Isocyanides palladium-catalyzed

The 2,3-substituted indols are formed via a palladium-catalyzed coupling reaction of aryl halide, o-alkenylphenyl isocyanide, and amine (Equation (122)).481 Oxidative addition of an aryl halide, insertion of both the isonitrile and alkene moieties of o-alkenylphenyl isocyanide, and 1,3-hydrogen migration may form a 7r-allylpalladium species, which is then attacked by an amine to afford an indol. 

Palladium-catalyzed bis-silylation of benzynes has been achieved. Reaction of 2-trimethylsilylaryl triflates with cyclic disilanes in the presence of KF/18-crown-6 affords cyclic bis-silylation products in good yields (Equation (29)). It is crucially important to use the palladium-isocyanide catalyst.99 100... 

Addition of disilanes to isocyanides is catalyzed by palladium complexes, giving A-substituted bis(silyl)imino-methanes (Equation (53)).132 A wide range of isocyanides including aryl isocyanides and alkyl isocyanides can take part in the reaction. However, it is important to note that tert-alkyl isocyanides hardly undergo the bis-silylation reaction. This low reactivity of / r/-alkyl isocyanides allows their use as spectator ligands in the catalytic bis-silylations. 

Early findings by Suzuki and co-workers [109] showed that the palladium-catalyzed iminocarbonylative cross-coupling reaction between 9-alkyl-9-BBN derivatives, t-butylisocyanide, and arylhalides gives access to alkyl aryl ketones 132 after hydrolysis of the corresponding ketimine intermediates 131. Presumably, the concentration of free isocyanide is kept to a minimum by its coordination with the borane. Formation of an iminoacylpalladium(II) halide 130 by insertion of isocyanide to the newly formed arylpalladium complex followed by a transmetallation step afford the ketimine intermediates 131 (Scheme 8.52). 

Based on this concept, Whitby and co-workers [110] reported an interesting palladium-catalyzed three-component synthesis of aromatic and heteroaromatic amidines 133 starting from unsaturated halides, amines, and t-butylisocyanide (Scheme 8.53). The catalytic cycle for this iminocarbonylative coupling reaction is analogous to the reactions incorporating carbon monoxide-isoelectronic with isocyanides-as the third partner [111]. 

Using a three-component palladium catalyzed reaction involving the isocyanides 86, allyl carbonates, and trimethylsilyl azide, 1-cyanoindoles 87 were prepared in moderate yields <02 JA11940. 

Ito and his coworkers have reported that palladium-catalyzed oxidative coupling reactions of Grignard reagents in the presence of V-substituted isocyanide dichloride afford diynes (equation 17). Isocyanide dichloride may serve as a reoxidant of the palladium catalyst in this sequence via a catalytic cycie. In addition Kiji and his coworkers have described the oxidative coupling of phenylacetylene by a Pd-Cu catalyst in the presence of 4-iodo-(3//) phenothiazin-3-one. ... 

No appreciable development had been noted in the palladium-catalyzed polymerization of isocyanide until Takashi s group reported a new palladium initiator for the polymerization of aryl isocyanides [32-34]. They tested a series of alkynylpalladium complexes, including mononuclear palladium acetylides 21, ( -ethynediyl) dipalladium complexes 22, and Pd-Pt heteronu-clear -ethynediyl complexes 23, as initiators for the polymerization of isocyanides (Fig. 1) [34]. Although the mononuclear acetylides 21 only under-... 

The palladium-catalyzed living polymerization involving the Pt-Pd het-eronuclear complex 23 was found to be suitable for screw-sense induction using optically active isocyanides (Scheme 30) [52, 53]. Since this catalyst system was only effective for aryl isocyanides, optically pure p- or m-men-... 

