Functional functionalized isocyanides

Coco, S., Espinet, E., Espinet, P. and Palape, I. (2007) Functional isocyanide metal complexes as building blocks for supramolecular materials hydrogen-bonded liquid crystals. Dalton Transactions, (30), 3267-3272. 

The method can be used for the synthesis of functionalized isocyanide complexes, e.g., reaction with ethanolamine produces a 2-hydroxy-ethylisocyanide complex,... 

The use of functionalized isocyanides containing both the isocyanide function and the nucleophile in the same molecule leads to complexes with heterocyclic carbene ligands via a 1,2-addition across the C=N triple bond. Complexes with functionalized isocyanide ligands can be generated in template reactions or a nucleophile functionalized isocyanide can be reacted directly with a suitable metal complex. 

Much simpler than the template-controlled generation of p-functionalized isocyanides is their direct use. 2-Hydroxyalkyl isocyanide 59, where the nucleophilic group and the isocyanide are linked together, spontaneously cyclizes upon activation of the isocyanide by coordination to an electron-poor metal center under... 

Fig. 20 Template-synthesis of (3-functionalized isocyanides followed by cyclization...

The template-controlled generation of ylidene ligands from (3-functionalized isocyanides constitutes an alternative access to complexes with cyclic diaminocar-benes. It proceeds via the complexes with NH,NH-stabilized ylidene ligands which are easily alkylated at the heteroatoms. Such complexes are valuable and reactive intermediates for the generation of complexes with macrocyclic ligands possessing NHC donors (see Sect. 4). 

For particular values see Table 3. iphosphonium functionalized isocyanides. 

Reactions between [M(CN)(CO)5] (M = Cr, Mo, or W) and arene-diazonium ions yield the functionalized isocyanide complexes [M(CO)5-(CNR)] (R = a-tetrahydrofuranyl, CHC12, or CC13) via the mechanism shown in Scheme 1 (56). The initial electron transfer also occurs electro-... 

Reductions (Me,Si)3GeH is a novel reducing agent based on a mechanism involving radicals. It replaces carbon-bound halogen atoms, xanthate functions, isocyanides, phenylseleno, and tertiary nitro groups (10 examples, 96-100%). 

Synthesis of many other functionalized isocyanide coordination compounds have also been developed. Oxidizable anionic cyanides react with diazonium salts to give a-functionalized isocyanide complexes. Arene diazonium chlorides [4-RC6H4N2]C1 (R = H, Cl, Br) react with [M(CN)(CO)5] (M = Cr, Mo, W) in THF, CH2CI2, CHCI3, PhCl, or MeCl to afford complexes of the type... 

ELECTROCHEMICAL LIGAND PARAMETERS FOR PHOSPHONIUM-FUNCTIONALIZED ISOCYANIDES AND DERIVED CARBENES AND INDOLES OF GROUP VI TRANSITION METAL CARBONYLS... 

For the functionalized isocyanide compounds [(CO)5M(o-R3PCH2C5H4NC)]Bp4, the oxidation potentials are only marginally higher than those commonly found in related non-functionalized aromatic isocyanide complexes, thus indicating that the phosphonium group has not a substantial effect on the metal-centred anodic process, possibly as a result of its distance to the metal. 

Electrochemical Ligand Parameters for Phosphonium-Functionalized Isocyanides and Derived Carbenes and Indoles of Group VI Transition Metal Carbonyls M.T.A. Ribeiro, A.J.L. Pombeiro, G. Facchin, M. Mozzon and R.A. MicheUn... 

Initially, the functionalized isocyanides were prepared in template syntheses at metal centers. Beck et al. [30], Fehlhammer et al. [31], and Michelin et al. [32] describe the reactions of complexes bearing isocyanic acid or isocyanide ligands with epoxides or aziridine. These reactions led to /3-functionalized ethyl isocyanides that subsequently cyclized at the metal template to yield cyclic heterocarbenes (Scheme 9.7, method a). Complexes bearing /3-nucleophile substituted isocyanide ligands can also be obtained by the reaction of ethylenediamine or ethanolamine with coordinated trichloromethyl isocyanide [33] or dichlorocarbene ligands [34] followed by cyclization of the intermediately formed /3-functionalized isocyanide ligand (Scheme 9.7, method b). 

