Isonitriles, also

Welwitindolinone A isonitrile also has a number of structural features that make it a very challenging target, most notably the sterically crowded spiro-fused cyclobutane ring, which at first sight might seem thermodynamically unstable (Fig. 3). 

Isonitriles also react with CpWCl(CF3C=CCF3)2 and CpMo-(CF3C=CCF3)2CF3 to form C5 rings (98). Condensation of the two alkynes with RNC to form Tj4-cyclopentadienimines [Eq. (64)] mimics the CO... 

This reaction was first reported by Hofmann in 1868. It is the synthesis of isonitriles (also known as isocyanides) from primary amines and chloroform in the presence of alkali and is known as the Hofmann isonitrile synthesis, Hofmann carbylamine reaction, or Hofmann carbylamine synthesis. This reaction has been used to test the presence of primary amines from the order of isocyanides. Alternatively, the isonitriles can be prepared by means of the treatment of formamide of primary amines with toluenesulfonyl chloride" or phosphorus oxychloride (POCls)." Currently, the isonitriles have gained much attention in organic synthesis because of their application as versatile building blocks for heterocycles and in multicomponent reactions to generate combinatorial libraries, such as that in the Passerini reaction and Ugi reaction ... 

A miscellany of papers dealing with the potency of the thioureido neighbouring group in nucleophilic substitution processes, the complexing ability of thioureas towards macrocyclic polyethers, and the cycloaddition reactions of thiocarbamoyl isothiocyanates (190) with ketens, ketenimines, imines, isocyanates, carbodi-imides, and isonitriles also deserve attention. 

Isonitriles also undergo carbene-like reactions with isocyanates and coreagents. For example, two isomeric [1+2+2] cycloadducts 50 and 51 are obtained from nitroso compounds, isonitriles and isocyanates. The reaction proceeds via addition across both the C=N and the C=0 bonds of the isocyanate . 

This method is particularly applicable to the more reactive benzyl halides which are easily hydrolyzed in the aqueous media usually employed for the metathetical reaction with alkali cyanides. For example, anisyl chloride treated with sodium cyanide in aqueous dioxane gives, as a by-product, 5-10% of anisyl alcohol as determined by infrared analysis. The use of anhydrous acetone not only prevents hydrolysis to the alcohol but also decreases the formation of isonitriles. This method was also applied successfully by the submitters to the preparation of -chlo-rophenylacetonitrile in 74% yield. 

It is noted that the related compounds, the isonitriles (R— N=C , also called isocyanides) have been reduced to N-methylamines with LiAlH4 as well as with other reducing agents. 

A very common combination in Pd-catalyzed domino reactions is the insertion of CO as the last step (this was discussed previously). However, there is also the possibility that CO is inserted as the first step after oxidative addition. This process, as well as the amidocarbonylation, the animation, the arylation of ketones, the isomerization of epoxides, and the reaction with isonitriles will be discussed in this section. 

Barton-Zard pyrrole synthesis is also applied to synthesis of pyrroles with a variety of substituents. Pyrroles substituted with long alkyl substituents at the 3 and 4 positions,30 pyrroles with P-CF3 (Eq. 10.26),31 3,4-diarypyrroles (Eq. 10.27),32 and pyrrole-2-phophonates (Eq. 10.28)33 are prepared in a similar manner based on isonitrile cyclization. 

The first marine isocyano metabolite was appropriately named axisonitrile-1 (1) based on the trivial name isonitrile and the genus of the sponge, Axinella cannabina, which also furnished axisothiocyanate-1 (2) [1] and, subsequently, a minor constituent, axamide-1 (3) [5]. This observation that isonitriles are often accompanied by isothiocyanates (-N=C=S) and formamides (-NHCHO) was later duplicated by the Hawaiian researchers working with a Halichondria sp. In... 

A minor isonitrile named acanthellin-2 with a specific rotation of — 24.1° was reported with no further details except some IR and MS data [3]. Isothiocyanate 15 and formamide 16 were also isolated from Axinella cannabina in a later study, in which isonitrile 14 and isomers 17-19 were also secured [35]. That 17-19 are C4(14)-ene isomers of 14 was concluded after extensive double resonance H NMR experiments. Coupling constants and nOe effects between the affected protons and various substituents of 17 established the relative stereochemistry of this series. 

Along with epi-eudesmanes, 25-27, alloaromadendranes 58-60 were separated from the chloroform solubles of a methanol extract of A. cannabina [36], As was the case with axisonitrile-2 (53), extensive spectroscopic analyses including Eu(fod)3 shift reagent experiments in XH- and 13C NMR permitted assignment of relative stereochemistry. Acanthella pulcherrima was also a source of isothiocyanate 59, although both isonitrile and formamido compounds appear to be absent [20],... 

In several related studies that involved Ciocalypta and Phyllidia spp., optically inactive isonitrile 85 was part of the mixture from a Sri Lankan Phyllidia sp. The mixture also contained a minor isothiocyanate which was not identified [55]. The observation that 7-isocyano-7,8-dihydrobisabolene 88 and isocyanato 89 were obtained from separate collections of Ciocalypta spp. was surprising... 

The indazoline products can also be made directly from the palladium complexes 78 by heating them with the isonitrile in toluene at 120CC.162 They are also formed in dicobalt octacarbonyl-catalyzed reactions of azo-arenes with isocyanides but in this case an alternative reaction pathway leading to indazolo[2,l- ]indazoles (79) is observed (Scheme 96).163 Products of the latter type are formed from sterically hindered isocyanides hence it is likely that in these cases a double metallation is favored over isocyanide insertion into a monometallated species (Scheme 97). 

Finally, Odom and co-workers reported a titanium-catalyzed three-component coupling between primary amines, alkynes, and isonitriles for the preparation of a, 3-unsaturatcd /3-iminoamines in good yields (Scheme 35).121 Beside the three-component coupling product, an. V,.V-disubstituted formamidine and an imine were also identified as minor... 

The synthesis of analogous iminoacyl complexes by isonitrile insertion into linear alkyl-zirconocene chlorides is also known. In an overall regiospecific hydrocyanation of alkenes, iminoacyls 21 derived from tBuNC or Me3SiCN (as the Me3SiNC isomer) may be treated with I2 to rapidly generate an imidoyl iodide and subsequently the nitrile 22 (Scheme 3.6) [22], Less hindered iminoacyl complexes (e. g. R = Bu, Cy) may be hydrolyzed to afford aldehydes 23 [23]. 

Abstract Described are the synthetic routes to precisely defined molecular wires which are of discrete length and constitution. They are fully conjugated systems and are expected to have nearly linear current-voltage response curves. Their ends are functionalized with molecular alligator clips, based on chalconides and isonitriles, for adhesion between proximal probes. Both solution and solid-phase approaches have been used to prepare these molecular wires that are based on oligofthiophene ethynylene)s and oligofphe-nylene ethynylene)s. Molecular device syntheses are also described that would be expected to have nonlinear current-voltage responses. 

A series of l/f-pyrrolo[2,l-r][l,4]oxazin-l-ones 196 are also the product of an LJgi multicomponent reaction between proline (and also other a-amino acids that gave the corresponding monocyclic compounds) and several isonitriles in the presence of commercially available glycolaldehyde dimer (Equation 3) <20010L4149>. 

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