbonyl ylides are an excellent route to five-membered heterocycles, such as 126 and 127 [61-63]. 

The generation of electrophilic carbene complexes in the presence of nitriles or other cyano-group-containing compounds can lead to the formation of nitrile ylides. With acylcarbene complexes the final products are often 1,3-oxazoles [1194], presumably formed by the mechanism sketched in Figure 4.10. 

Decarboxylation of 1,3-dimethylorotic acid in the presence of benzyl bromide yields 6-benzyl-1,3-dimethyluracil and presumably involves a C(6) centered nucleophilic intermediate which could nonetheless have either a carbene or ylide structure. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry has been used to explore the gas-phase reactions of methyl nitrate with anions from active methylene compounds anions of aliphatic ketones and nitriles react by the 5n2 mechanism and Fco reactions yielding N02 ions are also observed nitronate ions are formed on reaction with the carbanions derived from toluenes and methylpyridines. 

The theoretical section introduced divalent carbon(O) compounds as molecules CL2 where the ligand L is a ct donor. In principle this task can be fulfilled by various neutral group 15 compounds (N2, nitriles, amines, phosphanes, arsanes, etc.), neutral group 16 compounds (sulfides, selenides, etc.) as well as by divalent C(II) with a free pair of electrons at a carbon atom, such as isonitriles, NHCs, carbenes, CO, ylides, etc. The neutral and isolable compound C2PPh3 [14,15] may also serve as a donor L to stabilize a carbon atom. 

Cycloaddition of nitrile ylides (204) to nitroso compounds gives mixtures of (205) and (206), which both slowly rearrange to quinazolines (207) (Scheme 89) <77CB605>. 

The second class of benzo-fused heterocycles accessible from benzofuroxans are benzimidazole oxides. In this case only one carbon from the co-reactant is incorporated in the product. With primary nitroalkanes 2-substituted l-hydroxybenzimidazole-3-oxides (46) are formed via displacement of nitrite, and / -sulfones behave similarly. The nitrile group of a-cyanoacetamides is likewise eliminated to alford 2-amide derivatives (46 R = CONRjX and the corresponding esters are formed in addition to the expected quinoxaline dioxides from acetoacetate esters. Under similar conditions secondary nitroalkyl compounds afford 2,2-disubstituted 2//-benzimidazole-1,3-dioxides (47). Benzimidazoles can also result from reaction of benzofuroxans with phosphorus ylides <86T3631>, nitrones (85H(23)1625>, and diazo compounds <75TL3577>. 

The use of thiirene dioxide 292 as a dipolarophile in the synthesis of thiazine 1,1-dioxides was already mentioned in CHEC(1984) <1975CL1153>. The same compound also reacts with nitrile ylide 293 to afford 294 <1984JOC1300> (Equation 97). 

Like many other 1,3-dipoles (e.g., nitrile ylides, imines, and oxides) (7), thiocarbonyl ylides undergo head-to-head dimerization to give sterically crowded 1,4-dithianes. The first reported example involves the formation of 2,2,3,3-tetraphenyl-l,4-dithiane (18) from thiobenzophenone (5)-methylide (16) (17,28) (cf. Scheme 5.3). Other (5)-methylides are known to form analogous 1,4-dithianes (e.g., thiofluorenone (5)-methylide yields 172) (17). The (5)-methylides of 4,4-dimethyl-2-phenyl-l,3-thiazole-5(4//)-thione (105) and methyl dithiobenzoate (60,104) dimerize to give compounds 173 and 174, respectively. 

In the first addition of nitrile ylides to a,()-unsaturated lactones (92), it was found that the reaction of benzonitrilio 4-nitrobenzylide with the lactones 178-180 were strongly regioselective. Compounds 178 and 179 reacted to give [e.g., 181 from 178 (51%)] and its methyl analogue from 179 (54%). The exocyclic double bond in 180 was, however, the most reactive and gave 182 (69%). The six-membered analogue of 178 was less reactive (34%) and the seven-membered analogue failed to react. 

The reaction of a-diazocarbonyl compounds with nitriles produces 1,3-oxazoles under thermal (362,363) and photochemical (363) conditions. Catalysis by Lewis acids (364,365), or copper salts (366), and rhodium complexes (367) is usually much more effective. This latter transformation can be regarded as a formal [3 + 2] cycloaddition of the ketocarbene dipole across the C=N bond. More than likely, the reaction occurs in a stepwise manner. A nitrilium ylide (319) (Scheme 8.79) that undergoes 1,5-cyclization to form the 1,3-oxazole ring has been proposed as the key intermediate. 

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