The adduct resulting from this Ugi-Smiles coupling contains an N-aryl unit that offers great synthetic potential for further functionalization. Scheme 5.26 shows just one such an example. The reaction of 2-iodo-4-nitrophenol (90) with allylamine, 3-methylbutanal, and benzyl isocyanide in the presence of ammonium chloride afford the Ugi-Smiles adduct 91, which, without purification, underwent palladium-catalyzed Heck cydization to afford indole 92 in 72% yield. Trifluoroacetic add (O.lequiv.) was introduced before addition of the palladium catalyst in order to destroy any remaining isocyanide, which was harmful to the subsequent cydization due to catalyst poisoning [51]. 

Scheme 5.37 Palladium-catalyzed three-component coupling involving isocyanides.

Whitby and co-workers developed general methods for the synthesis of ami-dines (129) [78] and imidates (130) [79] by palladium-catalyzed three-component reactions without using an organometallic reagent as coupling partner [Scheme 5.38, reactions (a) and (b)]. Using an excess of isocyanide, conditions were established for the synthesis of a-iminoimidates [Scheme 5.38, reaction (c)] [80]. The use of a bidentate ligand was found to be important for the success of these reactions. 

Isocyanides undergo palladium catalyzed insertion into the Si—Si bond of disilanes, and, in the case of l,l,2,2-tetramethyl-l,2-disilacyclopentane, ring expansion occurs and the 1,3-disilacyclo-hexane (15) results <87TL1293>. A 1,3-disilacyclohexane may also result from the photolysis of a... 

Palladium-catalyzed reactions of arynes with isocyanides also afford the corresponding [2+2+1] cycloaddition products [67]. For instance, reaction of triflate 55 with isocyanide 160 leads to fluorenimine (161), which can be hydrolysed to fluorenone (154) (Scheme 45). 

Unravelling the labyrinth of palladium-catalyzed syntheses of heterocycles involving isocyanides 13CSR4867. 

In contrast with arylations of other heterocycles, the palladium-catalyzed arylation of benzoxazoles at C-2 proceeds readily at ambient temperature (Scheme 11.21) [67]. Although, as in other cases no kinetic isotope effect was found for 59a, a Hammett plot revealed a correlation with ct with a positive p, which indicates that a phenolate intermediate is formed in this reaction. Therefore, this reaction has been shown to proceed by a totally different mechanism. According to experimental results and DFT calculations, the reactions proceed by the deprotonation of benzoxazoles 59 to form 61, which is in equilibrium with o-phenoxyisocyanide 62. Coordination of the oxidative addition product PdI(Ph)L2 to the isocyanide then forms 63 which cyclizes to form palladate 64, from which the 2-phenylbenzoxazoles 60 are formed by reductive ehmination. 

Other reports of type ac indole syntheses include a traceless directing strategy with nitrosoanilines (130L5394) or A/ -acylhydrazines (13AG(I) 12426), the synthesis of 3-acyl-2-arylindole via a palladium-catalyzed isocyanide insertion and oxypalladation of alkynes (130L3754), and a Fischer indole synthesis with vinyl halides (13AG(I)1266). 

Wu and collaborators devised a palladium-catalyzed one-pot synthesis of 4-imino-3,4-dihydroquinazolin-2-ylphosphonates 88, involving the treatment of 2-iodoarylcarbodiimides 89 with isocyanides, and phosphites in the presence of palladium(II) acetate as the catalyst, 1,1 -bis(diphenylphosphino) ferrocene (dppf) as the ligand, ferric chloride as the Lewis acid, which aids... 

A regioselective three-component domino process involving an initial ring opening of aziridine 151 with 2-iodophenol 152, followed by palladium-catalyzed insertion of isocyanide 153, afforded substituted 1,4-ben-zoxazepines 154 (13ASC3401). 

In 2013, Takemoto and co-workers developed a palladium-catalyzed isocyanide insertion and alkyne functionalization for the synthesis of 2-arylindole derivatives, including tetracyclic carbazoles (Scheme 2.105). In this process, the formation of two C-C bonds via isocyanide insertion was achieved, and isocyanide was effectively used by incorporating both the C and N atoms as components of the indole skeleton. Regarding the reaction mechanism, the reaction started with the oxidative addition of Pd(0) to aryl... 

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