Isocyanides, additions

In the reaction of Ni(CNBu )4 and methyl iodide oligomerization of the isocyanide was observed the only isolable nickel complex was (I), shown below. This product is believed to arise through sequential insertions of three isocyanides into a nickel-carbon bond. Upon further treatment with additional isocyanide at a temperature greater than 60° C one obtains a polymer (RNC) presumably through multiple isocyanide insertion reactions. The addition of benzoyl chloride to Ni(CNBu )4 gave two isolable compounds Ni(CNBu )3(COPh)Cl (74%) and (II) (8.2%). This latter reaction, and the isolation of (II) in particular, suggests that the proposed mechanism for polymerization of isocyanides is reasonable. 

Uson and collaborators described an A-frame PdPt complex [C6F5Pd (p-C=N-p-tolyl)(p,-dppa)2PtC6F5] (75),85 and more recently, [XPd(p,-dppm)2 (p-C=N-R)Pt(CN-R)]+ (76-78) and [ClPd(p,-dppm)2(p,-C=N-R)PtCl] (79-81) were reported by Knorr and collaborators86-88 (Fig. 32). In the bis(isonitrile) heterobimetallics 76—78, a site selectivity in the second CNR ligand coordination (Pd vs. Pt) was noticed. The additional isocyanide is systematically coordinated on the Pt site.86,88 This distinct selectivity between Pd and Pt was explained by the greater lability of the Cl- ion on the Pt center as well as a better stabilization of the positive charge on the electron-rich Pt1 center.88 The question arises as to why the addition of ligand isocyanide sometimes produces the A-frame compound whereas under similar conditions, a d9-d9 isocyanide... 

Hulme and colleagues prepared pyrrolo[3,4-c]pyrrole-l,3-dione 47 via the [3 + 2] cycloaddition—elimination of oxazolin-2-ones with pyrrole-2,5-diones (13SL1801). 2-Acylpyrrole 48 was constructed from TosMIC and various enones via a tandem Michael addition—isocyanide insertion sequence.The reaction was expanded to prepare seven- and eight-membered ring fused pyrroles in good yields (130BC7393). 

The interaction of isocyanides with acetylene complexes has been found to produce various organic and organometallic products differing in the number of alkyne and.isocyanide units incorporated. Cp(Ph3P)Co(PhC2Ph) reacts with two equivalents of isocyanide to form the diimino cobaltacycle (XVni) (Yamazaki et aU 1975). Further reaction of these complexes with additional isocyanide led to the novel cyclopentene derivatives (XIX). These... 

The use of a vinylphosphonium salt as the source of the QQ fragment instead of the more commonly employed 1,2-dicarbonyl substrate is illustrated by the pyrrole synthesis in Scheme 79b (8UOC2570). A particularly interesting feature is the intramolecular Wittig reaction with an amide carbonyl group. A very useful synthesis of pyrroles depends upon the addition of the anion of p-toluenesulfonylmethyl isocyanide (TOSMIC) to a,/3-unsatur-... 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

Four-membered heterocycles can be formed by the addition of isocyanides to 1,3-dipoles (80AG(E)45) and by the reaction of carbon monoxide with -haloamines, with the aid of palladium catalysis (Scheme 10) (79CC699). 

Tolylaulfonylmethyl isocyanide is a useful and versatile reagent in organic chemistry. It has been used for the synthesis of several azole ring systems by base-induced addition of its C—N=C moiety to various... 

The addition of hydrogen fluoride to an aromatic isocyanide dichloride provides a route to the respective aryl-Af tnfluoromethyl amine [34] (equation 24)... 

A rather rare perfluoroalkyl iodide addition to divalent carbon atom has been performed in the case of isocyanides under thermal or copper catalyzed conditions [14I (equation 122)... 

The addition of isocyanides and azide to aldehyde-derived enamines has led to tetrazoles (533,536). On the other hand the vinylogous amide of acetoacetic ester and related compounds reacted with aldehydes, isocyanides and acids to give a-acylaminoamides (534). Iminopyrrolidones and imino-thiopyrrolidones were obtained from the addition of cyclohexylisocyanide and isocyanates or isothiocyanates to enamines (535). An interesting method for the formation of organophosphorus compounds is found in the reactions of imonium salts with dialkylphosphites (536). 

The propensity of isocyanides to undergo nucleophilic a-additions at the terminal carbon, together with the presence of an activated methylene and a potential leaving group (i.e. tosyl), led van Leusen to suggest the following reaction path ... 

Van Leusen and co-workers also demonstrated the utility of dilithio-tosylmethyl isocyanide (dilithio-TosMIC) to extend the scope of the application. Dilithio-TosMIC is readily formed from TosMIC and two equivalents of n-butyllithium (BuLi) in THF at -70"C. Dilithio-TosMIC converts ethyl benzoate to oxazole 14 in 70% yield whereas TosMIC monoanion does not react. In addition, unsaturated, conjugated esters (15) react with dilithio-TosMIC exclusively through the ester carbonyl to provide oxazoles (16). On the other hand, use of the softer TosMIC-monoanion provides pyrroles through reaction of the carbon-carbon double bond in the Michael acceptor. 

Like the Strecker synthesis, the Ugi reaction also involves a nucleophilic addition to an imine as the crucial step in which the stereogenic center of an a-amino acid derivative is formed4. The Ugi reaction, also denoted as a four-component condensation (A), is related to the older Passerini reaction5 (B) in an analogous fashion as the Strecker synthesis is to cyanohydrin formation. In both the Ugi and the Passerini reaction, an isocyanide takes the role of cyanide. 

The mechanistic analogy to the Streckcr synthesis becomes obvious in the addition of the isocyanide to the imine to produce the a-amino nitrilium intermediate. Since all four components are involved in this step, it might be expected that every chiral component (chiral groups R1, R2, R3, R4) contributes to diastereofacial differentiation in the nucleophilic attack on the imine. However, in peptide syntheses by four-component condensation5, the chiral isocyanide or a chiral carboxylic acid component has only limited influence on the diastereoselectivity of the a-amino amide formation5. 

Isophthalic acid, 2-hydroxy-, 40,48 Isoprene, addition to dichlorophenyl-phosphine, 43, 73 Isopropyl isocyanide, 41,14 5 Isopropyl-1,2,3,4,5-pen tachlorocyclo-pentadiene, 43, 92... 

Isocyanides can be reduced to the corresponding hydrocarbons by (TMS)3SiH. The reaction can be considered as a smooth route for the deamination of primary amines. An example is given in Reaction (20). The key step for these chain reactions is expected to be the fragmentation of the intermediate radical derived from the fast addition of (TMSlsSi radical to the terminal carbon atom. 

We shall discuss first reactions in which hydrogen or a metallic ion (or in one case phosphorus or sulfur) adds to the hetero atom, and then reactions in which carbon adds to the hetero atom. Within each group, the reactions are classified by the nature of the nucleophile. Additions to isocyanides, which are different in character, are treated at the end. 

Formamides can be prepared by the acid-catalyzed addition of water to isocyanides. The mechanism is probably ... 

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