Reactions of isocyanides

Reaction of isocyanides with organometallic compounds (metalated... 

The work on insertion reactions of isocyanides was initiated by Yamamoto et ah, and described in a communication in 1968 followed by a full paper a year later (164). This study described the reaction of C5H5Ni(PPh3)CH3 with several isocyanides, from which the products C5HjNi(CNR)- C(=NR)CH3 were isolated [Eq. (2)]. 

The reaction of isocyanide complexes with nucleophiles gives metal-carbene complexes [49], which constitute an important branch of organometallic chemistry and are effective catalyst systems for a variety of processes [50, 51]. 

In the presence of Bu OK, (benzotriazole-l-yl)methyl isocyanide (BetMIC) 697 undergoes alkylation on the methylene group to give isocyanide 698. The anion derived from 698, upon its treatment with Bu OK, adds to the electron-deficient double bonds of ajl-unsaturated ketones, esters or nitriles to produce pyrroles 699. A similar reaction of isocyanide 698 with Schiff bases provides imidazoles 700. In both cases, use of unsubstituted isonitriles 697 in the reactions leads to heterocycles 699 and 700 with R1 = H (Scheme 108) <1997H(44)67>. 

Aldol reactions of isocyanides with aldehydes are catalyzed by cationic platinum complexes having P-C-P or N-C-N ligands in the presence of a catalytic amount of an amine base to give 2-oxazolines (Equation (126)) 48S>485a>485b Platinum-coordinated a-isocyano carbanions presumably serve as nucleophiles toward aldehydes. Low to moderate enantioselectivities were obtained by using chiral platinum complexes.485 4853... 

In the 1890s, Nef mentioned that the functional group —NC of the isocyanides contains a divalent carbon atom C° and therefore there is a large difference between their chemistry and that of the other chemical compounds that contain only tetravalent carbon atoms Any synthesis of isocyanides corresponds to a conversion of into and all chemical reactions of isocyanides correspond to transitions of the carbon atoms C into... 

Lazar, M. and Angelici, R.J. (2005) Gold metal-catalyzed reactions of isocyanides with primary amines and oxygen analogies with reactions of isocyanides in transition metal complexes. J. Am. Chem. Soc., 128, 10513. 

More recently, Aitken and coworkers described a short and convergent formal total synthesis of cyclotheonamide C using a process that involves a Passerini reaction, amine deprotection, and an acyl migration (PADAM sequence. Scheme 22) [90]. The key linear pentapeptide 22e is obtained by a Passerini reaction of isocyanide a, Fmoc-amino aldehyde b, and Boc-dipeptide acid e followed by Fmoc removal and consequently 0,N-acyl migration [91]. The macrocyclization was achieved with TBTU and HOBt after Boc and fBu removal in good yield (52%) to furnish intermediate f. 

Scheme 1 Reaction of isocyanide Pd-complex with Ph3Bi...

Reaction of isocyanide dichlorides with primary amine hydrochlorides in an inert solvent at 180°C [71]. 

For a review of other melallation reactions of isocyanides, see Ho Murakami Synlen 1990, 245-250. 

Reaction of isocyanides with organ-ometallic compounds (metalated imines)... 

Alkylation of the cyanide ligands in Ag4M(CN)8 with RX (X = halides) has provided the only route to the complexes M(CN)4(CNR)4 (M = Mo, W R = alkyl, allyl, CH2Ph, CPh3) (72, 73), as direct reaction of isocyanides on the cyanide anions has given only reduced products (74). 

Reactions of isocyanides with metal-metal multiple-bonded dimers of molybdenum, rhenium, ruthenium, and rhodium have effected cleavage of... 

The reaction of isocyanides with organolithium reagent affords a-lithiated isocyanides (105), which react with isoselenocyanates to give ambident anions... 

A simple and practical useful synthetic method for l-benzo-l,3-selenazoles (115) having a heteroatom substituent such as NR R2, OR, or SR groups at the 2-position was developed by the copper(I)-catalyzed reaction of isocyanides (114) with selenium and heteroatom nucleophiles (Scheme 35) [187],... 

