Isonitriles reactions with

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. 

Perfluorinated isonitriles are of special interest as ligands in metallorganic chemistry [73]. Generally, W-perfluoroalkylated itmnes result from addition reactions A -Trifluoroniethylhalomethaneimines are obtained on reaction with HX (X = F, Cl, Br) [74] Via this route, the remarkably stable and distillable V-trifluo-romethylforraamide is obtained from trifluoromethyhsonitrile and trifluoroacetic acid [75] (equation 7)... 

This photodriven benzannulation was used in the synthesis of indolocar-bazoles (Eq. 22) [96] and calphostins (Eq. 23) [97]. The thermal insertion of isonitriles into these same classes of carbenes provided a complementary approach to similar benzannulations [98-100]. Manganese alkoxycarbene complexes underwent both inter- [101] and intramolecular [102] photodriven benzannulation reactions with alkynes (Eqs. 24 and 25). 

Formation, reaction with phosphines, isonitriles 6.5.3.1 C3oH3iB,Pd... 

A60. J. P. Candlin, K. A. Taylor, and D. T. Thompson, "Reactions of Transition-Metal Complexes. Elsevier, Amsterdam, 1968. A review of types of reactions of metal complexes (e.g., substitution, combination, redox) reactions with various reagents (e.g., hydrocarbons, halides, carbon monoxide, and isonitrile) and preparation of new stabilised organic systems (e.g., metallocenes, carbenes). Intended for research workers, consequently written at a fairly high level, with emphasis on organometallics. A61. H. J. Keller, NMR-Untersuchungen an Komplexverbindungen. Springer, Berlin, 1970. Expansion of review article 37.1. 

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. 

Nucleophilic additions of titanium nucleophiles to nitriles or isonitriles are relatively rare. Eisch et al. recently reported the formation of three-membered ring titanacycles of type 84 and their reactions with benzonitrile and carbon dioxide, respectively (Scheme 34).119,120... 

The synthetic utility of the carbonylation of zirconacycles was further enhanced by the development of a pair of selective procedures producing either ketones or alcohols [30] and has been extensively applied to the synthesis of cyclic ketones and alcohols, most extensively by Negishi [22—27,29—33,65,87,131—134], as detailed below in Section I.4.3.3.4. The preparation of unsaturated aldehydes by carbonylation with CO is not very satisfactory. The use of isonitriles in place of CO, however, has provided a useful alternative [135], and this has been applied to the synthesis of curacin A [125]. Another interesting variation is the cyanation of alkenes [136]. Further developments and a critical comparison with carbonylation using CO will be necessary before the isonitrile reaction can become widely useful. The relevant results are shown in Scheme 1.35. 

Many pyridine-indole compounds are biologically active. A growing number of methods for the preparation of indolylstannanes have been developed. 2-Trialkylstannylindoles, for example, have been synthesized via directed metalation followed by reaction with tin chloride [91-93]. The latest indolylstannane syntheses include Fukuyama s free radical approach to 2-trialkylstannylindoles from novel isonitrile-alkenes [94], and its extension to an isonitrile-alkyne cascade [95]. Assisted by the chelating effect of the SEM group oxygen atom, direct metalation of 1-SEM-indole and transmetalation with BujSnCl afforded 2-(tributylstannyl)-l//-indole 108, which was then coupled with 2,6-dibromopyridine to give adduct 109. 

The isonitrile reaction (p. 167) should be carried out with this salt, and its behaviour on warming with a little nitrite in faintly acid aqueous solution should be examined. 

Isonitrile Reaction.—Like the primary aliphatic amines of the methylamine type, aniline and its analogues give a characteristic odour with chloroform and alkali. 

In contrast to silylcarbenes, the analogous stannylcarbenes 2p are not stable, which explains why they have attracted little interest. Their instability is probably due to the long carbon-tin bond, which does not allow sufficient steric protection of the carbene center. Their reactivity seems to be quite similar to that of stable (phosphino)(silyl)carbenes Cyclopropanation reactions have been reported with methyl acrylate as well as coupling reactions with tert-butyl isonitrile.73... 

Isonitrile complexes, having a similar electronic structure to carbonyl complexes, can also react with nucleophiles. Amino-substituted carbene complexes can be prepared in this way (Figure 2.6) [109-112]. Complexes of acceptor-substituted isonitriles can undergo 1,3-dipolar cycloaddition reactions with aldehydes, electron-poor olefins [113], isocyanates [114,115], carbon disulfide [115], etc., to yield heterocycloalkylidene complexes (Figure 2.6). 

Esters of -hydroxy- or )8-mercapto-AAs react with n-butyl isonitrile to give 5-substituted methyloxazoline (or thiazoline)-4-carboxylates in the presence of PdCla as a catalyst (74SC97). The enamine-protected AAs were also tranformed into oxazolidin-5-ones after reaction with alkyl chloroform-ates (Scheme 28) (75S724). 

Guanidines have been prepared by the reaction between an amine, or an amine salt, and a host of other reagents, such as a thiourea in the presence of lead or mercuric oxide [83, 157, 158], carbodi-imides [140, 174, 175],calcium cyanamide [176, 177], isonitrile dichlorides [178—180], chloroformamidines [181], dialkyl imidocarbonates [182], orthocarbonate esters [183], trichloro-methanesulphenyl chloride [184], and nitro- or nitroso-guanidines [185-188]. Substituted ureas can furnish guanidines, either by treatment with amines and phosphorus oxychloride [189], or by reaction with phenylisocyanate [190] or phosgene [191]. 

Ugi reaction of acid 88 with isonitrile 85, isobutyraldehyde and isopropylamine furnished dipeptide 89 in 67% yield. Similar Ugi reactions with other components afforded linear cyclization precursors in yields up to 98%. The final macrocyclization was not straightforward (no similar reactions were described in literature), but after optimization of the reaction conditions (varying base, solvent, concentration and reaction time) cyclopeptide alkaloid analogue 90 was obtained in 96% yield after treatment with K2CO3 and catalytic 18-crown-6 in acetone. 

The most important application of organolithium reagents is their nucleophilic addition to carbonyl compounds. One of the simplest cases would be the reaction with the molecule CO itself, whose products are stable at room temperature. Recently, it was shown that a variety of RLi species are able to react with CO or f-BuNC in a newly developed liquid xenon (LXe) cell . LXe was used as reaction medium because it suppresses electron-transfer reactions, which are known to complicate the reaction . In this way the carbonyllithium and acyllithium compounds, as well as the corresponding isolobal isonitrile products, could be characterised by IR spectroscopy for the first time. 

By carrying out the Ugi-reaction with a large number of isonitrils, aldehydes, carboxylic acids, and amines, it was found that formation of different products of the reaction occurred depending on the structure of the amines used. Thus, 3-aminoimidazoles 88 were isolated when aldehyde reacted with isocyanide and heterocyclic aromatic 2-aminoazine as primary amine (Scheme 38). 

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