Isonitriles nucleophilic attack

Recently, a combination of the UAC and UDC protocols was reported by Wessjohann s group [40]. In this work, the acid-activated, well-behaved 1-iso-cyano-2-(2,2-dimethoxyethyl)-benzene was employed as convertible isocyanide in an Ugi-4CR [41]. The advantage of this one-pot procedure is the in situ deprotection of the W-protected amino acid along with the simultaneous activation of the isonitrile-bom carboxylate, enabling the nucleophilic attack of the free amine... 

In conclusion, it should be noted that the Barton-Zard condensation formally might be considered as a tandem SnH-Sn ipso process (see Section III.B.3). However, the corresponding crH-complcx is stabilized here not via elimination of any auxiliary leaving group or oxidation but by means of an intramolecular nucleophilic attack on an isonitrile fragment. This is due to the amphoteric nature of isocyanoacetate ion acting at first as a nucleophile and then as an electrophile. 

Little evidence is available, therefore, that reductants induce redistribution of electronic charge within the prosthetic group in such a manner that oxygen of EO becomes the locus of the nucleophilic attack. The best reductants of Compound I are hard donors rather than polarizable substrates (cyanide, thiols, carbon monoxide, and isonitriles)—observations which cannot be readily reconciled with the hydroxylation mechanisms... 

As an example related to equation (1), isonitriles are very sensitive to nucleophilic attack, and a wide range of bis-heteroatom stabilized carbenes can be obtained (equation 6). ... 

Nucleophilic attack at the carbon of a coordinated isonitrile molecule in the complex cations [7r-C5H5Fe(CO)3, j(CNMe),(] (x = 1, 2) using QFjLi produced inter alia the imino derivatives [7r-C5H5Fe(CO)(L)C(C5F5)= NMe] (L = CO, CNMe). Chromatographic separation of the products gave the complex (L = CNMe) in two isomeric forms, shown by IR spectroscopy to arise from cis or trans orientation of the Al-methyl group... 

The reaction has also been carried out under alkaline conditions, with hydroxide in aqueous dioxane. The mechanism here involves nucleophilic attack by hydroxide at the carbon atom. An intramolecular addition of an alkyne (in an ortho alky-nyl phenyl isonitrile) to the carbon of an isonitrile occurred with heating in methanol to give quinoline derivatives. ... 

TFA-CH2CI2 [191]. Ugi 4CC products prepared in solution from the interconvertible isonitrile may be captured on a solid support by nucleophilic attack of the benzylic alcohol of resin 5e on the cyclic dipole that is formed in the presence of acid carboxylic acids can then be released from the resin by treatment with TFA [192]. 

Isonitrile solid support 8j functions as a safety-catch anchor for acyl-aminoamides formed by a Ugi 4CC reaction [356]. Boc derivatization of the secondary amide anchoring site causes activation toward nucleophilic attack, and thus products could be cleaved by reaction with alkoxide ion. 

Palladium isocyanide complexes react with amines and alcohols to give palladium Carbene Complexes (equation 15) in a reaction that is a nucleophilic attack on the isonitrile carbon. These complexes easily lose a halide if it is trans to the carbene ligand, since the carbene carbon has a high trans influence. The structures of these compounds have the carbene carbon and its two heteroatom groups in one plane, which is perpendicular to the coordination plane of the Pd. 

Examples of Nucleophilic Attack on Carbon Monoxide and Isonitriles... 

Although many more examples of attack on coordinated CO have been published than examples of attack on isonitriles, the attack on isonitrile ligands is well established. The reaction in Equation 11.7 illustrates one example of such a nucleophilic attack on a coordinated isonitrile. The kinetics of this reaction are consistent with the direct nucleophilic attack of the amine on the coordinated isonitrile to form a stable intermediate, which undergoes a subsequent proton transfer to form the observed carbene complex. The resulting electron-rich carbene complex resists further nucleophilic attack. 