The story of the reaction of isocyanide dichlorides with bis(trimethylsilyl)phenylphosphane, however, does not end here. Like the reaction of t-butyl-bis(trimethylsilyl)phosphane with phosgene, the conversions with isocyanide dichlorides depend very much upon the reaction conditions. If the reaction is carried out at ambient temperature in a molar ratio of 1 1 in such a way that the isocyanide dichloride is rapidly dropped into the phos-phane solution, the hitherto unknown, 2,4-bis(phenylimino)-l,3-diphenyl-1,3-diphosphetanes are obtained besides the phosphinomethylenephosphanes. Several findings, suggest that their... 

Work from the Grigg group since the late 1990s has focused on extensions of the chemistry detailed above. In one effort, it was shown how the unique reactivity of isocyanides allows them to function as azomethine ylide precursors. The reaction of isocyanide 120 with dipolarophiles 121 proceeds in the presence of silver acetate to afford dehydropyrroles 122 in good yield (Scheme 2.32, Table 2.10). Reaction with dimethyl maleate (76) afforded the corresponding product in excellent yield and diastereoselectivity. In contrast, its stereoisomer, dimethyl fumarate (26), furnished a 6 4 mixture of isomers under identical conditions.59 The authors proposed a stepwise mechanism for this reaction (Scheme 2.33). 

A one-pot, three-component reaction of isocyanides 45, dialkyl acetylenedicarboxylates 46 and ethyl 2-oxo-2-(l,3-thiazol-2-ylamino)acetates 44 provides easy access to 5H-[1,3]thiazolo[3,2- pyrimidinc derivatives 52 <07SL2703>. Presumably, addition of... 

A series of imidazo[2,l-6]thiazole derivatives 71 has been prepared through a catalyst-free three-component reaction in water <07TL7263>. Reaction of isocyanides 66, aryl aldehydes 67, and 2-aminothiazoles 65 in water at 70 °C produces the fused aminothiazoles 71 in good yields. 

Finally, although not a reaction of isocyanide complexes as such, except as labile intermediates, it can be noted that metal hydrido or alkyl compounds can undergo insertion reactions to give acylimidoyl complexes, which can react further ... 

Also, NiCl2 is used as catalyst in this reaction. For example, from 3-amino-5-chlorobenzonitrile and t-pentylisocyanide the corresponding carbodiimide is obtained in 62 % yield. Even bulk gold is used to catalyze the reaction of isocyanides with primary amines in the presence of oxygen. ... 

Mechanistically related processes include the reaction of isocyanides with aldehydes for in situ generation of the activated species, which is then attacked by the azine (Scheme 41a). This strategy has been harnessed in a convenient s)mthesis of... 

Scheme 43 Reactions of isocyanides, DHPs and different iodonium sources...

Phosphazenes, derived from hydrazines and acetylenic esters, were employed in the regioselective synthesis of 5-pyrazolones and pyrazoles <1999T14451>. Reactions of isocyanides 637 and dialkyl acetylenedicarboxylates 638 in the presence of 1,2-diacylhydrazines 639 led to highly functionalized pyrazolines 640 (Equation 133) <2005TL6545>. 

Ugi, I., Werner, B., Domiing, A. Multicomponent reactions of isocyanides and the formation of heterocycles. Targets in Heterocyclic... 

Isocyanides have attracted much attention in synthetic organic chemistry, and have led to the development of a variety of useful synthetic transformations [1]. In particular, carbon-carbon bond forming reactions using isocyanides as key reagents have been extensively studied during the past 50 years, as they allow the realization of useful multi-component assembly reactions, such as the Ugi and Passerini reactions [2]. These have once again been highlighted in recent years with the development of combinatorial chemistry. The characteristic reactions of isocyanides are mostly ascribed to the unique reactivity of the isocyano carbon atom, which can be represented by a divalent, carbene-like electronic structure (Scheme 1). In this respect,... 

---