Much simpler than the template-controlled generation of /3-functionalized isocyanides is their direct use in the synthesis of NHC complexes. Hydroxyalkylisocyanides such as 2-hydroxyethyl isocyanide are stable molecules but they are also known to become activated on contact with selected metal ions where they isomerizes to Al,0-heterocycles. FehUiammer et al. [40]... 

Scheme 9.7 Syntheses of j8-functionalized isocyanides followed by cylization at a metal template.

While the template-stabilized 2-aminoethyl isocyanide ligand in 48 was observed more or less by accident, the directed stabilization of /3-amino functionalized isocyanides is possible at electron-rich metal templates. Isocyanides 35, 41 and 2-nitrophenyl isocyanide form the electron-rich complexes of types 50 and 51. Reduction of the 2-azido or 2-nitro functions leads to the 2-amino-substituted isocyanides in complexes 52 and 53 that are stabilized by M CsNR backbonding and thus undergo no cyclization to the NH,NH-NHC ligands (Scheme 9.16) [64]. 

Complexes bearing protic NHC ligands are accessible by various synthetic routes such as the deprotonation of azoles followed by reaction with a transition metal complex, the template-controlled cyclization of functionalized isocyanides, and the oxidative addition of different azoles to transition metal complexes. The complexes with simple monodentate NR,NH-NHCs often tend to tautomerize to give the N-bound azoles. This type of tautomerization is prevented in complexes with donor-functionalized NR,NH-NHCs. Recent smdies demonstrate that complexes with protic NHCs obtained from C2-H azoles are formed by an oxidative addition/reductive elimination reaction sequence. The N—H group in complexes with protic NR,NH-NHCs can serve as a hydrogen bond donor and thus as a molecular recognition unit and may enable various types of bifunctional catalysis. Recent smdies indicate that even biomolecules such as caffeine can be C8-metallated. It... 

For the synthesis of highly defined and complex polymer architectures, the Ugi-4CR serves as conjugation method for two kinds of polymers benzaldehyde-terminated PMMA and aniline-terminated PEG 5000 (Scheme 11) [73], For this purpose, the remaining components, isocyanide and carboxyhc acid, were added in high excess (ten and five equivalents, respectively) to achieve full conversion of the parent polymers. Removal of the excess was accomplished via dialysis. Attractively, this approach not only combines two different polymers, but also facilitates the synthesis of mid-functionalized block copolymers by simple introduction of functional isocyanides or carboxylic acids. In this way, Tao and coworkers introduced a fluorescent molecule via the carboxylic acid (using dansylglycine) or a terminal double bond (using 2-acrylamido acetic acid) to obtain a mid-vinyl PMMA-Z -PEG polymer. Mid-reactive polymers are known to behave differently to their end-functionalized counterparts due to the umbrella-effect [74]. Therefore, it was... 

Figure 8 Sponge terpenoids containing the rare isocyanide, isothiocyanide, and dichloroimine functional groups...

Other functional groups that are easily differentiated are cyanide (5c =110-120) from isocyanide (5c = 135- 150), thiocyanate (5c =110-120) from isothiocyanate (5c = 125 - 140), cyanate (5c = 105- 120) from isocyanate (5c = 120- 135) and aliphatic C atoms which are bonded to different heteroatoms or substituents (Table 2.2). Thus ether-methoxy generally appears between 5c = 55 and 62, ester-methoxy at 5c = 52 N-methyl generally lies between 5c = 30 and 45 and. S-methyl at about 5c = 25. However, methyl signals at 5c = 20 may also arise from methyl groups attached to C=X or C=C double bonds, e.g. as in acetyl, C//j-CO-. 

The Ugi reaction is the four-component condensation of an amine, aldehyde or ketone, carboxylic acid and isocyanide to give an o -acylamino amide [22-24], Although this process has the potential to introduce considerable diversity, the products themselves are not heterocycles but through appropriate choice of substrates, latent functionality in one of the precursors can intercept either an intermediate or further derivatize the acylamino amide Ugi product through post-modification. Thus variants of the Ugi reaction have been investigated under microwave-assisted conditions for the synthesis of diverse heterocyclic libraries [16,19-24],... 

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