Isocyanides further reactions

Several examples of [5C+1S] cycloaddition reactions have been described involving in all cases a 1,3,5-metalahexatriene carbene complex as the C5-syn-thon and a CO or an isocyanide as the Cl-synthon. Thus,Merlic et al. described the photochemically driven benzannulation of dienylcarbene complexes to produce ortho alkoxyphenol derivatives when the reaction is performed under an atmosphere of CO, or ortho alkoxyanilines when the reaction is thermally performed in the presence of an isonitrile [111] (Scheme 63). In related works, Barluenga et al. carried out analogous reactions under thermal conditions [36a, c, 47a]. Interestingly, the dienylcarbene complexes are obtained in a first step by a [2+2] or a [3S+2C] process (see Sects. 2.3 and 2.5.1). Further reaction of these complexes with CO or an isonitrile leads to highly functionalised aromatic compounds (Scheme 63). 

In the reaction of Ni(CNBu )4 and methyl iodide oligomerization of the isocyanide was observed the only isolable nickel complex was (I), shown below. This product is believed to arise through sequential insertions of three isocyanides into a nickel-carbon bond. Upon further treatment with additional isocyanide at a temperature greater than 60° C one obtains a polymer (RNC) presumably through multiple isocyanide insertion reactions. The addition of benzoyl chloride to Ni(CNBu )4 gave two isolable compounds Ni(CNBu )3(COPh)Cl (74%) and (II) (8.2%). This latter reaction, and the isolation of (II) in particular, suggests that the proposed mechanism for polymerization of isocyanides is reasonable. 

A first terminal imido complex of nickel (121) was prepared according to Equation (3).468 The synthesis goes via the Ni11 amido compound (122) and uses the steric bulk of the arylimido group for stabilization. The Ni11 center in (121) is planar and three-coordinate. Reaction of (121) with CO or benzyl isocyanide leads to formal nitrene transfer with formation of (124) and (125), respectively. Further reaction with CO liberates the isocyanate and carbodiimide (Equation (4)). 69... 

Other multicomponent reactions are exemplified in the following two schemes. A new highly diastereoselective four-component reaction was developed for the synthesis of dihydropyridones 191 substituted with an isocyanide functionality <06OL5369>, thereby generating a synthetically useful complex isocyanide for use in further reactions. In this strategy, a phosphonate, a nitrile, and an aldehyde are used to generate an azadiene intermediate 192, which is trapped by an isocyanoacetate in the same pot. 

Group IV Donors. A new class of Pt complex of the formula [Pt(PPh3)2-(CNBu )] has been isolated from the reaction between [Pt(PPh3)2(C2H4)] and free isocyanide. Further treatment with CO gave [Pt(PPh3)2(CNBu )(CO)], and comparison of the v(NC) frequencies in these two new complexes suggests that CO is a more effective ji-acceptor than the isoelectronic isocyanide. Oxidative addition reactions were also reported. ... 

A free radical can add to CO or an isocyanide (RNC) in the course of a free-radical cyclization reaction, too, to give an acyl radical (RC=0) or an iminyl radical (RC=NR), either of which can undergo further reactions. In the following example, an alkyl radical adds to the terminal C of f-BuNC to give an iminyl radical. The iminyl radical then fragments to give t-Bu- and an alkyl cyanide N=CR. In a different substrate, the iminyl radical may undergo an addition or an abstraction reaction instead. 

A very versatile application of the Ugi reaction has been reported by Keating and Armstrong [42]. They use cyclohexenyl isonitrile (1) as a universal isocyanide in an Ugi four-component condensation. The other components are varied. The reaction products, 2-acylamino-alkanoic acid amides of generic structure 2, can undergo a number of further reactions leading in parts to new types of structures and increased diversity (Scheme 3.4). If a resin with free alcoholic groups is used the acylaminoacyl moiety can be bound to the solid phase before it is subjected to further modifications (resin capture). 

Carbonyl compounds and imines are the electrophilic partner of isocyanides in the Passerini-3CR and the Ugi-4CR, respectively. Other highly electrophilic multiple bonds, such as in dimethyl acetylenedicarboxylate (DMAD), are also known to react with isocyanides. The initially formed 1 1 zwitterionic species having carbanion, carbene character can undergo further reaction with DMAD and isocyanides in different molar ratios, leading to a variety of heterocyclic systems (Scheme 5.32) [69]. 

The adducts from these reactions can be transformed in a variety of compounds. As mentioned earlier, the unstable a-hydrazinoaldehydes are often not isolated but rather subjected to further reactions to yield a more stable compound, such as amino alcohols or oxazolidinones. Other transformations are illustrated in Scheme 11.5. For example, the so-formed a-hydrazinoaldehyde can further react with acetone under catalysis by 1 in a one-pot fashion to give optically active amino alcohols containing two stereogenic centers [19]. A subsequent Passerini reaction of the a-hydrazinoal-dehyde can be performed by reacting the aldehyde with an isocyanide. Schmidt and co-workers [20] have shown that this sequential reaction can provide rapid access to... 

The formation of the chiral formamidine 1658 from octahydroisoquinoline 1656 and the isocyanide 1657 derived from valinol tert-butyl ester gives an intermediate with high chirality-inducing potential, which, through further reaction steps, allows an asymmetric synthesis of (+)-morphinane with high enantiomeric purity (>98% ee in the decisive asymmetric reaction step) [1229]. The isocyanide 1657 is obtained in 85% yield by dehydration of the corresponding formamide with thionyl chloride. 

Since the publication of COMC (1995), significant reports of new platinum(O) isocyanide complexes are restricted to fullerene derivatives, where direct reaction of ( 7 -C6o)Pt with 2 equiv. of isocyanide leads to (7/ -C6o)Pt(CNR)2, 89. Subsequent reaction with 2 further equivalents of isocyanide leads to ( -C6o)Pt(CNR)4, 90, but only with less bulky isocyanides (i.e., not the /-butyl derivative) (Scheme 17). Both new species have 17 resonances for the fullerene, indicating a C- y symmetric complex the tetrakis(isocyanide) complex has IR bands at 2,217, 2,156, and 1,608cm , indicating both bridging and terminal isocyanides. Subsequent reaction of the tetrakis(isocyanide) complex with dppe yields the known complex ( 7 -C-60)Pt(dppe), 91. 

The structural investigation of organometallic intermediates benefits the understanding of reaction mechanism and further reaction chemistry (Scheme 2.6). The reactive intermediate 2-6 features Zr-C(sp ) bond, which was proved to be useful for further synthetic application. 2-6 could react with several unsaturated compounds or electrophiles such as isocyanide, formamide, acid chloride, and aldehyde, alfording a series of A -heterocycles upon hydrolysis (Scheme 2.7). 

The interaction of isocyanides with acetylene complexes has been found to produce various organic and organometallic products differing in the number of alkyne and.isocyanide units incorporated. Cp(Ph3P)Co(PhC2Ph) reacts with two equivalents of isocyanide to form the diimino cobaltacycle (XVni) (Yamazaki et aU 1975). Further reaction of these complexes with additional isocyanide led to the novel cyclopentene derivatives (XIX). These... 

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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