The protonation by the carboxylic acid moiety to give an imi-nium ion followed by a nucleophilic attack of the isonitrile leads to the formation of a nitrilium ion intermediate, which is subsequently intercepted by the corresponding carboxylate anion. The resulting imino anhydride typically undergoes an irreversible transacylation (Mumm rearrangement) to give a final Ugi product (Fig. Ic). For the construction of a 2D library array, only two of the four possible components involved in the Ugi reaction are varied. 

Reactions A carbyne can couple with another carbyne to give an alkyne or alkyne complex.For instance, Br(CO)4Cr CPh reacts with Ce(IV) to give free PhC CPh. Carbynes also have extensive photochemistry. In the Fischer series, the carbyne carbon is electrophilic and subject to nucleophilic attack, for example, by PMcj, pyridine, RLi, or isonitrile (= Nu) to give a carbene of the type L M=CR(Nu). Alternatively, the nucleophile may attack the metal in L (CO)M=CR and produce a ketenyl complex... 

A survey of the many examples of Lewis acid-promoted Passerini-type reactions, finds that most are characterized by one of four distinct processes a) nucleophilic attack of an additional equivalent(s) of isonitrile to form oligomeric products " (17) b) nitrogen dealkylation to give cyanohydrin-type products (18) c) intramolecular capture of tethered-nucleophiles to form cyclic products (19) and d) intermolecular capture of other weakly-basic nucleophiles such as dissociable counterions of the Lewis acid (20) such as the chloride ion for TiCk. 

Because of the inherently low reactivity of most components, a very large number of other functional groups are tolerated in the reaction. Functionalities that are not compatible within the Passerini reaction include those that are reactive toward activated or unhindered aldehydes or ketones under the mildly acidic conditions, lest such reactivity be competitive with the slow Passerini reaction. As a direct consequence, unprotected primary or secondary amines are not compatible because of the facility by which they form imines and iminiums by acid-catalyzed condensation. Iminiums, themselves are susceptible to nucleophilic attack by isonitriles and the formation of a-acylamino amides by this process is called the Ugi reaction (see chapter 3.6). In reactions where the Ugi and Passerini reactions are possible competitive processes the Ugi products are generally favored to the detriment of any Passerini products. ... 

U. Belluco, B. Corciani, R. Michelin, and P. Uguagliati, Pure Appl. Chem., 1983, 55, 47-54. Electrophilic and Nucleophilic Attacks on Alkyl, Nitrile, and Isonitrile Complexes of Pd(II) and Pt. 

The azide ligand of a PMes complex reacts with isonitrile to form a complex with 67-coordinated tetrazolate rings (243-245, Equations (69) and (70)). " " Insertion of isonitrile into the Pt-N bond is followed by cyclization via intramolecular nucleophilic attack at the coordinated carbon atom. Since the tetrazolato ring is perpendicular to the square-planar coordination plane, the trans-complcx with two 5-alkyltetrazolate ligands exists as a mixture of isomers with the alkyl substituents in syn- and < //-orientations 244 and 245. 

Nucleophilic attacks on the sp-hybridized carbon atom of nitrile and isonitrile ligands are well known, so in principle the coupling between these unsaturated Hgands and C2-deprotonated N-alkyHmidazole coHgands could offer a potential pathway to access new anisobidentate chelates within the coordination sphere of a metal. Two possible difficulties were considered, one for each type of monodentate unsaturated Hgand nitriles are labile therefore, attack to the metal by either the base or the deprotonated N-Rlm ligand could compete with attack at the coordinated nitrile as for isonitriles, the planned attack at the metal-bonded carbon atom would afford a four-member ring, perhaps of limited stabihty note that such a... 

Nucleophilic Attack on Other Electrophiles. PhMe2SiLi reacts withcarbenes like isonitriles to makeynediamines (eq 23) and with carbon monoxide to make an enediolate (eq 24). ... 

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