Isocyanides rearrangement

Preparation of cyanides.1 An attractive route to cyanides involves as the first step dehydration of alkylformamides with phosgene-tricthylamine (1,857) or phosphoryl chloride-diisopropylamine (13,249) to form isocyanidcs followed by isocyanidc-cyanide rearrangement. This rearrangement traditionally was conducted in the gas phase, but proceeds in almost quantitative yield when carried out by flash pyrolysis at 600°. This route to cyanides is attractive because allyl isocyanides rearrange without allylic rearrangement. Moreover, optically active carboxylic acids can be obtained from optically active amines without raccmization. 

P. Saxe, Y. Yamaguchi, P. Pulay, and H. F. Schaefer III, Transition state vibrational analysis for the methyl isocyanide rearrangement, CH3NC CH3CN, J. Amer. Chem. Soc. 102 3718 (1980). 

Bisa2iridine compounds and A/-(2-chloroethyl)carbodiimides have also been prepared using isocyanide dichlorides and ethyleneimine (178,179). The iodide-cataly2ed rearrangement of the formerly mentioned compounds provides a method for preparing the tetrahydroimida2oimida2ole system ... 

Isocyanides, when heated in the gas phase or in nonpolar solvents, undergo a 1,2-intramolecular rearrangement to nitriles RNC — RCN. In polar solvents the mechanism is different. 

In analogy, Ugi et al. reported on a lactam formation by running a one-pot three components reaction the condensation of L-lysine 7, isobutyraldehyde and methyl isocyanide led to the corresponding a-amino-c-caprolactam 9, but the yield was not given. The authors presumed either a nucleophilic substitution of the ester 8 as the primary Ugi product by the amino function of the side chain or, alternatively, the nucleophilic attack of the NH2-group on an intermediately formed 0-acylamide and a subsequent rearrangement (Scheme 1) [4]. 

Reactions of Pt(PPhj)2(R)X (R = CH3, C Hj X = Cl, Br, I) and methyl isocyanide 144) and analogous reactions of Pd(phos)2(CH3)I (phos = PPh3, PPhMc2) complexes with cyclohexyl isocyanide 169, 170) were reported about the same time. As might perhaps be anticipated, the platinum reactions were slower and one can isolate the intermediate species and observe their rearrangement to the inserted products [Eq. (8)]. The isolation of the... 

It is interesting to observe that the product in the above reaction sequence will add another isocyanide ligand to give [Pt(PPh3)2(CNCH3)- C(=NCH3)R ]X but that this product does not further rearrange, at least under the relatively mild reaction conditions used 144). 

It has been shown by Zanardi, Nanni and coworkers that, instead of isocyanides, isothiocyanates can be used in the radical process [90]. Treatment of the mixture of the diazonium tetrafluoroborates 3-217 and the isothiocyanates 3-218 with pyridine or a mixture of 18-crown-6 and potassium acetate in ethyl acetate, furnished the benzothienoquinoline derivatives 3-219. In addition, in some cases the rearranged products 3-220 were furnished in low to reasonable yields (Scheme 3.57). 

The diversity of the Ugi-MCR mainly arises from the large number of available acids and amines, which can be used in this transformation. A special case is the reaction of an aldehyde 9-26 and an isocyanide 9-28 with an a-amino acid 9-25 in a nucleophilic solvent HX 9-30 (Scheme 9.5). Again, initially an iminium ion 9-27 is formed, which leads to the a-adduct 9-29. This does not undergo a rearrangement as usual, but the solvent HX 9-30 attacks the lactone moiety. Such a process can be used for the synthesis of aminodicarboxylic acid derivatives such as 9-31 [3, 30],... 

Rearrangement of the ruthenium (diaminocarbene) isocyanide complex 28 has been noted above. Migration of the carbene substituent group is thought to occur via an intramolecular cyclization reaction (57,58) ... 

During the first month of this experiment, it was realized that this reaction is extremely variable. Thus, diverse amines (ammonia, primary and secondary amines, hydrazine derivatives, hydroxylamines) 13, carbonyl compounds (aldehydes, ketones) 14, acid components 15 or their anions (H2O, Na2S203, H2Se, R2NH, RHN-CN, HN3, HNCO, HNCS, RCO2H, RCOSH, ROCO2H, etc.), and the isocyanides could form the a-adducts 16 that rearrange into their products 17 (Scheme 1.5). 

In 1993 the first MCR composed of seven educts was introduced, and it was soon recognized that such higher MCRs are usually unions of the U-4CR and additional reactions. In the first 7-CR, the intermediate 63 was formed by an A-4CR and underwent with the equilibrating product 67 the a-addition of the cations and ions onto the isocyanide 27. Finally, this a-adduct, 69, rearranges into the final product, 71 (Scheme 1.17). 

Let us consider the rearrangement of hydrogen cyanide to hydrogen isocyanide ... 

Products isolated from the thermal fragmentation of A-arylbenzamide oximes and A-arylbenzamide O-phenylsulfonyl oximes have been accounted for by invoking a free-radical mechanism which is initiated by the preferential homolysis of the N-O bond." Time-resolved IR spectroscopy has revealed that photolysis of A, A -diphenyl-l,5-dihydroxy-9,10-anthraquinone diimine affords acridine-condensed aromatic products via excited-state intramolecular proton transfer." The absolute and relative rates of thermal rearrangements of substituted benzyl isocyanides have been measured,and it has been found that the relative rates are independent of temperature and exhibit excellent Hammett correlations. Thionitrosoarene (25), thought to be generated by desulfurization of the stable A-thiosulfinylaniline (24), has been established" " as an intermediate in the formation of 3,3a-dihydro-2,l-benzisothiazole (26) from o-alkylthionitrosoarene (24). 

Imidates, rearrangement of, 14, 1 Imines, additions of allyl, allenyl, propargyl stannanes, 64, 1 additions of cyanide, 70, 1 as dienophiles, 65, 2 synthesis, 70, 1 Iminium ions, 39, 2 65, 2 Imino Diels-Alder reactions, 65, 2 Indoles, by Nenitzescu reaction, 20, 3 by reaction with TosMIC, 57, 3 Ionic hydrogenation, 71, 1 Isocyanides, in the Passerini reaction, 65, 1... 

Both cyclic and acyclic ketoximes may be used in this transformation and the reaction is usually performed in an alcohol solution containing equimolar quantities of alkoxide. For a successful reaction, the starting material usually contains at least an a-methylene group but the presence of only one a-hydrogen may suffice. When treated with base the 0-acylated aldoximes do not react via the Neber rearrangement and instead they undergo an E2 elimination to cyanides or isocyanides. 

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