Imidoyl chlorides, nitrile ylides

This method has been used extensively for the generation of diene- and triene-conjugated nitrile ylides (see Section 7.4.1.2) using strong bases. Potasium tert-butoxide (58) was used for the most part but in recent work (59,60) it was reported that lithium bisftrimethylsilyl)amide is both more effective and more convenient. It has also been shown that thermally unstable imidoyl chlorides for use in these reactions can be prepared by reaction of the corresponding amides with chlorodi-methylformiminium chloride at 0 °C, a reaction that is more effective than using either thionyl chloride or phosphoms pentachloride at higher temperatures (61). 

Phosphoryl substituted nitrile ylides have also been generated via the imidoyl chloride-base route using precursors 118 (R=Et, c-CeHn, f-Bu) prepared by the addition of an acid chloride to diethyl isocyanomethylphosphonate (120) (65). Treatment of the imidoyl chloride with triethylamine at —10 to 0 °C in the presence of dipolarophiles gave adducts in yields of up to 55% (e.g., 119 and 121) in ratios 1 4, 1 3 for R=Et and c = CgHn, respectively. 

Nitrile ylides, generated by the imidoyl chloride-base route, have been added to 1-azetines (185) (X = 0, S) to give the adducts 186 in moderate to good yields (42-68%) (94,95). These examples are among the first cycloadditions to 1-azetines. In the case where Ar = Ph, the NMR spectrum of the product showed only one set... 

Extensive work has been done to determine and understand the factors controlling diastereoselectivity in the cycloaddition of nitrile oxides to alkenes but very little is known about nitrile ylides in this regard. Work on their reactions with alkenes that are geminally disubstituted with electron-withdrawing groups (e.g., 187) has illustrated some of the difficulties in such studies. When the imidoyl chloride-base route was used to generate the nitrile ylides it was found that the products 188 epimerized under the reaction conditions. When the azirine route was used, the reaction was complicated by the photochemical isomerization of the dipolarophiles (96,97). Thus, in both cases, it proved impossible to determine the kinetic product ratio. 

Reactions of this type have been used in the construction of the pyrrolylfuran derivatives (309) (R = H, 57% and R = C1, 24%) using nitrile ylides generated by the imidoyl chloride-KOf-Bu method (191). This reaction was a key step en route to simplified analogues of roseophilin, however, the reaction failed for the derivative with a methoxy group at the 4 position of the furan ring. 

The nitrile ylides were generated from amides via the imidoyl chloride-base method and hence the reaction is, overall, the electrocyclic equivalent of a Bischler-Napieralski type of process. However, it has the advantage that it is effective for cyclization on to both electron-rich and electron-poor aromatic rings, unlike the Bischler-Napieralski reaction itself, which is an electrophihc process and only works well for electron-rich rings. 

Cyclization of the nitrile ylide generated from amide (150a) via an imidoyl chloride led to an 18% yield of a fused tricyclic pyrrole (Scheme 46).77 Similarly, the nitrile ylide derived from (150b) cyclized in 6% yield. 

Treatment of the imidoyl chloride (106) with triethylamine yields the nitrile ylide (107), which undergoes cycloaddition with a variety of reagents giving imidazole products. With ethyl cyanoformate a mixture of esters is obtained with 2,4-xylyl cyanate the 4-aryloxy... 

The azetes (87.3) undergo addition by nitrile ylides, ArCHN = C (formed in sii from the imidoyl chlorides and TEA) at room temperature. 

Huisgen and his co-workers190 have recently reported that the addition of aromatic nitrile ylides to carbonyl compounds results in the formation of A3-oxazolines, which are easily oxidizable to oxazoles. Typically, benzonitrile 4-nitrobenzylide (131, Ar = p-OsNC6H4), generated from the imidoyl chloride (130) by 1,3-elimination of hydrogen chloride with triethylamine, reacts smoothly with benzaldehyde to give a pair of... 

R ( l -Et3N.HCI Nitrileylide " SCHEME 5.30 Nitrile ylide from imidoyl chloride. 

Several additional examples in the literature demonstrate the generality of the 1,1 trapping of nitrile ylides. Thus treatment of o-allyl-substituted imidoyl chloride 194 with triethylamine gave benzobicyclo[3.1.0]hex-2-ene 196. Irradiation of the closely related methyl-substituted azirine system 197 produced a mixture of endo- and ex o-benzobicyclohexenes 199 in quantitative yield.No detectable quantities of the isomeric 1,3-dipolar adduct were observed in either system. In the case of 197, the major product (exo-199) is the thermodynamically more favored exo isomer. 

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